WO2004089416A2 - Combination of an 11beta-hydroxysteroid dehydrogenase type 1 inhibitor and an antihypertensive agent - Google Patents

Combination of an 11beta-hydroxysteroid dehydrogenase type 1 inhibitor and an antihypertensive agent Download PDF

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Publication number
WO2004089416A2
WO2004089416A2 PCT/DK2004/000254 DK2004000254W WO2004089416A2 WO 2004089416 A2 WO2004089416 A2 WO 2004089416A2 DK 2004000254 W DK2004000254 W DK 2004000254W WO 2004089416 A2 WO2004089416 A2 WO 2004089416A2
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Prior art keywords
phenyl
methyl
methanone
alkyl
triazol
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PCT/DK2004/000254
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French (fr)
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WO2004089416A3 (en
Inventor
Gita Camilla Tejlgaard Kampen
Henrik Sune Andersen
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Novo Nordisk A/S
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Priority to JP2006504357A priority Critical patent/JP2006522750A/en
Priority to EP04725887A priority patent/EP1615666A2/en
Publication of WO2004089416A2 publication Critical patent/WO2004089416A2/en
Publication of WO2004089416A3 publication Critical patent/WO2004089416A3/en
Priority to US11/254,125 priority patent/US7501405B2/en
Priority to US12/363,056 priority patent/US20090137574A1/en

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Definitions

  • the instant invention involves a combination therapy comprising the administration of an 11 ?-hydroxysteroid dehydrogenase type 1 inhibitor and an antihypertensive agent for treating, preventing and reducing the risk of developing insulin resistance, dyslipidemia, obesity, hypertension and other related diseases and disorders.
  • the metabolic syndrome is a major global health problem.
  • the metabolic syndrome is characterized by a combination of insulin resistance, dyslipidemia, obesity and hypertension leading to increased morbidity and mortality of cardiovascular diseases.
  • People with the metabolic syndrome are at increased risk of developing frank type 2 diabetes mellitus, the frequency of which is equally escalating.
  • type 2 diabetes the combination of insulin resistance with obesity and dyslipidemia is also highly prevalent and around 70% of people with type 2 diabetes additionally have hypertension, once again leading to increased mortality of cardiovascular diseases.
  • 11 ?-Hydroxysteroid dehydrogenase type 1 (11 ?-HSD1 ) catalyses the local generation of active glucocorticoid in several tissues and organs including predominantly the liver and adipose tissue, but also e.g. skeletal muscle, bone, pancreas, endothelium, ocular tissue and certain parts of the central nervous system.
  • 11 ? ⁇ HSD1 serves as a local regulator of glucocorticoid actions in the tissues and organs where it is expressed (Tannin et al., J. Biol.
  • 11 ⁇ -HSD1 in the metabolic syndrome and type 2 diabetes is supported by several lines of evidence.
  • treatment with the non-specific 11y#-HSD1 inhibitor carbenoxolone improves insulin sensitivity in lean healthy volunteers and people with type 2 diabetes.
  • 11 MHSD1 knock-out mice are resistant to insulin resistance induced by obesity and stress.
  • the knock-out mice present with an anti-atherogenic lipid profile of decreased VLDL triglycerides and increased HDL-cholesterol.
  • mice that over-express 11 -HSD1 in adipocytes develop insulin resistance, hyperlipidemia, visceral obesity and hypertension, a phenotype that resembles the human metabolic syndrome
  • 11 MHSD1 promotes the features of the metabolic syndrome by increasing hepatic expression of the rate-limiting enzymes in gluconeogenesis, namely phosphoenolpyuvate carboxykinase and glucose-6-phosphatase, promoting the differentiation of preadipocytes into adipocytes thus facilitating obesity, directly and indirectly stimulating hepatic VLDL secretion, decreasing hepatic LDL uptake and increasing vessel contractility, presumably by decreasing the levels of endothelial nitric oxide synthase and consequently the levels of the vasodialating substance nitric oxide (Kotelevtsev et al., Proc. Natl. Acad. Sci. USA, 94, 14924(1997); Morton et al., J. Biol. Chem. 276, 4
  • 11 ?-HSD1 inhibitors constitute a new therapeutic principle for the treatment of insulin resistance, dyslipidemia, obesity and hypertension.
  • monotherapeutic treatment of hypertension often lacks efficacy due, at least in part, to the induction of compensatory mechanisms.
  • the instant invention addresses this problem by providing a combination therapy comprising an 11 ?-HSD1 inhibitor and an antihypertensive agent for the treatment of e.g. the metabolic syndrome and type 2 diabetes.
  • a combination therapy comprising an 11 ?-HSD1 inhibitor and an antihypertensive agent for the treatment of e.g. the metabolic syndrome and type 2 diabetes.
  • the 11 7-HSD1 inhibitor together with the antihypertensive agent provide improved control of hypertension and/or improved treatment ofthe metabolic syndrome and type 2 diabetes thereby reducing the risk for late complications, e.g. cardiovascular diseases and nephropathy.
  • lesser dosage amounts of the 11 7-HSD1 inhibitor and more particularly the antihypertensive agent may be needed to achieve the desired clinical result, thereby resulting in improved safety.
  • inhibitors and/or modulators of the human 1 ⁇ -hydroxysteroid dehydrogenase type 1 enzyme can be found in WO 01/90090, WO 01/90091, WO 01/90092, WO 01/90093, WO 01/90094, WO 02/72084 and WO 02/076435, as well as the following patent applications under common ownership of the present application: PA 200300569 filed 11 April 2003 DK, PA 200300565 filed 11 April 2003 DK, PA 200300571 filed 11 April 2003 DK, PA 2003 00570 filed 11 April 2003 DK, PA 2003 00566 filed 11 April 2003 DK, PA 2003 00972 filed 27 June 2003 DK, PA 200300998 filed 02 July 2003 DK, PA 2003 00988 filed 30 June 2003 DK, PA 200300989 filed 30 June 2003 DK, PA 200300990 filed 30 June 2003 DK, and PA 200301910 filed 22 December 2003 DK, the contents of which are hereby incorporated by reference in their entirety.
  • An object of the present invention is to provide a novel combination therapy comprised of a therapeutically effective amount of an antihypertensive agent in combination with an 1 ⁇ - hydroxysteroid dehydrogenase type 1 inhibitor (11 ?-HSD1) for the treatment, prevention and to reduce the risk of developing, metabolic syndrome, insulin resistance, dyslipidemia, obesity, hypertension and related diseases and disorders.
  • an antihypertensive agent in combination with an 1 ⁇ - hydroxysteroid dehydrogenase type 1 inhibitor (11 ?-HSD1) for the treatment, prevention and to reduce the risk of developing, metabolic syndrome, insulin resistance, dyslipidemia, obesity, hypertension and related diseases and disorders.
  • halo includes fluorine, chlorine, bromine, and iodine.
  • trihalomethyl includes trifluoromethyl, trichloromethyl, tribromomethyl, and triiodomethyl.
  • trihalomethoxy includes trifluorometoxy, trichlorometoxy, tribromometoxy, and triiodometoxy.
  • alkyl includes C C 6 straight chain saturated and methylene aliphatic hydrocarbon groups, C 3 -C 6 branched saturated hydrocarbon groups having the specified number of carbon atoms.
  • this definition shall include but is not limited to methyl (Me), ethyl (Et), propyl (Pr), butyl (Bu), pentyl, hexyl, isopropyl (i-Pr), isobutyl (i-Bu), tert-butyl (-•Bu), sec-butyl (s-Bu), isopentyl, neopentyl, and the like.
  • alkenyl includes C 2 -C 6 straight chain unsaturated aliphatic hydrocarbon groups and branched C 3 -C 6 unsaturated aliphatic hydrocarbon groups having the specified number of carbon atoms.
  • this definition shall include but is not limited to ethenyl, propenyl, butenyl, pentenyl, hexenyl, methylpropenyl, methylbutenyl and the like.
  • alkynyl includes C 2 -C 6 straight chain unsaturated aliphatic hydrocarbon groups and C 4 -C 6 branched unsaturated aliphatic hydrocarbon groups having the specified number of carbon atoms.
  • this definition shall include but is not limited to ethynyl, propynyl, butynyl, pentynyl, hexynyl, methylbutynyl, and the like.
  • saturated or partially saturated cyclic, bicyclic or tricyclic ring system represents but are not limit to aziridinyl, pyrrolinyl, pyrrolidinyl, 2-imidazolinyl, imidazolidinyl, 2- pyrazolinyl, morpholinyl, piperidinyl, thiomorpholinyl, piperazinyl, phthalimide, 1,2,3,4- tetrahydro-quinolinyl, 1,2,3,4-tetrahydro-isoquinolinyl, 1,2,3,4-tetrahydro-quinoxalinyl, and indolinyl.
  • saturated or partially saturated cyclic ring system represents but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cydoheptenyl, cyclooctenyl, cyclononenyl, cyclodecenyl, tetrahydrofuranyl or tetrahydropyranyl.
  • saturated or partially saturated aromatic ring system represents but are not limited to cyclopentyl, cyclohexyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cydoheptenyl, cyclooctenyl, cyclononenyl, cyclodecenyl, tetrahydrofuranyl, tetrahydropyranyl, phenyl, pyridyl or pyrimidinyl.
  • cycloalkyl e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, bicyclo[3.2.1]octyl, spiro[4.5]decyl, norpinyl, norbonyl, norcaryl, adamantyl and the like
  • cycloalkylalkyl e.g. cyclopropylmethyl, cyclobutylethyl, adamantylmethyl and the like
  • cycloalkenyl e.g.
  • cyclobutenyl represents a partially saturated, mono-, bi-, tri- or spirocarbocyclic group having the specified number of carbon atoms.
  • heteroalkyl (tetrahydrofuranyl, tetrahydropyranyl, tertahydrothiopyranyl, and the like) represents a saturated mono-, bi-, tri- or spirocarbocyclic group having the specified number of carbon atoms and one or two additional heteroatoms or groups selected from nitrogen, oxygen, sulphur, SO or S0 2 .
  • alkyloxy (e.g. methoxy, ethoxy, propyloxy, allyloxy, cyclohexyloxy) represents an alkyl group as defined above having the indicated number of carbon atoms attached through an oxygen bridge.
  • alkyloxyalkyl (e.g. methyloxymethyl and the like) represents an alkyloxy group as defined above attached through an "alkyl” group.
  • aryloxyhetaryl e.g. 2-phenoxy-pyridyl and the like
  • aryloxy e.g. phenoxy, naphthyloxy and the like
  • hetaryloxy e.g. 2-pyridyloxy and the like
  • arylalkyloxy e.g. phenethyloxy, naphthylmethyloxy and the like
  • arylalkyloxy represents an arylalkyl group as defined below attached through an oxygen bridge.
  • hetarylalkyloxy e.g. 2-pyridylmethyIoxy and the like
  • hetarylalkyloxy represents a hetarylalkyl group as defined below attached through an oxygen bridge.
  • alkyloxycarbonyl e.g. methylformiat, ethylformiat and the like
  • alkyloxycarbonyl represents an alkyloxy group as defined above attached through a carbonyl group.
  • aryloxycarbonyl e.g. phenylformiat, 2-thiazolylformiat and the like
  • arylalkyloxycarbonyl e.g. benzylformiat, phenyletylformiat and the like
  • arylalkyl e.g. benzyl, phenylethyl, 3-phenylpropyl, 1-naphtylmethyl, 2-(1- naphtyl)ethyl and the like
  • arylalkyl represents an aryl group as defined below attached through an alkyl having the indicated number of carbon atoms or substituted alkyl group as defined above.
  • hetarylalkyl e.g. (2-furyl)methyl, (3-furyl)methyl, (2-thienyl)methyl, (3- thienyl)methyl, (2-pyridyl)methyl, 1 -methyl-1 -(2-pyrimidyl)ethyl and the like
  • alkylcarbonyl e.g. octylcarbonyl, pentylcarbonyl, 3-hexenylcarbonyl
  • alkylcarbonyl represents an alkyl group as defined above having the indicated number of carbon atoms attached through a carbonyl group.
  • arylcarbonyl e.g. benzoyl
  • hetarylcarbonyl e.g. 2-thiophenylcarbonyl, 3-methoxy-anthrylcarbonyl, oxazolylcarbonyl and the like
  • carbonylalkyl e.g. acetyl and the like
  • alkylcarbonylalkyl e.g. propan-2-one, 4,4-dimethyl-pentan-2-one and the like
  • alkylcarbonylalkyl represents an alkylcarbonyl group as defined above attached through an alkyl group as defined above having the indicated number of carbon atoms.
  • arylcarbonylalkyl e.g. 1-phenyl-propan-l-one, 1-(3-chloro-phenyl)-2- methyl-butan-1-one and the like
  • arylcarbonylalkyl represents a arylcarbonyl group as defined above attached through an alkyl group as defined above having the indicated number of carbon atoms.
  • hetarylcarbonylalkyl e.g. 1-pyridin-2-yl-propan-1-one, 1-(1-H-imidazol-2-yl)- propan-1-one and the like
  • arylalkylcarbonyl e.g. phenylpropylcarbonyl, phenylethylcarbonyl and the like
  • hetarylalkylcarbonyl (e.g. imidazolylpentylcarbonyl and the like) represents an hetarylalkyl group as defined above wherein the alkyl group is in turn attached through a carbonyl.
  • alkylcarboxy e.g. heptylcarboxy, cyclopropylcarboxy, 3-pentenylcarboxy
  • alkylcarboxy represents an alkylcarbonyl group as defined above wherein the carbonyl is in turn attached through an oxygen bridge.
  • arylcarboxy e.g. benzoic acid and the like
  • arylcarbonyl group as defined above wherein the carbonyl is in turn attached through an oxygen bridge.
  • alkylcarboxyalkyl e.g. heptylcarboxymethyl, propylcarboxy tert-butyl, 3- pentylcarboxyethyl
  • arylalkylcarboxy e.g. benzylcarboxy, phenylpropylcarboxy and the like
  • arylalkylcarbonyl group as defined above wherein the carbonyl is in turn attached through an oxygen bridge.
  • arylalkylcarboxyalkyl e.g. benzylcarboxymethyl, phenylpropylcarboxypropyl and the like
  • arylalkylcarboxyalkyl represents an arylalkylcarboxy group as defined above wherein the carboxy group is in turn attached through an alkyl group as defined above having the indicated number of carbon atoms.
  • hetarylcarboxy e.g. pyridine-2-carboxylic acid and the like
  • hetarylalkylcarboxy e.g. (1-H-imidazol-2-yl)-acetic acid, 3-pyrimidin-2-yl- propionic acid and the like
  • alkylthio e.g. methylthio, ethylthio and the like
  • alkyl group as defined above attached through a sulphur bridge.
  • arylthio e.g. benzenthiol, naphthylthiol and the like
  • hetarylthio e.g. pyridine-2-thiol, thiazole-2-thiol and the like
  • arylthioalkyl e.g. methylsulfanyl benzene, ethylsulfanyl naphthalene and the like
  • arylthioalkyl represents an arylthio group as defined below attached through an alkyl group having the indicated number of carbon atoms.
  • hetarylthioalkyl e.g. 2-methylsulfanyl-pyridine, 1-ethylsulfanyl-isoquinoline and the like
  • hetaryloxyaryl e.g. 1-phenoxy-isoquinolyl, 2-phenoxypyridyl and the like
  • aryloxyaryl represents a hetaryloxy group as defined above attached through an “aryl” group as defined below.
  • hetaryloxyhetaryl e.g. 1-(2-pyridyloxy-isoquinoline), 2-(imidazol ⁇ 2-yloxy- pyridine) and the like
  • hetaryloxyhetaryl represents a hetaryloxy group as defined above attached through a "hetaryl” group as defined below.
  • aryloxyalkyl e.g. phenoxymethyl, naphthyloxyethyl and the like
  • alkyl e.g. phenoxymethyl, naphthyloxyethyl and the like
  • aryloxyaryl e.g. 1-phenoxy-naphthalene, phenyloxyphenyl and the like
  • aryloxyalkyl e.g. ethoxymethyl-benzene, 2-methoxymethyl- naphthalene and the like
  • alkyl alkyl
  • hetaryloxyalkyl e.g. 2-pyridyloxymethyl, 2-quinolyloxyethyl and the like
  • hetaryloxyalkyl represents a hetaryloxy group as defined above attached through an “alkyl” group having the indicated number of carbon atoms.
  • hetarylalkyloxyalkyl (e.g. 4-methoxymethyl-pyrimidine, 2-methoxymethyl- quinoline and the like) represents a hetarylalkyloxy group as defined above attached through an "alkyl” group having the indicated number of carbon atoms.
  • alkylcarbonylamino e.g. methylcarbonylamino, cyclopentylcarbonyl- aminomethyl, methylcarbonylaminophenyl
  • alkylcarbonylamino represents an "alkylcarbonyl” group as defined above wherein the carbonyl is in turn attached through the nitrogen atom of an amino group.
  • the nitrogen atom may itself be substituted with an alkyl or aryl group.
  • alkylcarbonylaminoalkyl e.g.N-propyl-acetamide, N-butyl-propionamide and the like
  • alkylcarbonylaminoalkyl represents an “alkylcarbonylamino” group attached through an alkyl group as defined above having the indicated number of carbon atoms.
  • arylalkylcarbonylamino e.g. phenylacetamide, 3phenyl-propionamide and the like
  • arylalkylcarbonylamino represents an “arylalkylcarbonyl” group as defined above attached through an amino group.
  • arylalkylcarbonylaminoalkyl e.g. N-ethyl-phenylacetamide, N-butyl-3- phenyl-propionamide and the like
  • arylalkylcarbonylaminoalkyl represents an “arylalkylcarbonylamino” group attached through an alkyl group as defined above having the indicated number of carbon atoms.
  • arylcarbonylamino e.g. benzamide, naphthalene-1 -carboxylic acid amide and the like
  • arylcarbonylaminoalkyl e.g. N-propyl-benzamide, N-Butyl-naphthalene-1- carboxylic acid amide and the like
  • alkyl group as defined above having the indicated number of carbon atoms.
  • aryl includes but is not limited to a carbocyclic aromatic ring system being either monocyclic, bicyclic, or polycyclic, such as phenyl, biphenyl, naphthyl, anthracenyl, phenanthrenyl, fluorenyl, indenyl, pentalenyl, azulenyl, biphenylenyl and the like.
  • Aryl is also intended to include the partially hydrogenated derivatives of the carbocyclic aromatic systems enumerated above. Non-limiting examples of such partially hydrogenated derivatives are 1 ,2,3,4-tetrahydronaphthyl, 1 ,4-dihydronaphthyl and the like.
  • heteroaryl includes but is not limited to pyrrolyl (2-pyrrolyl), pyrazolyl (3- pyrazolyl), imidazolyl (1 -imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl), triazolyl (1,2,3- triazol-1-yl, 1,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-3-yl), oxazolyl (2-oxazolyl, 4- oxazolyl, 5-oxazolyl), isoxazolyl (3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl), thiazolyl (2-thiazolyl, 4-thiazolyl, 5-thiazolyl), thiophenyl (2-thiophenyI, 3-thiophenyl, 4-thiophenyl, 5-thiophenyl), furanyl (2-
  • NR R 5 carbonylalkyl e.g. ⁇ /./V-dimethyl- propionamide, ⁇ /-isopropyl- ⁇ /-methyl-propionamide and the like
  • alkylR 6 alkyl e.g. 2-ethoxymethyl, N-ethyl-N- methy amine, methyl-propyl-amide, ethanesulfonic acid methylamide and the like
  • R 6 represents an alkyl group as defined above, substituted by R 6 , which is substituted by an alkyl group as defined above, wherein R 6 is as defined for Formula II herein.
  • arylR 6 alkyl e.g. ethoxy-benzene, ethyl-methyl- phenyl-amine, ⁇ /-ethyl-benzamide, ⁇ /-isobutyl-benzenesulfonamide and the like
  • R 6 represents an aryl group as defined above, substituted by R 6 , which is substituted by an alkyl group as defined above, wherein R 6 is as defined for Formula II herein.
  • arylalkylR 6 alkyl e.g.
  • benzyloxymethyl, ethyl- methyl-benzyl-amine, ⁇ /-ethyl-benzylamide and the like represents an arylalkyl group as defined above, substituted by R 6 , which is substituted by an alkyl group as defined above, wherein R 6 is as defined for Formula II herein.
  • R 6 is as defined for Formula II herein.
  • hetarylR 6 alkyl e.g.
  • 2-ethoxy-1H-imidazol, ethyl- quinolin-2-yl-amine, thiazole-2-carboxylic acid, methyl-propyl-amide, pyridine-3-sulfonic acid isobutyl-amide and the like) represents a hetaryl group as defined above, substituted by R 6 , which is substituted by an alkyl group as defined above, wherein R 6 is as defined for Formula II herein.
  • arylcarbonylNR 15 e.g. ⁇ /-benzyl- ⁇ /-methyl- benzamide and the like
  • alkylSO n (e.g. ethylsulfonyl, ethylsulfinyl and the like) represents an alkyl group as defined above, wherein the alkyl group is in turn attached through a sulphur bridge wherein the sulphur is substituted with n oxygen atoms, wherein n is as defined for Formula II herein.
  • arylSO m (e.g. phenylsulfinyl, naphthyl-2-sulfonyl and the like) represents an aryl group as defined above, wherein the aryl group is in turn attached through a sulphur bridge wherein the sulphur is substituted with m oxygen atoms, wherein m is as defined for Formula II herein.
  • hetarylSO m (e.g. thiazol-2-sulfinyl, pyridine-2- sulfonyl and the like) represents a hetaryl group as defined above, wherein the hetaryl group is in turn attached through a sulphur bridge wherein the sulphur is substituted with m oxygen atoms, wherein is as defined for Formula II herein.
  • arylSO m NR 8 e.g.
  • W-methyl-benzenesulfonamide and the like represents an aryl group as defined above, wherein the aryl group is in turn attached through a SO m NR 8 group wherein the sulphur is substituted with m oxygen atoms and the nitrogen atom substituted by R 8 , wherein R 8 and m are as defined for Formula II herein.
  • NR 4 R 5 carbonylalkyl e.g. ⁇ /, ⁇ /-dimethyl- propionamide, ⁇ /-isopropyl- ⁇ /-methyl-propionamide and the like
  • arylR 8 alkyl e.g. ethoxy-benzene, ethyl-methyl- phenyl-amine, ⁇ /-ethyl-benzamide, ⁇ /-isobutyl-benzenesulfonamide and the like
  • R 8 represents an aryl group as defined above, substituted by R 8 , which is substituted by an alkyl group as defined above, wherein R 8 is as defined for Formula V herein.
  • hetarylR 8 alkyl e.g. 2-ethoxy-1 H-imidazol, ethyl- quinolin-2-yl-amine, thiazole-2-carboxylic acid, methyl-propyl-amide, pyridine-3-sulfonic acid isobutyl-amide and the like
  • R 8 represents a hetaryl group as defined above, substituted by R 8 , which is substituted by an alkyl group as defined above, wherein R 8 is as defined for Formula V herein.
  • arylcarbonyl NR 15 (e.g. ⁇ /-benzyl- ⁇ /-methyl- benzamide and the like) represents an arylcarbonyl group as defined above, substituted by NR 15 , wherein R 15 is as defined for Formula V herein.
  • treatment is defined as the management and care of a patient for the purpose of combating or alleviating the disease, condition or disorder, and the term includes the administration of the active compound to prevent the onset of the symptoms or complications, or alleviating the symptoms or complications, or eliminating the disease, condition, or disorder.
  • pharmaceutically acceptable is defined as being suitable for administration to humans without adverse events.
  • prodrug is defined as a chemically modified form of the active drug, said prodrug being administered to the patient and subsequently being converted to the active drug. Techniques for development of prodrugs are well known in the art.
  • combination therapy is defined as the administration of a single pharmaceutical dosage formulation which comprises the 11 ?-HSD1 inhibitor and the antihypertensive agent, as well as administration of each active agent in its own separate pharmaceutical dosage formulation.
  • the 11/?- HSD1 inhibitor and the anti-hypertensive agent can be administered to the patient at essentially the same time, i.e. concurrently, or at separate staggered times, i.e. sequentially.
  • the route of administration may be the same or different for each agent. Any route of administration known or contemplated for the individual agents is acceptable for the practice of the present invention.
  • terapéuticaally effective amount is defined as the amount of drug or pharmaceutical agent that will elicit the biological or medical response of a tissue, a system or a mammal that is sought by the treating individual, i.e. medical doctor or other clinician.
  • modulation are intended to include stimulation (e.g., increasing or upregulating a particular response or activity) and inhibition (e.g., decreasing or downregulating a particular response or activity).
  • agonist is intended to indicate a substance that activates the receptor(s).
  • R 3 and R 5 independently are hydrogen, NR 13 R 14 trihalomethyl, trihalomethoxy, C ⁇ -C 6 alkyl, C 2 - C 6 alkenyl, C 2 -C 6 alkynyl, CrC 6 alkyloxy, C C 6 alkylthio, aryl, aryld-Cealkyl, hetaryl or hetarylCrC 6 alkyl, wherein alkyl, alkynyl, alkenyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R 8 ;
  • R 6 and R 7 independently are d-C ⁇ alkyl, C 3 -C 10 cycloalkyl, hetC 3 -C 10 cycloalkyl, aryld-C 6 alkyl or hetarylCrCealkyl, wherein the alkyl, cycloalkyl, hetcycloalkyl, arylalkyl, and hetarylalkyl groups independently are optionally substituted with one or more of R 10 ; or
  • R 6 and R 7 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC 6 alkyl, aryl, hetaryl, arylCrCealkyl, halo, hydroxy, oxo, CrC 6 alkyloxy, aryld-Cealkyloxy, hetarylCrCealkyloxy, CrC 6 alkyloxyCr C 6 alkyl, d-C 6 alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetaryld- C 6 alkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarbox
  • R 8 and R 9 independently are hydrogen, halo, hydroxy, oxo, cyano, nitro, C 3 -C 10 cycloalkyl, C 3 - dohetocycloalkyl, d-C 6 alkyl, CrC 6 alkyloxy, trihalomethyl, trihalomethoxy, aryld-C 6 alkyloxy, hetarylCrCealkyloxy, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy, hetaryld-Cealkylcarboxy, CrC 6 alkylcar bonylamino or aryld-C 6 alkylcarbonyl- amino;
  • R 10 is hydrogen, halo, cyano, nitro, hydroxy, oxo, C 3 -C 10 cycloalkyl, C 3 -C 10 hetcycloalkyl, CrCealkyl, CrC 6 alkyloxy, trihalomethyl, trihalometh dialkylamino oxy, aryld-C 6 alkyloxy, hetaryld- C 6 alkyloxy, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, d-Cealkylcarboxy, arylcarboxy or aryld-C 6 alkylcarboxy;
  • R 11 is d-Cealkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, aryld-C e alkyl, hetaryld-dalkyl, d-C 6 alkyl- carbonylCrC 6 alkyl, d-C-ealkyloxy, aryloxy, C C 6 alkyloxy, arylcarbonyl, arylCrC 6 alkyl- carbonyl, hetarylcarbonylC C 6 alkyl, wherein the alkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R 9 ;
  • R 2 is d-Cealkylcarbonylaminod-Cealkyl, arylcarbonylaminoCrC 6 alkyl or arylCrC 6 alkyl- carbonylaminod-C 6 alkyl;
  • R 13 and R 14 independently are hydrogen, oxo, C 3 -C 10 cycloalkyl, CrC 6 alkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl;
  • R 15 is hydrogen, C 3 -C 10 cycloalkyl, CrC 6 alkyl, aryl, hetaryl, arylCrC 6 alkyl, hetaryld-Cealkyl, CrC 6 alkyloxyalkyl or arylCrC 6 alkyloxyalkyl; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
  • R 3 and R 5 independently are hydrogen, NR 13 R 14 trihalomethyl, trihalomethoxy, d-Cealkyl, C 2 - C 6 alkenyl, C 2 -C 6 alkynyl, CrC 6 alkyloxy, CrC 6 alkylthio, aryl, aryld-C 6 alkyl, hetaryl or hetarylCrCealkyl, wherein alkyl, alkynyl, alkenyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R 8 ;
  • R 6 and R 7 independently are d-Cealkyl, C 3 -C 10 cycloalkyl, hetC 3 -C 10 cycloalkyl, arylCrCealkyl or hetaryld-Cealkyl, wherein the alkyl, cycloalkyl, hetcycloalkyl, arylalkyl, and hetarylalkyl groups independently are optionally substituted with one or more of R 10 ; or
  • R 6 and R 7 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, aryl CrC 6 al kyl, halo, hydroxy, oxo, CrCealkyloxy, aryld-Cealkyloxy, hetarylCrCealkyloxy, d-Cealkyloxyd- C 6 alkyl, CrC 6 alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetaryld- C 6 alkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetaryl
  • R 8 and R 9 independently are hydrogen, halo, hydroxy, oxo, cyano, nitro, C 3 -C ⁇ 0 cycloalkyl, C 3 - dohetocycloalkyl, d-Cealkyl, CrC 6 alkyloxy, trihalomethyl, trihalomethoxy, arylCrC 6 alkyloxy, hetarylCrCealkyloxy, d-Cealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy, hetarylCrC 6 alkylcarboxy, CrC 6 aIkylcarbonylamino or arylC ⁇ -C 6 alkylcarbonyl- amino
  • R 10 is hydrogen, halo, cyano, nitro, hydroxy, oxo, C 3 -C 10 cycloalkyl, C 3 -C 10 hetcycloalkyl, CrCealkyl, CrC 6 alkyloxy, trihalomethyl, trihalometh dialkylamino oxy, arylCrC 6 alkyloxy, hetaryld- C 6 aIkyloxy, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrC 6 alkylcarboxy, arylcarboxy or aryld-C 6 alkylcarboxy;
  • R 11 is d-C ⁇ alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, arylCrC 6 alkyl, hetaryld-Cealkyl, d-C 6 alkyl- carbonylCrC 6 alkyl, CrC ⁇ alkyl, arylcarbonyl, arylCrCealkylcarbonyl, hetarylcarbonylCrC 6 - alkyl, wherein the alkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R 9 ;
  • R 12 is d-CealkylcarbonylaminoCrCealkyl, arylcarbonylaminoC C 6 alkyl or arylCrC 6 alkyl- carbonylaminoCrC 6 alkyl;
  • R 13 and R 14 independently are hydrogen, oxo, C 3 -C 10 cycloalkyl, CrC 6 alkyl, CrC 6 alkyloxy, trihalomethyl, trihalomethoxy, aryld-C 6 alkyloxy, hetarylCrCealkyloxy, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy;
  • R 15 is hydrogen, C 3 -C 10 cycloalkyl, CrC 6 alkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrCealkyl, CrC 6 alkyloxyalkyl or arylCrC 6 alkyloxyalkyl; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
  • said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R 3 and R 5 independently are hydrogen, trihalomethyl, d-Cealkyl, CrC 6 alkyloxy, aryl, arylCrCealkyl, hetaryl or hetaryld-Cealkyl, wherein alkyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R 8 .
  • said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R 6 and R 7 independently are d-Cealkyl, C 3 -C 10 cycloalkyl, hetC 3 - Ciocycloalkyl, arylCrC 6 alkyl or hetaryld-Cealkyl, wherein the alkyl, cycloalkyl, hetcycloalkyl, arylalkyl, and hetarylalkyl groups independently are optionally substituted with one or more of R 10 .
  • said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I)
  • R 6 and R 7 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, arylCrC 6 alkyl, halo, hydroxy, oxo, CrC 6 alkyloxy, arylCrCealkyloxy, hetaryld- C 6 alkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylC C 6 al
  • said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R 6 and R 7 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional nitrogen atoms, the ring system optionally being substituted with at least one of d-C 6 alkyl, aryl, hetaryl, arylCrCealkyl, halo, hydroxy, oxo, CrCealkyloxy, aryld-C 6 alkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl.
  • said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R 8 and R 9 independently are hydrogen, halo, hydroxy, oxo, cyanoC 3 -C 10 cycloalkyl, C 3 -C 10 hetocycloalkyl, d-Cealkyl, C ⁇ -C 6 alkyloxy, trihalomethyl, aryld- Cealkyloxy, hetarylCrCealkyloxy.
  • said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R 0 is hydrogen, halo, cyano, nitro, hydroxy, oxo, C 3 -C ⁇ 0 cycloalkyl, C 3 -Ci 0 hetcycloalkyl, d-C 6 alkyl, CrCealkyloxy, arylCrC 6 alkyloxy, hetarylCrCealkyloxy, d- C 6 alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or aryld-C 6 alkylcarboxy.
  • said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R 1 is d-Cealkyl, arylCrC 6 alkyl, hetary!d-C 6 alkyl, d-Cealkyloxy, aryloxy, CrC 6 alkyloxy, wherein the alkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R 9 .
  • said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R 12 is CrCealkylcarbonylaminod-Cealkyl, arylcarbonylaminod- C 6 alkyl or aryld-CealkylcarbonylaminoCrCealkyl.
  • said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R 13 and R 14 independently are hydrogen, C 3 -C ⁇ 0 cycloalkyl, Ci- Cealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl.
  • said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R 15 is hydrogen, C 3 -C 10 cycloalkyl, CrC 6 alkyl, aryl, hetaryl, aryld- C 6 alkyl, hetarylCrCealkyl, d-Cealkyloxyalkyl or arylCrC 6 alkyloxyalkyl.
  • said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of:
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II)
  • R 1 is C 3 -C 10 cycloalkyl, C 3 -C ⁇ 0 hetcycloalkyl, C C 8 alkyl, aryl, hetaryl, aryld-Cealkyl or hetarylCrCealkyl, wherein the cycloalkyl, hetcycloalkyl, alkyl, arylalkyl and hetarylalkyl groups independently are optionally substituted with one or more of R 4 .
  • R 2 is hydrogen, CrC 8 alkyl, aryl, hetaryl, arylCrC 6 alkyl, C 3 -C ⁇ ocycloalkylCrC 6 alkyI, d-C 6 alkyl- carboxyd-C 6 alkyI wherein the alkyl, aryl and cycloalkyl groups independently are optionally substituted with one or more of R 5 ; or
  • R 1 and R 2 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC 8 alkyl, aryl, hetaryl, arylCrC 6 alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrCealkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C 6 alkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, aryl
  • R 3 is CrC 8 alkyl, CrC 6 alkenyl, d-C 6 alkynyl, C 3 -d 0 cycloalkyl, C 3 -C 10 hetcycloalkyl, aryl, hetaryl, aryld-Cealkyl, CrCealkyloxyCrCealkyl, hetarylCrCealkyl, aryl-R 6 -CrC 6 alkyl, hetaryl- R 6 -CrC 6 alkyl or arylCrCealkyl-R ⁇ d-Cealkyl wherein the alkyl, cycloalkyl, hetcycloalkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R 7 ;
  • R 4 and R 5 independently are hydrogen, hydroxy, oxo, cyano, halo, methylendioxo, NR 8 R 9 , d- C 8 alkyl, Crdalkyloxy, trihalomethyl, trihalomethyloxy, C 3 -C 10 cycloalkyl, C 3 -C 10 hetcycloalkyl, C 3 -C 10 cycloalkenyl, aryl, hetaryl, hetarylSO n , arylCrCealkyloxy, hetarylCrCealkyloxy, C C 6 alkyl-R 6 -CrC 6 alkyl, arylCrC 6 alkyl-R 6 -CrC e alkyl, CrCealkylcarbonyl, arylcarbonyl, aryld- C 6 alkylcarbonyl, hetarylcarbonyl, hetarylCrC 6 alkyl-carbonyl
  • R 6 is oxygen, sulphur, SO n or NR 16.
  • R 7 is hydrogen, halo, hydroxy, cyano, nitro, COOR 17 , C r C 8 alkyl, C 3 -C 10 cycloalkyl, C 3 -C ⁇ 0 het- cycloalkyl, methylendioxo, trihalomethyl, trihalomethyloxy, aryl, aryld-C 6 alkyl, CrC 6 alkyloxy, CrCealkyloxyCrCealkyl, aryloxy, aryld-Cealkyloxy, aryloxyCrC 6 alkyl, aryld-Cealkyloxyd- C 6 alkyl, hetaryl, hetarylCrCealkyl, hetaryloxy, hetarylCrCealkyloxy, hetaryloxyCrC 6 alkyl, hetarylCrCealkyloxyC ⁇ -Cealkyl, NR 8 R 9 , S
  • R 8 and R 9 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one halo, cyano, CrC 8 alkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrCealkyl, hydroxy, oxo, CrC 6 alkyloxy, arylCrCealkyloxy, hetaryld- C 6 alkyloxy,, CrCealkyloxyCrCealkyl, CrC 6 alkyl-carbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy,
  • R 10 and R 11 independently are hydrogen, hydroxy, oxo, halo, cyano, nitro, d-C 8 alkyl, d- C 6 alkyloxy, NR 12 R 13 , methylendioxo, trihalomethyl or trihalomethyloxy;
  • R 12 and R 13 independently are hydrogen, d-C 8 alkyl or aryld-Cealkyl
  • R 14 is hydrogen, halo, hydroxy, oxo, nitro, cyano, C r C 8 alkyl, C C 6 alkyloxy or aryloxy;
  • R 15 is hydrogen, halo, hydroxy, oxo, nitro, cyano, CONR 8 R 9 or COOR 17 ;
  • R 16 is hydrogen, C C 8 alkyl, C 3 -C 10 cycloalkyl, C 3 -C 10 hetcycloalkyl, aryl, aryld-Cealkyl, hetaryl, hetarylCrC 6 alkyl, alkylcarbonyl, arylcarbonyl, aryld-C 6 alkylcarbonyl, aryloxyd-C 6 alkyl, hetaryloxyCrC 6 alkyl, arylthioCrC 6 alkyl or hetarylthioCrC 6 alkyl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R 10 ;
  • R 1 ' is hydrogen, CrC 8 alkyl, aryl or aryld-Cealkyl
  • R 18 is CrC 6 alkyl, C 2 -C 6 alkenyl, aryl, arylCrC 6 alkyl, hetaryl, hetarylCrCealkyl, C 3 -C 10 cycloalkyl, C 3 -Ci 0 hetcycloalkyl, CrC 6 alkyloxy, aryloxy, arylCrCealkyloxy, arylCrCealkyloxyCrCealkyl, hetaryloxy, hetarylCrCealkyloxy, hetarylCrC 6 alkyloxyCrC 6 alkyl or R 8 R 9 NCrC 6 alkyl wherein the alkyl, alkenyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups are optionally substituted with R 15 ; R 19 is CrC 6 alkyl, C 3 -C 10 cycloalkyl, C
  • n 0, 1 or 2;
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein: R 1 is Qrdocycloalkyl, C 3 -C 10 hetcycloalkyl, d-C 8 alkyl, aryl, hetaryl, aryld-C 6 alkyl or hetarylCrCealkyl, wherein the cycloalkyl, hetcycloalkyl, alkyl, arylalkyl and hetarylalkyl groups independently are optionally substituted with one or more of R 4 ;
  • R 2 is hydrogen, d-C 8 alkyl, aryl, hetaryl, aryld-C 6 alkyl, C 3 -C ocycloalkylCrC 6 alkyl, d-C 6 alkyl- carboxyd-C 6 alkyI wherein the alkyl, aryl and cycloalkyl groups independently are optionally substituted with one or more of R 5 ; or
  • R 1 and R 2 are together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C 8 alkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrCealkyloxy, arylC C 6 alkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylC C 6 alkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, ary
  • R 3 is d-C 8 alkyl, C C 6 alkenyl, C ⁇ -C 6 alkynyl, C 3 -d 0 cycloalkyl, C 3 -C 10 hetcycloalkyl, aryl, hetaryl, aryld-Cealkyl, CrC 6 alkyloxyCrC 6 alkyI, hetarylCrCealkyl, aryl-R 6 -C ⁇ -C 8 aIkyl, hetaryl- R 6 -CrC 6 alkyl or aryICrC 6 alkyI-R 6 -CrC 6 alkyl wherein the alkyl, cycloalkyl, hetcycloalkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R 7 ; R 4 and R 5 independently are hydrogen, hydroxy, oxo, cyano, halo, methylend
  • R 6 is oxygen, sulphur, SO n , NR 16 ;
  • R 7 is hydrogen, halo, hydroxyl, cyano, nitro, COOR 17 , d-C 8 alkyl, C 3 -C 10 cycloalkyl, C 3 -C ⁇ 0 het- cycloalkyl, methylendioxo, trihalomethyl, trihalomethyloxy, aryl, aryld-Cealkyl, CrC 6 alkyloxy, CrCealkyloxyCrCealkyl, aryloxy, aryloxyCrC 6 alkyl, arylCrCealkyloxyCrCealkyl, hetaryl, hetarylCrCealkyl, hetaryloxy, hetaryld-Cealkyloxy, hetaryloxyd-C 6 alkyl, hetarylCrCealkyloxyCrCealkyl, NR 8 R 9 , S0 2 NR 8 R 9 , NR 4
  • R 8 and R 9 independently are hydrogen, d-C 8 alkyl, aryl, hetaryl, arylCrC 6 alkyl or hetaryld- C 6 alkyl wherein the alkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R 11 ; or
  • R 8 and R 9 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one C C 8 alkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrCealkyl, hydroxy, oxo, d-C 6 alkyloxy, aryld-Cealkyloxy, hetarylCrCealkyloxy, d- CealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrC 6 alkylcarboxy, arylcarboxy,
  • R 10 and R 11 independently are hydrogen, hydroxy, oxo, halo, cyano, nitro, d-Cealkyl, d-C 6 - alkyloxy, NR 12 R 13 , methylendioxo, trihalomethyl or trihalomethyloxy;
  • R 12 and R 13 independently are hydrogen, C C 8 alkyl or arylCrC 6 alkyl;
  • R 14 is hydrogen, halo, hydroxy, oxo, nitro, cyano, C C 8 alkyl, CrC 6 alkyloxy or aryloxy;
  • R 15 is hydrogen, halo, hydroxy, oxo, nitro, cyano or COOR 17 ;
  • R 6 is hydrogen, d-C 8 alkyl, C 3 -C ⁇ 0 cycloalkyl, C 3 -C 10 hetcycloalkyl, aryl, arylCrC 6 alkyl, hetaryl, hetarylCrCealkyl, alkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, aryloxyd-Cealkyl, hetaryloxyCrC 6 alkyl, aryIthioCrC 6 alkyl or hetarylthioCrC 6 alkyl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R 10 ;
  • R 17 is hydrogen, d-C 8 alkyl, aryl or arylCrC 6 alkyl
  • n 1 or 2;
  • n 0, 1 or 2;
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R 1 is C 3 -C 10 cycloalkyl or C 3 -C ⁇ 0 hetcycloalkyl wherein the cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R 4 as defined above.
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R 1 is C 3 -C 10 cycloalkyl optionally substituted with one or more of R 4 as defined above.
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R 2 is hydrogen or d-C 8 alkyl, wherein the the alkyl group is optionally substituted with one or more of R 5 as defined above.
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R 2 is CrC 8 alkyl optionally substituted with one or more of R 5 as defined above.
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R 3 is C 3 -Ci 0 cycloalkyl, C 3 -C ⁇ 0 hetcycloalkyl, aryl, hetaryl, arylCrCealkyl, hetaryld-Cealkyl, aryl-R 6 - d-Cealkyl, hetaryl-R 6 -C C 6 alkyl or aryld-Cealkyl-R ⁇ d-Cealkyl wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R 7 .
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R 3 is aryl or hetaryl, wherein the aryl and hetaryl groups are optionally substituted with one or more of R 7 as defined above.
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R 3 is is phenyl optionally substituted with one or more of R 7 as defined above.
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R 3 is phenyl optionally substituted independently in position 2(ortho) or 4(para) with one or more of R 7 as defined above.
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R 4 and R 5 independently are hydrogen, hydroxy, oxo, halo, d-C 8 alkyl, wherein the alkyl group is optionally substituted with one ore more of R 15 .
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R 6 is oxygen.
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R 7 is hydrogen, halo, hydroxy, cyano, d-C 8 alkyl, C 3 -C ⁇ 0 cycloalkyl, C 3 -d 0 het-cycloalkyl, trihalomethyl, aryl, aryld-Cealkyl, CrC 6 alkyloxy, CrC 6 alkyloxyCrC 6 alkyl, aryloxy, aryld- Cealkyloxy, aryloxyd-Cealkyl, arylCrCealkyloxyCrCealkyl, hetaryl, hetarylCrCealkyl, hetaryl, hetarylCr
  • NR 8 R 9 NR 4 R 5 carbonyICrC 6 alkyI, R 18 carbonylNR 8 , R 19 SO m NR 8 , wherein the aryl and hetaryl groups independently are optionally substituted with one or more R 10 .
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R 8 and R 9 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one halo, cyano, CrC 8 alkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrCealkyl, hydroxy, oxo, CrC 6 alkyloxy, arylCrCealkyloxy, hetaryld-
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R 5 is CONR 8 R 9 .
  • said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R 18 is C C 6 alkyl optionally substituted with R 15 .
  • said substituted amide, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of: 3-(10,11-Dihydro-dibenzo[b,f]azepin-5-yl)-1-[4-(1H-imidazol-4-yl)-piperidin-1-yl]-propan-1-one;
  • Adamantane-1 -carboxylic acid 4-[(adamantane-1 -carbonyl)-amino]-2,6-dimethyl-pyridin-3-yl ester; 2-Phenyl-1 -(3-phenyI-pyrrolidin-1 -yl)-ethanone;
  • Biphenyl-4-yl-piperidin-1 -yl-methanone Azepan-1 -yl-(3,5-dichloro-phenyl)-methanone;
  • N,N-Dibenzyl-4-methyl-benzamide (2-Chloro-phenyl)-(2-methyl-piperidin-1 -yI)-methanone;
  • N,N-Dibenzyl-2-fluoro-benzamide (2-ChIoro-phenyl)-piperidin-1 -yl-methanone;
  • Furan-2-carboxylic acid [4-(4-methyl-piperidine-1 -sulfonyl)-phenyl]-amide; N-(2-Cyclohex-1 -enyI-ethyI)-2-o-tolyloxy-acetamide;
  • N-Cycloheptyl-2,4-dimethoxy-benzamide N-(3-Chloro-phenyl)-2-(8,11 ,11-trimethyl-3,4,6-triaza-tricydo[6.2.1.0 2 ' 7 ]undeca-2(7),3,5-trien-5- ylsulfanyl)-acetamide;
  • N-Benzyl-4-bromo-N-ethyl-benzamide (3-Methyl-piperidin-1 -yl)-[4-(naphthalen-1 -yloxymethyl)-phenyl]-methanone;
  • N-Cyclooctyl-2-p-tolyloxy-acetamide (3,5-Dimethyl-piperidin-1-yl)-(4-methyl-3-nitro-phenyl)-methanone;
  • Adamantane-1 -carboxylic acid (2,6-dihydroxy-pyrimidin-4-yl)-amide; Adamantane-1 -carboxylic acid [3-(1 H-benzoimidazol-2-ylsulfanyl)-5-nitro-phenyl]-amide;
  • Dec-3-enoic acid (4-hydroxy-benzyl)-(4-trifluoromethyl-benzyl)-amide; 6-Oxo-6-phenyl-hexanoic acid (4-hydroxy-benzyl)-(4-trifluoromethyl-benzyl)-amide;

Abstract

Combination therapy comprising the administration of an 11ß-hydroxysteroid dehydrogenase type 1 inhibitor and an antihypertensive agent useful for treating, preventing and reducing the risk of developing insulin resistance, dyslipidemia, obesity, hypertension and other related diseases and disorders.

Description

TITLE
Combination Therapy Using an 11 ?-Hydroxysteroid Dehydrogenase Type 1 Inhibitor and an Antihypertensive Agent for the Treatment of Metabolic Syndrome and Related Diseases and Disorders
FIELD OF THE INVENTION
The instant invention involves a combination therapy comprising the administration of an 11 ?-hydroxysteroid dehydrogenase type 1 inhibitor and an antihypertensive agent for treating, preventing and reducing the risk of developing insulin resistance, dyslipidemia, obesity, hypertension and other related diseases and disorders.
BACKGROUND OF THE INVENTION
The metabolic syndrome is a major global health problem. In the US, the prevalence of metabolic syndrome in the adult population is currently estimated to be approximately 25%, and it continues to increase both in the US and worldwide. The metabolic syndrome is characterized by a combination of insulin resistance, dyslipidemia, obesity and hypertension leading to increased morbidity and mortality of cardiovascular diseases. People with the metabolic syndrome are at increased risk of developing frank type 2 diabetes mellitus, the frequency of which is equally escalating. In type 2 diabetes the combination of insulin resistance with obesity and dyslipidemia is also highly prevalent and around 70% of people with type 2 diabetes additionally have hypertension, once again leading to increased mortality of cardiovascular diseases.
In the clinical setting, it has long been known that glucocorticoids are able to induce all of the cardinal features of the metabolic syndrome and type 2 diabetes. 11 ?-Hydroxysteroid dehydrogenase type 1 (11 ?-HSD1 ) catalyses the local generation of active glucocorticoid in several tissues and organs including predominantly the liver and adipose tissue, but also e.g. skeletal muscle, bone, pancreas, endothelium, ocular tissue and certain parts of the central nervous system. Thus, 11 ?~HSD1 serves as a local regulator of glucocorticoid actions in the tissues and organs where it is expressed (Tannin et al., J. Biol. Chem., 266, 16653 (1991); Bujalska et al., Endocrinology, 140, 3188 (1999); Whorwood et al., J. Clin. Endocrinol. Metab., 86, 2296 (2001); Cooper et al., Bone, 27, 375 (2000); Davani et al., J. Biol. Chem., 275, 34841 (2000); Brem et al., Hypertension, 3J., 459 (1998); Rauz et al., Invest Ophthalmol. Vis. Sci., 42, 2037 (2001); Moisan et al., Endocrinology, 127, 1450 (1990)).
The role of 11β-HSD1 in the metabolic syndrome and type 2 diabetes is supported by several lines of evidence. In humans, treatment with the non-specific 11y#-HSD1 inhibitor carbenoxolone improves insulin sensitivity in lean healthy volunteers and people with type 2 diabetes. Likewise, 11 MHSD1 knock-out mice are resistant to insulin resistance induced by obesity and stress. Additionally, the knock-out mice present with an anti-atherogenic lipid profile of decreased VLDL triglycerides and increased HDL-cholesterol. Conversely, mice that over-express 11 -HSD1 in adipocytes develop insulin resistance, hyperlipidemia, visceral obesity and hypertension, a phenotype that resembles the human metabolic syndrome
(Andrews et al., J. Clin. Endocrinol. Metab., 88, 285 (2003); Walker et al., J. Clin. Endocrinol. Metab., 80, 3155 (1995); Morton et al., J. Biol. Chem. 276, 41293 (2001); Kotelevtsev et al., Proc. Natl. Acad. Sci. USA, 94, 14924 (1997), Masuzaki et al., Science, 294, 2166 (2001), Masuzaki et al., J. Clin Invest, 112, 83 (2003)). 110-HSD1 has also been demonstrated to play a role in increasing vessel wall contractility (Souness et al., Steroids 67, 195 (2002).
The more mechanistic aspects of 11 .SD1 modulation and thereby modulation of intracellular levels of active glucocorticoid have been investigated in several rodent models and different cellular systems. 11 MHSD1 promotes the features of the metabolic syndrome by increasing hepatic expression of the rate-limiting enzymes in gluconeogenesis, namely phosphoenolpyuvate carboxykinase and glucose-6-phosphatase, promoting the differentiation of preadipocytes into adipocytes thus facilitating obesity, directly and indirectly stimulating hepatic VLDL secretion, decreasing hepatic LDL uptake and increasing vessel contractility, presumably by decreasing the levels of endothelial nitric oxide synthase and consequently the levels of the vasodialating substance nitric oxide (Kotelevtsev et al., Proc. Natl. Acad. Sci. USA, 94, 14924(1997); Morton et al., J. Biol. Chem. 276, 41293 (2001); Bujalska et al.,
Endocrinology, 140, 3188 (1999); Souness et al., Steroids, 67, 195 (2002); Brindley & Salter, Prog. Lipid Res., 30, 349 (1991); Whitworth et al., J. Hypertens. 20, 1035 (2002)).
Hence, 11 ?-HSD1 inhibitors constitute a new therapeutic principle for the treatment of insulin resistance, dyslipidemia, obesity and hypertension. In the clinical setting, however, monotherapeutic treatment of hypertension often lacks efficacy due, at least in part, to the induction of compensatory mechanisms.
The instant invention addresses this problem by providing a combination therapy comprising an 11 ?-HSD1 inhibitor and an antihypertensive agent for the treatment of e.g. the metabolic syndrome and type 2 diabetes. When administered as a part of a combination therapy, the 11 7-HSD1 inhibitor together with the antihypertensive agent provide improved control of hypertension and/or improved treatment ofthe metabolic syndrome and type 2 diabetes thereby reducing the risk for late complications, e.g. cardiovascular diseases and nephropathy. Due to the greater benefit of the drug combination, lesser dosage amounts of the 11 7-HSD1 inhibitor and more particularly the antihypertensive agent may be needed to achieve the desired clinical result, thereby resulting in improved safety. Examples of inhibitors and/or modulators of the human 1 β -hydroxysteroid dehydrogenase type 1 enzyme can be found in WO 01/90090, WO 01/90091, WO 01/90092, WO 01/90093, WO 01/90094, WO 02/72084 and WO 02/076435, as well as the following patent applications under common ownership of the present application: PA 200300569 filed 11 April 2003 DK, PA 200300565 filed 11 April 2003 DK, PA 200300571 filed 11 April 2003 DK, PA 2003 00570 filed 11 April 2003 DK, PA 2003 00566 filed 11 April 2003 DK, PA 2003 00972 filed 27 June 2003 DK, PA 200300998 filed 02 July 2003 DK, PA 2003 00988 filed 30 June 2003 DK, PA 200300989 filed 30 June 2003 DK, PA 200300990 filed 30 June 2003 DK, and PA 200301910 filed 22 December 2003 DK, the contents of which are hereby incorporated by reference in their entirety.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a novel combination therapy comprised of a therapeutically effective amount of an antihypertensive agent in combination with an 1 \β- hydroxysteroid dehydrogenase type 1 inhibitor (11 ?-HSD1) for the treatment, prevention and to reduce the risk of developing, metabolic syndrome, insulin resistance, dyslipidemia, obesity, hypertension and related diseases and disorders.
DEFINITIONS In the following structural formulas and throughout the present specification, the following terms have the indicated meaning:
The term "halo" includes fluorine, chlorine, bromine, and iodine. The term "trihalomethyl" includes trifluoromethyl, trichloromethyl, tribromomethyl, and triiodomethyl. The term "trihalomethoxy" includes trifluorometoxy, trichlorometoxy, tribromometoxy, and triiodometoxy.
The term "alkyl" includes C C6 straight chain saturated and methylene aliphatic hydrocarbon groups, C3-C6 branched saturated hydrocarbon groups having the specified number of carbon atoms. For example, this definition shall include but is not limited to methyl (Me), ethyl (Et), propyl (Pr), butyl (Bu), pentyl, hexyl, isopropyl (i-Pr), isobutyl (i-Bu), tert-butyl (-•Bu), sec-butyl (s-Bu), isopentyl, neopentyl, and the like.
The term "alkenyl" includes C2-C6 straight chain unsaturated aliphatic hydrocarbon groups and branched C3-C6 unsaturated aliphatic hydrocarbon groups having the specified number of carbon atoms. For example, this definition shall include but is not limited to ethenyl, propenyl, butenyl, pentenyl, hexenyl, methylpropenyl, methylbutenyl and the like. The term "alkynyl" includes C2-C6 straight chain unsaturated aliphatic hydrocarbon groups and C4-C6 branched unsaturated aliphatic hydrocarbon groups having the specified number of carbon atoms. For example, this definition shall include but is not limited to ethynyl, propynyl, butynyl, pentynyl, hexynyl, methylbutynyl, and the like. The term "saturated or partially saturated cyclic, bicyclic or tricyclic ring system" represents but are not limit to aziridinyl, pyrrolinyl, pyrrolidinyl, 2-imidazolinyl, imidazolidinyl, 2- pyrazolinyl, morpholinyl, piperidinyl, thiomorpholinyl, piperazinyl, phthalimide, 1,2,3,4- tetrahydro-quinolinyl, 1,2,3,4-tetrahydro-isoquinolinyl, 1,2,3,4-tetrahydro-quinoxalinyl, and indolinyl. The term "saturated or partially saturated cyclic ring system" represents but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cydoheptenyl, cyclooctenyl, cyclononenyl, cyclodecenyl, tetrahydrofuranyl or tetrahydropyranyl.
The term "saturated or partially saturated aromatic ring system" represents but are not limited to cyclopentyl, cyclohexyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cydoheptenyl, cyclooctenyl, cyclononenyl, cyclodecenyl, tetrahydrofuranyl, tetrahydropyranyl, phenyl, pyridyl or pyrimidinyl.
The term "cycloalkyl" (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, bicyclo[3.2.1]octyl, spiro[4.5]decyl, norpinyl, norbonyl, norcaryl, adamantyl and the like) represents a saturated, mono-, bi-, tri- or spirocarbocyclic group having the specified number of carbon atoms.
The term "cycloalkylalkyl" (e.g. cyclopropylmethyl, cyclobutylethyl, adamantylmethyl and the like) represents a cycloalkyl group as defined above attached through an alkyl group having the indicated number of carbon atoms or substituted alkyl group as defined above. The term "cycloalkenyl" (e.g. cyclobutenyl, cyclopentenyl, cyclohexenyl, cydoheptenyl, cyclooctenyl, cyclononenyl, cyclodecenyl and the like) represents a partially saturated, mono-, bi-, tri- or spirocarbocyclic group having the specified number of carbon atoms.
The term "hetcycloalkyl" (tetrahydrofuranyl, tetrahydropyranyl, tertahydrothiopyranyl, and the like) represents a saturated mono-, bi-, tri- or spirocarbocyclic group having the specified number of carbon atoms and one or two additional heteroatoms or groups selected from nitrogen, oxygen, sulphur, SO or S02.
The term "alkyloxy" (e.g. methoxy, ethoxy, propyloxy, allyloxy, cyclohexyloxy) represents an alkyl group as defined above having the indicated number of carbon atoms attached through an oxygen bridge. The term "alkyloxyalkyl" (e.g. methyloxymethyl and the like) represents an alkyloxy group as defined above attached through an "alkyl" group. The term "aryloxyhetaryl" (e.g. 2-phenoxy-pyridyl and the like) represents an aryloxy group as defined below attached through a "hetaryl" group.
The term "aryloxy" (e.g. phenoxy, naphthyloxy and the like) represents an aryl group as defined below attached through an oxygen bridge. The term "hetaryloxy" (e.g. 2-pyridyloxy and the like) represents a hetaryl group as defined below attached through an oxygen bridge.
The term "arylalkyloxy" (e.g. phenethyloxy, naphthylmethyloxy and the like) represents an arylalkyl group as defined below attached through an oxygen bridge.
The term "hetarylalkyloxy" (e.g. 2-pyridylmethyIoxy and the like) represents a hetarylalkyl group as defined below attached through an oxygen bridge.
The term "alkyloxycarbonyl" (e.g. methylformiat, ethylformiat and the like) represents an alkyloxy group as defined above attached through a carbonyl group.
The term "aryloxycarbonyl" (e.g. phenylformiat, 2-thiazolylformiat and the like) represents an aryloxy group as defined above attached through a carbonyl group. The term "arylalkyloxycarbonyl" (e.g. benzylformiat, phenyletylformiat and the like) represents an "arylalkyloxy" group as defined above attached through a carbonyl group.
The term "arylalkyl" (e.g. benzyl, phenylethyl, 3-phenylpropyl, 1-naphtylmethyl, 2-(1- naphtyl)ethyl and the like ) represents an aryl group as defined below attached through an alkyl having the indicated number of carbon atoms or substituted alkyl group as defined above.
The term "hetarylalkyl" (e.g. (2-furyl)methyl, (3-furyl)methyl, (2-thienyl)methyl, (3- thienyl)methyl, (2-pyridyl)methyl, 1 -methyl-1 -(2-pyrimidyl)ethyl and the like) represents a hetaryl group as defined below attached through an alkyl having the indicated number of carbon atoms or substituted alkyl group as defined above. The term "alkylcarbonyl" (e.g. octylcarbonyl, pentylcarbonyl, 3-hexenylcarbonyl) represents an alkyl group as defined above having the indicated number of carbon atoms attached through a carbonyl group.
The term "arylcarbonyl" (e.g. benzoyl) represents an aryl group as defined below attached through a carbonyl group. The term "hetarylcarbonyl" (e.g. 2-thiophenylcarbonyl, 3-methoxy-anthrylcarbonyl, oxazolylcarbonyl and the like) represents a hetaryl group as defined below attached through a carbonyl group.
The term "carbonylalkyl" (e.g. acetyl and the like) represents a carbonyl group attached through alkyl group as defined above having the indicated number of carbon atoms. The term "alkylcarbonylalkyl" (e.g. propan-2-one, 4,4-dimethyl-pentan-2-one and the like) represents an alkylcarbonyl group as defined above attached through an alkyl group as defined above having the indicated number of carbon atoms.
The term "arylcarbonylalkyl" (e.g. 1-phenyl-propan-l-one, 1-(3-chloro-phenyl)-2- methyl-butan-1-one and the like) represents a arylcarbonyl group as defined above attached through an alkyl group as defined above having the indicated number of carbon atoms.
The term "hetarylcarbonylalkyl" (e.g. 1-pyridin-2-yl-propan-1-one, 1-(1-H-imidazol-2-yl)- propan-1-one and the like) represents a hetarylcarbonyl group as defined above attached through an alkyl group as defined above having the indicated number of carbon atoms. The term "arylalkylcarbonyl" (e.g. phenylpropylcarbonyl, phenylethylcarbonyl and the like) represents an arylalkyl group as defined above having the indicated number of carbon atoms attached through a carbonyl group.
The term "hetarylalkylcarbonyl" (e.g. imidazolylpentylcarbonyl and the like) represents an hetarylalkyl group as defined above wherein the alkyl group is in turn attached through a carbonyl.
The term "alkylcarboxy" (e.g. heptylcarboxy, cyclopropylcarboxy, 3-pentenylcarboxy) represents an alkylcarbonyl group as defined above wherein the carbonyl is in turn attached through an oxygen bridge.
The term "arylcarboxy" (e.g. benzoic acid and the like) represents an arylcarbonyl group as defined above wherein the carbonyl is in turn attached through an oxygen bridge.
The term "alkylcarboxyalkyl" (e.g. heptylcarboxymethyl, propylcarboxy tert-butyl, 3- pentylcarboxyethyl) represents an
The term "arylalkylcarboxy" (e.g. benzylcarboxy, phenylpropylcarboxy and the like) represents an arylalkylcarbonyl group as defined above wherein the carbonyl is in turn attached through an oxygen bridge.
The term "arylalkylcarboxyalkyl" (e.g. benzylcarboxymethyl, phenylpropylcarboxypropyl and the like) represents an arylalkylcarboxy group as defined above wherein the carboxy group is in turn attached through an alkyl group as defined above having the indicated number of carbon atoms. The term "hetarylcarboxy" (e.g. pyridine-2-carboxylic acid and the like) represents a hetarylcarbonyl group as defined above wherein the carbonyl is in turn attached through an oxygen bridge.
The term "hetarylalkylcarboxy" (e.g. (1-H-imidazol-2-yl)-acetic acid, 3-pyrimidin-2-yl- propionic acid and the like) represents a hetarylalkyl group as defined above wherein the carbonyl is in turn attached through an oxygen bridge. The term "alkylthio" (e.g. methylthio, ethylthio and the like) represents an alkyl group as defined above attached through a sulphur bridge.
The term "arylthio" (e.g. benzenthiol, naphthylthiol and the like) represents an aryl group as defined below attached through a sulphur bridge. The term "hetarylthio" (e.g. pyridine-2-thiol, thiazole-2-thiol and the like) represents an hetaryl group as defined below attached through a sulphur bridge.
The term "arylthioalkyl" (e.g. methylsulfanyl benzene, ethylsulfanyl naphthalene and the like) represents an arylthio group as defined below attached through an alkyl group having the indicated number of carbon atoms. The term "hetarylthioalkyl" (e.g. 2-methylsulfanyl-pyridine, 1-ethylsulfanyl-isoquinoline and the like) represents a hetarylthio group as defined below attached through an alkyl group having the indicated number of carbon atoms.
The term "hetaryloxyaryl" (e.g. 1-phenoxy-isoquinolyl, 2-phenoxypyridyl and the like) represents a hetaryloxy group as defined above attached through an "aryl" group as defined below.
The term "hetaryloxyhetaryl" (e.g. 1-(2-pyridyloxy-isoquinoline), 2-(imidazol~2-yloxy- pyridine) and the like) represents a hetaryloxy group as defined above attached through a "hetaryl" group as defined below.
The term "aryloxyalkyl" (e.g. phenoxymethyl, naphthyloxyethyl and the like) represents an aryloxy group as defined above attached through an "alkyl" group having the indicated number of carbon atoms.
The term "aryloxyaryl" (e.g. 1-phenoxy-naphthalene, phenyloxyphenyl and the like) represents an aryloxy group as defined above attached through an "aryl" group as defined below. The term "arylalkyloxyalkyl" (e.g. ethoxymethyl-benzene, 2-methoxymethyl- naphthalene and the like) represents an arylalkyloxy group as defined above attached through an "alkyl" group having the indicated number of carbon atoms.
The term "hetaryloxyalkyl" (e.g. 2-pyridyloxymethyl, 2-quinolyloxyethyl and the like) represents a hetaryloxy group as defined above attached through an "alkyl" group having the indicated number of carbon atoms.
The term "hetarylalkyloxyalkyl" (e.g. 4-methoxymethyl-pyrimidine, 2-methoxymethyl- quinoline and the like) represents a hetarylalkyloxy group as defined above attached through an "alkyl" group having the indicated number of carbon atoms.
The term "alkylcarbonylamino" (e.g. methylcarbonylamino, cyclopentylcarbonyl- aminomethyl, methylcarbonylaminophenyl) represents an "alkylcarbonyl" group as defined above wherein the carbonyl is in turn attached through the nitrogen atom of an amino group. The nitrogen atom may itself be substituted with an alkyl or aryl group.
The term "alkylcarbonylaminoalkyl" (e.g.N-propyl-acetamide, N-butyl-propionamide and the like) represents an "alkylcarbonylamino" group attached through an alkyl group as defined above having the indicated number of carbon atoms.
The term "arylalkylcarbonylamino" (e.g. phenylacetamide, 3phenyl-propionamide and the like) represents an "arylalkylcarbonyl" group as defined above attached through an amino group.
The term "arylalkylcarbonylaminoalkyl" (e.g. N-ethyl-phenylacetamide, N-butyl-3- phenyl-propionamide and the like) represents an "arylalkylcarbonylamino" group attached through an alkyl group as defined above having the indicated number of carbon atoms.
The term "arylcarbonylamino" (e.g. benzamide, naphthalene-1 -carboxylic acid amide and the like) represents an "arylcarbonyl" group as defined above attached through an amino group. The term "arylcarbonylaminoalkyl" (e.g. N-propyl-benzamide, N-Butyl-naphthalene-1- carboxylic acid amide and the like) represents an "arylcarbonylamino" group attached through an alkyl group as defined above having the indicated number of carbon atoms.
The term "aryl" includes but is not limited to a carbocyclic aromatic ring system being either monocyclic, bicyclic, or polycyclic, such as phenyl, biphenyl, naphthyl, anthracenyl, phenanthrenyl, fluorenyl, indenyl, pentalenyl, azulenyl, biphenylenyl and the like. Aryl is also intended to include the partially hydrogenated derivatives of the carbocyclic aromatic systems enumerated above. Non-limiting examples of such partially hydrogenated derivatives are 1 ,2,3,4-tetrahydronaphthyl, 1 ,4-dihydronaphthyl and the like.
The term "hetaryl" includes but is not limited to pyrrolyl (2-pyrrolyl), pyrazolyl (3- pyrazolyl), imidazolyl (1 -imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl), triazolyl (1,2,3- triazol-1-yl, 1,2,3-triazol-2-yl, 1 ,2,3-triazol-4-yl, 1 ,2,4-triazol-3-yl), oxazolyl (2-oxazolyl, 4- oxazolyl, 5-oxazolyl), isoxazolyl (3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl), thiazolyl (2-thiazolyl, 4-thiazolyl, 5-thiazolyl), thiophenyl (2-thiophenyI, 3-thiophenyl, 4-thiophenyl, 5-thiophenyl), furanyl (2-furanyl, 3-furanyl, 4-furanyl, 5-furanyl), pyridyl (2-pyridyl, 3-pyridyl, 4-pyridyl, 5- pyridyl), 5-tetrazolyl, pyrimidinyl (2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl), pyrazinyl, pyridazinyl (3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl), quinolyl (2-quinolyl, 3- quinolyl, 4-quinolyI, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl), isoquinolyl (1 -isoquinolyl, 3- isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl), benzo[b]furanyl (2-benzo[b]furanyl, 3-benzo[b]furanyl, 4-benzo[b]furanyl, 5-benzo[b]furanyl, 6- benzo[b]furanyl, 7-benzo[b]furanyl), 2,3-dihydro-benzo[b]furanyl (2-(2,3-dihydro-ben- zo[b]furanyl), 3-(2,3-dihydro-benzo[b]furanyl), 4-(2,3-dihydro-benzo[b]furanyl), 5-(2,3-dihydro- benzo-[b]furanyl), 6-(2,3-dihydro-benzo-[b]furanyl), 7-(2,3-dihydro-benzo[b]furanyl)), ben- zo[b]thiophenyl (2-benzo[b]thiophenyl, 3-benzo[b]thiophenyl, 4-benzo[b]thiophenyl, 5- benzo[b]thiophenyl, 6-benzo[b]thiophenyl, 7-benzo[b]thiophenyl), 2,3-dihydro-benzo[b]thio- phenyl (2-(2,3-dihydro-benzo[b]thiophenyl), 3-(2,3-dihydro-benzo[b]thiophenyl), 4-(2,3- dihydro-benzo[b]thiophenyl), 5-(2,3-dihydro-benzo[b]thiophenyl), 6-(2,3-dihydro-benzo[b]thio- phenyl), 7-(2,3-dihydro-benzo[b]thiophenyl)), 4,5,6,7-tetrahydro-benzo[b]thiophenyl (2- (4,5,6,7-tetrahydro-benzo[b]thiophenyl), 3-(4,5,6,7-tetrahydro-benzo[b]thiophenyl), 4-(4,5,6,7- tetrahydro-benzo[b]thiophenyl), 5-(4,5,6,7-tetrahydro-benzo[b]thiophenyl), 6-(4,5,6,7-tetra- hydro-benzo[b]thiophenyl), 7-(4,5,6,7-tetrahydro-benzo[b]thiophenyl)), 4,5,6,7-tetrahydro- thieno[2,3-c]pyridyl (4-(4)5,6,7-tetrahydro-thieno[2,3-c]pyridyl), 5-4,5,6,7-tetrahydro-thieno[2,3- c]pyridyl), 6-(4,5,6,7-tetrahydro-thieno[2,3-c]pyhdyl), 7-(4,5,6,7-tetrahydro-thieno[2,3- yridyl)), indolyl (1 -indolyl, 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indoIyl), isoindolyl (1-isoindolyl, 2-isoindolyl, 3-isoindolyl, 4-isoindolyl, 5-isoindolyl, 6-isoindolyl, 7- isoindolyl), 1 ,3-dihydro-isoindolyl (1-(1 ,3-dihydro-isoindolyl), 2-(1 ,3-dihydro-isoindolyl), 3-(1,3- dihydro-isoindolyl), 4-(1 ,3-dihydro-isoindolyl), 5-(1 ,3-dihydro-isoindolyl), 6-(1 ,3-dihydro- isoindolyl), 7-(1,3-dihydro-isoindolyl)), indazole (1-indazolyl, 3-indazolyl, 4-indazolyl, 5- indazolyl, 6-indazolyl, 7-indazolyl), benzimidazolyl (1 -benzimidazolyl, 2-benzimidazolyl, 4- benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl, 8-benzimidazolyl), benzoxazolyl (1-benz-oxazolyl, 2-benzoxazolyl), benzothiazolyl (1-benzothiazolyl, 2- benzothiazolyl, 4-benzothiazolyl, 5-benzothiazolyl, 6-benzothiazolyl, 7-benzothiazolyl), carbazolyl (1-carbazolyl, 2-carbazolyl, 3-carbazolyl, 4-carbazolyl), piperidinyl (2-piperidinyl, 3- piperidinyl, 4-piperidinyl), pyrrolidinyl (1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl).
With respect to Formula II, the term "NR R5carbonylalkyl" (e.g. Λ/./V-dimethyl- propionamide, Λ/-isopropyl-Λ/-methyl-propionamide and the like) represents NR4R5 substituted by a carbonylalkyl group as defined above, wherein R4 and R5 are as defined for Formula II herein.
With respect to Formula II, the term "alkylR6alkyl" (e.g. 2-ethoxymethyl, N-ethyl-N- methy amine, methyl-propyl-amide, ethanesulfonic acid methylamide and the like) represents an alkyl group as defined above, substituted by R6, which is substituted by an alkyl group as defined above, wherein R6is as defined for Formula II herein.
With respect to Formula II, the term "arylR6alkyl" (e.g. ethoxy-benzene, ethyl-methyl- phenyl-amine, Λ/-ethyl-benzamide, Λ/-isobutyl-benzenesulfonamide and the like) represents an aryl group as defined above, substituted by R6, which is substituted by an alkyl group as defined above, wherein R6 is as defined for Formula II herein. With respect to Formula II, the term "arylalkylR6alkyl" (e.g. benzyloxymethyl, ethyl- methyl-benzyl-amine, Λ/-ethyl-benzylamide and the like) represents an arylalkyl group as defined above, substituted by R6, which is substituted by an alkyl group as defined above, wherein R6is as defined for Formula II herein. With respect to Formula II, the term "hetarylR6alkyl" (e.g. 2-ethoxy-1H-imidazol, ethyl- quinolin-2-yl-amine, thiazole-2-carboxylic acid, methyl-propyl-amide, pyridine-3-sulfonic acid isobutyl-amide and the like) represents a hetaryl group as defined above, substituted by R6, which is substituted by an alkyl group as defined above, wherein R6 is as defined for Formula II herein. With respect to Formula II, the term "arylcarbonylNR15" (e.g. Λ/-benzyl-Λ/-methyl- benzamide and the like) represents an arylcarbonyl group as defined above, substituted by NR15, wherein R15is as defined for Formula II herein.
With respect to Formula II, the term "alkylSOn" (e.g. ethylsulfonyl, ethylsulfinyl and the like) represents an alkyl group as defined above, wherein the alkyl group is in turn attached through a sulphur bridge wherein the sulphur is substituted with n oxygen atoms, wherein n is as defined for Formula II herein.
With respect to Formula II, the term "arylSOm" (e.g. phenylsulfinyl, naphthyl-2-sulfonyl and the like) represents an aryl group as defined above, wherein the aryl group is in turn attached through a sulphur bridge wherein the sulphur is substituted with m oxygen atoms, wherein m is as defined for Formula II herein.
With respect to Formula II, the term "hetarylSOm" (e.g. thiazol-2-sulfinyl, pyridine-2- sulfonyl and the like) represents a hetaryl group as defined above, wherein the hetaryl group is in turn attached through a sulphur bridge wherein the sulphur is substituted with m oxygen atoms, wherein is as defined for Formula II herein. With respect to Formula II, the term "arylSOmNR8" (e.g. W-methyl-benzenesulfonamide and the like) represents an aryl group as defined above, wherein the aryl group is in turn attached through a SOmNR8 group wherein the sulphur is substituted with m oxygen atoms and the nitrogen atom substituted by R8, wherein R8and m are as defined for Formula II herein. With respect to Formula V, the term "NR4R5carbonylalkyl" (e.g. Λ/,Λ/-dimethyl- propionamide, Λ/-isopropyl-Λ/-methyl-propionamide and the like) represents NR4R5 substituted by a carbonylalkyl group as defined above, wherein R4and R5 are as defined for Formula V herein.
With respect to Formula V, the term "arylR8alkyl" (e.g. ethoxy-benzene, ethyl-methyl- phenyl-amine, Λ/-ethyl-benzamide, Λ/-isobutyl-benzenesulfonamide and the like) represents an aryl group as defined above, substituted by R8, which is substituted by an alkyl group as defined above, wherein R8 is as defined for Formula V herein.
With respect to Formula V, the term "hetarylR8alkyl" (e.g. 2-ethoxy-1 H-imidazol, ethyl- quinolin-2-yl-amine, thiazole-2-carboxylic acid, methyl-propyl-amide, pyridine-3-sulfonic acid isobutyl-amide and the like) represents a hetaryl group as defined above, substituted by R8, which is substituted by an alkyl group as defined above, wherein R8 is as defined for Formula V herein.
With respect to Formula V, the term "arylcarbonyl NR15" (e.g. Λ/-benzyl-Λ/-methyl- benzamide and the like) represents an arylcarbonyl group as defined above, substituted by NR15, wherein R15 is as defined for Formula V herein.
Certain of the above defined terms may occur more than once in the structural formulae, and upon such occurrence each term shall be defined independently of the other.
The term "optionally substituted" as used herein means that the groups in question are either unsubstituted or substituted with one or more ofthe substituents specified. When the groups in question are substituted with more than one substituent, the substituents may be the same or different.
The term "treatment" is defined as the management and care of a patient for the purpose of combating or alleviating the disease, condition or disorder, and the term includes the administration of the active compound to prevent the onset of the symptoms or complications, or alleviating the symptoms or complications, or eliminating the disease, condition, or disorder.
The term "pharmaceutically acceptable" is defined as being suitable for administration to humans without adverse events.
The term "prodrug" is defined as a chemically modified form of the active drug, said prodrug being administered to the patient and subsequently being converted to the active drug. Techniques for development of prodrugs are well known in the art.
The term "combination therapy" is defined as the administration of a single pharmaceutical dosage formulation which comprises the 11 ?-HSD1 inhibitor and the antihypertensive agent, as well as administration of each active agent in its own separate pharmaceutical dosage formulation. Where separate dosage formulations are used, the 11/?- HSD1 inhibitor and the anti-hypertensive agent can be administered to the patient at essentially the same time, i.e. concurrently, or at separate staggered times, i.e. sequentially. When given by different dosage formulations, the route of administration may be the same or different for each agent. Any route of administration known or contemplated for the individual agents is acceptable for the practice of the present invention. The term "therapeutically effective amount" is defined as the amount of drug or pharmaceutical agent that will elicit the biological or medical response of a tissue, a system or a mammal that is sought by the treating individual, i.e. medical doctor or other clinician. As used herein, the various forms of the term "modulation" are intended to include stimulation (e.g., increasing or upregulating a particular response or activity) and inhibition (e.g., decreasing or downregulating a particular response or activity).
As used herein, the term "agonist" is intended to indicate a substance that activates the receptor(s).
DETAILED DECSRIPTION OF THE INVENTION
Synthetic schemes for general formula (I) through general formula (V) compounds described herein, as well as examples, are found in the following patent applications under common ownership of the present application: PA 2003 00569 filed 11 April 2003 DK, PA 2003 00565 filed 11 April 2003 DK, PA 2003 00571 filed 11 April 2003 DK, PA 2003 00570 filed 11 April 2003 DK, PA 2003 00566 filed 11 April 2003 DK, PA 2003 00972 filed 27 June 2003 DK, PA 2003 00998 filed 02 July 2003 DK, PA 2003 00988 filed 30 June 2003 DK, PA 2003 00989 filed 30 June 2003 DK, PA 2003 00990 filed 30 June 2003 DK, and PA 2003 01910 filed 22 December 2003 DK, the contents of which are hereby incorporated by reference in their entirety. In one embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I)
Figure imgf000013_0001
Formula (I)
wherein
R1 and R2 independently are hydrogen, halo, C(=0)NR6R7, C02R15, NR6C(=0)R11, OR12 or SR12;
R3and R5 independently are hydrogen, NR13R14 trihalomethyl, trihalomethoxy, Cι-C6alkyl, C2- C6alkenyl, C2-C6alkynyl, CrC6alkyloxy, C C6alkylthio, aryl, aryld-Cealkyl, hetaryl or hetarylCrC6alkyl, wherein alkyl, alkynyl, alkenyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R8;
R4 is hydrogen, cyano, halo, C02R15, C(=0)NR6R7, C.-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, aryl, hetaryl, aryld-C6alkyl, hetarylC C6alkyl, hydroxy, CrCealkyloxy, aryld-Cealkyloxy, hetarylCrCealkyloxy, or CrC6alkyloxyCrC6alkyl, wherein the alkyl, alkynyl, alkenyl, cycloalkyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R9;
R6 and R7 independently are d-Cβalkyl, C3-C10cycloalkyl, hetC3-C10cycloalkyl, aryld-C6alkyl or hetarylCrCealkyl, wherein the alkyl, cycloalkyl, hetcycloalkyl, arylalkyl, and hetarylalkyl groups independently are optionally substituted with one or more of R10; or
R6 and R7 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, arylCrCealkyl, halo, hydroxy, oxo, CrC6alkyloxy, aryld-Cealkyloxy, hetarylCrCealkyloxy, CrC6alkyloxyCr C6alkyl, d-C6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetaryld- C6alkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy or hetarylCrC6alkylcarboxy;
R8 and R9 independently are hydrogen, halo, hydroxy, oxo, cyano, nitro, C3-C10cycloalkyl, C3- dohetocycloalkyl, d-C6alkyl, CrC6alkyloxy, trihalomethyl, trihalomethoxy, aryld-C6alkyloxy, hetarylCrCealkyloxy, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy, hetaryld-Cealkylcarboxy, CrC6alkylcar bonylamino or aryld-C6alkylcarbonyl- amino;
R10 is hydrogen, halo, cyano, nitro, hydroxy, oxo, C3-C10cycloalkyl, C3-C10hetcycloalkyl, CrCealkyl, CrC6alkyloxy, trihalomethyl, trihalometh dialkylamino oxy, aryld-C6alkyloxy, hetaryld- C6alkyloxy, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, d-Cealkylcarboxy, arylcarboxy or aryld-C6alkylcarboxy;
R11 is d-Cealkyl, C2-C6alkenyl, C2-C6alkynyl, aryld-Cealkyl, hetaryld-dalkyl, d-C6alkyl- carbonylCrC6alkyl, d-C-ealkyloxy, aryloxy, C C6alkyloxy, arylcarbonyl, arylCrC6alkyl- carbonyl, hetarylcarbonylC C6alkyl, wherein the alkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R9;
R 2 is d-Cealkylcarbonylaminod-Cealkyl, arylcarbonylaminoCrC6alkyl or arylCrC6alkyl- carbonylaminod-C6alkyl;
R13and R14 independently are hydrogen, oxo, C3-C10cycloalkyl, CrC6alkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl;
R15 is hydrogen, C3-C10cycloalkyl, CrC6alkyl, aryl, hetaryl, arylCrC6alkyl, hetaryld-Cealkyl, CrC6alkyloxyalkyl or arylCrC6alkyloxyalkyl; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R1 and R2 independently are hydrogen, halo, C(=0)NR6R7, NC(=0)R11, OR12 or SR12;
R3and R5 independently are hydrogen, NR13R14 trihalomethyl, trihalomethoxy, d-Cealkyl, C2- C6alkenyl, C2-C6alkynyl, CrC6alkyloxy, CrC6alkylthio, aryl, aryld-C6alkyl, hetaryl or hetarylCrCealkyl, wherein alkyl, alkynyl, alkenyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R8;
R4 is hydrogen, cyano, halo, C02R15, C(=0)NR6R7, d-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrC6alkyl, hydroxy, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, or CrCealkyloxyCrCealkyl, wherein the alkyl, alkynyl, alkenyl, cycloalkyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R9;
R6 and R7 independently are d-Cealkyl, C3-C10cycloalkyl, hetC3-C10cycloalkyl, arylCrCealkyl or hetaryld-Cealkyl, wherein the alkyl, cycloalkyl, hetcycloalkyl, arylalkyl, and hetarylalkyl groups independently are optionally substituted with one or more of R10; or
R6 and R7 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, aryl CrC6al kyl, halo, hydroxy, oxo, CrCealkyloxy, aryld-Cealkyloxy, hetarylCrCealkyloxy, d-Cealkyloxyd- C6alkyl, CrC6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetaryld- C6alkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy or hetarylCrC6alkylcarboxy;
R8 and R9 independently are hydrogen, halo, hydroxy, oxo, cyano, nitro, C3-Cι0cycloalkyl, C3- dohetocycloalkyl, d-Cealkyl, CrC6alkyloxy, trihalomethyl, trihalomethoxy, arylCrC6alkyloxy, hetarylCrCealkyloxy, d-Cealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy, hetarylCrC6alkylcarboxy, CrC6aIkylcarbonylamino or arylCι-C6alkylcarbonyl- amino;
R10 is hydrogen, halo, cyano, nitro, hydroxy, oxo, C3-C10cycloalkyl, C3-C10hetcycloalkyl, CrCealkyl, CrC6alkyloxy, trihalomethyl, trihalometh dialkylamino oxy, arylCrC6alkyloxy, hetaryld- C6aIkyloxy, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or aryld-C6alkylcarboxy;
R11 is d-Cβalkyl, C2-C6alkenyl, C2-C6alkynyl, arylCrC6alkyl, hetaryld-Cealkyl, d-C6alkyl- carbonylCrC6alkyl, CrCβalkyl, arylcarbonyl, arylCrCealkylcarbonyl, hetarylcarbonylCrC6- alkyl, wherein the alkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R9;
R12 is d-CealkylcarbonylaminoCrCealkyl, arylcarbonylaminoC C6alkyl or arylCrC6alkyl- carbonylaminoCrC6alkyl;
R13 and R14 independently are hydrogen, oxo, C3-C10cycloalkyl, CrC6alkyl, CrC6alkyloxy, trihalomethyl, trihalomethoxy, aryld-C6alkyloxy, hetarylCrCealkyloxy, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy;
R15 is hydrogen, C3-C10cycloalkyl, CrC6alkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrCealkyl, CrC6alkyloxyalkyl or arylCrC6alkyloxyalkyl; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms. In another embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R1 and R2 independently are hydrogen and/or C(=0)NR6R7. In another embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R3and R5 independently are hydrogen, trihalomethyl, d-Cealkyl, CrC6alkyloxy, aryl, arylCrCealkyl, hetaryl or hetaryld-Cealkyl, wherein alkyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R8. In another embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R4 is hydrogen, cyano, halo, C(=0)NR6R7, d-Cealkyl, aryl, hetaryl, arylCrCealkyl, hetaryld-Cealkyl, hydroxy, d-C6alkyloxy, arylCrCealkyloxy, hetaryld- C6alkyloxy, wherein the alkyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R9.
In another embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R6 and R7 independently are d-Cealkyl, C3-C10cycloalkyl, hetC3- Ciocycloalkyl, arylCrC6alkyl or hetaryld-Cealkyl, wherein the alkyl, cycloalkyl, hetcycloalkyl, arylalkyl, and hetarylalkyl groups independently are optionally substituted with one or more of R10.
In another embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) R6 and R7 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, arylCrC6alkyl, halo, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, hetaryld- C6alkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylC C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy or hetaryICrC6alkylcarboxy.
In another embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R6 and R7 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional nitrogen atoms, the ring system optionally being substituted with at least one of d-C6alkyl, aryl, hetaryl, arylCrCealkyl, halo, hydroxy, oxo, CrCealkyloxy, aryld-C6alkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl.
In another embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R8 and R9 independently are hydrogen, halo, hydroxy, oxo, cyanoC3-C10cycloalkyl, C3-C10hetocycloalkyl, d-Cealkyl, Cι-C6alkyloxy, trihalomethyl, aryld- Cealkyloxy, hetarylCrCealkyloxy.
In another embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R 0 is hydrogen, halo, cyano, nitro, hydroxy, oxo, C3-Cι0cycloalkyl, C3-Ci0hetcycloalkyl, d-C6alkyl, CrCealkyloxy, arylCrC6alkyloxy, hetarylCrCealkyloxy, d- C6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or aryld-C6alkylcarboxy.
In another embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R 1 is d-Cealkyl, arylCrC6alkyl, hetary!d-C6alkyl, d-Cealkyloxy, aryloxy, CrC6alkyloxy, wherein the alkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R9.
In another embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R12 is CrCealkylcarbonylaminod-Cealkyl, arylcarbonylaminod- C6alkyl or aryld-CealkylcarbonylaminoCrCealkyl.
In another embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R13and R14 independently are hydrogen, C3-Cι0cycloalkyl, Ci- Cealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl.
In another embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is of the general formula (I) wherein R15 is hydrogen, C3-C10cycloalkyl, CrC6alkyl, aryl, hetaryl, aryld- C6alkyl, hetarylCrCealkyl, d-Cealkyloxyalkyl or arylCrC6alkyloxyalkyl.
In another embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of:
(3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(2,6-dimethyl- piperidin-1-yl-)methanone; (3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(2-ethyl-piperidin-1- yl-)methanone;
(5-Thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(1,3,3-trimethyl-6-aza- bicyclo[3.2.1]oct-6-yl)methanone; (3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(2-methyl-piperidin-
1-yl-)methanone;
5-Methyl-7-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexylamide;
Azepan-1-yl-(3-chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-ajpyrimidin-2-yl)- methanone; Azepan-1 -yl-(3-chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)- methanone;
(2,6-Dimethyl-piperidin-1-yl-)-(3-chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-3-yl)methanone;
3-Bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-carboxylic acid cyclohexylamide;
(7-Methyl-5-phenyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(4-methyl-piperidin-1-yl)methanone;
5-(-4-Methoxy-phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid benzyl- methyl amide;
[5-(-4-Ethoxy-phenyl-7-methyl-pyrazolo[1,5-a]pyrimidine-2-yl])-piperidin-1-yl-methanone; Azepan-1-yl-(3-bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-ajpyrimidin-2-yl)methanone;
5-Benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid cyclohexyl-methyl amide;
(3,4-Dihydro-1/-/-isoquinolin-2-yl)-[5-(-4-Methoxy-phenyl-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-3-yl]methanone; Azepan-1 -yl-[5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)methanone
Azepan-1-yl-(5,7-diphenyl)-pyrazolo[1,5-a]pyrimidin-3-yl)methanone;
[5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl]-(2-methyl-piperidin-1-yl)- methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(2-methyl-piperidin-1-yl)- methanone;
(2,6-Dimethyl-piperidin-1-yl-)-[7-(4-ethoxy-phenyl)-5-methyl-pyrazolo[1,5-a]pyrimidin-2-yl] methanone;
5-(4-Ethoxy-phenyl)-7-methyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl amide;
Piperidin-1-yl-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)methanone; (5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(2-methyl-piperidin-1-yl)- methanone; (2-Methyl-piperidin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)- methanone;
Azepan-1-yl-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-ylj- methanone; 5-Thiophen-2-yI -7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid benzyl-methyl- amide;
5-p-Tolyl-7-trifluoromethyI-pyrazolo[1 ,5-a]pyrimidine-3-carboxyIic acid (1 ,3-dimethyl-1H- pyrazol-4-ylmethyl)-methyI amide; 5-Methyl-7-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl amide; 7-Methyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl amide; (5-Phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone; 5-Naphthalen-1-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl- methyl amide; 5-Naphthalen-1-yl-7-trifluoromethyl-pyrazolo[1 ,5-ajpyrimidine-2-carboxylic acid cyclohexyl amide;
(5-Naphthalen-1-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone
(2-Methyl-piperidin-1-yl)-(5-naphthalen-1-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone;
5,7-Diphenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl amide; 5,7-Diphenyl-pyrazolo[1 ,5-ajpyrimidine-2-carboxylic acid cyclohexyl-methyl amide; (5,7-Diphenyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(2-methyl-piperidin-1-yl)methanone; (5,7-DiphenyI-pyrazolo[1 ,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone; 5-Methyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2~carboxylic acid cyclohexyl amide; (5-Methyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1 -yl-methanone; 5-Methyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl- amide;
(2-Methyl-piperidin-1-yl)-(5-methyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-methanone; 5-Phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl amide; (5-Phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone; 7-Phenyl-5-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl- amide;
5-Phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid cyclohexyl amide; (5-Phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-piperidin-1 -yl-methanone; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms. In another embodiment of the present invention said substituted pyrazolo[1 ,5- ajpyrimidines, or a prodrug thereof, as a component of the combination therapy is selected from the group of
5-Methyl-7-trifluoromethyl-pyrazoIo[1 ,5-a]pyrimidine-2-carboxylic acid methyl ester; 5-Methyl-7-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid methyl ester;
7-Methyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid methyl ester;
(5-methyl-7-trif luoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)- (piperidin-1 -yl)methanone;
(5-methyI-7-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl amide;
7-Methyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxyIic acid cyclohexyl-methyl-amide; 7-Phenyl-5-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl- amide;
(5-Phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone;
(2-Methyl-piperidin-1-yl)-(5-methyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone;
5-Methyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl- amide;
(5-Methyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone;
(5,7-Diphenyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone;
(5,7-Diphenyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(2-methyl-piperidin-1-yl)-methanone;
5,7-Diphenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl-amide; (2-Methyl-piperidin-1 -yl)-(5-naphthalen-1 -yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)- methanone;
(5-Naphthalen-1-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone;
5-Naphthalen-1-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl- methyl-amide; [7-(4-Ethoxy-phenyl)-5-methyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-(1 ,3,3-trimethyl-6-aza- bicyclo[3.2.1]oct-6-yl)-methanone;
(2-Methyl-piperidin-1-yl)-(7-phenyl-5-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone;
(5-Methyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(1,3,3-trimethyI-6-aza- bicyclo[3.2.1 ]oct-6-yl)-methanone; (5-Phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(1 ,3,3-trimethyl-6-aza- bicyclo[3.2.1]oct-6-yl)-methanone;
(6-Bromo-3-chloro-pyrazolo[1 ,5-a]pyrimidin-2-yl)-morpholin-4-yl-methanone;
(5-Phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone;
Morpholin-4-yl-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-ajpyrimidin-2-yl)-methanone; (6-Bromo-pyrazolo[1 ,5-a]pyrimidin-2-yl)-piperidin-1 -yl-methanone;
(6-Bromo-pyrazolo[1,5-a]pyrimidin-2-yl)-morpholin-4-yl-methanone; (3,6-Dibromo-pyrazolo[1,5-a]pyrimidin-2-yl)-morpholin-4-yl-methanone;
(3-Bromo-5-phenyI-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone;
(3-Bromo-5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-morpholin-4-yl-methanone;
(3-Chloro-5-phenyl-7-trifluoromethyl-pyrazolo[1 ,5-ajpyrimidin-2-yl)-piperidin-1-yl-methanone; (3-Chloro-5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-morpholin-4-yl-methanone;
(3,6-Dibromo-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone;
[4-(4-Fluoro-phenyl)-piperazin-1-yl]-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-
2-yl)-methanone;
5-Thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl- methyl-amide;
(5-Benzo[1,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(4-methyl-piperazin-1- yl)-methanone;
[5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(2-methyl-piperidin-1- yl)-methanone; 3-Chloro-5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid methyl-(2-pyridin-2-yl-ethyl)-amide;
[3-Chloro-5-(4-chloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(3,4-dihydro-2H- quinolin-1-yl)-methanone;
[5-(3,4-Dichloro-phenyl)-7-trifluoromethyI-pyrazolo[1 ,5-a]pyrimidin-2-yl]-[4-(2-methoxy-phenyl)- piperazin-1 -ylj-methanone;
(4-Benzoyl-piperazin-1-yl)-[3-chIoro-5-(4-chloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-2-yl]-methanone; 4-(5-Benzo[1,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-2-carbonyl)-piperazine-
1 -carboxylic acid ethyl ester;
(5-Benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(6,7-dimethoxy-1 - methyl-3,4-dihydro-1H-isoquinolin-2-yl)-methanone;
[4-(Furan-2-carbonyl)-piperazin-1-yl]-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-2-yl]-methanone;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazoIo[1 ,5-a]pyrimidin-2-yl)-[4-(2-methoxy- phenyl)-piperazin-1-yl]-methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-1-yl- methanone; (3,4-Dihydro-2H-quinolin-1-yl)-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone; (3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazoIo[1,5-a]pyrimidin-2-yl)-(2,6-dimethyl- piperidin-1 -yl)-methanone;
(3-Bromo-5-thiophen-2-yl-7-trifluoromethyI-pyrazolo[1,5-a]pyrimidin-2-yl)-(2-ethyl-piperidin-1- yl)-methanone; 3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl-amide;
[5-(4-Bromo-phenyl)-3-chloro-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-pyrrolidin-1-yl- methanone;
(3-Chloro-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-[4-(4-fluoro-phenyl)- piperazin-1-yl]-methanone;
(3-Chloro-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(4-phenyl-piperazin-1- yl)-methanone;
[3-Chloro-5-(4-chloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-(4-methyI- piperazin-1 -yl)-methanone; Azepan-1 -yl-[3-chloro-5-(4-chloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-ylj- methanone;
[3-Chloro-5-(3,4-dimethoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-pyrrolidin-
1 -yl-methanone;
[5-(4-Chloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-(2-methyl-piperidin-1-yl)- methanone;
(5-Thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(1,3,3-trimethyl-6-aza- bicyclo[3.2.1]oct-6-yl)-methanone;
[4-(2-Chloro-phenyl)-piperazin-1-yl]-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-
2-yl)-methanone; (3,4-Dihydro-1H-isoquinolin-2-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- yl)-methanone;
(4-Methyl-piperazin-1 -yl)-[5-(4-nitro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]- methanone;
[5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-thiomorpholin-4-yl- methanone;
(3-Bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(3,4-dihydro-2/-- quinolin-1 -yl)-methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-pyrrolidin-1-yl-methanone;
[4-(Furan-2-carbonyl)-piperazin-1-yl]-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-2-yl]-methanone;
[5-(4-Nitro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-1-yl-methanone; (5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-pyrrolidin-1-yl-methanone;
(4-Methyl-piperidin-1-yl)-(5-phenyl-7-trifluoromethyI-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone;
(3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-[4-(4-fluoro-phenyl)- piperazin-1 -ylj-methanone; [4-(4-Fluoro-phenyl)-piperazin-1-yl]-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone;
[4-(4-Fluoro-phenyl)-piperazin-1-yl]-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-
2-yl)-methanone;
[3-Bromo-5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone;
[4-(4-Fluoro-phenyl)-piperazin-1-yl]-(7-methyl-5-phenyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone;
(4-Benzoyl-piperazin-1-yl)-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-ajpyrimidin-2-yl)- methanone; (3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(4-phenyl-piperazin-
1-yl)-methanone;
(2-Ethyl-piperidin-1-yl)-(5-phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-methanone;
(5,7-Diphenyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(4-methyl-piperazin-1-yl)-methanone;
(4-Benzyl-piperazin-1-yl)-(3-chloro-5-phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)- methanone;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(4-methyl-piperazin-
1-yl)-methanone;
(4-Phenyl-piperazin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone; [5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-pyrrolidin-1-yl-methanone;
(5,7-Diphenyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-pyrrolidin-1-yl-methanone;
(3-ChIoro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(2-ethyl-piperidin-1- yl)-methanone;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazoIo[1,5-a]pyrimidin-2-yl)-(2-methyl-piperidin- 1-yl)-methanone;
5-Methyl-7-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl-amide;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-morpholin-4-yl- methanone;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-[4-(4-fluoro-phenyl)- piperazin-1 -ylj-methanone; (3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(4-methyl-piperazin-
1-yl)-methanone;
(7-Methyl-5-phenyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yI-methanone;
Azepan-1-yl-(3-chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone;
Azepan-1-yl-[3-bromo-5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]- methanone;
3-Bromo-5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl-amide; (2,6-Dimethyl-piperidin-1-yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-
2-yl]-methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-(4-methyl-piperazin-1-yl)- methanone;
5-Phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid benzyl-methyl-amide; [5-(4-Ethoxy-phenyl)-7-methyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-(4-phenyl-piperazin-1 -yl)- methanone;
(3,4-Dihydro-1/-/-isoquinolin-2-yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-2-yl]-methanone;
Morpholin-4-yl-[5-(4-nitro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-methanone; (Hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- yl)-methanone;
(Hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- yl)-methanone;
(Hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-2-yl)-methanone;
(3-Chloro-5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(hexahydro-pyrrolo[1,2- a]pyrazin-2-yl)-methanone;
[5-(4-Fluoro-phenyl)-7-methyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morphoIin-4-yl-methanone;
(5,7-Diphenyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(2-methyl-piperidin-1-yl)-methanone; 5-Phenyl-7-trifluoromethyl-pyrazoIo[1 ,5-a]pyrimidine-2-carboxylic acid (1 ,3-dimethyl-1 H- pyrazol-4-ylmethyl)-methyl-amide;
5-Thiophen-2-yl-7-trifluoromethyI-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid (1 ,5-dimethyl-
1 --pyrazol-4-ylmethyl)-methyl-amide;
5-Thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-ajpyrimidine-2-carboxylic acid methyl-(1 ,3,5- trimethyl-1 H-pyrazol-4-ylmethyl)-amide; 3-Chloro-5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid
(1 ,3-dimethyl-1 H-pyrazol-4-ylmethyl)-methyl-amide;
5-(4-Chloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxyIic acid (1 ,3- dimethyl-1H-pyrazol-4-ylmethyl)-methyl-amide; 5-(3,4-Dimethoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-ajpyrimidine-2-carboxylic acid (1 ,3- dimethyl-1H-pyrazol-4-ylmethyl)-methyl-amide;
(2,5-Dimethyl-piperidin-1-yl)-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone;
5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid methyl-(1 ,3,5- trimethyl-1 H-pyrazol-4-ylmethyl)-amide;
5-(4-Chloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid (1 ,5- dimethyl-1H-pyrazol-4-ylmethyl)-methyl-amide;
(2,4-Dimethyl-piperidin-1-yi)-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone; (3-Bromo-5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(hexahydro-pyrrolo[1,2- a]pyrazin-2-yl)-methanone;
[5-(3,4-Dimethoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-(hexahydro- pyrrolo[1,2-a]pyrazin-2-yl)-methanone;
(3-Chloro-5-p-tolyI-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(hexahydro-pyrrolo[1,2- a]pyrazin-2-yl)-methanone;
(3-Bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl- methanone;
(3-Chloro-5-phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-pyrrolidin-1-yl-methanone;
(7-Methyl-5-phenyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(4-methyl-piperidin-1-yl)-methanone; (4-Methyl-piperazin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)- methanone;
[3-Bromo-5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-1-yl- methanone;
(4-Methyl-piperazin-1-yl)-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone; [4-(4-Fluoro-phenyl)-piperazin-1-yl]-(5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- yl)-methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone;
(3,4-Dihydro-2H-quinolin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone; (3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-morpholin-4-yl- methanone;
Azepan-1-yl-(3-chloro-5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone;
(4-BenzoyI-piperazin-1-yl)-[5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-ylj- , methanone;
(4-Benzyl-piperazin-1-yl)-[5-(4-bromo-phenyl)-3-chloro-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-2-yl]-methanone;
[5-(4-Bromo-phenyI)-3-chloro-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(4-methyl- piperazin-1 -yl)-methanone; Azepan-1-yl-[5-(4-bromo-phenyl)-7-trifluoromethyI-pyrazolo[1,5-a]pyrimidin-2-yl]-methanone;
[3-Bromo-5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(3,4-dihydro-2H- quinolin-1 -yl)-methanone;
[5-(3,4-Dimethoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone; (3-Bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(4-methyl-piperazin-1- yl)-methanone;
(4-Benzoyl-piperazin-1-yl)-(3-bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- yl)-methanone;
(3-Bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(3,4-dihydro-2ry- quinolin-1-yl)-methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-1 -yl-methanone;
[5-(4-Ethoxy-phenyl)-7-methyl-pyrazolo[1,5-a]pyrimidin-2-ylj-piperidin-1 -yl-methanone;
[5-(4-Ethoxy-phenyl)-7-methyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yl-methanone;
Azepan-1-yl-(3-bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone; (3,4-Dihydro-1H-isoquinolin-2-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazoIo[1,5-a]pyrimidin-2- yl)-methanone;
(4-Benzyl-piperazin-1-yl)-(3-bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-ajpyrimidin-2- yl)-methanone;
Azepan-1-yl-[5-(4-bromo-phenyl)-3-chloro-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]- methanone;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyI-pyrazolo[1,5-a]pyrimidin-2-yl)-(3,4-dihydro-1ry- isoquino!in-2-yl)-methanone;
(5-Benzo[1 ,3]dioxol-5-yI-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-piperidin-1 -yl- methanone; Azepan-1 -yl-(5,7-diphenyl-pyrazolo[1,5-ajpyrimidin-2-yl)-methanone; Azepan-1 -yI-(5-benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)- methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone; [3-Bromo-5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-thiomorpholin-4-yl- methanone;
[5-(4-Bromo-phenyl)-3-chloro-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-piperidin-1-yl- methanone;
(5-Benzo[1,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(3,4-dihydro-2H- quinolin-1 -yl)-methanone;
(5-Benzo[1,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(4-benzyl-piperazin-1- yl)-methanone; (5-Benzo[1 ,3jdioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-morpholin-4-yl- methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-[4-(2-methoxy-phenyl)- piperazin-1 -ylj-methanone;
[3-Bromo-5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(4-methyl- piperazin-1 -yl)-methanone;
Azepan-1 -yl-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]- methanone;
(2,6-DimethyI-piperidin-1-yl)-[7-(4-ethoxy-phenyl)-5-methyl-pyrazolo[1,5-a]pyrimidin-2-ylj- methanone; (3,4-Dihydro-2H-quinolin-1-yl)-(5,7-diphenyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone;
(3,6-Dibromo-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone;
(3-Bromo-5-furan-2-yI-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl- methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-thiomorpholin-4-yl- methanone;
[5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-ylj-thiomorpholin-4-yl- methanone;
(3,4-Dihydro-1H-isoquinolin-2-yl)-[5-(4-nitro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-
2-yl]-methanone; Azepan-1 -yl-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-ajpyrimidin-2-ylj- methanone; Azepan-1-yl-[5-(4-nitro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-methanone;
[5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone;
Azepan-1-yl-[5-(3,4-dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-ylj- methanone;
(3,4-Dihydro-1H-isoquinolin-2-yl)-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone;
[5-(4-Bromo-phenyl)-3-chloro-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-pyrrolidin-1-yl- methanone; 5,7-Diphenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl-amide;
(3,4-Dihydro-1 --isoquinolin-2-yl)-(5-furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)- methanone;
(4-Benzyl-piperazin-1-yl)-(3-chloro-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)- methanone; [3-Chloro-5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-1 -yl- methanone;
(3-Chloro-5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(4-methyl-piperazin-1-yl)- methanone;
(3-Chloro-5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(4-phenyl-piperazin-1-yl)- methanone;
[3-Chloro-5-(3,4-dimethoxy-phenyI)-7-trifluoromethyl-pyrazoIo[1,5-a]pyrimidin-2-yl]-piperidin-1- yl-methanone;
[4-(4-Fluoro-phenyl)-piperazin-1-yl]-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone; (4-Phenyl-piperazin-1-yl)-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone;
Morpholin-4-yl-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-methanone;
(4-Benzyl-piperazin-1-yl)-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone;
[5-(4-Chloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-ajpyrimidin-2-ylj-(4-methyl-piperazin-1-yl)- methanone; [5-(4-ChIoro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone;
(4-Benzyl-piperazin-1-yl)-[5-(4-chloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-ylj- methanone;
[5-(4-Fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone;
[5-(4-Fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-1 -yl-methanone; (3,4-Dihydro-2H-quinolin-1-yl)-[5-(4-fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- ylj-methanone;
Azepan-1-yl-[5-(3,4-dimethoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-ylj- methanone; (4-Benzyl-piperazin-1-yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- ylj-methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazoIo[1,5-a]pyrimidin-2-ylj-pyrrolidin-1-yl- methanone;
(5-Benzo[1,3]dioxoI-5-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-pyrrolidin-1-yl- methanone;
(3,4-Dihydro-2H-quinolin-1-yl)-[5-(4-nitro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- ylj-methanone;
[3-Chloro-5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(4-methyl- piperidin-1 -yl)-methanone; [3-Chloro-5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(3,4-dihydro-
2H-quinolin-1-yl)-methanone;
3-Chloro-5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl-amide;
[3-Chloro-5-(4-fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(4-methyl- piperazin-1 -yl)-methanone;
(3-Chloro-5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-ajpyrimidin-2-yl)-morpholin-4-yl-methanone;
Azepan-1 -yl-(3-chloro-5-p-tolyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-methanone;
Azepan-1 -yl-[3-chIoro-5-(3,4-dimethoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- ylj-methanone; [5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-ajpyrimidin-2-yl]-(4-methyl-piperazin-1- yl)-methanone;
5,7-Diphenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid benzyl-methyl-amide;
(5,7-Diphenyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(4-phenyl-piperazin-1-yl)-methanone;
Morpholin-4-yl-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone; Morpholin-4-yl-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-methanone;
Piperidin-1-yl-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone;
[3-Bromo-5-(4-bromo-thiophen-2-yl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-
1 -yl-methanone;
(3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(3,4-dihydro-2H- quinolin-1-yl)-methanone; (3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl- methanone;
(7-Methyl-5-phenyl-pyrazolo[1,5-a]pyrimidin-2-yl)-morpholin-4-yl-methanone;
(7-Methyl-5-phenyl-pyrazolo[1,5-a]pyrimidin-2-yl)-pyrrolidin-1-yl-methanone; 7-MethyI-5-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid benzyl-methyl-amide;
(2,6-Dimethyl-piperidin-1-yl)-[5-(4-fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- ylj-methanone;
Azepan-1-yI-[5-(4-fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-ylj-methanone;
[5-(4-Fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(4-methyl-piperazin-1-yl)- methanone;
[5-(4-Fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(4-phenyl-piperazin-1-yl)- methanone;
(2-Ethyl-piperidin-1-yl)-[5-(4-fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-ylj- methanone;
(5-Phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-piperidin-1-yl-methanone;
(5-Methyl-7-phenyI-pyrazolo[1 ,5-a]pyrimidin-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)- methanone;
(5-Thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(1,3,3-trimethyl-6-aza- bicyclo[3.2.1]oct-6-yl)-methanone;
(4-Phenyl-piperazin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl-methanone;
Pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid benzyl-(2-hydroxy-ethyl)-amide;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-(3,4-dihydro-1H- isoquinolin-2-yl)-methanone; (5,7-Dimethyl-pyrazolo[1 ,5-ajpyrimidin-3-yl)-[4-(4-methoxy-phenyl)-piperazin-1-yl]-methanone;
(3,4-Dihydro-2H-quinolin-1-yl)-[5-(4-fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3- ylj-methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-piperidin-1 -yl-methanone;
Azepan-1-yl-[7-trifluoromethyl-5-(3,4,5-trimethoxy-phenyl)-pyrazolo[1,5-a]pyrimidin-3-ylj- methanone;
(5-Benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-pyrrolidin-1 -yl- methanone;
Azepan-1-yl-(5,7-diphenyl-pyrazoIo[1,5-a]pyrimidin-3-yl)-methanone;
4-(5,7-Dimethyl-pyrazolo[1,5-a]pyrimidine-3-carbonyl)-piperazine-1 -carboxylic acid ethyl ester; (3,4-Dihydro-1 H-isoquinolin-2-yl)-(5,7-dimethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-methanone; [4-(3-Chloro-phenyl)-piperazin-1-ylj-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)- methanone;
(4-Methyl-piperidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl-methanone;
[4-(2-Methoxy-phenyl)-piperazin-1-yl]-pyrazolo[1,5-a]pyrimidin-3-yl-methanone; (3,4-Dihydro-2H-quinolin-1 -yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5- a]pyrimidin-3-yl]-methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-thiomorpholin-4-yl- methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(2-methyl-piperidin-1-yl)- methanone;
(4-Benzyl-piperazin-1-yl)-(5,7-dimethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-morpholin-4-yl- methanone;
(5,7-Dimethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-piperidin-1-yl-methanone; (5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-[4-(2-methoxy-phenyl)-piperazin-
1-yl]-methanone;
(5-Phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-piperidin-1 -yl-methanone;
Azepan-1 -yl-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-ajpyrimidin-3-yl)-methanone;
(2,6-Dimethyl-piperidin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)- methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl]-(4-methyl-piperazin-1- yl)-methanone;
(4-Methyl-piperazin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)- methanone; [5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-(4-methyl-piperazin-1-yl)- methanone;
(Hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3- yl)-methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-ajpyrimidin-3-yl]-(hexahydro-pyrrolo[1,2- a]pyrazin-2-yl)-methanone;
[5-(3,4-Dimethoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-(hexahydro- pyrrolo[1,2-a]pyrazin-2-yl)-methanone;
1-[5-(3-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-carbonyl]-piperidine-4- carboxylic acid ethyl ester; 4-[5-(3-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carbonyl]-piperazine-1- carboxylic acid ethyl ester; (3,4-Dihydro-2H-quinolin-1-yl)-[5-(3-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5- a]pyrimidin-3-yl]-methanone;
[4-(4-Fluoro-phenyl)-piperazin-1-yI]-[5-(3-methoxy-phenyl)-7-trifIuoromethyl-pyrazolo[1,5- a]pyrimidin-3-yl]-methanone; 5-p-Tolyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid (1 ,3-dimethyl-1 H- pyrazol-4-ylmethyl)-methyl-amide;
5-p-Tolyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxyIic acid methyl-(1 ,3,5-trimethyl-
1 /--pyrazol-4-ylmethyl)-amide;
[7-DifluoromethyI-5-(4-methoxy-phenyl)-pyrazolo[1 ,5-a]pyrimidin-3-yl]-(2-ethyl-imidazol-1-yl)- methanone;
[7-Difluoromethyl-5-(4-methoxy-phenyl)-pyrazolo[1,5-a]pyrimidin-3-yl]-morpholin-4-yl- methanone;
1 -[7-Difluoromethyl-5-(4-methoxy-phenyl)-pyrazolo[1 ,5-ajpyrimidine-3-carbonyl]-1 H-indole-3- carboxylic acid methyl ester; [4-(4-Chloro-phenyI)-piperazin-1-yl]-[7-difluoromethyl-5-(4-methoxy-phenyl)-pyrazolo[1,5- a]pyrimidin-3-yl]-methanone;
[7-Difluoromethyl-5-(4-methoxy-phenyl)-pyrazolo[1,5-a]pyrimidin-3-yl]-(2-ethyl-piperidin-1-yl)- methanone;
7-Difluoromethyl-5-p-tolyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid (1-ethyl-5-methyl-1/-/- pyrazol-4-ylmethyl)-methyl-amide;
1-(7-Difluoromethyl-5-methyl-pyrazolo[1,5-a]pyrimidine-3-carbonyl)-piperidine-4-carboxylic acid amide;
(7-Difluoromethyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-(2-ethyl-imidazol-1-yl)-methanone;
(7-Difluoromethyl-5-phenyl-pyrazolo[1,5-a]pyrimidin-3-yI)-thiomorpholin-4-yl-methanone; (7-Difluoromethyl-5-p-tolyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-(4-pyridin-2-yl-piperazin-1-yl)- methanone;
[7-Difluoromethyl-5-(4-methoxy-phenyl)-pyrazolo[1,5-a]pyrimidin-3-yl]-[4-(furan-2-carbonyl)- piperazin-1 -ylj-methanone;
7-Difluoromethyl-5-phenyl-pyrazolo[1 ,5-ajpyrimidine-3-carboxylic acid (1 -ethyl-3-methyl-1 H- pyrazol-4-ylmethyl)-methyl-amide;
[7-Difluoromethyl-5-(4-methoxy-phenyl)-pyrazolo[1,5-a]pyrimidin-3-yl]-thiomorpholin-4-yl- methanone;
(7-Difluoromethyl-5-phenyI-pyrazolo[1 ,5-a]pyrimidin-3-yl)-(3,4-dihydro-1H-isoquinolin-2-yl)- methanone; (7-Difluoromethyl-5-methyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-piperidin-1 -yl-methanone;
Azepan-1 -yl-(7-difluoromethyl-5-phenyl-pyrazolo[1,5-a]pyrimidin-3-yl)-methanone; 7-Dif luoromethyl-5-p-tolyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid methyl-(1 -methyl-1 H- pyrazol-4-ylmethyl)-amide;
(7-DifluoromethyI-5-p-tolyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(3-methyl-piperidin-1-yl)-methanone;
(7-Difluoromethyl-5-p-tolyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(4-ethyl-piperazin-1-yl)-methanone; (7-Difluoromethyl-5-p-tolyl-pyrazolo[1,5-a]pyrimidin-3-yl)-morpholin-4-yl-methanone;
7-Difluoromethyl-5-phenyl-pyrazolo[1 ,5-ajpyrimidine-3-carboxylic acid methyl-(1 ,3,5-trimethyl-
1 H-pyrazoI-4-ylmethyl)-amide;
(7-Difluoromethyl-5-phenyl-pyrazolo[1,5-a]pyrimidin-3-yl)-[4-(2-methyl-2H-pyrazole-3- carbonyl)-piperazin-1 -ylj-methanone; 7-Difluoromethyl-5-p-tolyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid benzyl-methyl-amide;
7-Difluoromethyl-5-(4-methoxy-phenyl)-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid (1-ethyl-3- methyl-1 /--pyrazol-4-ylmethyl)-methyl-amide;
7-Difluoromethyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid methyl-(4-pyrazol-1-yl- benzyl)-amide; Azepan-1 -yl-(5-cyclopropyl-7-difluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-methanone;
(4-Benzyl-piperazin-1-yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3- ylj-methanone;
(3,4-Dihydro-2r -quinolin-1-yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-3-yl]-methanone; 5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-ajpyrimidine-3-carboxylic acid benzyl- methyl-amide;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(4-methyl-piperazin-1-yl)- , methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-thiomorpholin-4-yl-methanone; [5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-morpholin-4-yl- methanone;
(4-Benzyl-piperazin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)- methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-morpholin-4-yl- methanone;
Azepan-1 -yl-(5-benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-ajpyrimidin-3-yl)- methanone;
(5-Benzo[1,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-(3,4-dihydro-2H- quinolin-1 -yl)-methanone; 5-Benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid cyclohexyl-methyl-amide; [5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-(3,4-dihydro-2 --quinolin-
1-yl)-methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-piperidin-1-yl-methanone;
Azepan-1-yl-(5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-methanone; (5-Benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-ajpyrimidin-3-yl)-pyrrolidin-1 -yl- methanone;
(5-Benzo[1,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(4-methyl-piperazin-1- yl)-methanone;
(3,4-Dihydro-1H-isoquinolin-2-yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-3-yl]-methanone;
Azepan-1 -yl-[5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-methanone;
(3,4-Dihydro-2H-quinolin-1-yl)-(5,7-diphenyl-pyrazolo[1,5-a]pyrimidin-3-yl)-methanone;
Azepan-1-yl-(5,7-diphenyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-methanone;
(5-Benzo[1,3jdioxol-5-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(4-benzyl-piperazin-1- yl)-methanone;
(4-Benzyl-piperazin-1-yl)-(5,7-diphenyl-pyrazolo[1,5-a]pyrimidin-3-yl)-methanone;
(5,7-Diphenyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(4-methyl-piperazin-1-yl)-methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-ylj-(2-methyl-piperidin-1-yl)- methanone; (3,4-Dihydro-2H-quinolin-1-yl)-(5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)- methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(2-methyl-piperidin-1-yl)- methanone;
[5-(4-Methoxy-phenyl)-7-trifIuoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl]-piperidin-1-yl- methanone;
(5-Benzo[1,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-morpholin-4-yl- methanone;
(5-Benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-piperidin-1 -yl- methanone; Morpholin-4-yl-[7-trifluoromethyl-5-(3,4,5-trimethoxy-phenyl)-pyrazolo[1,5-a]pyrimidin-3-ylj- methanone;
(4-Benzyl-piperazin-1-yl)-[7-trifluoromethyl-5-(3,4,5-trimethoxy-phenyl)-pyrazolo[1,5- a]pyrimidin-3-yl]-methanone;
(3,4-Dihydro-2/-y-quinolin-1-yl)-[7-trifluoromethyl-5-(3,4,5-trimethoxy-phenyl)-pyrazolo[1,5- a]pyrimidin-3-yl]-methanone; (4-Methyl-piperazin-1-yl)-[7-trifluoromethyl-5-(3,4,5-trimethoxy-phenyl)-pyrazolo[1,5- a]pyrimidin-3-yl]-methanone;
Azepan-1-yI-[7-trifluoromethyl-5-(3,4,5-trimethoxy-phenyl)-pyrazolo[1,5-a]pyrimidin-3-yl]- methanone; [5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl]-piperidin-1 -yl- methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-pyrrolidin-1 -yl- methanone;
Piperidin-1-yl-(5-thiophen-2-yl-7-trifluoromethyl-pyrazoIo[1,5-a]pyrimidin-3-yl)-methanone; (4-Benzyl-piperazin-1-yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3- yl]-methanone;
(3,4-Dihydro-2H-quinolin-1-yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-3-yl]-methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(2-methyl-piperidin-1-yl)- methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-morpholin-4-yl-methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-thiomorpholin-4-yl-methanone;
[4-(4-Fluoro-phenyl)-piperazin-1-yl]-(5-thiophen-2-yl-7-trifluoromethyl-pyrazoIo[1,5-a]pyrimidin-
3-yl)-methanone; (4-Methyl-piperidin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)- methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(4-methyl-piperazin-1-yl)- methanone;
(4-Benzyl-piperazin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)- methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl]-morpholin-4-yl- methanone;
Piperidin-1-yl-[7-trifluoromethyl-5-(3,4,5-trimethoxy-phenyl)-pyrazolo[1,5-a]pyrimidin-3-yl]- methanone; (2-Methyl-piperidin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)- methanone;
Azepan-1-yl-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]- methanone;
5-Thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid benzyl-methyl- amide; [5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl]-pyrrolidin-1-yl- methanone;
[5-(4-Chloro-phenyl)-2-methyI-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-piperidin-1-yl- methanone; Azepan-1 -yl-[5-(4-chloro-phenyl)-2-methyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl]- methanone;
[5-(4-Chloro-phenyl)-2-methyl-7-trifluoromethyl-pyrazoIo[1,5-a]pyrimidin-3-yl]-(4-methyl- piperazin-1 -yl)-methanone;
Morpholin-4-yl-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-methanone; (4-Benzyl-piperazin-1-yl)-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-methanone;
5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid benzyl- methyl-amide;
(4-BenzyI-piperazin-1-yl)-(5-phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)- methanone; Morpholin-4-yl-(5-phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-methanone; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II)
O
R3/%-Rl R Formula (II)
wherein
R1 is C3-C10cycloalkyl, C3-Cι0hetcycloalkyl, C C8alkyl, aryl, hetaryl, aryld-Cealkyl or hetarylCrCealkyl, wherein the cycloalkyl, hetcycloalkyl, alkyl, arylalkyl and hetarylalkyl groups independently are optionally substituted with one or more of R4.
R2 is hydrogen, CrC8alkyl, aryl, hetaryl, arylCrC6alkyl, C3-CιocycloalkylCrC6alkyI, d-C6alkyl- carboxyd-C6alkyI wherein the alkyl, aryl and cycloalkyl groups independently are optionally substituted with one or more of R5; or
R1 and R2 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC8alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrCealkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or aryld-
C6alkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R14;
R3 is CrC8alkyl, CrC6alkenyl, d-C6alkynyl, C3-d0cycloalkyl, C3-C10hetcycloalkyl, aryl, hetaryl, aryld-Cealkyl, CrCealkyloxyCrCealkyl, hetarylCrCealkyl, aryl-R6-CrC6alkyl, hetaryl- R6-CrC6alkyl or arylCrCealkyl-R^d-Cealkyl wherein the alkyl, cycloalkyl, hetcycloalkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R7;
R4 and R5 independently are hydrogen, hydroxy, oxo, cyano, halo, methylendioxo, NR8R9, d- C8alkyl, Crdalkyloxy, trihalomethyl, trihalomethyloxy, C3-C10cycloalkyl, C3-C10hetcycloalkyl, C3-C10cycloalkenyl, aryl, hetaryl, hetarylSOn, arylCrCealkyloxy, hetarylCrCealkyloxy, C C6alkyl-R6-CrC6alkyl, arylCrC6alkyl-R6-CrCealkyl, CrCealkylcarbonyl, arylcarbonyl, aryld- C6alkylcarbonyl, hetarylcarbonyl, hetarylCrC6alkyl-carbonyl, CrC6alkylSOn, d-C6alkyl- carboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy or hetarylCrC6alkylcarboxy wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one ore more of R15;
R6 is oxygen, sulphur, SOn or NR 16.
R7 is hydrogen, halo, hydroxy, cyano, nitro, COOR17, CrC8alkyl, C3-C10cycloalkyl, C3-Cι0het- cycloalkyl, methylendioxo, trihalomethyl, trihalomethyloxy, aryl, aryld-C6alkyl, CrC6alkyloxy, CrCealkyloxyCrCealkyl, aryloxy, aryld-Cealkyloxy, aryloxyCrC6alkyl, aryld-Cealkyloxyd- C6alkyl, hetaryl, hetarylCrCealkyl, hetaryloxy, hetarylCrCealkyloxy, hetaryloxyCrC6alkyl, hetarylCrC6alkyl-oxyCι-Cealkyl, NR8R9, S02NR8R9, NR4R5carbonylCrC6alkyl, arylthio, hetarylthio, R18carbonylNR8, arylSOn, hetarylSOn, R19S0mNR8, arylthioCrC6alkyl, hetarylthiod-C6alkyl or arylCrC6alkylR6CrC6alkyl; wherein the aryl and hetaryl groups independently are optionally substituted with one or more R10; R8 and R9 independently are hydrogen, C C8alkyl, aryl, hetaryl, arylCrC6alkyl or hetaryld- Cealkyl wherein the alkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R11; or
R8 and R9 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one halo, cyano, CrC8alkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrCealkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, hetaryld- C6alkyloxy,, CrCealkyloxyCrCealkyl, CrC6alkyl-carbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy or hetarylCrC6alkylcarboxy;
R10 and R11 independently are hydrogen, hydroxy, oxo, halo, cyano, nitro, d-C8alkyl, d- C6alkyloxy, NR12R13, methylendioxo, trihalomethyl or trihalomethyloxy;
R12 and R13 independently are hydrogen, d-C8alkyl or aryld-Cealkyl;
R14 is hydrogen, halo, hydroxy, oxo, nitro, cyano, CrC8alkyl, C C6alkyloxy or aryloxy;
R15 is hydrogen, halo, hydroxy, oxo, nitro, cyano, CONR8R9 or COOR17;
R16 is hydrogen, C C8alkyl, C3-C10cycloalkyl, C3-C10hetcycloalkyl, aryl, aryld-Cealkyl, hetaryl, hetarylCrC6alkyl, alkylcarbonyl, arylcarbonyl, aryld-C6alkylcarbonyl, aryloxyd-C6alkyl, hetaryloxyCrC6alkyl, arylthioCrC6alkyl or hetarylthioCrC6alkyl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R10;
R1' is hydrogen, CrC8alkyl, aryl or aryld-Cealkyl;
R18 is CrC6alkyl, C2-C6alkenyl, aryl, arylCrC6alkyl, hetaryl, hetarylCrCealkyl, C3-C10cycloalkyl, C3-Ci0hetcycloalkyl, CrC6alkyloxy, aryloxy, arylCrCealkyloxy, arylCrCealkyloxyCrCealkyl, hetaryloxy, hetarylCrCealkyloxy, hetarylCrC6alkyloxyCrC6alkyl or R8R9NCrC6alkyl wherein the alkyl, alkenyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups are optionally substituted with R15; R19 is CrC6alkyl, C3-C10cycloalkyl, C3-Cι0hetcycloalkyl, aryl, arylCrCealkyl, hetaryl, hetaryld Cealkyl;
is 1 or 2;
n is 0, 1 or 2; or
a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein: R1 is Qrdocycloalkyl, C3-C10hetcycloalkyl, d-C8alkyl, aryl, hetaryl, aryld-C6alkyl or hetarylCrCealkyl, wherein the cycloalkyl, hetcycloalkyl, alkyl, arylalkyl and hetarylalkyl groups independently are optionally substituted with one or more of R4;
R2 is hydrogen, d-C8alkyl, aryl, hetaryl, aryld-C6alkyl, C3-C ocycloalkylCrC6alkyl, d-C6alkyl- carboxyd-C6alkyI wherein the alkyl, aryl and cycloalkyl groups independently are optionally substituted with one or more of R5; or
R1 and R2 are together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C8alkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrCealkyloxy, arylC C6alkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylC C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or aryld- 6alkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R14;
R3 is d-C8alkyl, C C6alkenyl, Cι-C6alkynyl, C3-d0cycloalkyl, C3-C10hetcycloalkyl, aryl, hetaryl, aryld-Cealkyl, CrC6alkyloxyCrC6alkyI, hetarylCrCealkyl, aryl-R6-Cι-C8aIkyl, hetaryl- R6-CrC6alkyl or aryICrC6alkyI-R6-CrC6alkyl wherein the alkyl, cycloalkyl, hetcycloalkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R7; R4 and R5 independently are hydrogen, hydroxy, oxo, cyano, halo, methylendioxo, NR8R9, d- C8alkyl, CrCealkyloxy, trihalomethyl, trihalomethyloxy, C3-C10cycloalkyl, C3-C10hetcycloalkyl, C3-Ci0cycloalkenyl, aryl, hetaryl, hetarylSOn, arylCrC6alkyloxy, hetarylCrCealkyloxy, Cr Cealkyl-R6-CrC6alkyl, arylCrCealkyl-R^d-Cealkyl, CrCealkylcarbonyl, arylcarbonyl, aryld- C6alkylcarbonyl, hetarylcarbonyl, hetarylCrC6alkyl-carbonyl, CrCealkylSOπ, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy or hetarylCrC6alkylcarboxy wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one ore more of R15;
R6 is oxygen, sulphur, SOn, NR16;
R7 is hydrogen, halo, hydroxyl, cyano, nitro, COOR17, d-C8alkyl, C3-C10cycloalkyl, C3-Cι0het- cycloalkyl, methylendioxo, trihalomethyl, trihalomethyloxy, aryl, aryld-Cealkyl, CrC6alkyloxy, CrCealkyloxyCrCealkyl, aryloxy, aryloxyCrC6alkyl, arylCrCealkyloxyCrCealkyl, hetaryl, hetarylCrCealkyl, hetaryloxy, hetaryld-Cealkyloxy, hetaryloxyd-C6alkyl, hetarylCrCealkyloxyCrCealkyl, NR8R9, S02NR8R9, NR4R5carbonylalkyl, arylcarbonylNR8, arylthio, hetarylthio, arylSOn, hetarylSOn, arylSOmNR8, arylthioCrC6alkyl, hetarylthioCrC6alkyl or arylC C6alkylR6CrC6alkyl; wherein the aryl and hetaryl groups independently are optionally substituted with one or more R10;
R8 and R9 independently are hydrogen, d-C8alkyl, aryl, hetaryl, arylCrC6alkyl or hetaryld- C6alkyl wherein the alkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R11; or
R8 and R9 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one C C8alkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrCealkyl, hydroxy, oxo, d-C6alkyloxy, aryld-Cealkyloxy, hetarylCrCealkyloxy, d- CealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy, hetarylcarboxy, aryld- C6alkyl-carboxy or hetarylC C6aIkylcarboxy;
R10 and R11 independently are hydrogen, hydroxy, oxo, halo, cyano, nitro, d-Cealkyl, d-C6- alkyloxy, NR12R13, methylendioxo, trihalomethyl or trihalomethyloxy; R12 and R13 independently are hydrogen, C C8alkyl or arylCrC6alkyl;
R14 is hydrogen, halo, hydroxy, oxo, nitro, cyano, C C8alkyl, CrC6alkyloxy or aryloxy;
R15 is hydrogen, halo, hydroxy, oxo, nitro, cyano or COOR17;
R 6 is hydrogen, d-C8alkyl, C3-Cι0cycloalkyl, C3-C10hetcycloalkyl, aryl, arylCrC6alkyl, hetaryl, hetarylCrCealkyl, alkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, aryloxyd-Cealkyl, hetaryloxyCrC6alkyl, aryIthioCrC6alkyl or hetarylthioCrC6alkyl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R10;
R17 is hydrogen, d-C8alkyl, aryl or arylCrC6alkyl;
m is 1 or 2;
n is 0, 1 or 2; or
a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R1 is C3-C10cycloalkyl or C3-Cι0hetcycloalkyl wherein the cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R4 as defined above.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R1 is C3-C10cycloalkyl optionally substituted with one or more of R4 as defined above.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R2 is hydrogen or d-C8alkyl, wherein the the alkyl group is optionally substituted with one or more of R5 as defined above.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R2 is CrC8alkyl optionally substituted with one or more of R5 as defined above. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R3 is C3-Ci0cycloalkyl, C3-Cι0hetcycloalkyl, aryl, hetaryl, arylCrCealkyl, hetaryld-Cealkyl, aryl-R6- d-Cealkyl, hetaryl-R6-C C6alkyl or aryld-Cealkyl-R^d-Cealkyl wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R7.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R3 is aryl or hetaryl, wherein the aryl and hetaryl groups are optionally substituted with one or more of R7 as defined above.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R3 is is phenyl optionally substituted with one or more of R7 as defined above.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R3 is phenyl optionally substituted independently in position 2(ortho) or 4(para) with one or more of R7 as defined above.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R4 and R5 independently are hydrogen, hydroxy, oxo, halo, d-C8alkyl, wherein the alkyl group is optionally substituted with one ore more of R15.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R6 is oxygen. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R7 is hydrogen, halo, hydroxy, cyano, d-C8alkyl, C3-Cι0cycloalkyl, C3-d0het-cycloalkyl, trihalomethyl, aryl, aryld-Cealkyl, CrC6alkyloxy, CrC6alkyloxyCrC6alkyl, aryloxy, aryld- Cealkyloxy, aryloxyd-Cealkyl, arylCrCealkyloxyCrCealkyl, hetaryl, hetarylCrCealkyl, hetaryloxy, hetarylCrCealkyloxy, hetaryloxyCrC6alkyl, hetarylCrCealkyl-oxyd-Cealkyl,
NR8R9, NR4R5carbonyICrC6alkyI, R18carbonylNR8, R19SOmNR8, wherein the aryl and hetaryl groups independently are optionally substituted with one or more R10.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R8 and R9 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one halo, cyano, CrC8alkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrCealkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, hetaryld-
C6alkyloxy, CrC6alkyloxyCrC6alkyl, d-C6alkyl-carbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy or hetarylCrC6alkylcarboxy.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R 5 is CONR8R9. In another embodiment ofthe present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (II) wherein R18 is C C6alkyl optionally substituted with R15.
In another embodiment of the present invention said substituted amide, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of: 3-(10,11-Dihydro-dibenzo[b,f]azepin-5-yl)-1-[4-(1H-imidazol-4-yl)-piperidin-1-yl]-propan-1-one;
4-(10, 11 -Dihydro-dibenzo[b,f]azepin-5-yl)-1 -[4-(3H-imidazol-4-yl)-piperidin-1 -yl]-butan-1 -one;
2,4-Bis-benzyloxy-benzamide;
(1 H-lndol-4-yl)-piperidin-1 -yl-methanone;
N-(1 ,4-Dioxo-1 ,4-dihydro-naphthalen-2-yl)-benzamide; N-(2,3-Dihydroxy-propyl)-2-(2-phenyl-adamantan-2-yl)-acetamide;
(6-Fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-phenyl-methanone;
(2-Chloro-phenyl)-(6-fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-methanone;
3-Cyclopentyl-1-(6-fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-propan-1-one;
(3-Chloro-thieno[2,3-b]thiophen-2-yl)-thiomorpholin-4-yl-methanone; 2-[2-(4-Chloro-phenyl)-adamantan-2-yl]-1 -[4-(4-methoxy-phenyl)-piperazin-1 -yl]-ethanone;
1-(4-Benzyl-piperazin-1-yl)-2-[2-(4-chloro-phenyl)-adamantan-2-yl]-ethanone;
2-[2-(4-Chloro-phenyl)-adamantan-2-yl]-1-(4-methyl-piperazin-1-yl)-ethanone;
1-[4-(6-Chloro-pyridin-2-yl)-piperazin-1-yl]-2-(2-phenyl-adamantan-2-yl)-ethanone;
4-Chloro-N-(1,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl)-benzamide; 3-Chloro-benzo[b]thiophene-2-carboxylic acid (2-cyano-ethyl)-cyclohexyl-amide;
2-[2-(Bicyclo[2.2.1]hept-5-en-2-ylamino)-4-oxo-4,5-dihydro-thiazol-5-yl]-N-(2-chloro-phenyl)- acetamide;
[3-(4-sec-ButyI-phenoxy)-phenyl]-piperidin-1-yl-methanone;
3-(6-Chloro-pyridin-2-yloxy)-N-ethyI-benzamide; N-Benzyl-2,4-dichloro-N-pyridin-2-yl-benzamide;
2-[Benzoyl-(3-chloro-4-fluoro-phenyl)-amino]-propionic acid butyl ester; 2-[Benzoyl-(3-chloro-4-fluoro-phenyl)-amino]-propionic acid pentyl ester;
3-(4-Fluoro-phenyI)-1 -(4-phenyl-piperidin-1 -yl)-but-2-en-1 -one;
N-(1 ,7,7-Trimethyl-bicyclo[2.2.1 ]hept-2-yl)-benzamide;
1-(3-Cyclopentyl-propionyl)-piperidine-3-carboxylic acid ethyl ester; 4-Phenyl-1 -phenylacetyl-piperidine-4-carbonitrile;
1-Octanoyl-4-phenyl-piperidine-4-carbonitrile;
2,2-Dimethyl-1-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-propan-1-one;
(4-ChIoro-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
N-[1-(4-Methanesulfonyl-phenyl)-ethyl]-N-(tetrahydro-furan-2-yImethyl)-benzamide; 2-(2-Amino-phenylsulfanyl)-1-(5-fluoro-2,3-dihydro-indol-1-yl)-ethanone;
N-(1-Methyl-2,3-dihydro-1H-indol-5-ylmethyl)-N-(tetrahydro-furan-2-ylmethyl)-benzamide;
1-Benzoyl-piperidine-2-carboxylic acid ethyl ester;
N-(2-Chloro-phenyl)-2-(1,2,3,4-tetrahydro-isoquinolin-1-yl)-acetamide;
(Decahydro-naphthalen-1-yl)-(4-methyl-piperazin-1-yl)-methanone; (4-Methyl-piperazin-1-yl)-(2-p-tolylsulfanyl-phenyl)-methanone;
Adamantane-1 -carboxylic acid (3-benzyloxy-2-ethyl-6-methyl-pyridin-4-yl)-amide;
(6-Fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-(3,4,5-trimethoxy-phenyl)-methanone;
N-Bicyclo[2.2.1]hept-2-yl-3-cyclopentyl-propionamide;
(2-Benzo[1,2,5]oxadiazol-5-yI-thiazol-4-yl)-piperidin-1 -yl-methanone; Thiophene-2-carboxylic acid [4-(4-fluoro-phenyl)-4-hydroxy-butyl]-isopropyl-amide;
N-Cyclohexyl-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propionamide;
2-[(Adamantane-1-carbonyl)-amino]-3-(1H-indol-3-yl)-propionic acid methyl ester;
Adamantane-1 -carboxylic acid [3-(1 H-benzoimidazol-2-ylsulfanyl)-5-nitro-phenyl]-amide;
N-Benzyl-N-(1-cyclopropyl-ethyl)-4-fluoro-benzamide; Thiophene-2-carboxylic acid 2-[2-(2-phenyl-adamantan-2-yl)-acetylamino]-ethyl ester;
N-(4-Acetyl-phenyl)-2-(2-phenyl-adamantan-2-yl)-acetamide;
2-[2-(4-Chloro-phenyl)-adamantan-2-yl]-N-(2-hydroxy-ethyl)-acetamide;
(4-Benzoyl-piperidin-1-yl)-thiophen-2-yl-methanone;
N-(2-Benzoyl-4-methyl-phenyl)-3-phenyI-acrylamide; N-(2-Benzoyl-4-methyl-phenyl)-2-fluoro-benzamide;
Adamantane-1 -carboxylic acid (4-ethoxy-benzothiazol-2-yl)-amide;
Adamantane-1 -carboxylic acid (5-benzoyl-4-phenyl-thiazol-2-yl)-amide;
3-(2-Hydroxy-phenyl)-1 ,3-di-piperidin-1 -yl-propan-1 -one;
N-(1-Methyl-2-phenyl-ethyl)-3-phenyl-propionamide; 4-Oxo-4-piperidin-1-yl-butyric acid 4-tert-butyI-cyclohexyl ester;
N-tert-Butyl-N-(4-methoxy-benzyl)-4-nitro-benzamide; {4-[(Adamantane-1 -carbonyl)-amino]-phenoxy}-acetic acid;
2-(4-lsobutyl-phenyl)-N-(1-phenyl-ethyl)-propionamide;
Adamantane-1 -carboxylic acid 4-[(adamantane-1 -carbonyl)-amino]-2,6-dimethyl-pyridin-3-yl ester; 2-Phenyl-1 -(3-phenyI-pyrrolidin-1 -yl)-ethanone;
Adamantane-1 -carboxylic acid 4-[(adamantane-1-carbonyl)-amino]-2-ethyl-6-methyl-pyridin-3- yl ester;
N-(1,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-N-(4-hydroxy-phenyl)-benzamide;
Biphenyl-4-yl-piperidin-1 -yl-methanone; Azepan-1 -yl-(3,5-dichloro-phenyl)-methanone;
Azepan-1-yl-biphenyl-4-yl-methanone;
Azepan-1 -yl-(4-ch!oro-phenyl)-methanone;
3-Heptylcarbamoyl-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid;
Adamantan-1 -yl-azepan-1 -yl-methanone; N,N-Dibenzyl-3,4-dimethoxy-benzamide;
N-Benzyl-N-isopropyl-4-nitro-benzamide;
N-[2-(1H-lndol-3-yl)-1-methyl-ethyl]-2-(4-isobutyl-phenyl)-propionamide;
N-tert-Butyl-2-(4-isobutyl-phenyI)-propionamide;
Adamantane-1 -carboxylic acid (2-acetyl-phenyl)-amide; N-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-N-(4-fluoro-phenyl)-benzamide;
(Octahydro-quinolin-l-yl)-phenyl-methanone;
(7-Hydroxy-octahydro-quinolin-1-yl)-phenyl-methanone;
N-(1,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-N-p-tolyl-benzamide;
N,N-Dibenzyl-4-methyl-benzamide; (2-Chloro-phenyl)-(2-methyl-piperidin-1 -yI)-methanone;
[4-Bromo-3-(piperidine-1-sulfonyl)-phenyl]-piperidin-1-yl-methanone;
2-Chloro-N-(3,4-dimethyl-phenyl)-benzamide;
1 -Azepan-1 -yl-2-(3,3-dimethyl-3,4-dihydro-2H-isoquinolin-1-ylidene)-ethanone;
N-Cyclohexyl-4-(2,4-dichloro-phenoxy)-butyramide; N-Benzo[1 ,3]dioxol-5-yl-2-chloro-benzamide;
(4-Benzyl-piperidin-1-yl)-(2-chloro-phenyl)-methanone;
2-(Benzothiazol-2-ylsulfanyl)-N-cyclohexyl-acetamide;
Cyclohexanecarboxylic acid (7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-quinazolin-2-yl)-amide;
2,4-Dichloro-N-ethyI-N-o-tolyl-benzamide; (4-Benzyl-piperidin-1 -yl)-(4-fluoro-phenyl)-methanone;
N-CyclohexyI-4-(2,4-dichloro-phenoxy)-N-methyl-butyramide; 3-[2-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-yl)-ethyl]-adamantane-1 -carboxylic acid;
Morpholin-4-yl-(3-p-tolyl-adamantan-1-yl)-methanone;
N-Benzyl-2,4-dichloro-N-methyl-benzamide;
Thiophene-2-carboxyIic acid dibenzylamide; Azepan-1 -yl-(2-bromo-phenyl)-methanone;
(3,4-Dichloro-phenyl)-(4-methyI-piperidin-1-yl)-methanone;
N,N-Dibenzyl-3,4-dichloro-benzamide;
4-(2,4-Dichloro-phenoxy)-1 -piperidin-1 -yl-butan-1 -one;
N,N-Dibenzyl-2-fluoro-benzamide; (2-ChIoro-phenyl)-piperidin-1 -yl-methanone;
2-Chloro-N-(3-trifluoromethyl-phenyl)-benzamide;
N-Benzyl-N-ethyl-2-phenyl-acetamide;
(3,4-Dihydro-2H-quinolin-1-yl)-p-tolyl-methanone;
Thiophene-2-carboxylic acid benzyl-ethyl-amide; N-Adamantan-1 -yl-2-dibenzylamino-acetamide;
N-Cyclohexyl-2-(1 ,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-phenyl-propionamide;
Thiophene-2-carboxylic acid cycloheptylamide;
N-Cyclohexyl-3-diethylsulfamoyI-4-methyl-benzamide;
4-Benzoyl-N-methyl-N-phenyl-benzamide; N-Benzyl-2-bromo-N-methyl-benzamide;
2-Chloro-N-methyl-N-phenyl-benzamide;
4-Chloro-N-ethyl-N-o-tolyl-benzamide;
N-Benzyl-4,N-dimethyl-benzamide;
2-(4-Chloro-3,5-dimethyl-phenoxy)-N-cycIohexyl-N-methyl-acetamide; N-Benzyl-2-bromo-N-isopropyl-benzamide;
3-(2-Chloro-phenyl)-N-cyclohexyl-N-methyl-acrylamide;
N-Phenyl-N-(2,2,5-trimethyl-hex-4-enyl)-acetamide;
N-m-Tolyl-N-(2,2,5-trimethyl-hex-4-enyl)-acetamide;
(3-Chloro-benzo[b]thiophen-2-yl)-(4-methyl-piperazin-1-yl)-methanone; Adamantane-1 -carboxylic acid (5-methyl-pyridin-2-yl)-amide;
3-Bromo-N-[2-methyl-1-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-butyl]- benzamide;
4-Chloro-N-[2-methyl-1-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-butyl]- benzamide; 4-Methyl-N-[2-methyl-1-(1,3,3-trimethyl-6-aza-bicycIo[3.2.1]octane-6-carbonyl)-butyl]- benzamide; Cyclohexanecarboxylic acid [2-methyl- 1-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6- carbonyl)-butyl]-amide;
3-Cydopentyl-N-[2-methyl-1 -(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-butyl]- propionamide; 2-Chloro-N-[2-(4-ethyl-benzoylamino)-ethyl]-N-(4-fluoro-phenyl)-benzamide;
N-{1-Benzyl-2-[4-(3-cyclopentyl-propionyl)-piperazin-1-yl]-2-oxo-ethyl}-3-cyclopentyl- propionamide;
N-Bicyclo[2.2.1]hept-5-en-2-ylmethyl-3-cyclopentyl-N-[2-(1H-indol-3-yl)-ethyl]-propionamide;
N-Bicyclo[2.2.1 ]hept-5-en-2-ylmethyl-2,4-dichloro-N-[2-(1 H-indol-3-yl)-ethyl]-benzamide; Naphthalene-2-carboxylic acid (2-oxo-azepan-3-yl)-thiophen-3-ylmethyl-amide;
3,4,5-Trimethoxy-N-(4-methyl-benzyl)-N-[6-(pyridin-2-ylamino)-hexyl]-benzamide;
3-Cyclopentyl-N-(4-methyl-benzyI)-N-[6-(pyridin-2-ylamino)-hexyl]-propionamide;
N-(3,4-Dimethoxy-benzyl)-3-methoxy-N-[6-(pyridin-2-ylamino)-hexyl]-benzamide;
N,N-Dimethyl-2-[3-(4-nitro-phenyl)-adamantan-1-yl]-acetamide; Adamantane-1 -carboxylic acid [4-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-yl)-butyl]-p-tolyl-amide;
2-(1,3-Dioxo-1 ,3-dihydro-isoindol-2-yl)-3-methyl-N-(2-trifluoromethyl-phenyl)-butyramide;
2-(4-Chloro-2-methyl-phenoxy)-N-(2-trifluoromethyl-phenyl)-propionamide;
4-(2,4-Dichloro-phenoxy)-1 -[4-(4-fluoro-phenyl)-piperazin-1 -yl]-butan-1 -one;
(3,4-Dihydro-2H-quinolin-1-yl)-[3-(piperidine-1-sulfonyl)-phenyl]-methanone; Acetic acid 4-(azepane-1-carbonyl)-phenyl ester;
N-Adamantan-1-ylmethyl-benzamide;
[3-(4-Nitro-phenyl)-adamantan-1-yl]-piperidin-1 -yl-methanone;
N-(1 ,1-Dimethyl-hexyl)-2-morpholin-4-yl-acetamide;
Adamantyl-1 -carboxylic acid (2-methoxy-ethyl)-amide; N-(4-Adamantan-1 -yl-2-methyl-phenyl)-acetamide;
3-p-Tolyl-adamantane-1 -carboxylic acid (2,5-dichloro-phenyl)-amide;
(3-Chloro-adamantan-1-yl)-pyrrolidin-1 -yl-methanone;
2-Amino-5-cyclohexylcarbamoyl-4-methyl-thiophene-3-carboxylic acid ethyl ester;
N-(2-Chloro-phenyl)-2-{3-[(2-chloro-phenylcarbamoyl)-methyl]-adamantan-1-yl}-acetamide; 3-p-Tolyl-adamantane-1 -carboxylic acid (2,4-difluoro-phenyl)-amide;
Adamantyl-1 -carboxylic acid tert-butylamide;
2-Adamantan-1-yl-N-tert-butyl-acetamide;
N-Methyl-N-phenyl-4-(pyrrolidine-1-sulfonyl)-benzamide;
N-(1 -Adamantan-1 -yl-ethyl)-2-fluoro-benzamide; Adamantane-1 -carboxylic acid [2-(3,4-dimethoxy-phenyI)-ethyl]-amide;
Adamantane-1 -carboxylic acid dimethylamide; N-Benzyl-4-chloro-N-(1-cyclopropyl-vinyl)-benzamide;
3,5-Dimethyl-adamantane-1 -carboxylic acid benzylamide;
2,4-Dichloro-N-cyclohexyl-N-(2-hydroxy-ethyl)-benzamide;
N-Adamantan-1-yl-2,4-dichloro-N-ethyl-benzamide; 2-[(3-p-Tolyl-adamantane-1-carbonyl)-amino]-propionic acid methyl ester;
N-Adamantan-1-yl-3-morpholin-4-yl-propionamide;
3-p-Tolyl-adamantane-1 -carboxylic acid isopropylamide;
N-Adamantan-1-yl-2-benzylamino-acetamide;
N-Benzyl-2,4-dichloro-N-(1-cyclopropyl-ethyl)-5-methyl-benzamide; 2-[(Adamantane-1-carbonyl)-amino]-benzoic acid ethyl ester;
N-Benzyl-N-isopropyl-4-methyl-3-nitro-benzamide;
(3,4-Dihydro-2H-quinolin-1-yl)-(2-fluoro-phenyl)-methanone;
N-Ethyl-2-fluoro-N-phenyl-benzamide;
2-Phenethyl-N-(2-trifluoromethyl-phenyl)-benzamide; 1-(3,4-Dihydro-2H-quinolin-1-yl)-2-o-tolyloxy-ethanone;
2-(1 -Benzyl-1 H-imidazol-2-ylsulfanyl)-N-cyclohexyl-acetamide;
Cyclohexanecarboxylic acid (2-propoxy-phenyl)-amide;
2-{3-[4-(2-Chloro-phenyl)-piperazin-1-yl]-3-oxo-propyl}-isoindole-1 ,3-dione;
N-Cyclopentyl-2-(2,4-dichloro-phenoxy)-propionamide; Adamantane-1 -carboxylic acid (2-trifluoromethyl-phenyl)-amide;
(4-Chloro-3-nitro-phenyl)-(2,6-dimethyl-piperidin-1-yl)-methanone;
4-(2-Ethyl-phenyl)-4-aza-tricyclo[5.2.2.02'6]undec-8-ene-3,5-dione;
2-Phenyl-N-(2-trifluoromethyl-phenyl)-butyramide;
N-Adamantan-1-yl-4-chloro-2-nitro-benzamide; 3-p-Tolyl-adamantane-1 -carboxylic acid (2,3-dimethyl-phenyl)-amide;
N-Benzyl-3-methyl-4-p-tolyl-butyramide;
N-(2-Cyclohex-1 -enyl-ethyl)-2-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-yl)-propionamide;
(4-tert-Butyl-phenyl)-(3,4-dihydro-1H-isoquinolin-2-yl)-methanone;
2-[1-(4-Chloro-benzenesulfonyl)-1 H-benzoimidazol-2-ylsulfanyl]-N-thiophen-2-ylmethyl- acetamide;
2-Phenoxy-1-[4-(2-trifluoromethyl-benzyl)-piperazin-1-yl]-ethanone;
Cyclohexanecarboxylic acid [5-(2-fluoro-benzylsulfanylmethyl)-[1,3,4]thiadiazol-2-yl]-amide;
4-Methyl-2-phenyl-thiazole-5-carboxylic acid naphthalen-1 -ylamide;
4-Fluoro-N-[4-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]- benzenesulfonamide;
(3-Methoxy-phenyl)-(4-o-tolyl-piperazin-1-yl)-methanone; N-Adamantan-1 -yl-3-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-yl)-propionamide;
N-Cyclooctyl-2-methoxy-3-methyl-benzamide;
2-[4-(2,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]-isoindole-1 ,3-dione;
(2,3-Diphenyl-quinoxalin-6-yl)-(2,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; Adamantan-1 -yl-(1,3,4,5-tetrahydro-pyrido[4,3-b]indol-2-yl)-methanone;
N-{4-[1-(Naphthalene-2-sulfonyl)-piperidin-3-yl]-butyl}-N'-p-tolyl-oxalamide;
N-Benzyl-N-(2-oxo-2-pyrrolidin-1-yl-ethyl)-benzenesulfonamide;
(4-Amino-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
1-[4-(4-Fluoro-phenyl)-piperazin-1-yl]-2-(2-isopropyl-5-methyl-phenoxy)-ethanone; Adamantane-1 -carboxylic acid benzyl-pyridin-2-yl-amide;
Adamantan-1 -yl-piperidin-1 -yl-methanone;
Adamantan-1 -yI-pyrrolidin-1 -yl-methanone;
(3,4-Dihydro-2H-quinolin-1-yl)-o-tolyl-methanone;
Adamantyl-1 -carboxylic acid benzylamide; Pyridine-2-carboxylic acid adamantan-2-ylamide;
(3-Chloro-adamantan-1 -yl)-piperidin-1 -yl-methanone;
Adamantan-1 -yl-(4-methyl-piperidin-1 -yl)-methanone;
2-[3-(Azepane-1 -carbonyl)-phenyl]-isoindo!e-1 ,3-dione;
2-[3-(Piperidine-1 -carbonyl)-phenyl]-isoindole-1 ,3-dione; 4-(Benzyl-methanesulfonyI-amino)-N-furan-2-ylmethyl-benzamide;
(4-Nitro-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
1 -Cyclohexyl-5-oxo-pyrrolidine-3-carboxylic acid (4-chloro-3-nitro-phenyl)-amide;
N-(2-Chloro-phenyl)-2-(2-oxo-2-phenyl-ethylsulfanyl)-acetamide;
3-(4-Hydroxy-phenyl)-N-isochroman-1-ylmethyl-3-phenyl-propionamide; (4-Ethoxy-phenyl)-(2-methyl-piperidin-1 -yl)-methanone;
1 -Cyclohexyl-5-oxo-pyrrolidine-3-carboxylic acid (3-chloro-phenyl)-amide;
N-[4-(Benzyl-isopropyl-sulfamoyl)-phenyl]-acetamide;
N-(3,4-Dimethyl-phenyl)-N-[4-(piperidine-1-carbonyl)-benzyl]-methanesulfonamide;
2-(5-Phenyl-1 H-imidazol-2-ylsulfanyl)-N-(1 ,1 ,3,3-tetramethyl-butyl)-acetamide; 2-(Benzothiazol-2-ylsulfanyl)-N-(1 ,1 ,3,3-tetramethyl-butyl)-acetamide;
2-(Benzooxazol-2-ylsulfanyl)-N-(1 , 1 ,3,3-tetramethyl-butyl)-acetamide;
2-(Naphthalen-2-ylcarbamoylmethylsulfanyl)-N-(1 , 1 ,3,3-tetramethyl-butyl)-acetamide;
Acetic acid 4-(3,5-dimethyl-piperidine-1-carbonyl)-phenyl ester;
(4-Chloro-3-nitro-phenyl)-(2,6-dimethyl-piperidin-1-yl)-methanone; [1-(4-Chloro-benzenesulfonyI)-piperidin-3-yl]-(octahydro-quinolin-1-yl)-methanone;
2,4-Dichloro-N-cyclohexyl-N-(2-hydroxy-ethyl)-benzamide; (4-Fluoro-phenyl)-(3,4,4a,8a-tetrahydro-2H-quinolin-1-yl)-methanone;
N-Adamantan-1-yl-2-ethoxy-acetamide;
2-(2-Oxo-2-phenothiazin-10-yl-ethyl)-hexahydro-isoindole-1 ,3-dione;
Adamantane-1 -carboxylic acid (tetrahydro-furan-2-ylmethyl)-amide; 2-Bromo-N-cycloheptyl-benzamide;
Bicyclo[2.2.1]hept-2-yl-[4-(2-ethoxy-phenyl)-piperazin-1-yl]-methanone;
N-Furan-2-ylmethyl-2-phenyl-2-phenylsulfanyl-acetamide;
Adamantane-1 -carboxylic acid benzyl-methyl-amide;
1-(3,4-Dihydro-2H-quinolin-1-yl)-3-(4-fluoro-phenyl)-propenone; Adamantan-1 -yl-(2,6-dimethyl-piperidin-1-yl)-methanone;
4-Methyl-N-homoadamantyl-3-yl-benzamide;
(3,5-Dimethyl-piperidin-1-yl)-(3-methyl-4-nitro-phenyl)-methanone;
Quinoline-2-carboxylic acid cyclooctylamide;
Adamantane-1 -carboxylic acid [2-(2,4-dimethoxy-phenyl)-ethyl]-amide; (3,4-Dihydro-1 H-isoquinolin-2-yl)-o-tolyl-methanone;
(3,6-Dichloro-benzo[b]thiophen-2-yl)-(4-methyl-piperazin-1-yl)-methanone;
3-(1-Benzyl-1H-imidazol-2-ylsulfanyl)-N-cyclohexyl-propionamide;
Propionic acid 2-amino-4-methyl-5-p-tolylcarbamoyl-thiophen-3-yl ester;
2-Cyclohexyl-N-(2,6-dimethyl-phenyl)-N-furan-2-ylmethyl-acetamide; (3-Methoxy-phenyl)-(2,2,4-trimethyl-4-phenyI-3,4-dihydro-2H-quinolin-1-yl)-methanone;
1-[4-(2,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]-pyrrolidine-2,5-dione;
1 -(3,4-Dihydro-2H-quinolin-1-yl)-2-(1 -naphthalen-1 -yl-1 H-tetrazol-5-ylsulfanyl)-ethanone;
[4-(2,3-DimethyI-phenyl)-piperazin-1-yl]-o-tolyl-methanone;
(4-Benzyl-piperidin-1-yl)-(4-methyl-3-nitro-phenyl)-methanone; N-(2-Cyano-phenyl)-2-(9-ethyl-9H-1,3,4,9-tetraaza-fluoren-2-ylsulfanyl)-acetamide;
N-(2-Cyano-phenyl)-2-(9-methyl-9H-1,3,4,9-tetraaza-fluoren-2-ylsulfanyl)-acetamide;
1-(Thiophene-2-carbonyl)-2,3-dihydro-1H-quinolin-4-one;
(3-Chloro-6-nitro-benzo[b]thiophen-2-yl)-piperidin-1-yl-methanone;
(4-Bromo-phenyl)-(3,5-dimethyl-piperidin-1-yl)-methanone; 2-Morpholin-4-yl-N-(1 -phenyl-cyclopentylmethyl)-acetamide;
9-Oxo-9H-fluorene-1 -carboxylic acid (3-methyl-butyl)-amide;
[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-(4-methyl-piperidin-1-yl)-methanone;
N-Cycloheptyl-3-diethylsulfamoyl-benzamide;
(4-Methoxy-phenyI)-(3-phenyl-piperidin-1-yl)-methanone; 3-Amino-N-cyclohexyl-N-methyl-benzamide;
N-Ethyl-3,4-dimethyl-N-phenyl-benzamide; N-Benzyl-3,4,N-trimethyl-benzamide;
(4-Fluoro-phenyl)-(3-phenyl-piperidin-1-yl)-methanone;
[4-(2,3-Dimethyl-phenyl)-piperazin-1-yl]-(3-methoxy-phenyl)-methanone;
Furan-2-carboxylic acid [4-(4-methyl-piperidine-1 -sulfonyl)-phenyl]-amide; N-(2-Cyclohex-1 -enyI-ethyI)-2-o-tolyloxy-acetamide;
5-(2-Chloro-phenoxymethyl)-furan-2-carboxylic acid (1-bicyclo[2.2.1]hept-2-yl-ethyl)-amide;
3-(2-Chloro-phenyl)-1-[4-(2,3-dimethyl-phenyl)-piperazin-1-yl]-propenone;
N-[3-(Azepane-1-carbonyl)-phenyl]-benzamide;
[3-(Piperidine-1 -carbonyl)-pyrazol-1 -yl]-o-to!yl-methanone; N-(1-Phenyl-cyclopentylmethyl)-2-piperidin-1-yl-propionamide;
2-Morpholin-4-yl-N-(1-phenyl-cyclopentylmethyl)-propionamide;
N-[4-(Azepane-1-sulfonyl)-phenyl]-2,2,2-trifluoro-acetamide;
2,3-Dihydro-benzo[1 ,4]dioxine-6-carboxylic acid (1 -adamantan-1 -yl-ethyl)-amide;
N-Adamantan-1-yl-2-(3-methoxy-phenoxy)-acetamide; 3-ChIoro-benzo[b]thiophene-2-carboxylic acid (2-cyano-ethyl)-phenyl-amide;
[4-(4-Nitro-benzyl)-piperidin-1-yl]-phenyl-methanone;
[4-(2-Nitro-benzyl)-piperidin-1-yl]-phenyl-methanone;
3-[5-(4-Fluoro-phenyl)-furan-2-yl]-1-(1,3,3-trimethyl-6-aza-bicydo[3.2.1]oct-6-yl)-propenone;
2-(3-Fluoro-benzoylamino)-4-methyl-5-(piperidine-1-carbonyl)-thiophene-3-carboxylic acid methyl ester;
N-(2-Ethyl-phenyl)-2-(3-methyl-piperidin-1-yl)-acetamide;
2-(2-Methoxy-benzoylamino)-4-methyl-5-(piperidine-1-carbonyl)-thiophene-3-carboxylic acid methyl ester;
1 -Phenyl-cyclopentanecarboxylic acid (4-phenyl-tetrahydro-pyran-4-ylmethyl)-amide; 4-(2,4-Dichloro-phenoxy)-1 -(4-phenyl-piperazin-1 -yl)-butan-1 -one;
Naphthalene-1 -carboxylic acid cycloheptylamide;
N-lndan-5-yl-2-methyl-3-nitro-benzamide;
N-CycIohexyl-3-(2,2,2-trifluoro-ethoxymethyl)-benzamide;
2-Methoxy-N-(1-phenyl-cyclopentylmethyl)-benzamide; [5-(2,5-Dichloro-phenoxymethyl)-furan-2-yl]-(2,6-dimethyl-morpholin-4-yl)-methanone;
[5-(2-Bromo-phenoxymethyl)-furan-2-yl]-(2-methyl-piperidin-1-yl)-methanone;
5-(2-Methoxy-phenoxymethyl)-furan-2-carboxylic acid cycloheptylamide;
(3,4-Dihydro-1H-isoquinolin-2-yl)-[1-(2-nitro-benzenesulfonyl)-piperidin-3-yl]-methanone;
N-Cyclooctyl-2-(4-methoxy-phenoxy)-acetamide; N-(2,3-Dimethyl-phenyl)-4-[methyl-(toluene-4-sulfonyl)-amino]-butyramide;
N-PhenyI-N-[4-(piperidine-1-carbonyl)-benzyl]-benzenesulfonamide;" N-[4-(3,4-Dihydro-1H-isoquinoline-2-carbonyl)-benzyl]-N-(3,4-dimethyl-phenyl)- methanesulfonamide;
2,3-Dihydro-benzo[1 ,4]dioxine-2-carboxylic acid bicyclo[2.2.1]hept-2-ylamide;
4,5,6,7-Tetrahydro-benzo[b]thiophene-3-carboxylic acid cycloheptylamide; N-(2-Azepan-1-yl-2-oxo-ethyl)-N-benzyl-4-fluoro-benzenesulfonamide;
1 -(2,6-Dimethyl-morpholin-4-yl)-3,3-diphenyl-propan-1 -one;
N-Bicyclo[2.2.1]hept-2-yl-4-morpholin-4-ylmethyl-benzamide;
[3-(2-Chloro-6-nitro-phenoxy)-phenyl]-piperidin-1-yl-methanone;
N-Adamantan-1-yl-2-(4-methyl-quinolin-2-ylsulfanyl)-acetamide; Cyclohexanecarboxylic acid (2-phenylsulfanyl-phenyl)-amide;
(4-Hydroxy-4-phenyl-octahydro-quinolin-1-yl)-phenyl-methanone;
3-Cyclohexyl-N-(3-phenyl-propyl)-propionamide;
2-[1-(2,5-Dimethyl-phenyl)-1H-tetrazol-5-ylsulfanyl]-N-isopropyl-N-phenyl-acetamide;
N-{2-[4-(3,4-Dihydro-1H-isoquinoline-2-sulfonyl)-phenyl]-ethyl}-acetamide; N-Benzyl-N-[2-oxo-2-(4-phenyl-piperazin-1-yl)-ethyl]-benzenesulfonamide;
[4-(2-ChIoro-6-nitro-phenoxy)-phenyl]-piperidin-1-yl-methanone;
N-Cycloheptyl-3-phenyl-propionamide;
(3-Chloro-6-methyl-benzo[b]thiophen-2-yl)-piperidin-1 -yl-methanone;
N-Cycloheptyl-2,4-dimethoxy-benzamide; N-(3-Chloro-phenyl)-2-(8,11 ,11-trimethyl-3,4,6-triaza-tricydo[6.2.1.02'7]undeca-2(7),3,5-trien-5- ylsulfanyl)-acetamide;
N-(2-Nitro-phenyl)-2-(8,11 ,11-trimethyl-3,4,6-triaza-tricyclo[6.2.1.02-7]undeca-2(7),3,5-trien-5- ylsulfanyl)-acetamide;
N-Phenyl-2-(8,11 ,11-trimethyl-3,4,6-triaza-tricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-5- ylsulfanyl)-acetamide;
N-Ethyl-3-methyl-N-o-tolyl-benzamide;
N-[5-(2,4-Dichloro-benzylsulfanyl)-[1,3,4]thiadiazol-2-yl]-2,2-dimethyl-propionamide;
4-Fluoro-N-[4-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-phenyl]- benzenesulfonamide; 4-Bromo-1 -ethyl-1 H-pyrazole-3-carboxylic acid (2-methylsulfanyl-phenyl)-amide;
5-Benzoyl-furan-2-carboxylic acid diisopropylamide;
2-[3-(Piperidine-1-carbonyl)-phenyl]-isoindole-1,3-dione;
N-{2-[2-(4-Bromo-phenyl)-2-oxo-ethylsulfanyl]-benzothiazol-6-yl}-acetamide;
2-(6-Amino-benzothiazol-2-ylsulfanyl)-N-cyclohexyI-acetamide; N-(2-Cyclohexylcarbamoylmethylsulfanyl-benzothiazol-6-yl)-2-methoxy-benzamide;
Benzofuran-2-yI-(4-phenyl-piperidin-1-yl)-methanone; 1-(2-Nitro-phenyl)-piperidine-3-carboxylic acid diethylamide;
1-(4-Nitro-phenyl)-piperidine-3-carboxylic acid diethylamide;
5-Bromo-furan-2-carboxylic acid adamantan-2-ylamide;
3,3-Dimethyl-pentanedioic acid bis-[(2,4-difluoro-phenyl)-amide]; 2-(3-Bromo-benzylsulfanyl)-1 -(4-phenyl-piperazin-1 -yl)-ethanone;
N-(2-Azepan-1-yl-2-oxo-ethyl)-N-benzyl-4-bromo-benzenesulfonamide;
1 -(2,3-Dihydro-indol-1 -yl)-2-p-tolylsulfanyl-ethanone;
[4-(4-Bromo-benzenesulfonyl)-piperazin-1-yl]-furan-2-yl-methanone;
[5-(2-Bromo-phenoxymethyl)-furan-2-yl]-(2,6-dimethyI-morpholin-4-yl)-methanone; 5-(2-Chloro-phenoxymethyl)-furan-2-carboxylic acid diethylamide;
5-(2-Bromo-phenoxymethyl)-furan-2-carboxylic acid diethylamide;
5-(2-Chloro-phenoxymethyl)-furan-2-carboxylic acid methyl-phenyl-amide;
[5-(2-Chloro-phenoxymethyI)-furan-2-yl]-(4-methyl-piperidin-1-yl)-methanone;
[3-(2,5-Dichloro-phenoxymethyl)-phenyl]-pyrrolidin-1-yl-methanone; [5-(4-Ethoxy-phenoxymethyl)-furan-2-yl]-(4-methyl-piperidin-1-yl)-methanone;
3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-N-(2-methyl-cyclohexyl)-propionamide;
3-(3,4-Dihydro-2H-quinoline-1-carbonyl)-N-phenyl-benzenesulfonamide;
[3-(2,3-Dihydro-indole-1-sulfonyl)-phenyI]-(3,4-dihydro-2H-quinolin-1-yl)-methanone;
[3-(2,5-Dimethyl-pyrrol-1-yl)-phenyi]-(4-methyl-piperidin-1-yl)-methanone; N-Cyclohexyl-3-(2-hydroxy-4-methyl-phenyl)-3-phenyl-propionamide;
2-Diethylamino-N-(1-phenyl-cyclopentylmethyl)-propionamide;
(6-Fluoro-2-methyI-3,4-dihydro-2H-quinolin-1-yl)-(3-trifluoromethyl-phenyl)-methanone;
(2,6-Dimethyl-morphoIin-4-yl)-[4-(naphthalen-1-yloxymethyl)-phenyl]-methanone;
N-Benzyl-4-bromo-N-ethyl-benzamide; (3-Methyl-piperidin-1 -yl)-[4-(naphthalen-1 -yloxymethyl)-phenyl]-methanone;
Azepan-1-yl-[5-(2-chloro-phenoxymethyl)-furan-2-yl]-methanone;
(4-Methyl-piperidin-1-yl)-[4-(naphthalen-1-yloxymethyl)-phenyl]-methanone;
Azepan-1-yl-[5-(2,4-dichloro-phenoxymethyl)-furan-2-yl]-methanone;
N-Cycloheptyl-4-(4-methoxy-2-methyl-phenyl)-butyramide; 2-(4-Benzothiazol-2-yl-piperazin-1-yl)-N-cyclohexyl-acetamide;
N-Cycloheptyl-2-(2,6-dimethyl-phenoxy)-acetamide;
(3,4-Dihydro-2H-quinolin-1-yl)-(3-iodo-phenyl)-methanone;
N-Cycloheptyl-3-(2,2,2-trifluoro-ethoxymethyl)-benzamide;
Azepan-1-yl-[4-(2-chloro-phenoxymethyl)-phenyl]-methanone; (2,6-Dimethyl-morpholin-4-yl)-[4-(naphthaIen-2-yloxymethyl)-phenyl]-methanone;
Azepan-1-yl-[3-(4-ethoxy-phenoxymethyl)-phenyl]-methanone; Benzo[b]thiophene-3-carboxylic acid (1 ,2,3,4-tetrahydro-naphthalen-1-yl)-amide;
2-(4-Chloro-2-methyl-phenoxy)-N-cycloheptyl-acetamide;
2,4-Dichloro-N-cyclohexyl-N-methyl-benzamide;
N-Cyclooctyl-2-p-tolyloxy-acetamide; (3,5-Dimethyl-piperidin-1-yl)-(4-methyl-3-nitro-phenyl)-methanone;
Biphenyl-4-yI-(2,6-dimethyI-piperidin-1-yl)-methanone;
N-Cyclohexyl-4-fluoro-N-methyl-benzamide;
N-[4-(Azepane-1-carbonyI)-phenyl]-N-methyl-benzenesulfonamide;
N-Cycloheptyl-2-fluoro-benzamide; N-Cycloheptyl-4-methyl-benzamide;
(3-Methyl-piperidin-1-yl)-p-toϊyl-methanone;
[2-(3,4-Dimethoxy-phenylcarbamoyl)-piperidin-1-yl]-acetic acid benzyl ester;
N-[4-(2-Methyl-piperidine-1-suIfonyl)-phenyl]-acetamide;
2-(2,4-Dichloro-phenoxy)-N-(2-methyl-butyl)-propionamide; [4-(2-Chloro-6-nitro-phenyl)-piperazin-1-yl]-(4-methoxy-phenyl)-methanone;
N-Cyclohexyl-4-(4-methoxy-3-methyl-phenyl)-butyramide;
(3-Chloro-6-methoxy-benzo[b]thiophen-2-yI)-(3,4-dihydro-1H-isoquinolin-2-yl)-methanone;
2-(4-Methyl-benzylsulfanyl)-1 -piperidin-1 -yl-ethanone;
N-Cyclohexyl-N-[(4-phenyl-thiazol-2-ylcarbamoyl)-methyl]-benzamide; N-(2-Azepan-1-yI-2-oxo-ethyl)-N-(4-isopropyl-phenyl)-methanesulfonamide;
N-Adamantan-1-yl-3-p-tolylsulfanyl-propionamide;
6-(2,4-Dichloro-phenylcarbamoyl)-3,4-dimethyl-cyclohex-3-enecarboxylic acid;
(4-Butyl-cydohexyl)-morpholin-4-yl-methanone;
(3,4-Dichloro-phenyl)-(3,4-dihydro-2H-quinolin-1-yl)-methanone; N-(2-Cyclohex-1 -enyl-ethyl)-3-methoxy-benzamide;
N-Adamantan-2-yl-3-(1 ,5-dimethyl-1 H-pyrazol-4-yl)-acrylamide;
N-Adamantan-1-yl-N-methyl-4-(4-nitro-pyrazol-1-ylmethyl)-benzamide;
5-(4-Chloro-3,5-dimethyl-pyrazol-1 -ylmethyl)-furan-2-carboxylic acid adamantan-2-ylamide;
2-(4-Chloro-phenoxy)-N-(2-fluoro-5-methyl-phenyl)-2-methyl-propionamide; N-Adamantan-1-yl-2-(4-chloro-3,5-dimethyl-phenoxy)-acetamide;
2-[(3-Carboxy-bicyclo[2.2.1]heptane-2-carbonyl)-amino]-5,6-dihydro-4H- cyclopenta[b]thiophene-3-carboxylic acid propyl ester;
2-Adamantan-1 -yl-N-[1 -(2,5-dimethyl-phenyl)-ethyl]-acetamide;
3-Methyl-thiophene-2-carboxylic acid cyclooctylamide; N-p-Tolyl-2-(8,11 ,11-trimethyl-3,4,6-triaza-tricyclo[6.2.1.02,7]undeca-2,4,6-trien-5-ylsulfanyl)- propionamide; Azepan-1-yl-[5-(4-chloro-5-methyl-3-nitro-pyrazol-1-ylmethyl)-furan-2-yl]-methanone;
N-Adamantan-2-yl-3-(4-bromo-3-nitro-pyrazol-1-ylmethyl)-benzamide;
N-Bicyclo[2.2.1 ]hept-2-yl-2-chloro-benzamide;
[5-(3-Chloro-phenoxymethyl)-furan-2-yl]-piperidin-1-yl-methanone; 1 -(4-Ethyl-benzoyl)-6-methoxy-2-methyl-2,3-dihydro-1 H-quinolin-4-one;
6-Fluoro-2-methyl-1 -{3-[4-(propane-1 -sulfonyl)-phenoxymethyl]-benzoyl}-2,3-dihydro-1 H- quinolin-4-one;
N-Cycloheptyl-2-(naphthalen-1-yloxy)-acetamide;
N-Cyclohexyl-4-o-tolyloxy-butyramide; (2-Benzylsulfanyl-phenyl)-morpholin-4-yl-methanone;
(2-Chloro-5,6-difluoro-3-methyl-phenyl)-(4-methyl-piperidin-1-yl)-methanone;
(3-Bromo-phenyl)-[4-(4-chloro-2-nitro-phenyl)-piperazin-1-yl]-methanone;
2-Bromo-N-(1 ,1 ,3,3-tetramethyl-butyl)-benzamide;
N-Adamantan-1 -yl-2-(2-benzoyl-5-methoxy-phenoxy)-acetamide; N-Cyclohexyl-3-methyl-4-p-tolyl-butyramide;
[5-(4-Methyl-2-nitro-phenoxymethyl)-furan-2-yl]-thiomorpholin-4-yl-methanone;
[5-(2,5-Dichloro-phenoxymethyl)-furan-2-yl]-thiomorpholin-4-yl-methanone;
5-(4-Chloro-2-nitro-phenoxymethyl)-furan-2-carboxylic acid adamantan-1 -ylamide;
4,5,6,7-Tetrahydro-benzo[b]thiophene-3-carboxylic acid cyclohexylamide; 4-Chloro-1 ,5-dimethyl-1 H-pyrazole-3-carboxylic acid adamantan-1 -yl-methyl-amide;
4-(4-Methoxy-3-methyl-phenyl)-N-(2-methyl-cyclohexyl)-butyramide;
3-Benzo[1,3]dioxol-5-yl-1-(3,4-dihydro-1H-isoquinolin-2-yl)-propenone;
N-Bicyclo[2.2.1]hept-2-yl-3-phenylsulfanyl-propionamide;
Azepan-1 -yl-[5-(2-nitro-phenoxymethyl)-furan-2-yl]-methanone; N-Benzyl-2-(4-chloro-phenylsulfanyl)-N-methyl-acetamide;
1 -(4-Benzyl-piperidin-1 -yl)-2-benzylsulfanyl-ethanone;
2-(4-tert-Butyl-phenoxy)-1-(4-ethyl-piperazin-1-yl)-ethanone;
[4-(4-Ethoxy-phenoxymethyl)-phenyl]-(4-methyl-piperidin-1-yl)-methanone;
5-(4-Bromo-3,5-dimethyl-pyrazol-1 -ylmethyl)-furan-2-carboxylic acid adamantan-2-ylamide; 1 -Azepan-1 -yl-3-(4-chloro-phenylsulfanyl)-propan-1 -one;
N-Bicyclo[2.2.1]hept-2-yl-2-(2-chloro-benzylsulfanyl)-acetamide;
2-(2-Methyl-benzylsulfanyI)-1-(4-phenyl-piperazin-1-yl)-ethanone;
N-[2-(1-Benzo[1 ,3]dioxol-5-yl-3-furan-2-yl-3-oxo-propylsulfanyl)-phenyl]-acetamide;
(3,5-Dimethyl-piperidin-1-yl)-(3-iodo-phenyl)-methanone; [5-(2-Bromo-phenoxymethyl)-furan-2-yl]-(6-fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)- methanone; N-Benzyl-N-cyclohex-1-enyl-isonicotinamide;
1-[4-(4-Fluoro-phenyl)-piperazin-1-yl]-2-(2-methyl-benzylsulfanyl)-ethanone;
2-(2-Bromo-4-methyl-phenoxy)-N-(2-cyclohex-1-enyl-ethyl)-acetamide;
2-[5-(2-Hydroxy-phenyl)-[1 ,3,4]oxadiazol-2-ylsulfanyl]-1 -piperidin-1 -yl-ethanone; 5-(4-Nitro-pyrazol-1-ylmethyl)-furan-2-carboxylic acid adamantan-2-ylamide;
3-Benzo[1 ,3]dioxol-5-yl-3-(2-methoxy-phenyI)-1 -pyrroIidin-1 -yl-propan-1 -one;
N-Adamantan-2-yl-3,4-dichloro-benzamide;
Benzo[b]thiophen-3-yl-(6-fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-methanone;
2-Adamantan-1-yl-1-(3,4-dihydro-1H-isoquinolin-2-yl)-ethanone; 4,5,6,7-Tetrahydro-benzo[b]thiophene-3-carboxylic acid (2-cyclohex-1-enyl-ethyl)-amide;
Benzo[b]thiophene-3-carboxylic acid (3,3,5-trimethyl-cyclohexyl)-amide;
2-(2,6-Dimethyl-phenoxy)-N-(2-isopropyl-phenyl)-acetamide;
4-Bromo-N-[3-(piperidine-1-carbonyl)-phenyl]-benzamide;
N-Benzo[1 ,3]dioxol-5-ylmethyI-2-(2-cyano-phenylsulfanyl)-benzamide; N-Adamantan-1 -yl-2-(naphthalen-2-yloxy)-acetamide;
[4-(4-ChIoro-phenylsulfanylmethyl)-phenyl]-morpholin-4-yl-methanone;
Thiophene-2-carboxylic acid (3,3,5-trimethyl-cyclohexyI)-amide;
Benzo[1,3]dioxol-5-yl-(3,4-dihydro-2H-quinolin-1-yl)-methanone;
3-Chloro-benzo[b]thiophene-2-carboxylic acid cyclooctylamide; 2-[2-Morpholin-4-yl-1 -(4-nitro-benzyl)-2-oxo-ethyl]-isoindole-1 ,3-dione;
2-Hydroxy-4,4-dimethyl-6-oxo-cyclohex-1 -enecarboxylic acid phenylamide;
(2,4-Dichloro-phenyl)-(2,6-dimethyl-piperidin-1-yl)-methanone;
Adamantane-1 -carboxylic acid furan-2-ylmethyl-p-tolyl-amide;
Azocan-1-yl-(4-tert-butyl-phenyl)-methanone; 3-Chloro-benzo[b]thiophene-2-carboxylic acid benzyl-methyl-amide;
Adamantane-1 -carboxylic acid (2-fluoro-phenyl)-amide;
2-(Piperidine-1-carbonyl)-5-piperidin-1-yl-oxazole-4-carbonitrile;
N-(4,6-Dimethyl-5-nitro-pyridin-3-yl)-benzamide;
Adamantan-1-yl-[4-(2-methoxy-phenyI)-piperazin-1-yl]-methanone; (2-Methyl-piperidin-1 -yl)-o-tolyl-methanone;
N-Benzyl-4-chloro-N-isopropyl-3-nitro-benzamide;
N-(3-Hexylsulfanyl-[1,2,4]thiadiazol-5-yl)-3-methyl-butyramide;
4,N-Dimethyl-N-[4-(piperidine-1-carbonyl)-phenyl]-benzenesulfonamide;
Azepan-1-yl-(5-tert-butyl-2H-pyrazol-3-yl)-methanone; 2-Amino-4-methyl-5-(piperidine-1-carbonyl)-thiophene-3-carboxylic acid ethyl ester;
5-Methyl-furan-2-carboxylic acid (1 -adamantan-1 -yl-ethyl)-amide; (3-Chloro-6-methyl-benzo[b]thiophen-2-yl)-(3,4-dihydro-1H-isoquinolin-2-yl)-methanone;
N-Adamantan-1-yl-2-trifluoromethyl-benzamide;
(3-Bromo-phenyl)-(2,2,4-trimethyl-4-phenyl-3,4-dihydro-2H-quinolin-1-yl)-methanone;
Benzo[1,3]dioxole-5-carboxylic acid dipropylamide; N-(3,3-Diphenyl-propyl)-4-methoxy-benzamide;
[4-(2-Chloro-6-nitro-phenyl)-piperazin-1-yl]-p-toIyl-methanone;
Furan-2-yl-[4-(toluene-4-sulfonyl)-piperazin-1-yl]-methanone;
3-(2-Chloro-6-fluoro-phenyl)-1 -(3,4-dihydro-2H-quinolin-1 -yl)-propenone;
2-Chloro-N-cycloheptyl-benzamide; 1-[4-(4-Nitro-phenyl)-piperazin-1-yl]-3-phenyl-propan-1-one;
(3,4-Dihydro-1H-isoquinolin-2-yl)-(3,4-dimethyl-phenyl)-methanone;
(1 -Adamantan-1 -yl-4-bromo-1 H-pyrazol-3-yl)-morpholin-4-yl-methanone;
2-Phenyl-cyclopropanecarboxylic acid cyclooctylamide;
3-[4-(2-Ethoxy-phenyl)-piperazine-1-carbonyl]-isochromen-1-one; [3-(4-Bromo-pyrazol-1-ylmethyl)-phenyl]-(4-methyl-piperidin-1-yl)-methanone;
2-Azepan-1-yl-N-biphenyl-2-yl-acetamide;
N-[5-(3,4-Dimethoxy-benzyl)-[1,3,4]thiadiazol-2-yl]-3-methyl-butyramide;
Adamantan-1 -yl-(4-phenyl-piperidin-1 -yl)-methanone;
N-(2-Azepan-1-yl-2-oxo-ethyl)-N-(4-ethoxy-phenyI)-4-methyIsulfanyl-benzenesulfonamide; 1 -Adamantan-1 -yl-4-bromo-1 H-pyrazole-3-carboxylic acid diethylamide;
(6-Fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-(2-fluoro-phenyl)-methanone;
3-[4-(2,3-Dimethyl-phenyl)-piperazine-1-carbonyl]-isochromen-1-one;
N-Cyclooctyl-2-(2-methoxy-phenoxy)-acetamide;
N-Cyclohexyl-N-methyl-2-nitro-benzamide; Adamantane-1 -carboxylic acid (1 ,1-dioxo-tetrahydro-thiophen-3-yl)-amide;
N-Adamantan-2-yl-2-(4-chloro-phenyl)-acetamide;
(2,4-Dichloro-phenyl)-(3-methyl-piperidin-1-yl)-methanone;
2-(4-tert-Butyl-phenoxy)-N-cyclooctyl-acetamide;
(4-Hydroxy-4-phenyl-octahydro-quinolin-1-yl)-phenyl-methanone; (2-Chloro-phenyl)-(2-methyl-piperidin-1 -yl)-methanone;
(10,11-Dihydro-dibenzo[b,fjazepin-5-yI)-(2-methoxy-phenyl)-methanone;
(3-Chloro-phenyl)-(2-methyl-piperidin-1-yl)-methanone;
(3-Chloro-6-nitro-benzo[b]thiophen-2-yl)-(3-methyl-piperidin-1-yl)-methanone;
(2,5-Dichloro-phenyl)-(4-methyl-piperidin-1-yl)-methanone; N-[5-(3,4-Dichloro-benzyl)-[1,3,4]thiadiazol-2-yl]-2,2-dimethyl-propionamide;
4-(4-Chloro-2-methyl-phenoxy)-1-(3,4-dihydro-2H-quinolin-1-yI)-butan-1-one; (3,4-Dichloro-phenyl)-[4-(2,3-dimethyl-phenyl)-piperazin-1-yl]-methanone;
Cyclooctanecarboxylic acid [1 -(naphthalene-2-sulfonyI)-pyrrolidin-2-yl]-amide;
1-Butyl-pyrrolidine-2-carboxylic acid benzo[1 ,3]dioxol-4-ylamide;
5-Methyl-furan-2-carboxylic acid dibenzylamide; (3,4-Dihydro-2H-quinolin-1-yl)-[3-(4-phenyl-piperazine-1-sulfonyl)-phenyl]-methanone;
Bicyclo[2.2.1]hept-2-yl-[4-(2,3-dimethyl-phenyl)-piperazin-1-yl]-methanone;
N-Adamantan-1-yl-2-benzoyl-benzamide;
[5-(2-Chloro-phenoxymethyl)-furan-2-yl]-(3-methyl-piperidin-1-yl)-methanone;
(3,5-Dimethyl-piperidin-1-yl)-(2-iodo-phenyl)-methanone; 1-Benzenesulfonyl-pyrrolidine-2-carboxylic acid cyclooctylamide;
(3,4-Dimethoxy-phenyl)-(6-fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-methanone;
3-(2,6-Dichloro-phenyl)-1 -(2-ethyl-piperidin-1 -yl)-propenone;
N-(3,4-Difluoro-phenyl)-2,6-difluoro-benzamide;
2,6-Difluoro-N-naphthalen-1-yl-benzamide; (4-Chloro-phenyl)-(3,5-dimethyl-piperidin-1 -yl)-methanone;
N-[4-(2,6-Dimethyl-piperidine-1-carbonyl)-phenyl]-2-(naphthalen-2-yloxy)-acetamide;
(2-Chloro-phenyl)-(3-methyl-piperidin-1-yl)-methanone;
N-{2-[4-(Piperidine-1-sulfonyl)-phenyl]-ethyl}-acetamide;
N-Biphenyl-2-yl-2-(pyridin-2-ylsulfanyl)-acetamide; Azepan-1 -yl-[5-(4-chloro-3,5-dimethyl-pyrazol-1-ylmethyl)-furan-2-yl]-methanone;
Acetic acid 4-(4-methyl-piperidine-1-carbonyl)-phenyl ester;
Acetic acid 4-(4-benzyl-piperidine-1-carbonyl)-phenyl ester;
Benzo[1 ,3]dioxole-5-carboxylic acid cycloheptylamide;
2-(2,4-Dimethyl-phenoxy)-1-(6-fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-ethanone; Acetic acid 4-(3,4-dihydro-2H-quinoline-1-carbonyl)-phenyl ester;
Azepan-1-yl-(3,5-dibromo-phenyl)-methanone;
(3,5-Dibromo-phenyl)-[4-(2-methoxy-phenyl)-piperazin-1-yl]-methanone;
N-Cyclooctyl-4-isopropyl-benzamide;
N-Cyclooctyl-2-(4-methoxy-phenyl)-acetamide; (4-tert-Butyl-piperidin-1 -yl)-phenyl-methanone;
N-(4-tert-Butyl-3-nitro-phenyl)-acetamide;
(2,6-Dimethyl-piperidin-1-yl)-[5-(2,3,5,6-tetrafluoro-phenoxymethyl)-furan-2-yl]-methanone;
2-(4-Chloro-3,5-dimethyl-phenoxy)-N-cyclohexyl-N-methyl-acetamide;
N-Cyclohexyl-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-N-methyl-propionamide; 2-(4-Chloro-3-methyl-phenoxy)-N-cyclohexyl-N-methyl-acetamide;
N-Cyclopentyl-3-(3,4-dihydro-2H-quinoline-1-carbonyl)-benzenesulfonamide; (3,4-Dihydro-1H-isoquinolin-2-yl)-(3-dimethylamino-phenyl)-methanone;
3-Cyclohexylcarbamoyl-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid isopropyl ester;
1-(3,4-Dihydro-1H-isoquinolin-2-yl)-2-(2-methoxy-phenyl)-ethanone;
N-Benzyl-N-cyclohex-1-enyl-benzamide; [1 -(Thiophene-2-sulfonyl)-piperidin-4-yl]-(1 ,3,3-trimethyl-6-aza-bicydo[3.2.1]oct-6-yl)- methanone;
N-Adamantan- 1-yl-2-(1 -phenyl- 1H-tetrazol-5-ylsulfanyl)-acetamide;
(3,4-Dihydro-2H-quinolin-1-yl)-[4-(morpholine-4-sulfonyl)-phenyl]-methanone;
(3,4-Dihydro-2H-quinolin-1-yl)-[4-(pyrrolidine-1-sulfonyl)-phenyl]-methanone; (3,4-Dihydro-2H-quinolin-1-yl)-[1-(thiophene-2-sulfonyl)-piperidin-4-yl]-methanone;
(1-Benzenesulfonyl-piperidin-3-yl)-(3,4-dihydro-1H-isoquinolin-2-yl)-methanone;
6,7-Dimethyl-4-oxa-tricyclo[4.3.0.03,7]nonane-3-carboxylic acid cyclohexylamide;
6,7-Dimethyl-4-oxa-tricyclo[4.3.0.03,7]nonane-3-carboxylic acid (2-chloro-phenyl)-amide;
(6,7-Dimethyl-4-oxa-tricyclo[4.3.0.03,7]non-3-yl)-piperidin-1-yl-methanone; 2-[(Adamantane-1-carbonyl)-amino]-3-(1 H-indol-3-yl)-propionic acid methyl ester;
2-(5,6-Dimethyl-4-oxo-3,4-dihydro-thieno[2,3-d]pyrimidin-2-ylsuIfanyl)-N-furan-2-ylmethyl- acetamide;
N-Allyl-2-(5,6-dimethyl-4-oxo-3,4-dihydro-thieno[2,3-d]pyrimidin-2-ylsulfanyl)-acetamide;
N-Adamantan-1-yl-2-(5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidin-4-ylsulfanyl)- acetamide;
1-(3,4-Dihydro-2H-quinoline-1-carbonyl)-4,7,7-trimethyl-2-oxa-bicyclo[2.2.1]heptan-3-one;
1-(3,4-Dihydro-1H-isoquinoline-2-carbonyl)-4,7,7-trimethyl-2-oxa-bicyclo[2.2.1]heptan-3-one;
Azepan-1-yl-(6,7-dimethyl-4-oxa-tricyclo[4.3.0.03,7]non-3-yl)-methanone;
2,5-Dimethyl-furan-3-carboxylic acid (1 -adamantan-1 -yl-ethyl)-amide; 1-Cyclohexyl-5-oxo-pyrrolidine-3-carboxylic acid (3-cyano-4,5,6,7-tetrahydro- benzo[b]thiophen-2-yl)-amide;
6-(2,4-Dichloro-phenylcarbamoyl)-3,4-dimethyl-cyclohex-3-enecarboxylic acid;
2-(2-Cyano-phenylsulfanyl)-N-cyclopentyl-benzamide;
[5-(2-Methoxy-4-propyl-phenoxymethyl)-furan-2-yl]-(3-methyl-piperidin-1-yl)-methanone; (4-tert-Butyl-phenyl)-(3,5-dimethyl-piperidin-1-yl)-methanone;
[4-(2-Methoxy-naphthalen-1-ylmethyI)-piperazin-1-yl]-(4-methoxy-phenyl)-methanone;
(3,4-Dichloro-phenyl)-(3,5-dimethyl-piperidin-1-yl)-methanone;
(4-Ethoxy-phenyI)-(4-methyl-piperidin-1-yl)-methanone;
2-Phenethyl-N-(tetrahydro-furan-2-ylmethyl)-benzamide; N-Cycloheptyl-2-phenoxy-benzamide;
Adamantane-1 -carboxylic acid (2-ethoxy-phenyl)-amide; N-Adamantan-2-yl-2-o-tolyloxy-acetamide;
(2-Chloro-phenyl)-(3,5-dimethyl-piperidin-1-yl)-methanone;
1-Morpholin-4-yl-2-[3-(4-nitro-phenyl)-adamantan-1-yl]-ethanone;
2-Dimethylamino-N-(2-nitro-phenyl)-benzamide; N-Benzyl-2-(4,4,6-trimethyl-1 -p-tolyl-1 ,4-dihydro-pyrimidin-2-ylsulfanyl)-acetamide;
[4-(3,5-Dinitro-phenoxy)-phenyl]-(2-ethyl-piperidin-1-yl)-methanone;
1-(4-Chloro-benzoyl)-2,3-dihydro-1H-benzo[g]quinolin-4-one;
2-[(Adamantane-1-carbonyl)-amino]-3-phenyl-propionic acid methyl ester;
[Benzyl-(4-nitro-benzoyl)-amino]-acetic acid ethyl ester; 9-Oxo-9H-fluorene-3-carboxylic acid methyl-(4-nitro-phenyl)-amide;
Adamantane-1 -carboxylic acid [2-(4-methoxy-phenyl)-ethyl]-amide;
(10,11-Dihydro-dibenzo[b,f]azepin-5-yl)-(4-fluoro-phenyl)-methanone;
2-Benzylsulfanyl-N-[2-(2-methoxy-phenoxy)-ethyl]-acetamide;
N-Adamantan-1-yl-2-(2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide; 2-Bromo-N-tricyclo[3.2.1.02'4]oct-6-yImethyl-benzamide;
Adamantane-1 -carboxylic acid (2,6-dimethoxy-pyrimidin-4-yl)-amide;
Hexanedioic acid (2,7,7-trimethyl-bicyclo[2.2.1]hept-1-yl)-amide (1 ,7,7-trimethyl- bicyclo[2.2.1]hept-2-yI)-amide;
2-Chloro-N-(2-cyclohexyI-ethyl)-benzamide; 2-[3-(2-Ethyl-piperidin-1-yl)-3-oxo-propyl]-isoindole-1 ,3-dione;
N-Adamantan-1-yl-2-(2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide;
N-Adamantan-1 -yl-2-hydroxy-2,2-diphenyl-acetamide;
Adamantane-1 -carboxylic acid (naphthalen-1 -ylmethyl)-amide;
Adamantane-1 -carboxylic acid (benzo[1 ,3]dioxol-5-ylmethyl)-amide; 1 -(Azepane-1 -carbonyl)-fluoren-9-one;
2-(Quinolin-2-ylsulfanyl)-N-p-tolyl-acetamide;
2,4-Dichloro-N-[3-(piperidine-1-carbonyl)-phenyl]-benzamide;
2-Chloro-4,5-difluoro-N-(3,3,5-trimethyl-cydohexyl)-benzamide;
2-(2-Chloro-benzylsulfanyl)-N-p-tolyl-acetamide; [4-(4-Chloro-phenylsulfanylmethyl)-phenyl]-pyrrolidin-1-yl-methanone;
N-Adamantan-1 -yl-N-methyl-isonicotinamide;
Azepan-1-yl-[4-(4-chloro-phenyIsulfanylmethyl)-phenyl]-methanone;
(2-Chloro-phenyl)-(1,5,7-trimethyl-3,7-diaza-bicyclo[3.3.1]non-3-yl)-methanone;
(3-Chloro-benzo[b]thiophen-2-yl)-(4-methyl-piperidin-1-yl)-methanone; Benzoic acid 1-benzoyl-decahydro-quinolin-4-yl ester;
2-(3-Bromo-benzylsulfanyl)-1-[4-(2-methoxy-phenyl)-piperazin-1-yl]-ethanone; 4-Methyl-N-[2-(phenoxazine-10-carbonyI)-phenyl]-benzenesulfonamide;
2-[1 -(Azepane-1 -carbonyl)-2-methyl-propyl]-isoindole-1 ,3-dione;
2-(3-Bromo-benzylsulfanyl)-1 -piperidin-1 -yl-ethanone;
1-[3-(4-Bromo-phenyl)-1-furan-2-yl-3-oxo-propyl]-pyrrolidin-2-one; 2-Chloro-N-cyclooctyl-4,5-difluoro-benzamide;
2,4-Dichloro-N-(2-furan-2-ylmethyl-cyclohexyl)-benzamide;
N-(4-Benzoyl-furazan-3-yI)-2-fluoro-benzamide;
N-Adamantan-1 -yl-2-(3-cyano-4-methoxymethyl-6-methyl-pyridin-2-ylsulfanyl)-acetamide;
4-tert-ButyI-N-cyclooctyl-benzamide; N-Adamantan-1 -yl-2-phenyl-butyramide;
(3-ChIoro-6-methoxy-benzo[b]thiophen-2-yl)-piperidin-1-yl-methanone;
(3,7-Dichloro-6-methoxy-benzo[b]thiophen-2-yl)-piperidin-1-yl-methanone;
Acetic acid 1-benzoyl-decahydro-quinolin-4-yl ester;
2-Bromo-N-methyl-N-phenyl-benzamide; N-Benzo[1 ,3]dioxol-5-yl-2,4-dichloro-benzamide;
(3-ChIoro-6-fluoro-benzo[b]thiophen-2-yl)-piperidin-1-yl-methanone;
N-(1 ,2,3,5,6,7-Hexahydro-s-indacen-1-yl)-2-piperidin-1-yl-acetamide;
2-[(Adamantane-1-carbonyl)-amino]-3-(1H-indol-3-yl)-propionic acid methyl ester;
2-[2-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-yl)-3-phenyl-propionylamino]-3-methyl-butyric acid methyl ester;
2-(6-Oxo-6-piperidin-1-yl-hexyl)-isoindole-1 ,3-dione;
2-[2-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-yl)-3-phenyI-propionylamino]-3-methyl-butyric acid methyl ester;
Adamantane-1 -carboxylic acid (2,6-dihydroxy-pyrimidin-4-yl)-amide; Adamantane-1 -carboxylic acid [3-(1 H-benzoimidazol-2-ylsulfanyl)-5-nitro-phenyl]-amide;
Adamantane-1 -carboxylic acid methyl-phenyl-amide;
3-Chloro-benzo[b]thiophene-2-carboxylic acid dibenzylamide;
N-Adamantan-1 -yl-2-(3-cyano-6-methyl-4-trifluoromethyl-pyridin-2-ylsulfanyI)-acetamide;
2-(3-Oxo-3-phenyl-propenyl)-isoindole-1 ,3-dione; Adamantane-1 -carboxylic acid (4-ethoxy-benzothiazol-2-yl)-amide;
N-[5-(5-Chloro-benzooxazol-2-yl)-2-methyl-phenyl]-2-methoxy-benzamide;
N-[2-(2-Bromo-phenyl)-benzooxazol-5-yl]-2-methoxy-benzamide;
2-(4-Chloro-phenoxy)-N-(4-chloro-3-trifluoromethyl-phenyl)-acetamide;
2,2-Dimethyl-N-(5-propyI-[1,3,4]thiadiazol-2-yl)-propionamide; 2-[2-(2,6-Dimethyl-morpholin-4-yl)-1 -methyl-2-oxo-ethyl]-isoindole-1 ,3-dione;
2-(2-Cyano-phenylsulfanyl)-N-(2-trifluoromethyl-phenyl)-benzamide; Azepan-1-yl-(3,6-dichloro-benzo[b]thiophen-2-yl)-methanone;
Benzo[1 ,3]dioxol-5-yl-(4-benzyl-piperidin-1 -yI)-methanone;
Azepan-1-yl-(3-chloro-6-methyl-benzo[b]thiophen-2-yl)-methanone;
N-(5-Hexyl-[1,3,4]thiadiazol-2-yl)-isobutyramide; (3-Chloro-phenyl)-(10,11 -dihydro-dibenzo[b,f]azepin-5-yl)-methanone;
(2-Chloro-phenyl)-(10,11-dihydro-dibenzo[b,f]azepin-5-yl)-methanone;
2-Amino-5-(azepane-1-carbonyl)-4-methyl-thiophene-3-carboxylic acid ethyl ester;
Adamantan-1-yl-(4-cyclopropyl-1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-methanone;
Adamantan-1-yl-(4-trifluoromethyl-1 ,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yI)-methanone; Adamantan-1 -yl-[4-(1H-benzoimidazol-2-ylsuIfanyl)-piperidin-1-yl]-methanone;
Adamantan-1-yI-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-methanone;
[4-(1H-lmidazol-4-yl)-piperidin-1-yl]-(4-pentyl-phenyl)-methanone;
3-Cyclohexyl-1 -[4-(1 H-imidazol-4-yI)-piperidin-1 -yl]-propan-1 -one;
1 -(4-Propyl-piperazin-1 -yl)-3-(4-trif luoromethyl-phenyl)-propan-1 -one; N-(2-Hydroxy-benzyl)-3-thiophen-3-yl-N-(2-thiophen-2-yl-ethyl)-acryIamide;
N-(1,3-Dimethyl-pentyl)-2-(3-fluoro-phenyl)-N-(4-hydroxy-benzyl)-acetamide;
N-Cyclobutyl-2-(3-fluoro-phenyl)-N-(4-hydroxy-benzyl)-acetamide;
N-Cyclobutyl-N-(4-hydroxy-benzyl)-4-trifluoromethyl-benzamide;
N-(3-Hydroxy-benzyl)-2-methyl-3-nitro-N-(4-sulfamoyl-benzyl)-benzamide; N-(4-Bromo-benzyl)-N-(4-hydroxy-benzyl)-2-naphthalen-1-yl-acetamide;
6-(2-Bromo-phenylsulfanyl)-hexanoic acid (3-amino-2,2-dimethyl-propyl)-amide;
N-(3-Amino-2,2-dimethyl-propyl)-4-[2-(2-isopropyl-phenylsulfanyI)-ethyl]-benzamide;
N-(3-Amino-2,2-dimethyl-propyl)-4-[4-(4-chloro-phenyl)-pyrimidin-2-ylsulfanylmethyl]-3-nitro- benzamide; 4-(4-Bromo-phenyl)-N-(2-hydroxy-benzyl)-4-oxo-N-thiophen-2-ylmethyl-butyramide;
N-[2-(2,4-Dichloro-phenyl)-ethyl]-N-(4-hydroxy-benzyl)-2-thiophen-3-yl-acetamide;
N-(2-Chloro-benzyl)-N-(4-hydroxy-benzyl)-2-thiophen-2-yl-acetamide;
Heptanoic acid benzyl-(4-hydroxy-benzyl)-amide;
N-(4-Fluoro-benzyl)-N-(4-hydroxy-benzyl)-2-thiophen-3-yl-acetamide; 4-Methyl-pentanoic acid (4-fluoro-benzyl)-(4-hydroxy-benzyl)-amide;
N-Allyl-2-(4-chloro-phenyl)-N-(4-hydroxy-benzyl)-acetamide;
N-Allyl-2-benzo[b]thiophen-3-yl-N-(4-hydroxy-benzyl)-acetamide;
Heptanoic acid (3-ethoxy-propyl)-(4-hydroxy-benzyl)-amide;
Dec-3-enoic acid (4-hydroxy-benzyl)-(4-trifluoromethyl-benzyl)-amide; 6-Oxo-6-phenyl-hexanoic acid (4-hydroxy-benzyl)-(4-trifluoromethyl-benzyl)-amide;
2-(3,4-Difluoro-phenyl)-N-(4-hydroxy-benzyl)-N-thiophen-2-ylmethyl-acetamide; 2-Methyl-pent-4-enoic acid (3-hydroxy-benzyl)-[2-(2-methoxy-phenyl)-ethyl]-amide;
Heptanoic acid (3-hydroxy-benzyl)-(4-isopropyl-benzyl)-amide;
5-(2,6-Dichloro-phenylsulfanyl)-pentanoic acid (naphthalen-1 -ylmethyl)-amide;
N-(6,6-Dimethyl-bicyclo[3.1.1]hept-2-ylmethyl)-4-[2-(5-methyl-1H-benzoimidazol-2-ylsulfanyl)- ethyl]-benzamide;
N-(6,6-Dimethyl-bicyclo[3.1.1]hept-2-ylmethyl)-4-[2-(4-phenoxy-pyrimidin-2-ylsulfanyl)-ethyl]- benzamide;
N-(6,6-Dimethyl-bicyclo[3.1.1]hept-2-ylmethyl)-4-[2-(4-fluoro-phenylsulfanyl)-ethyl]-benzamide;
4-(2,6-Dichloro-phenylsulfanyl)-N-(6,6-dimethyl-bicyclo[3.1.1]hept-2-ylmethyl)-butyramide; N-(6,6-Dimethyl-bicyclo[3.1.1]hept-2-ylmethyl)-4-[2-(5-methyl-1H-benzoimidazol-2-ylsulfanyl)- ethyl]-benzamide;
N-(6,6-Dimethyl-bicyclo[3.1.1]hept-2-ylmethyl)-4-[2-(4-fluoro-phenylsulfanyl)-ethyl]-benzamide;
5-(3-Methylsulfanyl-[1 ,2,4]thiadiazol-5-ylsulfanyl)-pentanoic acid (6,6-dimethyl- bicyclo[3.1.1 ]hept-2-ylmethyl)-amide; 5-(2,6-Dichloro-phenylsulfanyl)-pentanoic acid [2-(3-trifluoromethyl-phenyl)-ethyl]-amide;
4-[2-(2,6-Dichloro-phenylsulfanyl)-ethyl]-N-[2-(2-fluoro-phenyl)-ethyl]-benzamide;
2-Cyclohexylamino-thiazole-4-carboxylic acid (1 ,2,3,4-tetrahydro-naphthalen-1-yl)-amide;
2-Cyclohexylamino-thiazole-4-carboxylic acid (3-chloro-4-hydroxy-phenyl)-amide;
2-Cyclohexylamino-thiazole-4-carboxylic acid (1 ,2-dimethyl-propyl)-amide; 2-Cyclohexylamino-thiazole-4-carboxylic acid (l-ethyl-propyl)-amide;
2-Cyclohexylamino-thiazole-4-carboxylic acid [3-(1-hydroxy-ethyl)-phenyl]-amide;
2-Cyclohexylamino-thiazole-4-carboxylic acid (1 -ethynyl-cyclohexyl)-amide;
2-Cyclohexylamino-thiazole-4-carboxylic acid (2-methoxy-dibenzofuran-3-yl)-amide;
2-Cyclohexylamino-thiazole-4-carboxylic acid [2-(4-hydroxy-phenyl)-ethyl]-amide; 2-Cyclohexylamino-thiazole-4-carboxylic acid (4-hydroxy-cyclohexyl)-amide;
2-(2,6-Difluoro-benzylamino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-acetamide;
4-{4-[2-(4-Dimethylamino-phenyl)-acetyl]-piperazin-1-yl}-3-(2-phenyl-propylamino)-benzamide;
2-(2-Ethyl-phenylsulfanyl)-3-[methyl-(2-pyridin-4-yl-ethyl)-amino]-N-prop-2-ynyl-propionamide;
4-Methyl-cyclohexanecarboxylic acid {[2-(2-chloro-6-fluoro-benzylsulfanyl)-ethylcarbamoyl]- methyl}-prop-2-ynyl-amide;
2-Benzylsulfanyl-N-{[2-(2-chloro-6-fluoro-benzylsulfanyl)-ethylcarbamoyl]-methyl}-N-(2- methoxy-ethyl)-acetamide;
4-[2-(5-Cyclopropylmethylsulfanyl-[1,3,4]thiadiazol-2-ylsulfanyl)-ethyl]-N-(6,6-dimethyl- bicyclo[3.1.1]hept-2-ylmethyl)-benzamide; N-(6,6-Dimethyl-bicyclo[3.1.1]hept-2-ylmethyl)-4-[2-(4-phenoxy-pyrimidin-2-ylsulfanyl)-ethyl]- benzamide; N-(6,6-Dimethyl-bicydo[3.1.1]hept-2-ylmethyl)-2-p-tolyloxy-acetamide;
Bicyclo[2.2.1]hept-5-ene-2-carboxyIic acid [4-(2,5-difluoro-phenoxy)-butyl]-amide;
4-Trifluoromethyl-cyclohexanecarboxylic acid [6-(2,6-difluoro-phenoxy)-hexyl]-amide;
N-Cyclopropyl-3-methoxy-N-(2-piperidin-4-yl-ethyl)-5-(pyridine-2-carbonyl)-benzamide; 3-Methoxy-N-(2-methoxy-ethyl)-N-(2-piperidin-4-yl-ethyl)-5-(pyridine-2-carbonyl)-benzamide;
3-Methoxy-N-(2-piperidin-4-yl-ethyl)-5-(pyridine-2-carbonyl)-N-(tetrahydro-furan-2-ylmethyl)- benzamide;
3-Methoxy-N-(2-oxo-azepan-3-yl)-N-(2-piperidin-4-yl-ethyl)-5-(pyridine-2-carbonyl)- benzamide; 3-Methoxy-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-N-(2-piperidin-4-yl-ethyl)-5-(pyridine-2- carbonyl)-benzamide;
3-Methoxy-N-methyl-N-(2-piperidin-4-yl-ethyl)-5-(pyridine-2-carbonyl)-benzamide;
[2-({Cyclopropyl-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-methyl)-phenoxy]-acetic acid; (2-{[[3-Methoxy-5-(pyridine-2-carbonyl)-benzoyl]-(3-methyl-butyl)-amino]-methyl}-phenoxy)- acetic acid;
[2-({Cyclopentyl-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-methyl)-phenoxy]-acetic acid;
[2-({(2-Methoxy-ethyl)-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-methyl)-phenoxy]- acetic acid;
[2-({Carbamoylmethyl-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-methyl)-phenoxy]- acetic acid;
[2-({[3-Methoxy-5-(pyridine-2-carbonyl)-benzoyl]-pyridin-4-yl-amino}-methyl)-phenoxy]-acetic acid; [2-({Cyclopropylmethyl-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-methyl)-phenoxy]- acetic acid;
[2-({[3-Methoxy-5-(pyridine-2-carbonyl)-benzoyl]-methyl-amino}-methyl)-phenoxy]-acetic acid;
[4-(4-Hydroxy-benzyl)-piperazin-1-yl]-[3-methoxy-5-(pyridine-2-carbonyl)-phenyl]-methanone;
{Carbamoylmethyl-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-acetic acid; {(3-lmidazol-1 -yl-propyl)-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-acetic acid;
{[3-Methoxy-5-(pyridine-2-carbonyl)-benzoyl]-pyridin-4-yl-amino}-acetic acid;
[[3-Methoxy-5-(pyridine-2-carbonyl)-benzoyl]-(2-oxo-azepan-3-yl)-amino]-acetic acid;
3-Methoxy-N-(2-methoxy-ethyl)-N-piperidin-3-ylmethyl-5-(pyridine-2-carbonyl)-benzamide;
4-[3-Methoxy-5-(pyridine-2-carbonyl)-benzoylamino]-piperidine-1 -carboxylic acid ethyl ester; 3-Methoxy-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-5-(pyridine-2-carbonyl)-benzamide; 3-({Carbamoylmethyl-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-methyl)-benzoic acid;
3-({(3-lmidazol-1-yl-propyl)-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyI]-amino}-methyl)- benzoic acid; 4-Amino-N-(3-hydroxy-benzyl)-N-indan-2-yl-2-propionylamino-butyramide;
5-Amino-2-propionylamino-pentanoic acid (3-hydroxy-benzyl)-indan-2-yl-amide; N-Ethyl-2-hexylamino-N-(4-hydroxy-benzyl)-acetamide; 2-Hexylamino-N-(4-hydroxy-benzyl)-N-methyl-acetamide; 1-[1-(6-Phenyl-hexanoyl)-piperidin-4-yl]-1,3-dihydro-benzoimidazol-2-one; 1-[1-(3-Cyclohexyl-propionyl)-piperidin-4-yl]-1,3-dihydro-benzoimidazol-2-one; N-(2-Hydroxy-benzyl)-N-isobutyl-benzamide; N-(2-Hydroxy-benzyl)-2-(4-hydroxy-phenyl)-N-isobutyl-acetamide; N-(2-Hydroxy-benzyl)-N-(3-methyl-butyl)-benzamide; N-(4-Hydroxy-benzyl)-N-isobutyl-benzamide; 4-Hydroxy-N-(4-hydroxy-benzyl)-N-isobutyI-benzamide;
N-(4-Hydroxy-benzyl)-2-(4-hydroxy-phenyl)-N-isobutyl-acetamide; N-(4-Hydroxy-benzyl)-N-(3-methyl-butyl)-benzamide; N-(2-Ethoxy-ethyl)-4-hydroxy-N-(4-hydroxy-benzyl)-benzamide; N-(4-Hydroxy-benzyl)-N-(3-isopropoxy-propyl)-benzamide; N-(3-Hydroxy-benzyl)-N-(4-methyl-pentyl)-benzamide;
N-(3-Hydroxy-benzyl)-2-(4-hydroxy-phenyl)-N-(4-methyl-pentyl)-acetamide; N-(3-Hydroxy-benzyl)-N-(3-isopropoxy-propyl)-benzamide; N-(2-Hydroxy-benzyl)-N-(3-methyl-butyl)-4-propyl-benzamide; N-(4-Hydroxy-benzyl)-N-(6-hydroxy-hexyl)-4-propyl-benzamide; N-(4-Hydroxy-benzyl)-N-(3-methyl-butyl)-4-propyl-benzamide;
N-[2-(4-Fluoro-benzylamino)-thiazol-4-ylmethyl]-N-phenethyl-butyramide; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amide, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of:: (4-Tetrazol-1 -yl-phenyl)-(1 ,3,3-trimethyI-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone;
N-Cyclohexyl-N-methyl-2-phenoxymethyl-benzamide;
4-Amino-N-cyclohexyl-N-methyI-benzamide;
N-Cycloheptyl-N-methyl-2-phenoxymethyI-benzamide;
N-Cyclohexyl-N-methyl-benzamide; 2-Chloro-N-cyclohexyl-6-fluoro-N-methyl-benzamide;
N-Cyclohexyl-N-methyl-4-trifluoromethoxy-benzamide;
N-Cyclohexyl-2,3,N-trimethyl-benzamide;
3,5-Dichloro-N-cyclohexyl-N-methyl-benzamide;
N-Cyclohexyl-N-methyl-2-phenoxy-benzamide;
2,4-Bis-benzyloxy-N-cyclohexyl-N-methyl-benzamide;
2-Benzyloxy-N-cyclohexyl-N-methyl-benzamide;
N-Cyclohexyl-N-methyl-4-phenoxy-benzamide;
4-Benzyloxy-N-cyclohexyl-N-methyl-benzamide;
N-CyclohexyI-N-methyl-4-phenoxymethyl-benzamide;
2-ChIoro-N-cyclohexyl-N-ethyl-4-nitro-benzamide;
4-Chloro-N-cyclohexyl-N-ethyl-3-nitro-benzamide;
6-Fluoro-4H-benzo[1 ,3]dioxine-8-carboxylic acid cyclohexyl-methyl-amide;
Azepan-1 -yl-(2-chloro-phenyl)-methanone;
Azepan-1-yl-(3-chloro-phenyl)-methanone;
Azepan-1 -yl-phenyl-methanone;
2-(Biphenyl-4-yloxy)-N-cyclohexyl-N-methyl-benzamide;
N-Cyclohexyl-2-(3,5-dimethoxy-phenoxy)-N-methyl-benzamide;
N-Cyclohexyl-2-(2,3-dimethoxy-phenoxy)-N-methyl-benzamide;
2,4-Dichloro-N-(3,3-dimethyl-1,5-dioxa-spiro[5.5]undec-9-yl)-N-methyl-benzamide;
2,4-Dichloro-N-methyl-N-(4-oxo-cyclohexyl)-benzamide;
N-Cydohexyl-2-hydroxy-N-methyl-benzamide;
N-Cyclohexyl-3-methoxy-N-methyl-benzamide;
Benzo[1 ,3]dioxole-5-carboxylic acid cyclohexyl-methyl-amide;
3-Benzyloxy-N-cyclohexyl-N-methyl-benzamide;
N-Cyclohexyl-3-hydroxy-N-methyl-benzamide;
[4-(Morpholine-4-sulfonyl)-phenyl]-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yI)-methanone;
N-Benzyl-3-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyI)-benzenesulfonamide;
[4-Fluoro-3-(morpholine-4-sulfonyl)-phenyl]-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
Thiophene-2-sulfonic acid [4-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)- phenyl]-amide;
N-Phenyl-4-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-benzenesulfonamide;
(4-Phenoxy-phenyl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yI)-methanone;
N-(2,4-Dimethyl-phenyl)-3-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)- benzenesulfonamide;
(2-Phenoxymethyl-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
4-(3-Aza-bicyclo[3.2.2]nonane-3-carbonyI)-N,N-dipropyl-benzenesulfonamide;
2-Bromo-N-cyclohexyl-N-methyl-benzamide;
N-[4-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]-acetamide;
(4-Dimethylamino-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(4-Pyrrol-1-yl-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(4-lmidazol-1-yl-phenyl)-(1,3,3-trimethyI-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(4-Amino-2-methoxy-phenyl)-(trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(4-Methanesulfonyl-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(3-Methanesulfonyl-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(4-Benzenesulfonyl-phenyI)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone;
Azepan-1 -yl-[4-(3,4-dihydro-1H-isoquinolin-2-ylmethyl)-phenyl]-methanone;
Azepan-1 -yI-(4-morpholin-4-ylmethyl-phenyl)-methanone;
[4-(3-Trifluoromethyl-pyrazol-1 -yl)-phenyl]-(1 ,3,3-trimethyI-6-aza-bicyclo[3.2.1 ]oct-6-yl)- methanone;
(4-[1,2,4]Triazol-1-yl-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(4-Pyrazol-1 -yl-phenyl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone;
2-Benzyloxymethyl-N-cyclohexyl-N-methyl-benzamide;
N-Cyclohexyl-N-methyl-4-(3-methyl-5-oxo-4,5-dihydro-pyrazol-1-yI)-benzamide;
5-Methyl-2-[4-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]-2,4-dihydro- pyrazol-3-one;
(9H-Carbazol-3-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
[4-(3,5-Dimethyl-pyrazol-1 -yl)-phenyl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)- methanone;
Phenyl-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
Azepan-1-yl-(2-bromo-phenyl)-methanone;
(3-Aza-bicyclo[3.2.2]non-3-yl)-(2-bromo-phenyl)-methanone;
(4-Benzyl-piperidin-1-yl)-quinolin-2-yl-methanone;
(2-Methyl-piperidin-1-yl)-quinolin-2-yl-methanone;
(3-Aza-bicyclo[3.2.2]non-3-yl)-quinolin-2-yl-methanone;
Quinoline-2-carboxylic acid cyclohexyl-methyl-amide;
Quinolin-2-yl-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone;
1-[4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]-pyrroIidine-2,5-dione;
Pyridin-3-yl-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; Pyridin-4-yl-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
Pyridin-2-yl-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone;
(6-Pyrazol-1-yl-pyridin-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
4-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-benzoic acid; lmidazo[2,1-b]thiazol-6-yl-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; 8-(4-Dimethylamino-benzoyl)-8-aza-bicyclo[3.2.1]octan-3-one; (4-Dimethylamino-phenyl)-(3-hydroxy-8-aza-bicyclo[3.2.1]oct-8-yI)-methanone; (4-Dimethylamino-phenyl)-(3-hydroxy-3-methyl-8-aza-bicyclo[3.2.1]oct-8-yl)-methanone; Trifluoro-acetic acid 8-(4-dimethylamino-benzoyl)-8-aza-bicyclo[3.2.1]oct-3-yl ester; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (I la)
Figure imgf000069_0001
(Na) wherein
R1 is aryl, aryld-Cealkyl, hetaryl or hetarylCrCealkyl optionally substituted with one or more of R6 independently;
R2 is halo, CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-Cι0cycloalkyl, C3-C10cycloalkylCrC6alkyl, trihalomethyl, aryl, arylCrCealkyl, CrCealkyloxyCrCealkyl, arylCrCealkyloxyCrCealkyl, C C6- alkylNR5CrC6alkyl, arylCrC6alkylNR5CrCealkyl, hetaryl or hetaryld-Cealkyl wherein the alkyl, alkenyl, alkynyl, cycloalkyl and aryl groups independently are optionally substituted with one or more R7;
R3 is CrC6alkyl optionally substituted with one or more of R8;
R4 is Ce-docycloalkyl, C6-C10hetcycloalkyl, Ce-CiocycloalkylCrCealkyl or C6-Cι0hetcyclo- alkylCrC6alkyl wherein the alkyl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R8; or R3 and R4 together with the nitrogen to which they are attached, are forming a saturated or partially saturated bicyclic/bridge ring system containing from 7 to 12 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cβalkyl, aryl, hetaryl, arylCrC6alkyl, hetaryl- CrC6alkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy or hetarylCrCealkyloxy, wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R9;
R5 is CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C10cycloalkyl, C3-Cι0hetcycloalkyl, C3-C10- cycloalkylCrC6alkyl, C3-C10hetcycloalkylCι-C6alkyl, aryl, hetaryl, aryld-Cealkyl or hetaryld- C6alkyl wherein the alkyl, alkenyl, alkynyl, aryl, hetaryl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R9;
R6 and R7 independently are hydrogen, hydroxy, oxo, halo, nitro, cyano, CrC6alkyl, CrCealkyloxy, trihalomethyl, trihalomethoxy, NR10R11, aryld-C6alkyloxy, hetarylCrCealkyloxy, d- C6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrC6alkylcarbonyl, CrCealkyloxycarbonyl, aryloxycarbonyl, arylCrCealkyloxycarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R8 and R9 independently are hydrogen, CrC6alkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrdr alkyl, hydroxy, oxo, cyano, NR10R11, CrC6alkyloxy, aryloxy, arylCrCealkyloxy, hetaryloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrC6alkylcarboxy;
R10 and R11 independently are hydrogen, CrC8alkyl, aryl, hetaryl, aryld-Cealkyl, C3-C10- cycloalkyl, C3-C10hetcycloalkyl, C3-Cι0cycloalkylCι-C6alkyl, CrCealkylcarbonyl, C C6aIkyIcarboxyCrC6alkyl; or
R10 and R11 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrCealkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C6alkylcarbonyI, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or aryld-e- alkylcarboxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ma) wherein:
R1 is aryl or hetaryl optionally substituted with one or more R6 independently;
R2 is halo, d-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C10cycloalkyl, C3-C10cycloalkylCrC6alkyl, aryl, arylCrC6alkyl, CrCealkyloxyCrCealkyl, arylCrCealkyloxyCrCealkyl, CrCealkylNR5Cr C6alkyl, arylCrC6alkylNR5CrC6alkyl, hetaryl or hetarylCrC6alkyl wherein the alkyl, alkenyl, alkynyl, cycloalkyl and aryl groups independently are optionally substituted with one or more R7;
R3 is CrC6alkyl optionally substituted with one or more of R8;
R4 is C6-Cι0cycloalkyl, C6-C10hetcycloalkyl, C6-C10cycloalkylCrC6alkyl or C6-C 0hetcyclo- alkylCrC6alkyl wherein the alkyl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R8;
R5 is CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C10cycloalkyl, C3-C10hetcyclbalkyl, C3-C10- cycloalkylCrC6alkyl, C3-C10hetcycloaIkylCrC6alkyl, aryl, hetaryl, aryld-C6alkyl or hetaryld- C6alkyl wherein the alkyl, alkenyl, alkynyl, aryl, hetaryl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R9;
R6 and R7 independently are hydrogen, hydroxy, oxo, halo, nitro, cyano, d-Cealkyl, CrCealkyloxy, trihalomethyl, trihalomethoxy, NR10R11, arylCrCealkyloxy, hetarylCrCealkyloxy, d- C6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, CrCealkyloxycarbonyl, aryloxycarbonyl, arylCrCealkyloxycarbonyl, CrCealkylcarboxy, arylcarboxy or aryld-C6alkyl- carboxy;
R8 and R9 independently are hydrogen, CrC6alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, NR10R11, CrC6alkyloxy, aryloxy, arylCrCealkyloxy, hetaryloxy, hetarylCrC6alkyloxy, CrCealkyloxyCrCealkyl, CrC6alkyI-carbonyl, arylcarbonyl, hetarylcarbonyl, arylCrC6alkyIcarbonyl, hetarylCrC6alkyl-carbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy; R10 and R11 independently are hydrogen, d-Cealkyl, aryl, hetaryl, aryld-Cealkyl, C3-C10- cycloalkyl, C3-C10hetcycloalkyl, C3-C10cycloalkylCrC6alkyI, CrCealkylcarboxyCι-C6alkyl; or
R 0 and R11 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of C C8alkyl, aryl, hetaryl, aryld-Cealkyl, hetaryld-Cealkyl, hydroxy, oxo, cyano, d-C6alkyloxy, aryld-Cealkyloxy, hetaryl CrC6alkyloxy, CrC6alkyloxyCrC6alkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or aryld-e- alkylcarboxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, a prodrug thereof, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein R1 is aryl, arylCrC6alkyl or hetaryl optionally substituted with one or more of R6.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein R1 is aryl optionally substituted with one or more of R6.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein R1 is arylCrCealkyl optionally substituted with one or more of R6. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein R1 is hetaryl optionally substituted with one or more of R6.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein R2 is CrC6alkyl, C3-d0cycloalkyl, d-docycloalkyld-Cealkyl, trihalomethyl, aryld-Cealkyl, or hetaryld-C6alkyl wherein the alkyl, cycloalkyl and aryl groups independently are optionally substituted with one or more R7.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein R2 is d-C6alkyl optionally substituted with one or more R7. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein R2 is trihalomethyl.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein R3 is d-Cealkyl optionally substituted with one or more of R8.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein R4 is Ce-Ciocycloalkyl, or C6-C10hetcycloalkyl, wherein the cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R8.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein R4 is Ce-Ciocycloalkyl optionally substituted with one or more of R8.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein R4 is C6 Ce-dohetcycloalkyl optionally substituted with one or more of R8.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein R3 and R4 together with the nitrogen to which they are attached, are forming a saturated or partially saturated bicydic/bridge ring system containing from 7 to 12 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, arylCrC6alkyl, hetaryld-Cealkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy or hetaryld-Cealkyloxy, wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R9. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein the saturated or partially saturated bicydic/bridge ring system is 6-aza-bicyclo[3.2.1]octane.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein R6 and R7 independently are hydrogen, hydroxy, oxo, halo, cyano, d-Cealkyl, CrC6alkyloxy, trihalomethyl, NR10R11, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrC6alkylcarbonyl, CrC6alkyloxycarbonyl, aryloxycarbonyl or arylCrCealkyloxycarbonyl.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein R8 and R9 independently are hydrogen, d-C6alkyl, hydroxy, oxo, CrC6alkyloxy or aryld-
C6aIkyloxy.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lla) wherein R10 and R11 independently are hydrogen or CrC8alkyl.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of:
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic acid cyclohexyl-methyl-amide; 1-(4-
Chloro-phenyl)-5-trifluoromethyl-1 H-pyrazole-4-carboxylic acid cyclohexyl-methyl-amide; [1-(4-Methoxy-phenyl)-5-methyl- ./-/-pyrazol-4-yl]-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone; 1 [1-(4-Chloro-phenyl)-5-propyl-1 H-pyrazol-4-yl]-(1 ,3,3-trimethyl-6-aza- bicyclo[3.2.1]oct-6-yI)-methanone;
[1-(3,5-Dichloro-phenyl)-5-propyl-1H-pyrazoI-4-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6- yl)-methanone; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of:
1 -(Phenyl)-5-methyl-1 H-pyrazole-4-carboxylic acid cyclohexyl-methyl-amide; 1 -(4-Fluoro-phenyl)-5-methyl-1 H-pyrazole-4-carboxyIic acid cyclohexyl-methyl-amide;
1 -(4-Methoxy-phenyl)-5-methyl-1 /-/-pyrazole-4-carboxylic acid cyclohexyl-methyl-amide;
1 -(4-Chloro-phenyl)-5-methyl-1 H-pyrazole-4-carboxylic acid cyclohexyl-methyl-amide;
1 -(2-Methyl-phenyl)-5-methyl-1 --pyrazole-4-carboxylic acid cyclohexyl-methyl-amide;
1 -(4-Amino-phenyl)-5-methyl-1 H-pyrazole-4-carboxylic acid cyclohexyl-methyl-amide; 1 -(2-Pyridyl)-5-methyl-1 --pyrazole-4-carboxylic acid cyclohexyl-methyl-amide;
1-(2-Pyridyl)-5-propyl-1 --pyrazole-4-carboxylic acid cyclohexyl-methyl-amide; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lib)
Figure imgf000075_0001
(lib) wherein
R1 is hydrogen, trihalomethyl, d-Cealkyl, CrC6alkyloxy, CrC6alkylthio, aryl, arylCrC6alkyl, hetaryl or hetaralkyl, wherein the alkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R8;
R2 , R3, R4 and R5 independently are hydrogen, halo, nitro, cyano, hydroxy, NR9R10, trihalomethyl, d-Cealkyl, CrC6alkyloxy, CrC6alkylthio, aryl, arylCrC6alkyl, hetaryl or hetaralkyl, wherein the alkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R8; or
R2 together with R3are forming a saturated or partially saturated cyclic ring system containing from 3 to 6 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrCealkyl, hydroxy, oxo, d-Cealkyloxy, aryloxy, aryld- Cealkyloxy or hetaryld-C6alkyloxy; or
R3 together with R4are forming a saturated or partially saturated cyclic ring system containing from 3 to 6 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, arylCrC6aIkyl, hetaryld-Cealkyl, hydroxy, oxo, CrC6aIkyloxy, aryloxy, aryld- Cealkyloxy or hetarylCrCealkyloxy; or
R4 together with R5are forming a saturated or partially saturated cyclic ring system containing from 3 to 6 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C6alkyI, aryl, hetaryl, arylCrC6alkyl, hetaryld-Cealkyl, hydroxy, oxo, CrC6alkyloxy, aryloxy, aryld- Cealkyloxy or hetarylCrCealkyloxy; R6 is aryl, hetaryl, aryld-Cealkyl, C3-C10cycloalkyl, C3-C10hetcycloalkyl, C3-Cι0cycIoalkylCr C6alkyl, CrCealkylcarboxyCrCealkyl, wherein the alkyl, aryl and cycloalkyl groups independently are optionally substituted with one or more of R11;
R7 is d-C8alkyl, aryl, hetaryl, arylCrC6alkyl, C3-C 0cycloalkyl, C3-C10hetcycloalkyl, C3- Cι0cycloalkylCrC6alkyl, CrC6alkylcarboxyCrC6alkyl, wherein the alkyl, aryl and cycloalkyl groups independently are optionally substituted with one o more of R11; or
R6 and R7, together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC8alkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, aryld-Cealkyloxy, hetarylCrCealkyloxy, Cι-C6aIkyloxyCrC6aIkyl, CrC6alkyIcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R8;
R9 and R10 independently are hydrogen, d-C8alkyl, aryl, hetaryl, arylCrC6alkyl, C3-C10- cycloalkyl, C3-C10hetcycloalkyl, QrdocycloalkylCi-Cealkyl, CrCealkylcarboxyCrCealkyl, wherein the alkyl, aryl and cycloalkyl groups independently are optionally substituted with one or more of R11; or
R9 and R10, together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C8alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrC6alkyloxyCrC6alkyl, CrC6alkyIcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C6aIkylcarbonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R8;
R8 and R11 independently are hydrogen, halo, hydroxy, oxo, nitro, cyano, CrC8alkyI, d-C6- a allkkvyllooxxvy o orr a arrvyllooxxvy:; o orr a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lib) wherein R is hydrogen or d-Cealkyl, wherein the alkyl group is optionally substituted with one or more of R8.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lib) wherein R1 is hydrogen.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lib) wherein R2, R3, R4 and R5 are hydrogen.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lib) wherein R3 together with R4are forming a saturated or partially saturated cyclic ring system containing from 3 to 6 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrC6alkyl, hydroxy, oxo, CrC6alkyloxy, aryloxy, aryld- C6alkyloxy or hetaryld-C6alkyIoxy.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lib) wherein R4 together with R5 are forming a saturated or partially saturated cyclic ring system containing from 3 to 6 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, CrC6alkyloxy, aryloxy, aryld- Cealkyloxy or hetarylCrCealkyloxy.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lib) wherein R6 and R7, together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of d-C8alkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrCealkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, d-Cealkyloxyd-Cealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylC
C6alkylcarbonyI, hetarylCrC6alkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrC6- alkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R8;
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lib) wherein R6 and R7; together with the nitrogen to which they are attached, are forming a saturated or partially saturated bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of CrC8alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or aryld- C6alkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R8.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lib) wherein R9 and R10, together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of d-C8alkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R8. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of: pyrazolo[1 ,5-a]pyridin-3-yl-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; (2-MethyI-pyrazolo[1 ,5-a]pyridin-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; Pyrazolo[1 ,5-a]pyridine-3-carboxylic acid cyclohexyl-methyl-amide; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie):
Figure imgf000079_0001
(He) wherein
R1 is hydrogen, CrC8alkyl, CrCealkyloxyCrCealkyl, aryl, hetaryl, arylCrC6alkyl, hetaryld- Cealkyl, CrC6S02, arylS02, hetarylS02, arylCrC6alkyiS02 or hetarylCrC6alkylS02 all of which is optionally substituted with one or more R8;
R2 and R5 independently are hydrogen, halo, nitro, cyano, trihalomethyl, d-Cealkyl, aryl, arylCrC6alkyl, hetaryl or hetarylCrC6alkyl wherein the alkyl, aryl, arylalkyl, hetaryl and hetarylalkyl groups independently are substituted with one or more R9; and
either R3 is hydrogen; and R4 is C(0)NR7R8; or R3 is C(0)NR7R8; and R4 is hydrogen; and
R6 is hydrogen, halo, cyano, trihalomethyl, NR12R13, CrCealkyl, aryl, aryld-C6alkyl, hetaryl or hetarylCrC6alkyl wherein the alkyl, aryl, arylalkyl, hetaryl and hetarylalkyl groups independently are substituted with one or more R9; and
R7 and R8 independently are CrC8alkyl, C3-Cι0cycloalkyl, C3-C10hetcycloalkyl, C3-C10cyclo- alkylCrC6alkyI, wherein the alkyl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R10; or
R7 and R8 together with the nitrogen to which they are attached, are forming a saturated or partially saturated bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of CrC8alkyl, arylCrC6alkyl, hetaryld-Cealkyl, hydroxy, cyano, CrC6alkyIoxy, arylCrCealkyloxy, hetaryld-Cealkyloxy, Cι-C6alkyloxyCr C6alkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetaryld- C6alkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrC6alkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R11; R9 is hydrogen, hydroxy, oxo, halo, nitro, cyano, CrC6aIkyl, C C6alkyloxy, trihalomethyl, trihalomethoxy, NR12R13, C(0)NR12R13, arylCrCealkyloxy, d-C6alkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R10 and R1 independently are hydrogen, halo, oxo, hydroxy, d-Cealkyl, aryl, arylCrC6alkyl, hetaryl or hetarylalkyl;
R12 and R13 independently are hydrogen, CrC8alkyl, aryl, hetaryl, arylCrCealkyl, C3-Cι0- cycloalkyl, C3-C10hetcycloalkyl, C3-CιocycloalkylCrC6alkyl, CrC6alkylcarbonyl, arylcarbonyl, arylC C8alkylcarbonyl, hetarylcarbonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxyCr C6alkyl; or
R12 and R13 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C8alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, d-C6alkyloxy, aryld-Cealkyloxy, hetarylCrCealkyloxy, CrC6alkyl-oxyCrC6alkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld-C6alkyl-car- bonyl, hetarylCrC6alkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, a prodrug thereof, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug ■ thereof, as a component of the combination therapy is of the general formula (lid)
Figure imgf000080_0001
(lid) wherein
R1 is hydrogen, d-C8alkyl, aryl, hetaryl, arylCrC6alkyl or hetarylCrC6alkyl optionally substituted with one or more R8; R2 and R5 independently are hydrogen, halo, nitro, cyano, trihalomethyl, CrCealkyl, aryl, arylCrCealkyl, hetaryl or hetaryld-Cealkyl wherein the alkyl, aryl, arylalkyl, hetaryl and hetarylalkyl groups independently are substituted with one or more R8; and
either R3 is hydrogen; and R4 is C(0)NR6R7; or R3 is C(0)NR6R7; and R4 is hydrogen;
R6 and R7 independently are C C8alkyl, C3-Cι0cycloalkyl, C3-C10hetcycloalkyl, C3-Cι0cyclo- alkylCrC6alkyl, wherein the alkyl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R9; or
R6 and R7 together with the nitrogen to which they are attached, are forming a saturated or partially saturated bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of CrC8alkyl, arylCrC6alkyl, hetaryld-Cealkyl, hydroxy, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetaryld-Cealkyloxy, CrC6alkyIoxyCr C6alkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetaryld- C6aIkylcarbonyl, CrCealkylcarboxy, arylcarboxy or aryld-C6alkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R10;
R8 is hydrogen, hydroxy, oxo, halo, nitro, cyano, d-C6alkyl, CrCealkyloxy, trihalomethyl, trihalomethoxy, NR11R12, arylCrCealkyloxy, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R9 and R10 independently are hydrogen, halo, oxo, hydroxy, d-Cealkyl, aryl, arylCrCealkyl, hetaryl or hetarylalkyl;
R11 and R12 independently are hydrogen, d-C8aIkyl, aryl, hetaryl, arylCrC6alkyl, C3-C10- cycloalkyl, C3-C10hetcycloalkyl, C3-C ocycloalkylCrCealkyl, d-Cealkyl-carboxyd-Cealkyl; or
R11 and R12 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC8alkyI, aryl, hetaryl, arylCrC6alkyl, hetarylCrC6alkyl, hydroxy, oxo, cyano, CrC6alkyloxy, aryICrC6alkyloxy, hetarylCrCealkyloxy, CrC6alkyl-oxyCrC6alkyl, CrC6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrC6alkyl-car- bonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) and (lid) wherein R1 is hydrogen, CrC8alkyl, arylCrC6alkyl, hetaryld-Cealkyl, arylS02, hetarylS02, arylCrC6alkylS02 or hetaryICrC6alkylS02 all of which is optionally substituted with one or more R8.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) and (lid) wherein R1 is hydrogen, CrC8alkyl, arylCrCealkyl, hetarylCrCealkyl all of which is optionally substituted with one or more R8.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) and (lid) wherein R1 is arylS02, hetarylS02, arylC C6alkylS02 or hetarylCrC6alkylS02 all of which is optionally substituted with one or more R8.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) and (lid) wherein R2 is hydrogen. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) and (lid) wherein R3 is hydrogen and R4 is C(0)NR7R8.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) and (lid) wherein R3 is C(0)NR7R8 and R4 is hydrogen.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) and (lid) wherein R5 is hydrogen.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) wherein R6 is hydrogen, NR12R13, CrC6alkyl, aryl or hetaryl wherein the alkyl, aryl and hetaryl independently are substituted with one or more R9.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) and (lid) wherein R7 and R8 independently are d-C8alkyl or C3-Cι0cycloalkyl, wherein the alkyl and cycloalkyl groups independently are optionally substituted with one or more of R10. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) and (lid) wherein R7 and R8 together with the nitrogen to which they are attached, are forming a saturated or partially saturated bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of CrC8alkyl, arylCrC6alkyl, hetaryld- Cealkyl, hydroxy, cyano, CrC6alkyloxy, aryld-C6alkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R11. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) and (lid) wherein R9 is hydrogen, hydroxy, oxo, halo, nitro, cyano, CrC6alkyl, CrC6alkyloxy, trihalomethyl, trihalomethoxy, NR12R13, C(0)NR12R13, aryld-Cealkyloxy, CrCealkylcarbonyl, arylcarbonyl, arylCrC6alkylcarbonyI.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (He) and (lid) wherein R10 and R11 independently are hydrogen, halo, oxo, hydroxy, C C6alkyl, aryl, aryld- Cealkyl, hetaryl or hetarylalkyl. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (He) and (lid) wherein R11 and R12 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of d-C8alkyl, aryl, hetaryl, aryld- Cealkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, aryld-Cealkyloxy, hetaryld- Cealkyloxy, d-Cealkyl-oxyd-Cealkyl, C C6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrC6alkyl-carbonyl, hetarylCrC6alkylarbonyl, CrC6alkylcarboxy, arylcarboxy or aryld- C6alkylcarboxy. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is selected from the gropu consisting of: 1 /-/-Benzoimidazole-5-carboxylic acid cyclohexyl-methyl-amide; 1 -Benzyl-1 H-benzoimidazoIe-5-carboxylic acid cyclohexyl-methyl-amide; (1 H-Benzoimidazol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicycIo[3.2.1]oct-6-yl)-methanone; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of: lsopropyl-2-trifluoromethyl-1 H-benzoimidazole-5-carboxylic acid cyclohexyl-methyl-amide;
1 -Benzyl-1 /.-benzoimidazoIe-5-carboxylic acid cyclohexyl-methyl-amide; 2-MethyI-1H-benzoimidazole-5-carboxylic acid cyclohexyl-methyl-amide;
2-Hydroxymethyl-1 H-benzoimidazole-5-carboxylic acid cyclohexyl-methyl-amide;
2-(4-Amino-phenyl)-1 /-/-benzoimidazole-5-carboxyIic acid cyclohexyl-methyl-amide;
(1H-Benzoimidazol-5-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(2-Methyl-1 -/-benzoimidazol-5-yl)-(1,3,3-trimethyl-6-aza-bicycIo[3.2.1]oct-6-yl)-methanone; (2-Amino-1H-benzoimidazol-5-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(2-Benzo[1 ,3]dioxol-5-yl- . H-benzoimidazol-5-yl)-(1 ,3,3-trimethyI-6-aza-bicyclo[3.2.1 ]oct-6-yl)- methanone; , 3-[5-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-' H-benzoimidazol-2-yl]-benzoic acid methyl ester; (2-Thiophen-2-yl-.H-benzoimidazol-5-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
[2-(2-Nitro-phenyl)-./.-benzoimidazol-5-yl]-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanon; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, a prodrug thereof, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug . thereof, as a component of the combination therapy is of the general formula (Ile)
Figure imgf000084_0001
(lie) wherein
X is oxygen or (CR1R2)n;
R1, R2, R3, and R4 independently are hydrogen, d-Cealkyl, aryl, arylCrCealkyl, hetaryl or hetaryICrC6alkyl optionally substituted with one or more R8 independently; or R1 and either R3 or R4 together are forming a saturated or partially saturated ring system containing from 4 to 8 carbon atoms, the ring system optionally being substituted with at least one of d-Cealkyl, hydroxy, oxo, aryl, hetaryl, arylCι-C6alkyl or hetaryld-Cealkyl; or
R1 and either R3 or R4 together with the single bond are forming a carbon-carbon double bond;
R5 is d-C8alkyl optionally substituted with one or more of R9;
R6 is C3-Ci0cycloalkyl, C3-Cι0hetcycloalkyl, CrdocycloalkylCrCealkyl, wherein the alkyl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R9; or
R5 and R6 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyIoxy, arylCrCealkyloxy, hetarylCrCealkyloxy, d-CealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or aryld- C6alkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R10;
R7 is hydrogen, halo, nitro, NR12R13, cyano, trihalomethyl, d-C6alkyl, aryl, arylCrC6alkyl, C C6alkyloxy, aryloxy, aryld-Cealkyloxy, hetaryl, hetaryICrC6alkyl, hetaryloxy or hetarylCrC6- alkyloxy optionally substituted with one or more R11 independently;
R8 and R9 independently are hydrogen, hydroxy, oxo, halo, nitro, cyano, CrC6alkyl, CrCealkyloxy, trihalomethyl, trihalomethoxy, NR12R13, aryld-Cealkyloxy, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R10 is hydrogen, CrC8alkyl, arylCrC6alkyl, hetaryld-Cealkyl, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy;
R11 is hydrogen, halo, hydroxy, oxo, nitro, cyano, d-C8alkyI, d-C6alkyloxy, aryloxy or hetaryloxy; R12 and R13 independently are hydrogen, d-C8alkyl, aryl, hetaryl, arylCrC6alkyl, C3-Cι0cyclo- alkyl, C3-C10hetcycloalkyl, CrCealkylcarbonyl, arylCrCealkylcarbonyl, C3-CιocycloalkylCrC6- alkyl, C C6alkyloxycarbonyI; or
R12 and R13 are together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyIoxy, arylCrCealkyloxy, hetaryld- C6alkyIoxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or aryld- 6alkylcarboxy;
n is 1 or 2; or
a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, a prodrug thereof, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ile) wherein X is (CR1R2)n, wherein R1, R2 and n are as defined above.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ile) wherein n is 1. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ile) wherein X is oxygen.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ile) wherein R1, R2, R3, and R4 independently are hydrogen, d-Cealkyl or arylCrC6alkyl, optionally substituted with one or more R8.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ile) wherein R1 and either R3 or R4 together with the single bond are forming a carbon-carbon double bond. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) wherein R5 is d-C8alkyl optionally substituted with one or more of R9.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ile) wherein R6 is C3-Ci0cycloalkyl or C3-Cι0hetcycloalkyl each of which is optionally substituted with one or more of R9.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ile) wherein R6 is C3-C10cycloalkyl optionally substituted with one or more of R9.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) wherein R5 and R6 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of C C6alkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, d-C6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or aryld- C6alkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R10.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ile) wherein R7 is hydrogen, halo, NR12R13, trihalomethyl, CrC6alkyloxy, aryloxy, aryId-C6alkyloxy or hetaryloxy optionally substituted with one or more R11 independently.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) wherein R8 and R9 independently are hydrogen, hydroxy, oxo, halo, nitro, cyano, d-Cealkyl, CrCealkyloxy, trihalomethyl, or NR12R13. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) wherein R10 is hydrogen or CrC8alkyl.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ile) wherein the bicyclic ring system is 6-aza-bicyclo[3.2.1]octane optionally substituted with one or more of d- C6alkyl. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (lie) wherein the bicyclic ring system is 1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of:
2,3-Dimethyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
2,5-Dimethyl-3-phenyl-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
2,2-Dimethyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
2-Methyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide; (2,3-Dimethyl-2,3-dihydro-benzofuran-7-yl)-(2,4,4-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
4-Methoxy-2-methyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
2-Methyl-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
(2-Methyl-2,3-dihydro-benzofuran-7-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
Benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
2,3-Dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
3,3-Dimethyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
Chroman-8-carboxylic acid cyclohexyl-methyl-amide; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of:
2,3-Dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide; Benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
2-Methyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
2-Methyl-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
3,3-Dimethyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
(2,3-Dimethyl-2,3-dihydro-benzofuran-7-yl)-(2,4,4-trimethyl-6-aza-bicycIo[3.2.1]oct-6-yl)- methanone;
4-Methoxy-2-methyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
2,2-Dimethyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
(2-Methyl-2,3-dihydro-benzofuran-7-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone; Chroman-8-carboxylic acid cyclohexyl-methyl-amide; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, a prodrug thereof, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llf)
Figure imgf000089_0001
(llf) wherein
R1 is hydrogen, CrC8alkyl, hetaryl, arylCι-C6alkyl or hetarylCrCealkyl optionally substituted with one or more R9;
R2, R3, R4, R5 and R6 independently are hydrogen, halo, nitro, cyano, trihalomethyl, carboxy, N(R12R13), C(0)NR7R8, C C8aIkyl, C3-Cι0cycloalkyl, C3-Cι0hetcycloalkyl, N(R12R13)d-C6aIkyl, Cι-C6alkyloxy, CrCealkyloxyCrCealkyl, aryl, arylCrC6alkyl, aryloxy, aryloxyd-Cealkyl, aryld- Cealkyloxy, arylCrCealkyloxyCrCealkyl, CrC6alkylcarboxy, arylcarboxy, arylCrCealkylcarboxy, hetaryl, hetaryld-Cealkyl, hetaryld-Cealkyloxy, hetaryIoxyCrC6aIkyl or hetaryld- C6alkyloxyCrCealkyl wherein wherein the alkyl, aryl, arylalkyl, hetaryl and hetarylalkyl groups independently are substituted with one or more R9;
R7 is hydrogen or d-C8alkyl optionally substituted with one or more of R10;
R8 is C3-Ci0cycloalkyl, C3-Cι0hetcycloalkyl, C3-CιocycloalkylCrC6aIkyl, wherein the cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R10; or
R7 and R8 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of d-C8alkyl, aryl, hetaryl, aryld-Cealkyl, hetaryld-Cealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld-C6- alkylcarbonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R11;
R9 is hydrogen, hydroxy, oxo, halo, nitro, cyano, CrC6aIkyl, d-C6alkyloxy, trihalomethyl, trihalomethoxy, NR12R13, arylCrCealkyloxy, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R10 and R11 independently are hydrogen, halo, oxo, hydroxy, CrC6alkyl, aryl, arylCrC6alkyl, hetaryl or hetarylalkyl;
R12 and R13 independently are hydrogen, CrC8alkyl, aryl, hetaryl, arylCrC6alkyl, C3-C10- cycloalkyl, C3-C10hetcycloalkyl, C3-CιocycloalkylCrC6alkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrC6alkylcarbonyl, C3-C 0cycloalkylcarbonyl, C3-Cι0hetcycloalkylcarbonyl or C3-Cι0cyclo- alkylCrC6alkylcarbonyl wherein the alkyl and aryl groups independently are optionally substituted with one or more of R11, wherein R11 is as defined above; or
R12 and R13 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C8alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, aryld-Cealkyloxy, hetarylCrCealkyloxy, CrC6alkyl-oxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrC6alkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or aryId-C6aIkylcarboxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llf) wherein
R1 is hydrogen, C C8alkyl, hetaryl, arylCrC6alkyl or hetarylCrCealkyl optionally substituted with one or more R9;
R2 and R5 independently are hydrogen, halo, nitro, cyano, trihalomethyl, d-Cealkyl, CrCealkyloxy, CrCealkyloxyCrCealkyl, aryl, arylCrC6alkyl, aryloxy, aryloxyd-Cealkyl, aryld-Cβ- alkyloxy, arylCrCealkyloxyCrCealkyl, hetaryl or hetarylCrCealkyl wherein the alkyl, aryl, arylalkyl, hetaryl and hetarylalkyl groups independently are substituted with one or more R9; and
either R3 is C(0)NR7R8, and R4 is hydrogen; or R3 is hydrogen, and R4 is C(0)NR7R8;
R6 is CrCealkyl, Crdocycloalkyl, C3-Cι0hetcycloalkyl, N(R12R13)CrC6alkyl, d-Cealkyloxyd- C6alkyl, aryloxyCrC6alkyl, aryld-C6alkyloxy or arylCrCealkyloxyCrCealkyl;
R7 is CrC8alkyl optionally substituted with one or more of R10;
R8 is C3-Ci0cycloalkyl, C3-Cι0hetcycloalkyl, C3-CιocycloalkylCrCealkyl, wherein the cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R10; or
R7 and R8 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of CrC8alkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, aryld-Cealkyloxy, hetarylCrC6alkyl- oxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R11;
R9 is hydrogen, hydroxy, oxo, halo, nitro, cyano, CrC6alkyl, CrCealkyloxy, trihalomethyl, trihalomethoxy, NR12R13, aryld-Cealkyloxy, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrC6alkyIcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R10 and R11 independently are hydrogen, halo, oxo, hydroxy, CrC6alkyl, aryl, arylCrC6alkyl, hetaryl or hetarylalkyl;
R12 and R13 independently are hydrogen, CrC8alkyl, aryl, hetaryl, aryld-Cealkyl, C3-C10- cycloalkyl, C3-Cι0hetcycloalkyl, C3-C10cycloalkylCrC6alkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, C3-C 0cycloalkylcarbonyl, C3-Cι0hetcycloalkylcarbonyl or C3-C10cyclo- alkylCrC6alkyIcarbonyl; or R12 and R13 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC8aIkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyl-oxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrC6aIkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrC6alkylcarboxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llf) wherein R2 is C(0)NR7R8 and R3 R4and R5 are hydrogen, wherein R7 and R8 are as defined above.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llf) wherein R3 is C(0)NR7R8 and R2 R and R5 are hydrogen, wherein R7 and R8 are as defined above.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llf) wherein R4 is C(0)NR7R8 and R2 R3and R5 are hydrogen, wherein R7 and R8 are as defined above. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llf) wherein R5 is C(0)NR7R8 and R2 R3and R4are hydrogen, wherein R7 and R8 are as defined above.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llf) wherein R6 is C(0)NR7R8, wherein R7 and R8 are as defined above.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llf) wherein R3 is C(0)NR7R8 and R4 is hydrogen, wherein R7 and R8 are as defined above.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llf) wherein R3 is hydrogen and R4 is C(0)NR7R8, wherein R7 and R8 are as defined above.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llf) wherein R8 is C3-Ci0cycloalkyl or C3-Cι0hetcycloalkyl, each of which is optionally substituted with one or more of R10, wherein R10 is as defined above. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llf) wherein R7 and R8 together with the nitrogen to which they are attached, are forming a saturated or partially saturated bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of d-C8alkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrC6alkyl- carboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R11, wherein R11 is as defined above.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llf) wherein the bicyclic ring system is 6-aza-bicycio[3.2.1]octane optionally substituted with one or more d- Cealkyl.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llf) wherein the bicyclic ring system is 1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of: (1H-lndol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; 1H-lndole-6-carboxylic acid cyclohexyl-methyl-amide; (1/-/-lndol-7-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; (1/.-lndol-6-yl)-(1 ,3,3-trimethyI-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; 1H-lndole-6-carboxylic acid adamantan-2-ylamide;
(6-Aza-bicyclo[3.2.1]oct-6-yl)-(1H-indol-6-yl)-methanone;
1 H-lndole-6-carboxylic acid (8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-amide;
1H-lndole-5-carboxylic acid adamantan-2-ylamide;
(6-Aza-bicyclo[3.2.1]oct-6-yI)-(1H-indol-5-yl)-methanone; (1/-/-lndol-4-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; (1 -/-lndol-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; (1H-lndol-2-yl)-(1,3,3-trimethyl-6-aza-bicydo[3.2.1]oct-6-yl)-methanone; (1-Methyl-1/.-indol-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; (3-Aza-bicyclo[3.2.2]non-3-yl)-(1H-indol-3-yl)-methanone; 1 -Methyl-1 H-indole-3-carboxylic acid cycloheptylamide;
1 -Methyl-1 H-indole-3-carboxylic acid adamantan-1 -ylamide; (3-Aza-bicyclo[3.2.2]non-3-yl)-(1-methyl-1H-indol-3-yl)-methanone;
(1 -Methyl-1 H-indol-3-yl)-(4-methyl-piperazin-1-yl)-methanone;
1 -Methyl-1 /-/-indole-3-carboxylic acid (3-hydroxy-adamantan-1-yl)-amide;
1 -Methyl-1 H-indole-3-carboxylic acid azepan-1 -ylamide; 1 -Methyl-1 /-/-indole-3-carboxylic acid (2-oxo-azepan-3-yl)-amide;
(4-Benzyl-piperidine-1 -yl)-(1 -methyl-1 r/-indol-3-yl)-methanone;
1 -Methyl-1 .-indole-3-carboxylic acid (2,6-dimethyl-piperidin-1 -yl)-amide;
1 -Methyl-1 /--indole-3-carboxylic acid (2-methyl-piperidin-1-yl)-amide;
(1-Cyclopropylmethyl-6-fluoro-1H-indol-3-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
Azepan-1 -yl-(1 -methyl-1 H-indol-3-yl)-methanone;
(5-Benzyloxy-1 --indol-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(5H-[1 ,3]Dioxolo[4,5]indol-7-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone;
(5-Chloro-1 H-indol-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; (6-Trifluoromethyl-1 H-indol-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(6-Methyl-1 .-indol-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(6-Nitro-1H-indol-3-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(5-Methoxy-1H-indol-3-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(6-Fluoro-1 H-indol-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone; (6-Methoxy-1/-/-indol-3-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(7-Nitro-1 .-indol-3-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(1H-lndol-4-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
2-(1H-lndol-3-yl)-1-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-ethanone;
1-(3-Aza-bicyclo[3.2.2]non-3-yl)-2-(1r.-indol-3-yl)-ethanone; 1 -(3-Aza-bicyclo[3.2.2]non-3-yl)-2-(1 -methyl-1 H-indol-3-yl)-ethanone;
2-(1-Methyl-1H-indol-3-yl)-1-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-ethanone;
[3-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indol-6-yloxy]-acetic acid tert- butyl ester;
6-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 H-indole-3-carboxylic acid; 6-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 H-indole-3-carboxylic acid ethyl ester;
5-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyI)-1H-indoIe-3-carboxylic acid;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indole-3-carboxylic acid ethyl ester; 4-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 H-indole-3-carboxylic acid; 4-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 H-indole-3-carboxylic acid ethyl ester;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 H-indole-3-carboxylic acid;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1/--indole-3-carboxylic acid ethyl ester;
4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 --indole-3-carboxylic acid;
4-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 H-indole-3-carboxylic acid ethyl ester;
[3-(Piperidine-1 -carbonyl)-1 H-indol-5-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)- methanone;
5-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indole-3-carboxylic acid cyanomethyl-amide;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 H-indole-3-carboxylic acid benzylamide; 5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indole-3-carboxylic acid dimethylamide;
5-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 -/-indole-3-carboxylic acid allylamide;
5-(1 ,3,3-TrimethyI-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 /--indole-3-carboxylic acid (2- dimethylamino-ethyl)-methyl-amide;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 H-indole-3-carboxylic acid (2- methoxy-ethyl)-amide;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-1 H-indole-3-carboxyIic acid 4- methoxy-benzylamide; 5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-1 /-/-indole-3-carboxylic acid
(tetrahydro-furan-2-ylmethyl)-amide;
[3-(2-Methoxymethyl-pyrrolidine-1 -carbonyl)-1 /--indol-5-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo-
[3.2.1 ]oct-6-yl)-methanone;
[3-(2,6-Dimethyl-morpholine-4-carbonyl)-1H-indol-5-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct- 6-yl)-methanone;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indole-3-carboxylic acid (1 ,1- dioxo-tetrahydro-thiophen-3-yl)-amide;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 H-indole-3-carboxylic acid [3-(4- methyl-piperazin-1-yl)-propyl]-amide; 5-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 -/-indole-3-carboxylic acid 4- trifluoromethyl-benzylamide; 5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 H-indole-3-carboxylic acid (furan-
2-ylmethyl)-amide;
[3-(2,3,5,6-Tetrahydro-[1,2']bipyrazinyl-4-carbonyl)-.ry-indol-5-yl]-(1 ,3,3-trimethyl-6-aza- bicyclo[3.2.1]oct-6-yl)-methanone; 5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyI)-1 -/-indole-3-carboxylic acid (2H- tetrazol-5-ylmethyl)-amide;
[3-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-1 H-indol-5-yl]-(1 ,3,3-trimethyl-6- aza-bicyclo[3.2.1]oct-6-yl)-methanone;
3-{[5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 H-indole-3-carbonyl]-amino}- propionic acid ethyl ester;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indole-3-carboxylic acid (4- methoxy-phenyl)-amide;
3-{[5-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 -/-indole-3-carbonyl]-amino}- propionic acid; Azepan-1 -yl-(1H-indol-5-yl)-methanone;
1 H-lndole-5-carboxylic acid dibenzylamide;
(3-Aza-bicyclo[3.2.2]non-3-yl)-( /-/-indol-5-yl)-methanone;
(4-Benzyl-piperidin-1 -yl)-(1 H-indol-5-yl)-methanone;
8-(1 H-lndole-5-carbonyI)-1 -phenyl-1 ,3,8-triaza-spiro[4.5]decan-4-one; [4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1 -yl]-(1 H-indol-5-yl)-methanone;
1-[1-(1H-lndole-5-carbonyl)-piperidin-4-yl]-1,3-dihydro-benzoimidazol-2-one; (4-tert-Butyl-piperidin-1 -yl)-(1 /--indol-5-yl)-methanone;
1-(1 /--lndole-5-carbonyl)-4-phenyl-piperidine-4-carbonitrile;
(1 H-lndol-5-yl)-(4-phenyl-piperidin-1 -yl)-methanone; (5-Benzyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-(1H-indol-5-yl)-methanone;
(1H-lndol-5-yI)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone;
1 H-lndole-5-carboxylic acid (5-hydroxy-1 ,3,3-trimethyl-cyclohexylmethyl)-amide;
1H-lndole-5carboxyIic acid (3,4-dihydrospiro(1H-indene-1 ,4-piperidine)-amide;
(3-Methanesulfonylmethyl-1 H-indol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)- methanone;
(3-Dimethylaminomethyl-1H-indol-6-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
1-{3-Acetyl-2-[5-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 y-indol-3-yl]-2,3- dihydro-imidazol-1-yl}-ethanone; 1-EthyI-3-[5-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyI)-1/.-indol-3-yl]-pyrrolidine-
2,5-dione; (3-Thiazol-2-yl-1H-indol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(3-lodo-1H-indol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
6-(1,3,3-TrimethyI-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indole-3-carbonitrile;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-1 H-indole-3-carbonitrile; 6-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1r -indole-3-carboxylic acid amide;
[3-(2H-Tetrazol-5-yl)-1 -.-indol-6-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
/V-[3-(1 ,3,3-TrimethyI-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 r7-indol-7-yl]-acetamide;
(1-BenzenesuIfonyl-1H-indol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(1-Benzenesulfonyl-2-methyl-1H-indol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
(1 -methyl-1 /-/-indol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicycIo[3.2.1]oct-6-yl)-methanone;
(1 -Benzyl-1 H-indol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
[6-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-indol-1-yl]-acetic acid ethyl ester;
[1 -(2-Ethoxy-ethyl)-1 /-.-indoI-6-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; {1-[2-(2-Methoxy-ethoxy)-ethyl]-1H-indol-6-yi}-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
3-[5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-indoI-1-yl]-propionic acid ethyl ester;
(1-Phenethyl-1H-indol-5-yI)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; [1-(Tetrahydro-furan-2-ylmethyl)-1H-indol-5-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
2-[5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-indol-1-yl]-acetamide;
[1 -(4-Trifluoromethoxy-benzyl)-1 A7-indol-5-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)- methanone; 3-[5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-indol-1 -ylmethylj-benzoic acid methyl ester;
4-[5-(1,3,3-Trimethyl-6-aza-bicycIo[3.2.1]octane-6-carbonyl)-indol-1-ylmethyl]-benzonitrile; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llg)
Figure imgf000098_0001
wherein
X is NR4, S or O;
R1 and R2 independently are hydrogen, halo, cyano, trihalomethyl, d-Cealkyl or CrCealkyloxy, wherein the alkyl groups independently are optionally substituted with one or more of R7;
R3 is hydrogen, d-Cealkyl, C3-Cι0cycloalkyl, Cι-C6alkyloxy, CrC6alkylthio, aryl, arylCrC6alkyl, hetaryl or hetarylalkyl, wherein the alkyl, cycloalkyl, aryl, hetaryl and hetarylalkyl groups independently are optionally substituted with one or more of R7;
R4 is hydrogen, d-C8alkyl, d-Cealkyloxyd-Cealkyl, aryl, hetaryl, hetarylCrCealkyl, aryld- Cealkyl, arylCrCealkyloxyCrCealkyl, C3-d0cycloalkyl, C3-Cι0hetcydoalkyl, C3-C10cyclo- alkylCrC6alkyl, CrC6alkylcarboxyCι-C6alkyl wherein the alkyl, aryl, hetaryl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R7;
R5 is hydrogen, and R6 is adamantyl optionally substituted with hydroxy, CrC6alkyloxy, aryl, arylCrCealkyl, aryloxy, arylCrCealkyloxy, hetaryl, hetaryloxy or hetarylCrCealkyloxy wherein the alkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R7; or
R5 and R6 are together with the nitrogen to which they are attached, forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, aryld-Cealkyl, hetarylalkyl, hydroxy, oxo, cyano, d-C6alkyloxy, arylCrCealkyloxy, hetaryld-Cealkyloxy, d- C6alkyloxyCrC6alkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or aryld- C6alkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R7; R7 are independently hydrogen, halo, hydroxy, oxo, nitro, NR9R10, cyano, COOR8, CONR9R10, d-C8aIkyl, CrC6aIkyloxy, aryloxy, arylCrCealkyloxy, hetaryloxy or hetarylCrCealkyloxy;
R8 is hydrogen, Cι-C6alkyl, aryl, arylCrC6alkyl, hetarylalkyl, wherein the alkyl, aryl and hetarylalkyl groups independently are optionally substituted with one or more of R7;
R9 and R10 independently are hydrogen, CrC8alkyl, C3-C10cycloalkyl, C3-Cι0hetcycloalkyl, C3- C10cycloalkylCι-C6alkyl, wherein the alkyl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R7; or
R9 and R10 together with the nitrogen to which they are attached, are forming a saturated or partially saturated bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of CrC8alkyl, aryld-Cealkyl, hetarylCrCealkyl, hydroxy, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetaryld-Cealkyloxy, CrC6alkyloxyCr C6alkyl, CrC6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrC6alkylcarbonyl, hetaryld- C6alkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R11;
R11 is hydrogen, halo, oxo, hydroxy, CrC6aIkyl, aryl, aryld-C6alkyI, hetaryl or hetarylalkyl;
a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In the definitions of R4, in the above formula (llg), hetcycloalkyl cannot be 7-aza[2,2,1]bicycle- heptane.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llg) wherein
X is NR4, S or O;
R1 and R2 independently are hydrogen, halo, cyano, trihalomethyl, d-C6alkyl or CrCealkyloxy, wherein the alkyl groups independently are optionally substituted with one or more of R7; R3 is hydrogen, d-C6alkyl, C3-Cι0cycloalkyl, CrC6alkyloxy, C C6alkylthio, aryl, arylCrC6alkyl, hetaryl or hetarylalkyl, wherein the alkyl, cycloalkyl, aryl, hetaryl and hetarylalkyl groups independently are optionally substituted with one or more of R7;
R4 is hydrogen, d-C8alkyl, CrCealkyloxyCrCealkyl, aryl, hetaryl, aryld-Cealkyl, aryld- CealkyloxyCrCealkyl, C3-C10cycloalkyl, C3-Cι0hetcycloalkyl, Qrdocycloalkyld-Cealkyl, C C6aIkylcarboxyCrC6alkyl wherein the alkyl, aryl, hetaryl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R7;
R5 is hydrogen, and R6 is adamantyl optionally substituted with hydroxy, CrC6alkyloxy, aryl, arylCrC6alkyl, aryloxy, arylCrCealkyloxy, hetaryl, hetaryloxy or hetarylCrC6aIkyloxy wherein the alkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R7; or
R5 and R6 are together with the nitrogen to which they are attached, forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 5 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, arylCrC6alkyl, hetarylalkyl, hydroxy, oxo, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, d- C6alkyloxyCrC6alkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld-
C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or aryld- C6alkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R7;
R7 are independently hydrogen, halo, hydroxy, oxo, nitro, NR5R6, cyano, COOR8, CONR5R6, CrC8alkyl, CrC6alkyloxy, aryloxy or hetaryloxy;
R8 is hydrogen, CrC6aIkyl, aryl, arylCrC6alkyl, hetarylalkyl, wherein the alkyl, aryl and hetarylalkyl groups independently are optionally substituted with one or more of R7; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llg) wherein X is NR4 or S wherein R4 is defined as above. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llg) wherein X is O.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llg) wherein X is S.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llg) wherein is NR4 wherein R4 is defined as above. In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llg) wherein R1 and R2 independently are hydrogen, halo, trihalomethyl or d-Cealkyl, wherein the alkyl groups independently are optionally substituted with one or more of R7.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llg) wherein R3 is hydrogen, d-C6alkyI, aryl, arylCrC6alkyl, hetaryl or hetarylalkyl, wherein the alkyl, cycloalkyl, aryl, hetaryl and hetarylalkyl groups independently are optionally substituted with one or more of R7.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llg) wherein R4 is hydrogen, CrC8alkyl, aryl, hetaryl, hetaryld-Cealkyl, arylCι-C6alkyl, wherein the alkyl, aryl, hetaryl, groups independently are optionally substituted with one or more of R7.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llg) wherein R5 and R6 are together with the nitrogen to which they are attached, forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C6alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylalkyl, hydroxy, oxo, cyano, CrC6alkyIoxy, arylCrC6aIkyloxy, hetaryld-Cealkyloxy, d- CealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld-
C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or aryld- C6alkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R7.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is of the general formula (llg) wherein R5 and R6, together with the nitrogen to which they are attached, are azepane, azocane, 6-aza- bicyclo[3.2.1]octane, 8-aza-bicyclo[3.2.1]octane, 3-aza-bicyclo[3.2.1]octane, 2-aza- bicyclo[3.2.1]octane, 3-oxa-6-aza-bicyclo[3.2.1]octane, 6-aza-bicydo[3.2.2]nonane, 3-aza- bicyclo[3.2.2]nonane, 4-aza-tricyclo[4.3.1.13,8]undecane.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of :
(4-Methyl-2-phenyl-thiazol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone ;
(2,4-Dimethyl-thiazol-5-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(4-Methyl-2-pyrazin-2-yl-thiazoI-5-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6- yl)-methanone;
(3-Aza-bicyclo[3.2.2]non-3-yl)-(2,4-dimethyl-thiazol-5-yl)-methanone;
(1 H-lmidazol-4-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone ;
(3-Aza-bicyclo[3.2.2]non-3-yl)-(4-methyl-2-phenyl-thiazol-5-yl)-methanone ;
2,4-Dimethyl-thiazole-5-carboxylic acid cycloheptylamide; Azepan-1 -yl-(2,4-dimethyI-thiazol-5-yl)-methanone;
2,4-DimethyI-thiazole-5-carboxylic acid adamantan-1 -ylamide;
(3-Aza-bicyclo[3.2.2]non-3-yl)-(1H-imidazol-4-yl)-methanone;
2,4-Dimethyl-thiazole-5-carboxylic acid (3-hydroxy-adamantan-1-yl)-amide; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted amides, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of :
(1 -Methyl-1 H-imidazol-4-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone;
[1-(6-Methyl-pyridin-2-yl)-1H-imidazol-4-yl]-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
[1 -(4-Chloro-benzyl)-5-methyl-1 H-imidazol-4-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)- methanone; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III)
Figure imgf000103_0001
Formula (III) wherein
R1 is C5-C 0cycloalkyl, C5-Cι0hetcycloalkyl, aryl, hetaryl, arylCrCealkyl or hetaryld-Cealkyl, wherein the cycloalkyl, hetcycloalkyl, aryl, hetaryl and arylalkyl groups independently are optionally substituted with one or more of R7;
R2 and R3 independently are hydrogen, CrC6alkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrCealkyl, aryloxy, hetaryloxy, arylCrC6alkyloxy or hetarylCrCealkyloxy wherein the alkyl, aryl, hetaryl, arylalkyl and hetarylalkyl groups independently are optionally substituted with one or more of R8; or
R2 and R3 together with the carbon atom to which they are attached, are forming a saturated or partially saturated cyclic ring system containing from 3 to 6 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, CrC6aIkyloxy, aryloxy, arylCrCealkyloxy or hetarylCrCealkyloxy;
R4 and R5 independently are hydrogen, halo, hydroxy, CrC6alkyI, C2-C6alkenyl, C2-C6alkynyl, CrC6alkyloxy, aryl, hetaryl, aryloxyCrC6alkyl, aryloxyaryl, hetaryloxyaryl, aryloxyhetaryl, hetaryloxyhetaryl or arylCrC6alkyloxyCrC6alkyl wherein the alkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R9; or
R4 and R5 together with the carbon atoms to which they are attached, are forming a saturated, partially saturated or aromatic ring system containing from 5 to 8 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C6alkyl, aryl, aryld-Cealkyl, NR10R11, halo, trihalomethyl, trihalomethoxy, hydroxy, oxo, d-C6alkyloxy, arylCrC6alkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy; or R4 and either R2 or R3 together are forming a saturated or partially saturated bridge containing from 1 to 4 carbon atoms, the bridge can optionally be substituted with at least one of Ci- Cealkyl, aryl, hetaryl, aryld-Cealkyl or hetarylCrCealkyl;
R6 is hydrogen, CrC6alkyl, aryl, hetaryl, arylCrC6alkyl or hetarylCrCealkyl; or
R6 and either R4 or R5 together with the carbon atoms to which they are attached, are forming a saturated, partially saturated or aromatic ring system containing from 5 to 8 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of C C6alkyl, aryl, arylCrCealkyl,
NR10R11, halo, trihalomethyl, trihalomethoxy, hydroxy, oxo, d-C6alkyloxy, aryld-Cealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, C C6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R7 and R8 independently are hydrogen, halo, hydroxy, cyano, nitro, CrC6alkyl, CrC6alkyloxy, trihalomethyl, trihalomethoxy, aryloxy, hetaryloxy, arylCrC6alkyloxy, hetarylCrCealkyloxy, d- C6alkyloxyC C6alkyl, aryloxyd-Cealkyl, arylCrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, aryld-C6alkylcarboxy or hetarylCrC6alkylcarboxy;
R9 is hydrogen, halo, hydroxy, cyano, CrC6alkyl, methylendioxo, trihalomethyl, trihalomethoxy, aryl, arylCrC6alkyl, aryloxy, NR10R11 or aryloxyCrC6alkyl, wherein the aryl group is optionally substituted with one or more of R12;
R10 and R11 independently are hydrogen, d-Cealkyl, aryl or aryld-C6alkyl wherein the alkyl and aryl groups independently are optionally substituted with one or more of R13; or
R10 and R11 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, arylCrC6alkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, d-C6alkylcarboxy, arylcarboxy or arylCrC6alkyl-carboxy;
R12 is oxo or halo; R13 is halo, hydroxy, cyano, d-Cealkyl, CrC6alkyloxy, NR14R15, methylendioxo, trihalomethyl, or trihalomethoxy;
R14 and R15 independently are hydrogen, d-Cealkyl, aryl, hetaryl, aryld-Cealkyl or hetaryld- Cealkyl;
A is a single, double or triple bond;
X is a chemical bond, (CR16R17)n or NR10, wherein R16 and R17 independently are hydrogen, oxo or CrC6alkyl, or
X, together with either R2 or R3, is a double bond;
Y is CR18 or nitrogen, wherein R18 is hydrogen, d-Cealkyl, aryl, hetaryl, arylC C6alkyl or hetarylCrC6alkyl; or
R18 and either R2 or R3 together are forming a saturated or partially saturated cyclic ring system containg from 1 to 4 carbon atoms, the ring system can optionally be substituted with at least one of d-C6alkyl, aryl, hetaryl, aryld-C6alkyl or hetarylCrCealkyl; or
R18 with either R2 or R3 and either R4 or R5 together are forming a saturated or partially saturated cyclic ring system having one common carbon atom containing from 8 to 12 carbon atoms, the ring system can optionally be substituted with at least one of d-C6alkyl, aryl, hetaryl, arylCrC6aIkyl or hetarylCι-C6alkyl;
n is 0, 1 or 2; or
a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R1 is C5-Ci0cycloalkyl, C5-C 0hetcydoalkyl, aryl, hetaryl, or arylCrC6alkyl, wherein the cycloalkyl, hetcycloalkyl, aryl, hetaryl and arylalkyl groups independently are optionally substituted with one or more of R7. In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R1 is C5-Ci0cycloalkyl, C5-C10hetcycloalkyl, aryl, wherein the cycloalkyl, hetcycloalkyl and aryl groups independently are optionally substituted with one or more of R7. In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R1 is C5-C10cycloalkyl optionally substituted with one or more of R7.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R1 is drdohetcycloalkyl optionally substituted with one or more of R7.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R1 is aryl, optionally substituted with one or more of R7.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R1 is hetaryl optionally substituted with one or more of R7.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R1 is arylCι-C6alkyl optionally substituted with one or more of R7. In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R2 and R3 independently are hydrogen or CrCealkyl.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R2 and R3 together with the carbon atom to which they are attached, are forming a saturated or partially saturated cyclic ring system containing from 3 to 6 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, aryICrC6alkyl, hetarylCrC6alkyl, hydroxy, oxo, d-C6alkyIoxy, aryloxy, aryld-C6alkyloxy or hetaryld-Cealkyloxy. In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R4 and R5 independently are hydrogen, d-Cealkyl, CrC6alkyloxy, aryloxyCrC6alkyl, wherein the alkyl and aryl groups independently are optionally substituted with one or more of R9.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R4 and R5 together with the carbon atoms to which they are attached, are forming a saturated or partially saturated ring system containing from 5 to 8 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of d-C6alkyl.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R4 and either R2 or R3 together are forming a saturated or partially saturated bridge containing from 1 to 4 carbon atoms, the bridge can optionally be substituted with at least one of Ci- Cealkyl or arylCrC6alkyl.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R6 is hydrogen or CrC6alkyl.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R6 and either R4 or R5 together with the carbon atoms to which they are attached, are forming a saturated, partially saturated or aromatic ring system containing from 5 to 8 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, halo, trihalomethyl, d- C6alkyloxy or aryld-C6alkyloxy.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R7 and R8 independently are hydrogen, halo, hydroxy, cyano, d-Cealkyl, CrC6alkyloxy, trihalomethyl, trihalomethoxy, aryloxy, hetaryloxy, arylCrC6alkyloxy, hetarylCrCealkyloxy, d- C6alkyloxyCrC6alkyl, aryloxyCi-C6alkyl or arylCrCealkyloxyCrCealkyl.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein R9 is hydrogen.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein A is a double or aromatic bond; X is (CR16R17)n, wherein R16 and R17 independently are hydrogen or CrC6alkyl and n is 1 ; Y is CR18 wherein R18 is hydrogen, CrC6alkyl, aryl, hetaryl, aryld- C6alkyl or hetarylCrCealkyl; R6 and either R4 or R5 together with the carbon atoms to which they are attached, are forming an aromatic ring system containing 6 carbon atoms, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, arylCrC6alkyl, NR 0R11, halo, trihalomethyl, trihalomethoxy, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, d- C6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy. In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein A is a double or aromatic bond.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein X is
(CR16R17)n, wherein R16 and R17 independently are hydrogen or d-C6alkyl and n is 1.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (III) wherein Y is
CR18 wherein R18 is hydrogen, d-Cealkyl, aryl, hetaryl, aryld-C6alkyl or hetarylCrCealkyl. In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting :
3-(2-Bromo-phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine;
3-Phenyl-[1,2,4]triazolo[3,4-a]isoquinoline;
(2-Methoxy-benzyl)-(3-phenyl-[1 ,2,4]triazolo[4,3-b]pyridazin-6-yl)-amine; 3-(2-Fluoro-phenyl)-5-(4-methoxy-phenoxy)-[1,2,4]triazolo[4,3-c]quinazoIine;
3-Phenyl-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine;
3-(4-Chloro-phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine;
3-(3-Chloro-phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine;
3-(3,4-Dichioro-phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine; 5,5-Dimethyl-3-thiophen-2-yl-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoline;
3-(2-Chloro-phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine;
5,5-Dimethyl-3-(3,4,5-trimethoxy-phenyl)-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoline;
3-Furan-2-yl-5,5-dimethyI-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoIine;
3-(3-Bromo-phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine; 3-(4-Bromo-phenyl)-5,5-dimethyl-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoline;
4-(5,5-Dimethyl-5,6-dihydro-[1 ,2,4]triazolo[3,4-a]isoquinolin-3-yl)-phenol;
3-(4-Methoxy-phenyl)-5,5,8,9-tetramethyl-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoline;
5,5-Dimethyl-3-phenyl-5,6-dihydro-[1 ,2,4]triazolo[3,4-a]isoquinoline;
3-(5,5-Dimethyl-5,6-dihydro-[1 ,2,4]triazolo[3,4-a]isoquinolin-3-yl)-phenol; 5,5-Dimethyl-3-p-tolyl-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoline;
5,5-Dimethyl-3-thiophen-2-yl-5,6-dihydro-[1,2,4]triazoIo[3,4-a]isoquinoline;
7,10-Dimethoxy-5,5-dimethyI-3-phenyl-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoline;
3-(2,4-Dichloro-phenyl)-6,6-dimethyl-5,6,7,8-tetrahydro-[1 ,2,4]triazolo[4,3-a]pyrimidine;
2-(6,6-Dimethyl-5,6,7,8-tetrahydro-[1,2,4]triazoIo[4,3-a]pyrimidin-3-yl)-phenoI; 3-(2-Chloro-phenyl)-6,6-dimethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrimidine;
4-Benzyl-3,5-di-p-tolyl-4H-[1,2,4]triazole; 3-p-Tolyl-6,7,8,9-tetrahydro-5H-[1 ,2,4]triazolo[4,3-a]azepine; 3-(4-Methoxy-phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine; 3-Pyridin-4-yl-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine; 3-(4-Bromo-phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine; 3-Furan-2-yl-5,5,8,9-tetramethyl-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoline; 6,6-Dimethyl-3-(2-nitro-phenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrimidine; 3-(2,4-Dichloro-phenyl)-5,5-dimethyl-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoline; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ilia)
Figure imgf000109_0001
wherein R1 is aryl or hetaryl, wherein the aryl and hetaryl groups independently are optionally substituted with one or more of R7;
R2 and R3 together with the atoms to which they are connected forms a C5-d0cycloalkyl or C5- Ciohetcycloalkyl, wherein the cycloalkyl and hetcycloalkyl rings independently are optionally substituted with one or more of R8; or
R2 and R3 are connected to one of the following ring systems at the carbon atoms marked with an asterix (*)
Figure imgf000109_0002
Figure imgf000109_0003
wherein the ring systems independently are optionally substituted with one or more R8; R7 is hydrogen, halo, hydroxy, cyano, nitro, CrC6alkyl, CrC6alkyloxy, trihalomethyl, trihalomethoxy, aryloxy, hetaryloxy, NR9R10, arylCrCealkyloxy, hetarylC C6alkyloxy, d- Cealkyloxyd-Cealkyl, aryloxyCrC6alkyl, arylCrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrC6alkylcarbonyl, hetarylCrCealkylcarbonyl, d-C6aIkyl- carboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy or hetarylCrC6alkylcarboxy;
R8 is hydrogen, d-Cβalkyl, halo, aryl, hetaryl, arylCrC6alkyl, NR9R10, trihalomethyl, trihalomethoxy, hydroxy, oxo, d-C6alkyloxy, aryloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, C C6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R9 and R10 independently are hydrogen, d-Cealkyl, aryl or arylCrC6alkyl wherein the alkyl and aryl groups independently are optionally substituted with one or more of R11; or
R9 and R10 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, arylCι-C6alkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R11 is d-Cealkyl, oxo or halo;
X is (CR12R13)n, wherein R12 and R13 independently are hydrogen, oxo, hydroxy or CrC6alkyl; and
n is 1 or 2; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ilia) wherein R1 is aryl optionally substituted with R7 as defined above.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ilia) wherein R1 is phenyl optionally substituted with R7 as defined above. In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ilia) wherein R2 and R3 are connected to one of the following ring systems at the carbon atoms marked with an asterix (*)
Figure imgf000111_0001
wherein the ring systems independently are optionally substituted with one or more R8 as defined above.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ilia) wherein R7 is hydrogen, halo, hydroxy, cyano, d-C6alkyl, CrC6alkyloxy, trihalomethyl, aryloxy, aryld- Cealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, aryloxyd-Cealkyl or aryld- C6alkyIoxyCrCealkyl.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (Ilia) wherein R8 is hydrogen, d-C6alkyl or halo.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (Illb)
Figure imgf000111_0002
wherein R1 is aryl or hetaryl, wherein the aryl and hetaryl groups independently are optionally substituted with one or more of R7;
R7 is hydrogen, halo, hydroxy, cyano, nitro, CrC6alkyl, CrC6alkyloxy, trihalomethyl, trihalomethoxy, aryloxy, hetaryloxy, NR9R10, arylCrCealkyloxy, hetaryld-Cealkyloxy, d- C6alkyloxyCrC6alkyl, aryloxyd-Cealkyl, arylCrC6alkyloxyCrC6alkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, aryld-C6alkylcarboxy or hetarylCrC6alkylcarboxy;
R9 and R10 independently are hydrogen, d-Cealkyl, aryl or aryld-C6alkyl wherein the alkyl and aryl groups independently are optionally substituted with one or more of R 1; or R9 and R10 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, arylCrC6alkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrC6alkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrC6a- alkylcarboxy;
R11 is CrC6alkyl, oxo or halo;
a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (Illb) wherein R1 is aryl optionally substituted with R7 as defined above.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (Illb) wherein R1 is phenyl optionally substituted with R7 as defined above. In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (Illb) wherein R1 is phenyl substituted in the ortho position.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (Illb) wherein R1 is phenyl substituted in both the ortho and para position.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (Illb) wherein R7 is halo, hydroxy, cyano, d-Cealkyl, d-dalkyloxy, trihalomethyl, trihalomethoxy, aryloxy, hetaryloxy, NR9R10, aryld-Cealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, aryloxyCrC6alkyl, arylCrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylC C6alkylcarbonyl or hetarylCrC6alkylcarbonyl; wherein R9 and R10 are defined as above.
In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (Illb) wherein R7 is CrCealkyloxy, trihalomethoxy, aryloxy, hetaryloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, aryloxyCrC6alkyl or arylCrC6alkyloxyCrC6alkyl. In another embodiment of the present invention said fused 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of:
3-(2-Bromo-phenyl)-6,7,8,9-tetrahydro-5H-[1 ,2,4]triazolo[4,3-a]azepine;
3-(2-Phenoxymethyl-phenyl)-5,6,7,8-tetrahydro-[1 ,2,4]triazolo[4,3-a]azepin-9-one; 3-(2-Phenoxymethyl-phenyl)-6,7,8,9,10,11-hexahydro-5/-/-5,9:7,11-dimethano[1 ,2,4]tria- zolo[4.3-a]azonine;
3-(5-Bromo-pyridin-3-yl)-6,7,8,9-tetrahydro-5H-[1 ,2,4]triazolo[4,3-a]azepine;
3-(5-Hex-1-ynyl-pyridin-3-yl)-6,7,8,9-tetrahydro-5H-[1 ,2,4]triazolo[4,3-a]azepine;
3-(6-Chloro-pyridin-3-yl)-6,7,8,9-tetrahydro-5H-[1 ,2,4]triazoIo[4,3-a]azepine; 3-(6-Morpholin-4-yl-pyridin-3-yl)-6,7,8,9-tetrahydro-5H-[1 ,2,4]triazolo[4,3-a]azepine;
3-Pyridin-3-yl-6,7,8,9-tetrahydro-5H-[1 ,2,4]triazolo[4,3-a]azepine;
3-(2-Benzyloxymethyl-phenyl)-6,7,8,9-tetrahydro-5H-5,9-methano[1 ,2,4]triazolo[4.3-a]azepine;
3-Phenyl-[1 ,2,4]triazolo[3,4-a]isoquinoline; or salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said alpha-amino ketones, or a prodrug thereof, as a component of the combination therapy is of the general formula (IV)
Figure imgf000113_0001
Formula (IV) wherein
R1 and R2 independently are hydrogen, d-C6alkyl, C3-Cι0cycloalkyl, C3-Cι0 het-cycloalkyl, aryl, hetaryl, aryld-C6alkyl or hetaryld-Cealkyl, wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R6; or
R1 and R2 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic or bicyclic ring system containing from 4 to 8 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6aIkyl, aryl, hetaryl, arylCrC6alkyl, hetaryl- CrC6alkyl, hydroxy, oxo, CrC6aIkyl-oxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrC6alkyl-carbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, d- C6alkylcarboxy, arylcarboxy, hetarylcarboxy or aryICrC6alkylcarboxy; R3 and R4 independently are hydrogen, CrC6alkyl, C C6alkenyl, CrC6alkynyl, aryl, hetaryl, arylCι-C6alkyl or hetarylCrC6alkyl, wherein the alkyl, alkenyl, alkynyl, aryl, and hetaryl groups independently are optionally substituted with one or more of R7;
R5 is C3-Ci0cycloalkyl, C3-C 0hetcycloalkyl, aryl or hetaryl, wherein the aryl, hetaryl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R8; or
R3 and R5 together with the carbon atoms to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, aryld- Cealkyl, hetarylCrCealkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, CrCBalkyloxyCr C6alkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, aryl-carboxy, hetarylcarboxy or arylCrCealkylcarboxy; or
R2, R3 and R5 together with the atoms to which they are attached, are forming a saturated or partially saturated bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, arylCrC6alkyl, hetaryl- CrC6alkyl, hydroxy, oxo, CrC6alkyl-oxy, arylCrCealkyloxy, CrCealkyloxyCrCealkyl, Cr C6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetaryl-carboxy or arylCι-C6alkylcarboxy;
R6 is hydrogen, hydroxy, oxo, halo, adamantyl, d-Cealkyl, d-C6alkyloxy, trihalomethyl, trihalomethoxy, NR9R10, aryld-Cealkyloxy, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R7 and R8 independently are hydrogen, hydroxy, oxo, halo, cyano, nitro, NR9R10, d-Cealkyl, CrC6alkyloxy, aryl, hetaryl, aryld-Cealkyloxy, hetaryld-Cealkyloxy, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, C C6alkyl- carboxy, arylcarboxy or arylCrCealkylcarboxy, wherein the aryl and hetaryl groups independently are optionally substituted with C3-C10cycloalkyl or C3-C10hetcycloalkyl;
R9 and R10 independently are hydrogen, CrC6alkyl, C3-C10cycloalkyl, C3-Cι0 hetcycloalkyl, aryl, hetaryl, arylCrC6alkyl or hetaryld-Cealkyl; or R9 and R10 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 5 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one CrC6alkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrCealkyl, hydroxy, oxo, CrC6alkyloxy, aryId-C6alkyIoxy, CrCealkyloxyCrCealkyl, d- C6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy or arylCrCealkylcarboxy; or
a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said alpha-amino ketones, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of: 1 -Adamantan-1 -yl-2-morpholin-4-yl-ethanone;
1 -Adamantan-1 -yl-2-benzylamino-propan-1 -one;
1 -Adamantan-1 -yl-2-benzylamino-ethanone;
2-Pyrrolidin-1-yl-1-(3-p-tolyl-adamantan-1-yl)ethanone;
1 -Adamantan-1 -yl-2-morpholin-4-yl-propan-1 -one; 1-[4-(5-Adamantan-1-yl-[1 ,2,3]triazol-1-yl)-phenyl]-2-phenylamino-ethanone;
6-Benzo[1 ,3]dioxol-5-yl-8-benzyl-8-aza-bicyclo[3.2.1]octan-2-one;
2-fert-Butylamino-1 -(3-p-tolyl-adamantan-1 -yl)ethanone;
2-Morpholin-4-yI-1 -(3-p-tolyl-adamantan-1 -yl)ethanone;
1 -Adamantan-1 -yl-2-[4-(4-nitro-phenyl)-piperazin-1 -yl]ethanone; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (V)
Figure imgf000115_0001
Formula (V) wherein X is O or S; R1 is hydrogen, d-Cealkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C10cycloalkyl, arylCrC6alkyl, hetaryld-Cealkyl, R4R5NcarbonylCrC6alkyl, aryIcarbonylCrC6alkyl, hetarylcarbonyICrC6alkyi; wherein the alkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R6;
R2 is CrC6alkyl, CrC6alkenyl, arylCrC6alkyl, C3-d0cycloalkyl or hetaryld-Cealkyl; wherein the alkyl, alkenyl, cycloalkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R7;
R3 is C3-Ci0cycloalkyl, C3-Cι0hetcycloalkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrCealkyl, arylR8CrC6alkyl or hetarylR8CrC6alkyl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and , hetaryl groups independently are optionally substituted with one or more of R9;
R4 and R5 independently are hydrogen, CrCβalkyl, C3-C10cycloalkyl, C5-C8hetcycloalkyl, aryl, hetaryl, arylCrCealkyl or hetarylCrCealkyl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R11; or
R4 and R5 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C6alkyl, aryl, aryId-C6alkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrC6alkyl-carbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R6, R7, R9 and R11 independently are hydrogen, halo, N02, NH2, cyano, NR4R5, CONR4R5, trihalomethyl, trihalomethoxy, hydroxy, oxo, CrC6alkyl, C3-d0cycloalkyl, C3-C10hetcycloalkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, CrC6alkylS02, R15R16NS02, C C6alkyloxy, aryloxy, hetaryloxy, arylCrC6alkyloxy, CrCealkylcarbonyl, arylcarbonyl, aryld- C6alkylcarbonyl, arylcarbonylNR15, carboxyCrC6alkyl or carboxyarylCrC6alkyl;
R8 is oxygen, NR10, C(=0)NR10 or SOnNR10; wherein n is 1 or 2;
R10 is hydrogen, CrC6alkyl, aryl, hetaryl, aryld-Cealkyl or hetaryl d-C6a I kyl; R15 and R16 independently are hydrogen, d-C6alkyl, C3-C10cycloalkyl, C5-C8hetcycloaIkyl, aryl or hetaryl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl or hetaryl groups independently are optionally substituted with one or more of R11; or
R15 and R16 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 8 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C6alkyl, aryl, arylCrC6alkyl, hydroxy, oxo, CrC6alkyloxy, arylCrC6alkyloxy, CrCealkyloxyCrCealkyl, CrC6alkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrC6alkyl-carboxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (V) wherein X is O or S;
R1 is hydrogen, d-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, arylCrC6alkyl, hetarylCrCealkyl,
NR4R5carbonylCrC6alkyl, arylcarbonyICrC6alkyl, hetarylcarbonylCrC6alkyl; wherein the alkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R6;
R2 is CrC6alkyl, CrC6alkenyl, arylC C6alkyl or hetarylCrCealkyl; wherein the alkyl, alkenyl, aryl and hetaryl groups independently are optionally substituted with one or more of R7;
R3 is C5-C8cycloalkyl, C5-C8hetcycloalkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrCealkyl, arylR8CrC6alkyl or hetarylR8CrC6alkyl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R9;
R4 and R5 independently are hydrogen, d-Cealkyl, C5-C10cycloalkyl, C5-C8hetcycloalkyl, aryl, hetaryl, aryld-Cealkyl or hetarylCrC6alkyl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R11; or R4 and R5 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C6alkyl, aryl, aryld-C6alkyl, hydroxy, oxo, CrC6alkyloxy, aryld-Cealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, aryld-C6alkyIcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrC6alkyl-carboxy;
R6, R7, R9 and R11 independently are hydrogen, halo, N02, NH2, cyano, trihalomethyl, trihalomethoxy, hydroxy, oxo, CrCβalkyl, aryl, hetaryl, arylC C6alkyl, hetaryld-Cealkyl, S02NR15R16, Cι-C6alkyloxy, aryloxy, hetaryloxy, arylCrCealkyloxy, CrCealkylcarbonyl, arylcarbonyl, aryld- C6alkylcarbonyl, arylcarbonylNR15, carboxyCrC6alkyl or carboxyarylCrC6alkyl;
R8 is oxygen, NR10, C(=0)NR1° or SOnNR10; wherein n is 1 or 2;
R10 is hydrogen, d-C6alkyl, aryl, hetaryl, arylCrC6alkyl or hetarylCrCealkyl;
R15 and R16 independently are hydrogen, CrC6alkyl, C5-Cι0cycloalkyl, C5-C8hetcycloaIkyl, aryl or hetaryl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl or hetaryl groups independently are optionally substituted with one or more of R11; or
R15 and R16 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 8 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, aryld-Cealkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrC6alkyl-carboxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (V) wherein X is O.
In another embodiment of the present invention said substituted 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (V) wherein X is S. In another embodiment of the present invention said substituted 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (V) wherein R1 is arylCrC6alkyl, hetarylCrC6alkyl, R4R5NcarbonyICrC6alkyl, arylcarbonyld- C6alkyl, hetarylcarbonylCrC6alkyl; wherein aryl and hetaryl groups independently are optionally substituted with one or more of R6.
In another embodiment of the present invention said substituted 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (V) wherein R2 is CrC6alkyl, aryICrC6alkyl, C3-C10cycloalkyl or hetarylCrC6alkyl; all of which is optionally substituted with one or more of R7. In another embodiment of the present invention said substituted 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (V) wherein R3 is C3-Cι0cycloalkyl, C3-Cι0hetcycloalkyl, aryl, hetaryl, aryICrC6alkyl, hetaryld- Cealkyl, arylR8CrC6alkyl or hetarylR8CrC6alkyl, wherein all groups indenpendently are optionally substituted with one or more of R9. In another embodiment of the present invention said substituted 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (V) wherein R3 is C3-C10hetcycloalkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, arylR8d- C6alkyl or hetarylR8CrC6alkyl, wherein all groups indenpendently are optionally substituted with one or more of R9. In another embodiment of the present invention said substituted 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (V) wherein R4 and R5 independently are aryl or hetaryl wherein both groups indenpendently are optionally substituted with one or more of R11.
In another embodiment of the present invention said substituted 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (V) wherein R4 and R5 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional nitrogen atoms, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, aryld-Cealkyl, hydroxy, oxo, d-C6alkyloxy, arylCrC6alkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy.
In another embodiment of the present invention said substituted 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (V) wherein R6, R7, R9 and R11 independently are hydrogen, halo, N02, NH2, cyano, NR4R5, CONR4R5, trihalomethyl, trihalomethoxy, hydroxy, oxo, d-Cealkyl, C3-C10cycloalkyl, C3-
Ciohetcycloalkyl, aryl, hetaryl, arylCrC6alkyl, hetaryld-Cealkyl, CrC6alkylS02, R15R16NS02, Cι-C6alkyloxy, aryloxy, hetaryloxy, arylCrCealkyloxy, CrCealkylcarbonyl, arylcarbonyl, aryld-
C6alkylcarbonyl, arylcarbonylNR15, carboxyCrC6alkyl or carboxyarylCrC6alkyl.
In another embodiment of the present invention said substituted 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (V) wherein R8 is oxygen, NR10, C(=0)NR10 or SOnNR10; wherein n is 1 or 2.
In another embodiment of the present invention said substituted 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is of the general formula (V) wherein R10 is hydrogen, CrC6alkyl, aryl, hetaryl, arylCι-C6aIkyl or hetaryld-C6alkyl.
In another embodiment of the present invention said substituted 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of:
3-(4-Allyl-5-mercapto-4H-[1,2,4]triazol-3-yl)-1-(2,4-dichIoro-benzyl)-1H-pyridin-2-one;
4-Methyl-3-(4-methyl-2-phenyl-thiazol-5-yl)-5-prop-2-ynylsulfanyl-4H-[1,2,4]triazole;
N-{1-[5-(4-ter--Butyl-benzyIsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-ethyl}-4-chloro- benzenesulfonamide;
4-Methyl-3-methyIsulfanyl-5-[3-(3-trifluoromethyl-benzyloxy)-thiophen-2-yl]-4H-[1,2,4]triazole;
N-(4-Chloro-phenyl)-2-(4-methyl-5-thiophen-3-ylmethyl-4H-[1 ,2,4]triazol-3-ylsulfanyI)- acetamide;
2-[4-Methyl-5-(2-oxo-2-phenyl-ethylsulfanyl)-4H-[1 ,2,4]triazol-3-ylmethyl]-4H- benzo[1 ,4]thiazin-3-one;
3-(4-Fluoro-benzylsulfanyl)-5-(2-fluoro-phenyl)-4-methyl-4H-[1,2,4]triazole;
3-(2-Fluoro-phenyl)-4-methyl-5-(4-methyl-benzylsulfanyl)-4H-[1,2,4]triazole;
4-MethyI-3-(4-methyl-benzylsulfanyl)-5-(3-trifluoromethyl-phenyl)-4H-[1,2,4]triazole;
3-(2,4-DichIoro-phenyl)-4-furan-2-ylmethyl-5-methylsulfanyI-4H-[1,2,4]triazole; 3-(4-tert-Butyl-phenyl)-5-(2,6-dichloro-benzylsuIfanyl)-4-furan-2-ylmethyl-4H-[1,2,4]triazole;
4-Methyl-3-(4-methyl-benzylsulfanyl)-5-(5-methyl-isoxazoI-3-yl)-4H-[1,2,4]triazole;
3-(3-Methoxy-benzylsulfanyl)-4-methyl-5-thiophen-2-yl-4H-[1,2,4]triazole;
3-(4-Fluoro-benzylsulfanyl)-4-methyI-5-thiophen-2-yI-4H-[1,2,4]triazoIe;
3-(4-tert-Butyl-benzylsulfanyl)-4-methyl-5-thiophen-2-yl-4H-[1,2,4]triazole; 4-Methyl-3-(2-methyl-benzyIsulfanyl)-5-thiophen-2-yl-4H-[1,2,4]triazole;
2-(5-Benzylsulfanyl-4-methyl-4H-[1 ,2,4]triazol-3-ylmethyl)-4H-benzo[1,4]thiazin-3-one;
2-[5-(4-Chloro-benzyisulfanyl)-4-methyl-4H-[1,2,4]triazoI-3-ylmethyl]-4H-benzo[1 ,4]thiazin-3- one;
5-[5-(2,6-Dichloro-benzylsuIfanyl)-4-methyl-4H-[1,2,4]triazol-3-yl]-benzo[1,2,5]oxadiazole; 1-(4-ChIoro-phenyl)-2-[4-methyl-5-(4-trifluoromethyl-pyridin-3-yl)-4H-[1,2,4]triazol-3-ylsulfanyl]- ethanone; 3-[5-(4-Chloro-benzylsulfanyl)-4-methyl-4H-[1 ,2,4]triazol-3-yl]-2-methyl-imidazo[1,2-a]pyridine;
3-[5-(2,4-Dichloro-benzylsulfanyl)-4-methyl-4H-[1,2,4]triazol-3-yl]-2,8-dimethyl-imidazo[1 ,2- a]pyridine;
4-AIIyl-5-(2,4-dichloro-phenyl)-4H-[1,2,4]triazole-3-thiol; 3-(5-Allylsulfanyl-4-methyl-4H-[1 ,2,4]triazol-3-yl)-1 -benzyl-1 H-pyridin-2-one;
3-(4-Allyl-5-methyIsulfanyl-4H-[1,2,4]triazol-3-yl)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
3-(4-Allyl-5-mercapto-4H-[1 ,2,4]triazol-3-yl)-1 -(4-chloro-benzyl)-1 H-pyridin-2-one;
3-(4-AIIyl-5-prop-2-ynylsuIfanyl-4H-[1,2,4]triazol-3-yl)-1-(4-chloro-benzyl)-1H-pyridin-2-one;
3-(5-Allylsulfanyl-4-ethyl-4H-[1,2,4]triazol-3-yl)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one; 1 -(2,4-Dichloro-benzyl)-3-[4-ethyl-5-(2-oxo-2-phenyl-ethylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-1 H- pyridin-2-one;
3-(4-Allyl-5-prop-2-ynylsulfanyl-4H-[1,2,4]triazol-3-yl)-1-(3,4-dichloro-benzyl)-1H-pyridin-2-one;
4-Allyl-5-(4-methyl-2-phenyl-thiazol-5-yl)-4H-[1,2,4]triazole-3-thiol;
3-Allylsulfanyl-4-methyl-5-(4-methyl-2-phenyl-thiazol-5-yl)-4H-[1 ,2,4]triazole; 4-Allyl-5-[2-(3,4-dimethoxy-phenyl)-thiazol-4-yl]-4H-[1,2,4]triazole-3-thiol;
N-[5-(4-tert-Butyl-benzylsulfanyl)-4-methyl-4H-[1,2,4]triazol-3-ylmethyl]-4-methyl- benzenesulfonamide;
4-Methyl-3-[3-(4-methyI-benzyloxy)-thiophen-2-yl]-5-methylsulfanyl-4H-[1 ,2,4]triazole;
5-[3-(2,4-Dichloro-benzyloxy)-thiophen-2-yl]-4-methyI-4H-[1 ,2,4]triazole-3-thiol; 3-[3-(2,4-Dichloro-benzyloxy)-thiophen-2-yl]-4-methyI-5-methylsulfanyl-4H-[1,2,4]triazole;
4-Methyl-5-[3-(3-trifluoromethyl-benzyloxy)-thiophen-2-yl]-4H-[1 ,2,4]triazole-3-thiol;
2-(5-Benzyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-iodo-phenyl)-acetamide;
3-(5-Allylsulfanyl-4-methyl-4H-[1 ,2,4]triazol-3-yl)-2,7-dimethyl-imidazo[1 ,2-a]pyridine;
3-(5-BenzylsuIfanyl-4-methyl-4H-[1,2,4]triazol-3-yl)-2,7-dimethyl-imidazo[1 ,2-a]pyridine; 3-(5-Benzylsulfanyl-4-methyl-4H-[1 ,2,4]triazol-3-yl)-2-methyl-imidazo[1 ,2-a]pyridine;
4-Butyl-5-(3-chloro-phenyl)-4H-[1 ,2,4]triazole-3-thioI;
4-Allyl-5-(3-chloro-phenyl)-4H-[1,2,4]triazole-3-thiol;
N-(5-{2-[5-(4-Methoxy-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl]-2-oxo-ethylsulfanyl}-4- methyl-4H-[1,2,4]triazoI-3-ylmethyl)-benzamide; N-(5-{2-[3,5-Bis-(4-methoxy-phenyl)-4,5-dihydro-pyrazol-1-yl]-2-oxo-ethylsulfanyl}-4-methyl-
4H-[1 ,2,4]triazol-3-ylmethyl)-3-methoxy-benzamide;
N-(5-{2-[5-(4-Methoxy-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl]-2-oxo-ethylsulfanyl}-4- methyl-4H-[1,2,4]triazol-3-ylmethyl)-4-(pyrrolidine-1-sulfonyI)-benzamide;
N-(5-{2-[5-(4-Methoxy-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl]-2-oxo-ethylsulfanyl}-4- methyl-4H-[1 ,2,4]triazol-3-ylmethyl)-4-(piperidine-1 -sulfonyl)-benzamide; N-(5-{2-[5-(4-Methoxy-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl]-2-oxo-ethylsulfanyl}-4- methyl-4H-[1,2,4]triazol-3-ylmethyl)-4-(morpholine-4-sulfonyI)-benzamide;
4-Benzyl-3-(4-fluoro-naphthalen-1-ylmethylsulfanyl)-5-phenyI-4H-[1,2,4]triazole;
2-[4-AIIyl-5-(4-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1 -naphthalen-1 -yl-ethanone; 1 -(4-Fluoro-phenyl)-4-(4-methyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-butan-1 -one
2-(4-Methyl-5-phenyI-4H-[1,2,4]triazol-3-ylsulfanyl)-1-(5,6,7,8-tetrahydro-naphthalen-2-yl)- ethanone;
5-(2-Carbazol-9-yl-ethyl)-4-(2-methyl-allyl)-4H-[1,2,4]triazole-3-thiol;
1-(4-Methoxy-phenyl)-2-[4-(2-methyl-allyl)-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-ethanone; 2-{2-[4-Allyl-5-(3-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetylamino}-benzoic acid methyl ester;
5-(2,4-Dichloro-phenyl)-4-(2-methyl-allyl)-4H-[1,2,4]triazole-3-thiol;
4-Allyl-3-(4-methoxy-benzylsulfanyl)-5-(3-methoxy-phenyl)-4H-[1,2,4]triazole;
2-[4-AllyI-5-(3-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-1-(9H-fiuoren-2-yi)-ethanone; 3-(4-Methoxy-benzylsulfanyl)-4-methyl-5-phenyl-4H-[1,2,4]triazole;
2-[4-AllyI-5-(3-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1-(4-ethyl-phenyl)-ethanone;
2-(4-Allyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyI)-N-(4-chloro-phenyl)-acetamide;
2-[4-Allyl-5-(4-tert-butyl-phenyl)-4H-[1,2,4]triazoI-3-ylsulfanyl]-1-(4-chloro-phenyl)-ethanone;
2-(4-Allyl-5-phenylaminomethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2,4-difluoro-phenyl)- acetamide;
2-(4-Allyl-5-phenoxymethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1-(4-methoxy-phenyl)-ethanone;
2-(4-AIIyl-5-phenoxymethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1-(4-bromo-phenyl)-ethanone;
(4-Allyl-5-benzylsulfanyl-4H-[1,2,4]triazol-3-ylmethyl)-phenyl-amine;
2-(4-Allyl-5-benzotriazol-1 -ylmethyl-4H-[1 ,2,4]triazol-3-yIsulfanyl)-1 -(4-methoxy-phenyl)- ethanone;
2-(4-Allyl-5-phenylaminomethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-chloro-phenyI)-acetamide;
1-(4-Methoxy-phenyl)-2-[4-(2-methyl-allyl)-5-phenyl-4H-[1,2,4]triazol-3-yIsulfanyl]-ethanone;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(4-methyl-3-nitro-phenyl)- acetamide; [5-(2-Methoxy-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-acetic acid isopropyl ester;
N-(4-Chloro-phenyl)-2-[4-ethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetamide;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-methoxy-phenyl)- acetamide;
N-(3-Cyano-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-2-[4-ethyl-5-(2-methoxy-phenyl)-4H- [1 ,2,4]triazol-3-ylsulfanyl]-acetamide;
N-(4-Acetyl-phenyl)-2-[4-ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-acetamide; 4-[5-(2,6-Dichloro-benzylsulfanyl)-4-furan-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-pyridine;
N-(4-Methyl-3-nitro-phenyl)-2-[4-methyl-5-(3,4,5-trimethoxy-phenyl)-4H-[1,2,4]triazol-3- ylsulfanyl]-acetamide;
N-(3-Cyano-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-2-(4-furan-2-ylmethyl-5-pyridin-4-yl-4H- [1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
2-[2-(4-EthyI-5-m-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetyIamino]-benzoic acid methyl ester;
2-(4-MethyI-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-thiazol-2-yl-acetamide;
N-(4-Chloro-phenyl)-2-(4-ethyl-5-m-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(4-Ethoxy-phenyl)-2-(4-ethyl-5-m-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide; 2-(4-Ethyl-5-m-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(2-nitro-phenyl)-acetamide;
2-(5-Benzyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-bromo-phenyl)-acetamide;
2-{5-[(2,6-Dimethyl-phenylamino)-methyl]-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl}-1-phenyl- ethanone;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-fluoro-phenyl)-acetamide; 2-[4-Ethyl-5-(4-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1 -(4-methoxy-phenyl)- ethanone;
N-(4-lodo-2-methyl-phenyl)-2-[5-(2-methoxy-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]- acetamide;
2-(5-BenzyI-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-(3,4-dihydro-2H-quinolin-1-yl)-ethanone; N-(2-Bromo-4-methyl-phenyl)-2-(4-furan-2-ylmethyI-5-pyridin-4-yl-4H-[1,2,4]triazol-3- ylsulfanyl)-acetamide;
N-(4-Chloro-phenyl)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(3-trifluoromethyl-phenyl)- acetamide; 2-[5-[(4-Fluoro-phenylamino)-methyl]-4-(tetrahydro-furan-2-ylmethyl)-4H-[1,2,4]triazol-3- ylsulfanyl]-1 -p-tolyl-ethanone;
2-(5-Methyl-4-phenethyI-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-naphthalen-1-yl-acetamide;
N-(5-Ethyl-[1,3,4]thiadiazol-2-yl)-2-(5-methyl-4-phenethyl-4H-[1,2,4]triazol-3-ylsulfanyl)- acetamide; 2-(5-Methyl-4-phenethyl-4H-[1 ,2,4]triazol-3-ylsulfanyi)-N-phenyI-acetamide;
[5-(4-Bromo-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-acetic acid cyclohexyl ester;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(3-chloro-phenyl)-acetamide;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-chloro-phenyl)-acetamide;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-m-tolyl-acetamide; N-(3-Cyano-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-2-[5-(4-hydroxy-phenyl)-4-methyl-4H-
[1,2,4]triazoI-3-ylsulfanyl]-acetamide; 2-(5-Benzyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(2-methyl-4-nitro-phenyl)-acetamide;
3-Benzylsulfanyl-4-methyl-5-phenyl-4H-[1 ,2,4]triazoIe;
3-Butylsulfanyl-5-(4-methoxy-phenyl)-4-methyl-4H-[1 ,2,4]triazole;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(4-ethoxy-phenyl)-acetamide; N-(4-Acetyl-phenyl)-2-(4-benzyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(2,4-dimethyl-phenyl)-acetamide;
N-(3-Nitro-phenyl)-2-(4-phenethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(4-Phenethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-phenyl-acetamide;
N-Naphthalen-1-yl-2-(4-phenethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide; (4-Benzyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetic acid cyclohexyl ester;
1-(3,4-Dihydro-2H-quinolin-1-yl)-2-(4-ethyI-5-phenyl-4H-[1 ,2,4]triazoI-3-ylsulfanyl)-ethanone;
N-(3-Cyano-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-2-(4-ethyl-5-phenyl-4H-[1 ,2,4]triazol-3- ylsulfanyl)-acetamide;
2-[5-(4-Methoxy-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1-phenyl-ethanone; 3-Benzylsulfanyl-5-(4-methoxy-phenyl)-4-methyI-4H-[1 ,2,4]triazole;
2-(4,5-Dibenzyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-thiazol-2-yl-acetamide;
2-(4-Phenethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-m-tolyl-acetamide;
2-(4-Phenethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-phenyl-propionamide;
3-(5-Benzylsulfanyl-4-phenethyl-4H-[1 ,2,4]triazol-3-yl)-pyridine; (4-Phenethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetic acid ethyl ester;
2-(4-Phenethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1-phenyl-ethanone;
2-(4-Phenethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-yIsulfanyl)-N-p-tolyI-propionamide;
1-(3,4-Dihydro-2H-quinolin-1-yl)-2-{4-ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1 ,2,4]triazol-
3-ylsulfanyl}-ethanone; 2-[5-(3,4-Dimethoxy-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsuIfanyl]-1 -p-tolyl-ethanone;
N-(3-Chloro-2-methyl-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(4-Ethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N,N-diphenyl-propionamide;
2-(5-Cyclohexyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(2-nitro-phenyl)-acetamide;
2-(5-Cyclohexyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(4-methyl-3-nitro-phenyl)-acetamide; N-(2-Bromo-4-methyl-phenyl)-2-(4-ethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)- acetamide;
1-(3,4-Dihydro-2H-quinolin-1-yl)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsuIfanyl)- ethanone;
N-(4-Fluoro-phenyl)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide; N-(4-Acetyl-phenyl)-2-(5-benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(5-Benzyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(2-chloro-phenyl)-acetamide; N-(3-Chloro-2-methyI-phenyl)-2-[4-ethyI-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]- acetamide;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-methyl-4-nitro-phenyl)- acetamide; 2-[5-(2-Methoxy-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-p-tolyl-propionamide;
[4-Ethyl-5-(2-methoxy-phenyI)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-acetic acid ethyl ester;
2-(4-MethyI-5-o-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3-nitro-phenyl)-acetamide;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-naphthalen-1-yl- propionamide; 2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-p-toIyl-propionamide;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-phenyl-propionamide;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(4-phenyl-thiazol-2-yl)- acetamide;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-p-tolyl-acetamide; N-(3-Chloro-4-methyl-phenyl)-2-[4-ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]- acetamide;
2-[5-(4-Hydroxy-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-nitro-phenyl)-acetamide;
4-{2-[5-(2-Bromo-phenyl)-4-methyI-4H-[1,2,4]triazol-3-ylsulfanyl]-acetylamino}-benzoic acid ethyl ester; 2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-o-toIyI-acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-chIoro-phenyl)-acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-methoxy-2-nitro-phenyl)- acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-methyI-4-nitro-phenyl)- acetamide;
1-(3,4-Dihydro-2H-quinolin-1-yl)-2-{5-[(2,4-dimethyl-phenylamino)-methyl]-4-ethyl-4H-
[1 ,2,4]triazol-3-ylsulfanyl}-ethanone;
N-(4-Chloro-3-nitro-phenyl)-2-[5-(4-chIoro-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl]- acetamide; 2-[5-(2-Bromo-phenyl)-4-ethyI-4H-[1,2,4]triazol-3-ylsulfanyl]-1-(3,4-dihydro-2H-quinolin-1-yl)- ethanone;
2-(5-Benzyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1 -p-tolyl-ethanone;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-methoxy-phenyl)-acetamide;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-chloro-phenyl)-acetamide; 2-(4-Benzyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)- acetamide; 4-{2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-acetylamino}-benzoic acid methyl ester;
2-(5-Benzyl-4-methyl-4H-[1,2,4]triazol-3-yIsulfanyl)-N-(2-nitro-phenyl)-acetamide;
2-(5-Benzyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3-cyano-4,5,6,7-tetrahydro- benzo[b]thiophen-2-yl)-acetamide;
2-[5-(4-Chloro-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-nitro-phenyl)-acetamide;
(5-BenzyIsulfanyl-4-ethyI-4H-[1,2,4]triazol-3-ylmethyl)-(4-chloro-phenyl)-amine;
N-(2-Methoxy-phenyl)-2-[5-(2-methoxy-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsuIfanyl]- acetamide; 2-(4-Allyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsuIfanyl)-N-(3,4-dichloro-phenyl)-acetamide;
2-(5-Benzyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-p-tolyl-acetamide;
2-(5-Benzyl-4-methyl-4H-[1,2,4]triazol-3-ylsuIfanyl)-N-(4-chloro-phenyl)-acetamide;
2-(5-Benzyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(4-methoxy-phenyl)-acetamide;
N-(5-Chloro-2-methyl-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1 ,2,4]triazol-3-ylsuIfanyl)-acetamide; N-(4-Methoxy-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(2,4-Dimethyl-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(4-Ethoxy-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1,2,4]triazoI-3-ylsulfanyI)-acetamide;
4-[2-(4-Methyl-5-o-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetylamino]-benzoic acid methyl ester;
N-(4-Chloro-phenyl)-2-(4-methyI-5-o-tolyI-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide; 2-[5-(4-Hydroxy-phenyl)-4-methyI-4H-[1,2,4]triazol-3-ylsuIfanyl]-N-(4-phenyl-thiazol-2-yl)- acetamide;
2-(5-Benzyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-bromo-4-methyl-phenyl)-acetamide;
2-(5-Benzyl-4-methyl-4H-[1,2,4]triazol-3-ylsuIfanyl)-1-phenyl-ethanone;
2-(5-Benzyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(4-nitro-phenyl)-acetamide; 2-(5-Cyclohexyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyI)-N-p-tolyl-acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-ethoxy-phenyl)-acetamide;
2-(5-Cyclohexyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-naphthalen-1-yl-acetamide;
4-[5-(4-tert-Butyl-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-pyridine;
4-[5-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-pyridine; 2-(5-CycIohexyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-methyl-4-nitro-phenyl)-acetamide;
2-(5-Cyclohexyl-4-ethyl-4H-[1 ,2,4]triazoI-3-ylsulfanyI)-N-(3-trifluoromethyl-phenyl)-acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-fluoro-phenyl)-acetamide;
4-{2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-acetylamino}-benzoic acid methyl ester; N-(3-Chloro-phenyl)-2-(5-cyclohexyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(5-CyclohexyI-4-ethyl-4H-[1,2,4]triazol-3-ylsuIfanyl)-N-(4-ethoxy-phenyl)-acetamide; 2-{5-[(4-Chloro-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-N-(2-nitro-phenyl)- acetamide;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3-chloro-2-methyI-phenyl)-acetamide;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-phenyl-acetamide; 3-Benzyl-5-(2-chloro-6-fluoro-benzylsulfanyl)-4-methyl-4H-[1,2,4]triazole;
2-(5-Cyclohexyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(4-nitro-phenyl)-acetamide;
2-[5-(4-Hydroxy-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1-phenyl-ethanone;
4-[5-(4-Chloro-benzylsulfanyl)-4-methyl-4H-[1,2,4]triazol-3-yl]-phenol;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-fluoro-phenyl)-acetamide; 2-(5-Cyclohexyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1-(4-methoxy-phenyl)-ethanone;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-bromo-phenyl)-acetamide;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-phenyl-acetamide;
2-(5-Cyclohexyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(4-nitro-phenyl)-propionamide;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazoI-3-ylsulfanyl)-N-(2-trifluoromethyl-phenyl)-acetamide; {5-[(3-Chloro-4-methyl-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-acetic acid cyclohexyl ester;
3-[5-(2,4-Dichloro-benzylsulfanyl)-4-methyI-4H-[1,2,4]triazol-3-yl]-pyridine;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsuIfanyl]-N-phenyl-acetamide;
N-(3-Chloro-4-methyl-phenyl)-2-[5-(4-hydroxy-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]- acetamide;
N-(4-Chloro-phenyl)-2-[5-(4-hydroxy-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]- acetamide;
3-Benzyl-5-(4-chloro-benzylsulfanyl)-4-methyI-4H-[1,2,4]triazoIe;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-nitro-phenyl)-acetamide; N-(4-Ethoxy-phenyl)-2-[5-(4-hydroxy-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]- acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-methoxy-phenyl)- acetamide;
{5-[(4-Chloro-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-acetic acid cyclohexyl ester;
3-Benzylsulfanyl-5-(2-methoxy-phenyl)-4-methyl-4H-[1,2,4]triazole;
N-(2-Chloro-phenyl)-2-(4-methyl-5-m-tolyl-4H-[1,2,4]triazoI-3-ylsulfanyl)-acetamide;
N-(2-Methoxy-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(5-Cyclohexyl-4-ethyI-4H-[1,2,4]triazol-3-ylsulfanyl)-N-phenyI-acetamide; 2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(3-nitro-phenyl)-acetamide; 2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsuIfanyl]-1-(3,4-dihydro-2H-quinolin-1-yl)- ethanone;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-bromo-4-methyl-phenyl)-acetamide;
N-(2-Chloro-phenyl)-2-[5-(2-methoxy-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]- acetamide;
(5-Benzylsulfanyl-4-ethyl-4H-[1,2,4]triazol-3-ylmethyl)-(3-trifluoromethyl-phenyl)-amine;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-1-(4-methoxy-phenyl)-ethanone;
[4-Allyl-5-(3-bromo-benzyIsulfanyl)-4H-[1,2,4]triazol-3-ylmethyl]-phenyl-amine;
2-(4-Furan-2-yImethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-(3-nitro-phenyl)-ethanone; 1-(4-Bromo-phenyl)-2-(4-furan-2-ylmethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)- ethanone;
4-{5-[2-(2-Methoxy-phenoxy)-ethylsulfanyl]-4-methyl-4H-[1,2,4]triazol-3-yl}-phenylamine;
4-[5-(4-Chloro-benzylsulfanyl)-4-methyl-4H-[1 ,2,4]triazol-3-yl]-phenylamine;
[4-Allyl-5-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-ylmethyl)-4H-[1,2,4]triazol-3-yIsulfanyl]- acetic acid ethyl ester;
2-{4-Allyl-5-[(4-chloro-phenylamino)-methyl]-4H-[1,2,4]triazol-3-ylsulfanyl}-1-phenyl-ethanone;
5-(3-Bromo-phenyl)-4-(2-methyl-allyl)-4H-[1 ,2,4]triazole-3-thiol;
2-(4-Allyl-5-benzotriazol-1-ylmethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-chloro-phenyl)- acetamide; 1-(4-Fluoro-phenyl)-2-(4-methyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyI)-ethanone;
8-(4-Methyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-5-nitro-quinoline;
3-(2-Bromo-benzylsulfanyl)-4-methyl-5-(4-nitro-phenyl)-4H-[1,2,4]triazole;
2-[4-Allyl-5-(3-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-1-(2,4-dimethyl-phenyl)- ethanone; 1 -(4-Bromo-phenyl)-2-(5-furan-2-yl-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-ethanone;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(5-methyl-thiazol-2-yl)- acetamide;
2-[4-Ethyl-5-(p-tolylamino-methyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-1-p-tolyl-ethanone;
2-(5-Benzyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(4-ethyl-phenyl)-acetamide; 2-(5-Benzyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsuIfanyl)-1 -(4-methoxy-phenyl)-ethanone;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-1 -p-tolyl-ethanone;
3-(2-Bromo-phenyl)-4-methyl-5-(4-nitro-benzylsulfanyl)-4H-[1,2,4]triazole;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-phenyl-thiazol-2-yl)- acetamide; 2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2,4-dimethyl-phenyl)- acetamide;
N-(4-Bromo-phenyl)-2-[5-(2-bromo-phenyI)-4-ethyl-4H-[1,2,4]triazoI-3-ylsulfanyl]-acetamide;
2-{5-[(2,4-Dimethyl-phenyIamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-1-(4-methoxy- phenyl)-ethanone;
2-{5-[(2,4-Dimethyl-phenyIamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-1-p-tolyl- ethanone;
{5-[(2,4-Dimethyl-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-acetic acid cyclohexyl ester; 2-{5-[(4-Fluoro-phenylamino)-methyl]-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl}-1 -phenyl- ethanone;
2-{4-Ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1,2,4]triazol-3-ylsulfanyl}-1-(4-methoxy- phenyl)-ethanone;
[4-Ethyl-5-(4-methyl-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-ylmethyl]-(4-fluoro-phenyl)-amine; (5-Benzylsulfanyl-4-ethyl-4H-[1,2,4]triazol-3-ylmethyl)-(4-fluoro-phenyl)-amine;
{4-Ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1,2,4]triazol-3-ylsulfanyl}-acetic acid cyclohexyl ester;
N-(4-Chloro-phenyl)-2-[4-ethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetamide;
N-(4-Acetyl-phenyl)-2-(5-cyclohexyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide; 2-[4-Ethyl-5-(4-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(4-methyl-3-nitro-phenyl)- acetamide;
N-CyclohexyI-2-(4-phenethyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(2,4-Dimethyl-phenyl)-2-[4-furan-2-ylmethyl-5-(4-hydroxy-phenyI)-4H-[1,2,4]triazol-3- ylsulfanylj-acetamide; 4-[2-(5-Cyclohexyl-4-methyI-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetylamino]-benzoic acid ethyl ester;
2-[4-Furan-2-ylmethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-methyl-3-nitro- phenyl)-acetamide;
3-lsobutylsulfanyl-4-methyl-5-p-tolyl-4H-[1,2,4]triazole; 2-[2-(4-Methyl-5-m-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyI)-acetylamino]-benzoic acid methyl ester;
2-{4-Ethyl-5-[4-(morpholine-4-sulfonyl)-phenyl]-4H-[1 ,2,4]triazol-3-ylsulfanyl}-1-p-tolyl- ethanone;
4-MethyI-3-phenethylsulfanyl-5-p-tolyl-4H-[1,2,4]triazole;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-p-tolyl-acetamide; 2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-nitro-phenyl)-acetamide;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-phenyl-acetamide; 2-(4-Benzyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(3-chloro-phenyl)-acetamide;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(4-nitro-phenyl)-propionamide;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(2,5-dichloro-phenyl)-acetamide;
N-(3-Chloro-phenyl)-2-(4-phenethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide; N-(4-Nitro-phenyl)-2-(4-phenethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-propionamide;
N-(2-Bromo-4-methyl-phenyI)-2-[5-(3,4-dimethoxy-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3- ylsulfanyl]-acetamide;
2-{4-Ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1 ,2,4]triazol-3-ylsulfanyl}-N-(4-nitro-phenyl)- acetamide; 3-Benzylsulfanyl-5-cyclohexyl-4-ethyl-4H-[1 ,2,4]triazole;
[5-(4-Hydroxy-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyI]-acetic acid cyclohexyl ester;
2-(5-Cyclohexyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(5-ethyl-[1 ,3,4]thiadiazol-2-yl)- acetamide;
N-(3-Chloro-4-methyl-phenyl)-2-[4-ethyI-5-(4-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]- acetamide;
[4-Benzyl-5-(4-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-acetic acid ethyl ester;
3-Benzylsulfanyl-4-methyI-5-(3,4,5-trimethoxy-phenyl)-4H-[1 ,2,4]triazole;
N-(2-Chloro-phenyl)-2-[4-ethyl-5-(4-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-acetamide;
N-(2,4-Dimethoxy-phenyl)-2-(4-methyl-5-o-tolyI-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide; 2-(5-Cyclohexyl-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(2-methyl-4-nitro-phenyl)- acetamide;
2-(5-CyclohexyI-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1-phenyl-ethanone;
3-Cyclohexyl-4-methyl-5-(4-methyl-benzylsulfanyl)-4H-[1 ,2,4]triazole;
N-(2-Bromo-phenyl)-2-(5-cyclohexyl-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide; 2-(5-Cyclohexyl-4-methyI-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(4-iodo-2-methyl-phenyl)-acetamide;
N-(3-Cyano-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-2-(5-cyclohexyl-4-methyI-4H-
[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(4-Acetyl-phenyl)-2-(5-cyclohexyl-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(5-Cyclohexyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-methoxy-phenyl)-acetamide; N-(4-Chloro-phenyl)-2-(5-cyclohexyl-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(5-Cyclohexyl-4-methyl-4H-[1 ,2,4]triazol-3-ylsuIfanyl)-N-phenyl-acetamide;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(2-methoxy-4-nitro-phenyl)- acetamide;
N-(3-Cyano-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-2-[5-(2-methoxy-phenyl)-4-methyl-4H- [1 ,2,4]triazol-3-ylsulfanyl]-acetamide;
N-(4-Bromo-phenyl)-2-(5-cyclohexyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyI)-acetamide; 2-[4-EthyI-5-(4-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-phenyI-acetamide;
N-(3-Chloro-phenyI)-2-[4-ethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetamide;
N-(4-Acetyl-phenyl)-2-[4-ethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetamide;
N-(4-Bromo-phenyl)-2-[4-ethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetamide; 2-[4-Ethyl-5-(4-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(4-iodo-2-methyl-phenyI)- acetamide;
N-(2,4-Dimethyl-phenyl)-2-[4-ethyI-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]- acetamide;
4-[5-(4-Chloro-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazol-3-yl]-phenol; [4-Ethyl-5-(4-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-yIsulfanyl]-acetic acid cyclohexyl ester;
2-[5-(2-Methoxy-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(4-phenyl-thiazol-2-yl)- acetamide;
N-(3-Chloro-phenyl)-2-[4-ethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-nitro-phenyI)-acetamide; 2-[4-Methyl-5-(4-nitro-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1 -phenyl-ethanone;
N-(4-Bromo-phenyl)-2-{4-ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1,2,4]triazol-3- ylsulfanylj-acetamide;
N-(4-Chloro-phenyl)-2-{4-ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1,2,4]triazol-3- ylsuϊfanylj-acetamide; 2-{4-Ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1 ,2,4]triazol-3-ylsulfanyl}-N-(2-nitro-phenyI)- acetamide;
1-(4-Methoxy-phenyl)-2-[4-methyl-5-(4-nitro-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-ethanone;
[5-(4-Chloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-ylmethyl]-(4-fluoro-phenyl)-amine;
2-{4-Ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1,2,4]triazol-3-ylsulfanyl}-1-p-tolyl-ethanone; 2-{4-Ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1,2,4]triazol-3-ylsulfanyl}-N-(4-methyl-3-nitro- phenyl)-acetamide;
N-(2-Bromo-4-methyl-phenyl)-2-{4-ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1 ,2,4]triazol-3- ylsulfanylj-acetamide;
4-Allyl-5-(3-bromo-phenyl)-4H-[1,2,4]triazole-3-thiol; N-(2-Nitro-phenyl)-2-(4-phenethyl-5-pyridin-3-yI-4H-[1,2,4]triazol-3-yIsulfanyl)-acetamide;
2-{4-Ethyl-5-[4-(piperidine-1-sulfonyl)-phenyl]-4H-[1,2,4]triazol-3-ylsulfanyl}-1-p-tolyl-ethanone;
2-{4-Ethyl-5-[4-(piperidine-1-sulfonyl)-phenyl]-4H-[1,2,4]triazol-3-ylsulfanyl}-1 -phenyl- ethanone;
N-Biphenyl-2-yl-2-(4-ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide; 2-(4-BenzyI-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(3-chloro-4-methyl-phenyl)- acetamide; N-(2-Bromo-phenyl)-2-(4-ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
4-Benzyl-5-cyclohexyl-4H-[1,2,4]triazole-3-thiol;
2-(5-Cyclohexyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1-phenyl-ethanone;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-1-phenyl-ethanone; (5-Benzyl-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetic acid cyclohexyl ester;
4-Methyl-3-(4-nitro-benzylsulfanyl)-5-phenyl-4H-[1,2,4]triazole;
2-(4-Methyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-p-tolyI-ethanone;
2-(4-Methyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-phenyl-ethanone;
3-Benzylsulfanyl-4-methyl-5-(naphthalen-2-yloxymethyl)-4H-[1,2,4]triazole; 2-(5-Cyclohexyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-p-tolyl-acetamide;
3-Benzylsulfanyl-5-cyclohexyl-4-methyl-4H-[1,2,4]triazole;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-chloro-3-nitro-phenyl)-acetamide;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-methyl-3-nitro-phenyl)-acetamide;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-methoxy-4-nitro-phenyl)-acetamide; N-(2-Bromo-4-methyl-phenyl)-2-(4-methyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
3-BenzylsuIfanyl-4-ethyl-5-(4-nitro-phenyl)-4H-[1,2,4]triazole;
4-Ethyl-3-(4-methyl-benzylsulfanyl)-5-(4-nitro-phenyl)-4H-[1,2,4]triazole;
2-[4-Ethyl-5-(4-nitro-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-1-p-toIyl-ethanone;
3-(4-Chloro-benzylsulfanyl)-4-ethyl-5-(4-nitro-phenyl)-4H-[1,2,4]triazole; 2-[4-Ethyl-5-(4-nitro-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1 -phenyl-ethanone;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(3,4-dimethyl-phenyl)- acetamide;
(2,4-Dimethyl-phenyl)-[4-ethyl-5-(4-nitro-benzylsuIfanyl)-4H-[1,2,4]triazol-3-ylmethyl]-amine
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-methyl-3-nitro-phenyl)- acetamide;
2-(4-Methyl-5-o-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-trifluoromethyl-phenyl)-acetamide;
2-[5-[(2,4-Dimethyl-phenylamino)-methyl]-4-(tetrahydro-furan-2-ylmethyl)-4H-[1,2,4]triazol-3- ylsulfanyl]-1 -p-tolyl-ethanone;
4-[5-(2,6-Dichloro-benzylsulfanyl)-4-(tetrahydro-furan-2-ylmethyl)-4H-[1,2,4]triazol-3-yl]- pyridine;
3-Benzylsulfanyl-5-(4-chloro-phenoxymethyl)-4-ethyl-4H-[1,2,4]triazoIe;
3-Butylsulfanyl-4-methyl-5-p-tolyl-4H-[1 ,2,4]triazole;
1-(5-Chloro-2-methoxy-phenyl)-2-(4-methyl-5-p-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-ethanone;
1-(4-Chloro-phenyl)-2-(4-methyl-5-p-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-ethanone; N-(2,4-Dimethoxy-phenyl)-2-(4-ethyl-5-phenyl-4H-[1,2,4]triazoI-3-ylsulfanyl)-acetamide;
2-(4-Ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyI)-N-(2-methyl-4-nitro-phenyl)-acetamide; N-(4-Ethoxy-phenyl)-2-(4-ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyI)-acetamide;
N-(4-Ethyl-phenyl)-2-(4-ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyI)-acetamide;
2-(4-Ethyl-5-phenyI-4H-[1,2,4]triazol-3-ylsulfanyl)-N-thiazol-2-yl-acetamide;
2-(4-Ethyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1 -phenyl-ethanone; 2-(4-Ethyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1 -p-tolyl-ethanone;
2-(4-Ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-nitro-phenyl)-acetamide;
N-(3-Chloro-phenyl)-2-(4-ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(2-Chloro-phenyl)-2-(4-ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
2-[5-(2-Hydroxy-phenyl)-4-phenethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-1-piperidin-1-yl-ethanone; 2-[5-(2-Morpholin-4-yI-ethylsulfanyl)-4-phenethyl-4H-[1,2,4]triazol-3-yl]-phenol;
N-(2-Methyl-4-nitro-phenyl)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)- acetamide;
N-(2-Methyl-5-nitro-phenyl)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)- acetamide; N-(4-Bromo-phenyl)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(3-Nitro-phenyl)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(4-Ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-fluoro-phenyl)-acetamide;
2-(4-Ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-methoxy-4-nitro-phenyl)-acetamide;
N-(2,5-Dichloro-phenyl)-2-[4-ethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]- acetamide;
2-(5-Cyclohexyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3-nitro-phenyl)-acetamide;
2-[4-Benzyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-methyl-4-nitro-phenyl)- acetamide;
2-(4-Phenethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3-trifluoromethyl-phenyl)- acetamide;
[4-Furan-2-ylmethyI-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetic acid cyclohexyl ester;
2-[4-Furan-2-ylmethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazoI-3-ylsulfanyl]-1-phenyl-ethanone;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(2-ethyl-phenyl)-acetamide; 2-(5-Cyclohexyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3,4-dichloro-phenyl)-acetamide;
2-(5-Cyclohexyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-(4-methoxy-phenyl)-ethanone;
2-(4-Benzyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-methoxy-2-nitro-phenyl)-acetamide;
2-(4-BenzyI-5-phenyI-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(5-methyl-thiazol-2-yl)-acetamide;
2-(4-Benzyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-thiazol-2-yl-acetamide; 2-(4,5-Dibenzyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-nitro-phenyl)-acetamide;
2-(4-Benzyl-5-phenyl-4H-[1,2,4]triazoI-3-ylsulfanyl)-N-(2-nitro-phenyl)-acetamide; 3-Benzylsulfanyl-5-(4-bromo-phenyl)-4-methyl-4H-[1,2,4]triazole;
2-[4-Ethyl-5-(4-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsuIfanyl]-N-(4-methyl-3-nitro-phenyl)- acetamide;
2-[4-Ethyl-5-(4-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-yIsulfanyl]-1 -phenyl-ethanone; 2-(4-Benzyl-5-methyl-4H-[1 ,2,4]triazoI-3-ylsulfanyl)-1 -phenyl-ethanone;
2-(5-Methyl-4-phenethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-p-tolyl-acetamide;
2-(5-Methyl-4-phenethyl-4H-[1,2,4]triazol-3-ylsulfanyI)-N-(3-trifluoromethyl-phenyl)-acetamide;
N-(3-Chloro-phenyl)-2-(5-methyl-4-phenethyl-4H-[1,2,4]triazol-3-ylsuIfanyl)-acetamide;
N-(4-Chloro-phenyl)-2-(5-methyl-4-phenethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide; 2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-methoxy-4-nitro-phenyl)- acetamide;
2-(5-CycIohexyl-4-ethyl-4H-[1,2,4]triazoI-3-ylsulfanyl)-N-(3-nitro-phenyl)-acetamide;
N-(2,3-Dichloro-phenyl)-2-[4-ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]- acetamide; N-(2,3-Dichloro-phenyl)-2-[4-ethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]- acetamide;
2-[4-Ethyl-5-(2-methoxy-phenyI)-4H-[1,2,4]triazoI-3-ylsulfanyl]-1-(4-methoxy-phenyl)- ethanone;
2-[4-Benzyl-5-(2-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1 -piperidin-1 -yl-ethanone; 2-[4-Benzyl-5-(2-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-p-tolyl-acetamide;
2-{5-[(2,4-Dimethyl-phenyIamino)-methyl]-4-furan-2-ylmethyl-4H-[1,2,4]triazol-3-ylsuIfanyl}-1- phenyl-ethanone;
2-(4-Methyl-5-m-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-p-tolyl-acetamide;
4-{4-Ethyl-5-[4-(piperidine-1-sulfonyl)-phenyl]-4H-[1,2,4]triazoI-3-ylsulfanylmethyl}-benzonitrile; N-(2-Methoxy-phenyl)-2-(4-methyl-5-m-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(4-Acetyl-phenyl)-2-(4-ethyl-5-m-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(4-Ethyl-5-m-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-methyl-3-nitro-phenyl)-acetamide;
2-[5-(4-Amino-phenyl)-4-methyl-4H-[1,2,4]triazol-3-yIsuIfanyl]-1-(4-nitro-phenyl)-ethanone;
N-{4-[5-(2-Chloro-benzylsulfanyl)-4-methyl-4H-[1 ,2,4]triazol-3-yl]-phenyl}-2-methoxy- benzamide;
2-(4-AIIyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyI)-1-(4-fluoro-phenyl)-ethanone;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(4-fluoro-phenyl)-acetamide;
2-[5-(4-Amino-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-1-(4-nitro-phenyl)-ethanone;
2-(4-Allyl-5-thiophen-2-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-chloro-phenyl)-acetamide; (4-Benzyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyI)-acetic acid ethyl ester;
4-[5-(4-tert-Butyl-benzylsulfanyl)-4-methyl-4H-[1,2,4]triazol-3-yl]-pyridine; 2-{5-[(3-Chloro-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-1-phenyl- ethanone;
{5-[(2-Chloro-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-acetic acid isopropyl ester; 2-[4-Ethyl-5-(4-methoxy-phenoxymethyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1 -phenyl-ethanone;
1-(4-Chloro-phenyl)-2-{5-[(2-chloro-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3- ylsulfanyl}-ethanone;
4-[5-(2-Chloro-6-fluoro-benzylsulfanyl)-4-methyl-4H-[1,2,4]triazol-3-yl]-pyridine;
3-Benzyl-5-benzylsulfanyl-4-ethyl-4H-[1,2,4]triazole; 3-Benzylsulfanyl-4-methyl-5-o-tolyl-4H-[1 ,2,4]triazole;
N-(4-Chloro-3-nitro-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(4-Methyl-5-o-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-p-tolyl-ethanone;
1-(4-Methoxy-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-ethanone;
[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-acetonitrile; [5-(2-Hydroxy-phenyl)-4-phenethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-acetonitrile;
1-[5-(2-Hydroxy-phenyl)-4-phenethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-propan-2-one;
N-(2,3-Dichloro-phenyl)-2-[4-furan-2-ylmethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3- ylsulfanyl]-acetamide;
N-(3-Chloro-phenyl)-2-[4-furan-2-ylmethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]- acetamide;
N-(4-Chloro-phenyl)-2-[4-furan-2-ylmethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]- acetamide;
2-[5-(4-Methoxy-phenoxymethyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1-phenyl-ethanone;
2-{5-[(2-Chloro-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-1-piperidin-1-yl- ethanone;
2-[5-(4-Methoxy-phenoxymethyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-1-(4-methoxy- phenyl)-ethanone;
N-(2,3-Dichloro-phenyl)-2-[4-furan-2-ylmethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3- ylsulfanyl]-acetamide; 2-[4-Furan-2-ylmethyl-5-(4-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1 -(4-methoxy- phenyl)-ethanone;
{5-[(2-Chloro-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-acetic acid cyclohexyl ester;
2-(4-Phenethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-thiazol-2-yl-acetamide; 2-(4-Ethyl-5-m-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-nitro-phenyl)-acetamide;
2-(4-Ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-methoxy-phenyI)-acetamide; 2-(4-Ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-trifluoromethyl-phenyl)-acetamide;
2-[4-Furan-2-ylmethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-methyl-4-nitro- phenyl)-acetamide;
N-(3-Chloro-2-methyl-phenyl)-2-[4-furan-2-ylmethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3- ylsulfanyl]-acetamide;
4-Allyl-5-m-tolyl-4H-[1,2,4]triazoIe-3-thiol;
4-(2-Methyl-allyl)-5-m-tolyl-4H-[1,2,4]triazole-3-thiol;
2-[4-Allyl-5-(3-bromo-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyI]-N-(4-ethyl-phenyl)-acetamide;
4-Allyl-3-(3-bromo-phenyl)-5-(2-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazole; 2-[4-AllyI-5-(3-bromo-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1 -biphenyl-4-yl-ethanone;
4-(2-Methyl-alIyl)-5-(3-nitro-phenyl)-4H-[1,2,4]triazole-3-thiol;
4-Allyl-5-(2-carbazol-9-yl-ethyl)-4H-[1,2,4]triazole-3-thiol;
5-(4-Bromo-phenyl)-4-(2-methyl-allyl)-4H-[1,2,4]triazole-3-thiol;
4-(2-MethyI-alIyl)-5-(3-methyl-2-nitro-phenyl)-4H-[1,2,4]triazole-3-thiol; 5-(4-Methoxy-phenyl)-4-(2-methyl-allyl)-4H-[1,2,4]triazole-3-thiol;
2-(4-Allyl-5-benzotriazol-1-yImethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-bromo-phenyl)- acetamide;
2-(4-Allyl-5-benzotriazol-1-ylmethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-pyridin-2-yl-acetamide;
{4-Allyl-5-[3-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl)-propyl]-4H-[1,2,4]triazol-3-ylsulfanyl}- acetic acid ethyl ester; and
4-Allyl-5-(4-phenyl-piperazin-1 -ylmethyl)-4H-[1 ,2,4]triazole-3-thioI; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
In another embodiment of the present invention said substituted 1 ,2,4-triazole, or a prodrug thereof, as a component of the combination therapy is selected from the group consisting of:
4-[2-(4-Ethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)ethyl]morpholine;
1-Benzothiazol-2-yl-2-(4-ethyl-5-phenyl-4/--[1,2,4]triazol-3-ylsulfanyl)-ethanone;
Λ/-Cyclohexyl-2-(4-ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-Λ/-methyl-acetamide; 2-(4-Ethyl-5-phenyl-4H-[1 ,2,4]triazoI-3-ylsuIfanyl)-1 -phenyl-ethanone;
2-(4-Ethyl-5-phenyl-4/- -[1,2,4]triazol-3-ylsulfanyl)-1-(4-methoxy-phenyl)-ethanone;
2-(4-Ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-pyridin-3-yl-ethanone;
2-(4-Ethyl-5-phenyl-4H-[1,2,4]triazoI-3-ylsuIfanyl)-1-(4-methanesulfonyI-phenyl)-ethanone;
2-(4-Phenethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1 -phenyl-ethanone; 1 -(4-Methoxy-phenyl)-2-(4-phenethyl-5-phenyl-4H-[1 ,2,4]triazol-3-yIsulfanyl)-ethanone;
2-(4-Phenethyl-5-phenyl-4 -/-[1,2,4]triazol-3-ylsulfanyl)-1-pyridin-3-yl-ethanone; 1-(4-Methanesulfonyl-phenyl)-2-(4-phenethyl-5-phenyl-4ry-[1,2,4]triazol-3-ylsulfanyl)- ethanone;
2-(4-Ethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1-phenyl-ethanone;
2-(4-Ethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1-(4-methoxy-phenyl)-ethanone; 2-(4-Ethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1 -pyridin-3-yl-ethanone;
2-(4-Ethyl-5.pyridin-4-yI-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1-(4-methanesulfonyl-phenyl)-ethanone;
2-(4-Phenethyl-5-pyridin-4-yl-4ry-[1 ,2,4]triazol-3-ylsulfanyl)-1-phenyl-ethanone;
1-(4-Methoxy-phenyl)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyI)-ethanone;
2-(4-PhenethyI-5-pyridin-4-yl-4 --[1 ,2,4]triazol-3-ylsulfanyl)-1-pyridin-3-yl-ethanone; 1-(4-Methanesulfonyl-phenyl)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)- ethanone;
2-(4-Ethyl-5-furan-2-yl-4/-/-[1,2,4]triazol-3-ylsulfanyl)-1-phenyl-ethanone;
2-(4-Ethyl-5-furan-2-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-(4-methoxy-phenyl)-ethanone;
2-(4-Ethyl-5-furan-2-yl-4/-/-[1,2,4]triazol-3-ylsulfanyl)-1-pyridin-3-yl-ethanone; 2-(4-Ethyl-5-furan-2-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-(4-methanesuIfonyl-phenyl)-ethanone;
2-(5-Furan-2-yl-4-phenethyl-4 -/-[1,2,4]triazol-3-ylsulfanyl)-1 -phenyl-ethanone;
2-(5-Furan-2-yl-4-phenethyl-4/-/-[1 ,2,4]triazol-3-ylsulfanyl)-1-(4-methoxy-phenyl)-ethanone;
2-(5-Furan-2-yl-4-phenethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1-pyridin-3-yl-ethanone;
2-(5-Furan-2-yl-4-phenethyl-4H-[1 ,2,4]triazol-3-ylsulfanyI)-1-(4-methanesulfonyl-phenyl)- ethanone;
1 -Adamantan-1 -yl-2-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-ethanone;
3-[5-(2-Chloro-benzylsulfanyl)-4-ethyl-4 .-[1 ,2,4]triazol-3-yl]-propan-1-ol;
4-[4-EthyI-5-(3-hydroxy-propyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyI]-benzonitrile;
3-[5-(6-Chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-4 - -[1,2,4]triazol-3-yl]-propan-1-ol; 3-[5-(3,4-Dichloro-benzyIsulfanyl)-4-ethyl-4H-[1 ,2,4]triazol-3-yl]-propan-1 -ol;
3-(5-CycIohexylmethylsulfanyl-4-ethyl-4H-[1 ,2,4]triazol-3-yl)-propan-1-ol;
3-[4-Ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4 -/-[1,2,4]triazoI-3-yl]-propan-1-ol;
3-(5-Benzylsulfanyl-4-ethyl-4H-[1,2,4]triazol-3-yl)-propan-1-ol;
3-[4-Ethyl-5-(4-methanesulfonyl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-propan-1-ol; 3-[4-Ethyl-5-(3-nitro-benzylsulfanyl)-4/-/-[1 ,2,4]triazol-3-yl]-propan-1 -ol;
3-[5-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-propan-1-ol;
3-[4-Ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4 --[1,2,4]triazol-3-yl]-propan-1-ol;
N-{4-[4-Ethyl-5-(3-hydroxy-propyI)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-acetamide;
3-[4-Ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4 -/-[1 ,2,4]triazol-3-yl]-propan-1-ol; 3-[4-Ethyl-5-(2-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-propan-1 -ol;
4-[4-Ethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyImethyl]-benzonitrile; 4-[5-(6-Chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-4/--[1,2,4]triazol-3-yl]-phenol;
4-[5-(4-Bromo-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-phenol;
4-[4-Ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol;
4-(5-Benzylsulfanyl-4-ethyl-4 -/-[1,2,4]triazol-3-yl)-phenol; 4-[4-Ethyl-5-(4-methanesulfonyI-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol;
4-[4-Ethyl-5-(3-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol;
4-[4-Ethyl-5-(4-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser;
4-[5-(4-Benzyloxy-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-phenol;
N-{4-[4-Ethyl-5-(4-hydroxy-phenyl)-4 --[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-acetamide; 4-[4-Ethyl-5-(4-methoxy-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol;
4-[4-EthyI-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-phenol;
4-[4-EthyI-5-(2-nitro-benzyIsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol;
4-[5-(2,4-DichIoro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-phenol;
3-Benzo[1,3]dioxol-5-yl-5-(2-chloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazole; 4-(5-Benzo[1 ,3]dioxol-5-yl-4-ethyl-4/--[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile;
3-Benzo[1,3]dioxol-5-yI-5-(6-chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-4 --
[1 ,2,4]triazole;
3-Benzo[1,3]dioxol-5-yl-5-(4-bromo-benzylsulfanyI)-4-ethyl-4/--[1,2,4]triazole;
4-[4-(5-Benzo[1,3]dioxol-5-yI-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-phenyl]- [1 ,2,3]thiadiazole;
3-Benzo[1,3]dioxol-5-yl-5-cyclohexylmethylsulfanyl-4-ethyl-4 --[1,2,4]triazole;
3-Benzo[1,3]dioxol-5-yl-4-ethyl-5-(4-trifluoromethoxy-benzylsulfanyl)-4r/-[1,2,4]triazole;
3-Benzo[1 ,3]dioxol-5-yl-5-(3,5-dimethoxy-benzylsulfanyl)-4-ethyl-4 --[1,2,4]triazole;
3-Benzo[1 ,3]dioxol-5-yl-4-ethyI-5-(4-methanesulfonyl-benzylsulfanyl)-4/--[1,2,4]triazole; 4-(5-Benzo[1 ,3]dioxol-5-yl-4-ethyl-4/--[1 ,2,4]triazol-3-ylsuIfanylmethyl)-benzoic acid methyl etser;
3-Benzo[1,3]dioxol-5-yl-5-(2,6-dichloro-benzylsuIfanyl)-4-ethyl-4H-[1,2,4]triazole;
3-Benzo[1,3]dioxoI-5-yl-5-(4-benzyloxy-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazole;
N-[4-(5-Benzo[1,3]dioxol-5-yl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-phenyl]-acetamide; 3-Benzo[1 ,3]dioxoI-5-yl-4-ethyl-5-(4-methoxy-benzylsulfanyl)-4/-.-[1 ,2,4]triazole;
3-Benzo[1,3]dioxol-5-yl-4-ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1,2,4]triazoIe;
3-Benzo[1,3]dioxol-5-yI-4-ethyl-5-(2-nitro-benzylsulfanyl)-4H-[1,2,4]triazole;
3-Benzo[1,3]dioxoI-5-yI-5-(2,4-dichloro-benzylsulfanyI)-4-ethyl-4H-[1 ,2,4]triazole;
4-[4-Ethyl-5-(2-phenoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile; 3-(6-ChIoro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-5-(2-phenoxy-phenyl)-4/--
[1 ,2,4]triazole; 3-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-5-(2-phenoxy-phenyl)-4H-[1,2,4]triazole;
3-(4-Bromo-benzylsulfanyl)-4-ethyl-5-(2-phenoxy-phenyl)-4H-[1,2,4]triazole;
4-{4_[4_Ethyl-5-(2-phenoxy-phenyl)-4/--[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-
[1 ,2,3]thiadiazole; 3-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-5-(2-phenoxy-phenyl)-4H-[1 ,2,4]triazole;
4-EthyI-3-(2-phenoxy-phenyl)-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1,2,4]triazole;
4-EthyI-3-(4-methanesulfonyl-benzylsulfanyl)-5-(2-phenoxy-phenyl)-4ry-[1,2,4]triazole;
4-[4-EthyI-5-(2-phenoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser; 3-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-5-(2-phenoxy-phenyl)-4H-[1 ,2,4]triazole;
3-(4-Benzyloxy-benzylsulfanyl)-4-ethyl-5-(2-phenoxy-phenyI)-4/--[1,2,4]triazole;
4-Ethyl-3-(4-methyl-benzylsulfanyl)-5-(2-phenoxy-phenyl)-4H-[1,2,4]triazole;
4-Ethyl-3-(2-phenoxy-phenyl)-5-(3-trifluoromethoxy-benzylsulfanyl)-4 --[1 ,2,4]triazole;
4-Ethyl-3-(4-methoxy-benzylsulfanyl)-5-(2-phenoxy-phenyl)-4H-[1,2,4]triazole; 4-Ethyl-3-(2-nitro-benzylsulfanyl)-5-(2-phenoxy-phenyl)-4H-[1,2,4]triazole;
3-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-5-(2-phenoxy-phenyl)-4H-[1,2,4]triazole;
3-CyclohexylmethylsulfanyI-4-ethyl-5-naphthalen-1-yl-4H-[1,2,4]triazole;
4-Ethyl-3-naphthalen-1-yl-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1,2,4]triazole;
4-Ethyl-3-(4-methanesulfonyl-benzylsulfanyl)-5-naphthalen-1-yl-4H-[1,2,4]triazole; 4-Ethyl-3-naphthalen-1 -yl-5-(3-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazole;
4-(4-EthyI-5-naphthalen-1-yl-4ry-[1,2,4]triazol-3-ylsulfanylmethyl)-benzoic acid methyl etser;
4-Ethyl-3-naphthalen-1-yl-5-(4-nitro-benzylsulfanyl)-4/-/-[1,2,4]triazole;
3-(2,6-Dichloro-benzylsuIfanyl)-4-ethyl-5-naphthalen-1-yl-4H-[1,2,4]triazole;
4-Ethyl-3-(4-methyl-benzylsulfanyl)-5-naphthalen-1-yl-4 -/-[1,2,4]triazole; 4-Ethyl-3-(4-methoxy-benzylsulfanyl)-5-naphthalen-1 -yl-4 --[1 ,2,4]triazole;
4-Ethyl-3-(5-methyl-2-nitro-benzylsulfanyl)-5-naphthalen-1-yl-4ry-[1,2,4]triazole;
3-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-5-naphthalen-1-yl-4/--[1,2,4]triazole;
[4-(5-Cyclohexylmethylsulfanyl-4-ethyl-4H-[1,2,4]triazol-3-yl)-phenyl]-dimethyl-amine
{4-[5-(3,5-Dimethoxy-benzylsulfanyI)-4-ethyl-4H-[1 ,2,4]triazol-3-yl]-phenyl}-dimethyl-amine {4-[4-Ethyl-5-(4-trifluoromethyl-benzyisulfanyl)-4 --[1,2,4]triazol-3-yl]-phenyl}-dimethyl-amine
4-[5-(4-Dimethylamino-phenyI)-4-ethyl-4/-/-[1,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser;
{4-[4-Ethyl-5-(4-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-phenyl}-dimethyl-amine;
{4-[4-Ethyl-5-(4-methoxy-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenyl}-dimethyl-amine; {4-[4-EthyI-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1,2,4]triazoI-3-yl]-phenyl}-dimethyl-amine;
{4-[5-(2,4-Dichloro-benzyIsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-phenyl}-dimethyl-amine; 4-(4-Ethyl-5-thiophen-2-yl-4H-[1 ,2,4]triazol-3-ylsulfanyImethyl)-benzonitriIe;
3-(6-Chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-5-thiophen-2-yl-4H-[1 ,2,4]triazole;
3-(3,4-Dichloro-benzylsuIfanyl)-4-ethyl-5-thiophen-2-yl-4H-[1,2,4]triazole;
3-(4-Bromo-benzylsulfanyl)-4-ethyl-5-thiophen-2-yl-4H-[1 ,2,4]triazole; 4-[4-(4-Ethyl-5-thiophen-2-yl-4r/-[1,2,4]triazol-3-yIsulfanylmethyl)-phenyl]-[1 ,2,3]thiadiazole;
4-Ethyl-3-thiophen-2-yl-5-(4-trifluoromethoxy-benzylsulfanyl)-4 - -[1 ,2,4]triazole;
3-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-5-thiophen-2-yl-4 -/-[1 ,2,4]triazole;
4-Ethyl-3-thiophen-2-yl-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1 ,2,4]triazole;
3-Benzylsulfanyl-4-ethyl-5-thiophen-2-yl-4H-[1 ,2,4]triazole; 4-Ethyl-3-(4-methanesulfonyl-benzylsulfanyl)-5-thiophen-2-yl-4 -/-[1 ,2,4]triazole;
4-(4-Ethyl-5-thiophen-2-yl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzoic acid methyl etser;
4-Ethyl-3-(4-nitro-benzylsulfanyl)-5-thiophen-2-yl-4H-[1 ,2,4]triazole;
3-(2,6-Dichloro-benzyIsulfanyl)-4-ethyl-5-thiophen-2-yl-4/.-[1 ,2,4]triazole;
4-Ethyl-3-(4-methyl-benzylsulfanyl)-5-thiophen-2-yl-4/- -[1 ,2,4]triazole; 4-Ethyl-3-(4-methoxy-benzylsulfanyl)-5-thiophen-2-yl-4H-[1 ,2,4]triazole;
4-Ethyl-3-(5-methyl-2-nitro-benzylsulfanyl)-5-thiophen-2-yl-4H-[1 ,2,4]triazole;
3-(2-Chloro-benzylsulfanyl)-4-ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazole;
3-(6-Chloro-benzo[1 ,3]dioxol-5-ylmethyIsulfanyI)-4-ethyI-5-(2-methoxy-phenyl)-4H-
[1 ,2,4]triazole; 4-EthyI-3-(2-methoxy-phenyl)-5-(4-trifluoromethoxy-benzylsulfanyl)-4/-/-[1 ,2,4]triazole;
3-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-5-(2-methoxy-phenyl)-4ry-[1 ,2,4]triazole;
4-Ethyl-3-(2-methoxy-phenyl)-5-(4-trifluoromethyl-benzylsulfanyl)-4ry-[1,2,4]triazole;
3-Benzylsulfanyl-4-ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazole;
4-Ethyl-3-(4-methanesulfonyl-benzylsulfanyl)-5-(2-methoxy-phenyI)-4/.-[1 ,2,4]triazole; 4-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-yIsulfanylmethyl]-benzoic acid methyl etser;
4-Ethyl-3-(2-methoxy-phenyl)-5-(4-nitro-benzylsulfanyl)-4/- -[1,2,4]triazole;
3-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazole;
3-(4-Benzyloxy-benzylsulfanyI)-4-ethyl-5-(2-methoxy-phenyl)-4/- -[1 ,2,4]triazole; 4-Ethyl-3-(2-methoxy-phenyl)-5-(4-methyl-benzylsulfanyl)-4H-[1 ,2,4]triazole;
4-Ethyl-3-(2-methoxy-phenyl)-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-[1 ,2,4]triazoIe;
4-Ethyl-3-(2-methoxy-phenyl)-5-(5-methyl-2-nitro-benzylsuIfanyl)-4H-[1 ,2,4]triazole;
4-Ethyl-3-(2-methoxy-phenyl)-5-(2-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazole;
3-(2-Chloro-benzylsuIfanyl)-4-ethyl-5-(4-methoxy-phenyl)-4H-[1 ,2,4]triazole; 4-[4-Ethyl-5-(4-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-yIsulfanylmethyl]-benzonitrile; 3-(6-Chloro-benzo[1 ,3]dioxoI-5-ylmethylsulfanyl)-4-ethyl-5-(4-methoxy-phenyl)-4H-
[1 ,2,4]triazole;
3-(3,4-Dichloro-benzylsuIfanyl)-4-ethyl-5-(4-methoxy-phenyl)-4H-[1,2,4]triazole;
3-(4-Bromo-benzylsulfanyl)-4-ethyl-5-(4-methoxy-phenyl)-4 -/-[1,2,4]triazole; 4-{4-[4-Ethyl-5-(4-methoxy-phenyl)-4 -/-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-
[1 ,2,3]thiadiazole;
3-Cyclohexylmethylsulfanyl-4-ethyl-5-(4-methoxy-phenyl)-4H-[1,2,4]triazole;
4-EthyI-3-(4-methoxy-phenyl)-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1,2,4]triazole;
4-Ethyl-3-(4-methanesulfonyl-benzylsulfanyl)-5-(4-methoxy-phenyl)-4r/-[1,2,4]triazoIe; 4-[4-Ethyl-5-(4-methoxy-phenyl)-4/-/-[1 ,2,4]triazol-3-ylsulfanyImethyl]-benzoic acid methyl etser;
3-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-5-(4-methoxy-phenyl)-4 -/-[1 ,2,4]triazole;
3-(4-Benzyloxy-benzylsulfanyl)-4-ethyl-5-(4-methoxy-phenyl)-4H-[1,2,4]triazole;
4-Ethyl-3-(4-methoxy-phenyl)-5-(3-trifluoromethoxy-benzyIsulfanyl)-4H-[1,2,4]triazole; N-{4-[4-Ethyl-5-(4-methoxy-phenyl)-4/--[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-acetamide;
4-Ethyl-3-(4-methoxy-benzylsulfanyl)-5-(4-methoxy-phenyl)-4H-[1,2,4]triazole;
4-Ethyl-3-(4-methoxy-phenyl)-5-(2-nitro-benzylsulfanyl)-4 --[1,2,4]triazoIe;
4-(4-Ethyl-5-pyridin-4-yl-4 --[1,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile;
4-[5-(4-Bromo-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazol-3-yl]-pyridine; 4-[5-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-pyridine;
4-[4-Ethyl-5-(4-methanesulfonyl-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-pyridine;
4-(4-Ethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzoic acid methyl etser;
4-[4-Ethyl-5-(4-methyl-benzylsuIfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine;
4-[4-Ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4ry-[1,2,4]triazol-3-yl]-pyridine; 4-[5-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-4/-.-[1,2,4]triazol-3-yl]-pyridine;
3-[5-(2-Chloro-benzylsulfanyl)-4-ethyl-4 -/-[1,2,4]triazol-3-yl]-pyridine;
4-(4-Ethyl-5-pyridin-3-yl-4H-[1,2,4]triazoI-3-ylsulfanylmethyl)-benzonitrile;
3-[5-(6-Chloro-benzo[1 ,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-pyridine;
3-[5-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-4/-/-[1,2,4]triazol-3-yl]-pyridine; 3-[5-(4-Bromo-benzylsulfanyl)-4-ethyl-4 --[1,2,4]triazol-3-yl]-pyridine;
3-[4-Ethyl-5-(4-[1,2,3]thiadiazol-4-yl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine;
3-[4-Ethyl-5-(4-trifluoromethoxy-benzylsulfanyI)-4H-[1,2,4]triazol-3-yl]-pyridine;
3-[5-(3,5-Dimethoxy-benzyIsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-pyridine;
3-[4-Ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine; 3-(5-BenzyIsuIfanyl-4-ethyl-4 .-[1,2,4]triazol-3-yl)-pyridine;
3-[4-Ethyl-5-(4-methanesulfonyl-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-pyridine; 3-[4-Ethyl-5-(3-nitro-benzylsulfanyl)-4Ay-[1 ,2,4]triazol-3-yl]-pyridine;
4-(4-EthyI-5-pyridin-3-yl-4r7-[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzoic acid methyl etser;
3-[5-(2,6-Dichloro-benzylsulfanyl)-4-ethyI-4 -.-[1,2,4]triazol-3-yl]-pyridine;
3-[5-(4-Benzyloxy-benzylsulfanyl)-4-ethyl-4 V-[1 ,2,4]triazol-3-yl]-pyridine; 3-[4-Ethyl-5-(4-methyl-benzylsulfanyl)-4/- -[1 ,2,4]triazol-3-yl]-pyridine;
3-[4-Ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-pyridine;
N-[4-(4-Ethyl-5-pyridin-3-yl-4/--[1 ,2,4]triazol-3-ylsulfanylmethyl)-phenyl]-acetamide;
3-[4-Ethyl-5-(4-methoxy-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-pyridine;
3-[4-Ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4 - -[1 ,2,4]triazol-3-yl]-pyridine; 3-[4-EthyI-5-(2-nitro-benzylsulfanyI)-4H-[1 ,2,4]triazol-3-yl]-pyridine;
3-[5-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazol-3-yl]-pyridine;
3-(2-Chloro-benzylsulfanyl)-5-(4-chloro-phenyl)-4-ethyl-4H-[1 ,2,4]triazoIe;
4-[5-(4-Chloro-phenyl)-4-ethyl-4ry-[1 ,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
3-(4-Chloro-phenyl)-5-(3,4-dichloro-benzylsulfanyl)-4-ethyl-4/- -[1,2,4]triazoIe; 4-{4-[5-(4-Chloro-phenyl)-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-
[1 ,2,3]thiadiazoIe;
3-(4-Chloro-phenyl)-4-ethyl-5-(4-methanesulfonyl-benzylsulfanyl)-4 - -[1 ,2,4]triazole;
3-(4-Chloro-phenyl)-4-ethyl-5-(3-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazole;
4-[5-(4-Chloro-phenyI)-4-ethyl-4 - -[1 ,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser; 3-(4-Chloro-phenyl)-5-(2,6-dichloro-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazole;
3-(4-Benzyloxy-benzylsulfanyl)-5-(4-chloro-phenyl)-4-ethyl-4ry-[1 ,2,4]triazoIe;
3-(4-Chloro-phenyl)-4-ethyl-5-(4-methyl-benzylsulfanyl)-4H-[1 ,2,4]triazoIe;
3-(4-Chloro-phenyl)-4-ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-[1,2,4]triazole;
N-{4-[5-(4-Chloro-phenyl)-4-ethyl-4ry-[1 ,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-acetamide; 3-(4-Chloro-phenyl)-4-ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazole;
3-(4-Chloro-phenyl)-5-(2,4-dichloro-benzylsulfanyl)-4-ethyl-4ry-[1 ,2,4]triazole;
5-[5-(2-Chloro-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazol-3-yl]-4-phenyl-[1 ,2,3]thiadiazole;
4-[4-Ethyl-5-(4-phenyl-[1 ,2,3]thiadiazol-5-yl)-4r/-[1 ,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
5-[5-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazol-3-yl]-4-phenyl-[1 ,2,3]thiadiazole; 5-[4-Ethyl-5-(4-trifluoromethoxy-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-4-phenyl-
[1 ,2,3]thiadiazole;
5-[5-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyI-4ry-[1,2,4]triazol-3-yl]-4-phenyl-[1,2,3]thiadiazole;
5-[4-Ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4r -[1 ,2,4]triazol-3-yl]-4-phenyl-
[1 ,2,3]thiadiazole; 5-(5-Benzylsulfanyl-4-ethyI-4H-[1 ,2,4]triazol-3-yl)-4-phenyl-[1 ,2,3]thiadiazole; 5-[4-Ethyl-5-(4-methanesulfonyl-benzylsulfanyI)-4/-/-[1,2,4]triazol-3-yl]-4-phenyI-
[1 ,2,3]thiadiazole;
5-[4-Ethyl-5-(4-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-4-phenyl-[1 ,2,3]thiadiazole;
5-[5-(2,6-DichIoro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-4-phenyl-[1 ,2,3]thiadiazole; 5-[4-EthyI-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-4-phenyl-
[1 ,2,3]thiadiazole;
5-[4-Ethyl-5-(4-methoxy-benzylsulfanyl)-4-/-[1,2,4]triazol-3-yl]-4-phenyl-[1 ,2,3]thiadiazole;
5-[4-Ethyl-5-(2-nitro-benzylsulfanyl)-4/-/-[1,2,4]triazol-3-yl]-4-phenyl-[1 ,2,3]thiadiazoIe;
4-{5-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-4/--[1,2,4]triazol-3-ylsulfanylmethyl}- benzonitrile;
3-(6-Chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-5-[4-(2,5-dimethyl-pyrrol-1-yl)-phenyl]-4- ethyl-4H-[1,2,4]triazole;
3-(3,4-Dichloro-benzylsulfanyl)-5-[4-(2,5-dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-4H-
[1 ,2,4]triazole; 3-[4-(2,5-Dimethyl-pyrrol-1 -yl)-phenyl]-4-ethyl-5-(4-trifluoromethoxy-benzylsulfanyl)-4H-
[1 ,2,4]triazoIe;
3-(3,5-Dimethoxy-benzylsulfanyl)-5-[4-(2,5-dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-4 --
[1 ,2,4]triazole;
3-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4/-- [1 ,2,4]triazole;
3-Benzylsulfanyl-5-[4-(2,5-dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-4H-[1,2,4]triazole;
3-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-5-(4-methanesulfonyl-benzylsulfanyl)-4 --
[1 ,2,4]triazole;
3-[4-(2,5-DimethyI-pyrrol-1-yl)-phenyl]-4-ethyl-5-(3-nitro-benzylsulfanyl)-4H-[1,2,4]triazole; 4-{5-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl}-benzoic acid methyl etser;
3-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-5-(4-nitro-benzylsulfanyl)-4H-[1,2,4]triazole;
3-(4-Benzyloxy-benzylsulfanyl)-5-[4-(2,5-dimethyl-pyrroI-1-yl)-phenyl]-4-ethyI-4/--
[1 ,2,4]triazole; N-(4-{5-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl}- phenyl)-acetamide;
3-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-5-(4-methoxy-benzylsulfanyl)-4H-[1,2,4]triazole;
3-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-
[1 ,2,4]triazole; 3-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-5-(2-nitro-benzyIsulfanyl)-4 .-[1,2,4]triazole; 3-(2,4-Dichloro-benzylsulfanyl)-5-[4-(2,5-dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-4H-
[1 ,2,4]triazole;
3-Benzo[b]thiophen-2-yl-5-(2-chloro-benzylsulfanyl)-4-ethyl-4/--[1 ,2,4]triazoIe;
4-(5-Benzo[b]thiophen-2-yl-4-ethyI-4 -/-[1,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile; 3-Benzo[b]thiophen-2-yI-5-(6-chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-4/-y-
[1 ,2,4]triazole;
3-Benzo[b]thiophen-2-yl-5-(4-bromo-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazole;
4-[4-(5-Benzo[b]thiophen-2-yl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-phenyl]-
[1 ,2,3]thiadiazole; 3-Benzo[b]thiophen-2-yl-4-ethyl-5-(3-nitro-benzylsulfanyl)-4 .-[1 ,2,4]triazole;
4-(5-Benzo[b]thiophen-2-yl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzoic acid methyl etser;
3-Benzo[b]thiophen-2-yl-4-ethyI-5-(4-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazole;
3-Benzo[b]thiophen-2-yl-5-(4-benzyloxy-benzylsulfanyl)-4-ethyI-4H-[1,2,4]triazole; 3-Benzo[b]thiophen-2-yl-4-ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-[1,2,4]triazoIe;
N-[4-(5-Benzo[b]thiophen-2-yl-4-ethyI-4/--[1,2,4]triazol-3-ylsulfanylmethyl)-phenyl]-acetamide;
3-Benzo[b]thiophen-2-yl-4-ethyI-5-(4-methoxy-benzylsulfanyl)-4H-[1,2,4]triazole;
3-Benzo[b]thiophen-2-yl-4-ethyl-5-(2-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazole;
3-(2-Chloro-benzylsulfanyl)-4-ethyl-5-(1-phenyl-5-trifluoromethyl-1/-.-pyrazol-4-yl)-4/-/- [1 ,2,4]triazole;
3-(6-Chloro-benzo[1 ,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-5-(1 -phenyl-5-trif luoromethyI-1 H- pyrazol-4-yI)-4H-[1,2,4]triazole;
4-{4-[4-Ethyl-5-(1 -phenyl-5-trifluoromethyl-1 H-pyrazol-4-yl)-4H-[1 ,2,4]triazol-3- ylsulfanylmethyl]-phenyl}-[1,2,3]thiadiazole; 4-Ethyl-3-(1-phenyl-5-trifluoromethyl-1ry-pyrazol-4-yI)-5-(4-trifluoromethoxy-benzylsulfanyl)-
4H-[1,2,4]triazole;
3-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-5-(1-phenyl-5-trifluoromethyl-1H-pyrazol-4-yl)-4H-
[ ,2,4]triazole;
3-Benzylsulfanyl-4-ethyl-5-(1 -phenyl-5-trifluoromethyl-1 H-pyrazol-4-yl)-4H-[1 ,2,4]triazole; 4-Ethyl-3-(4-methanesulfonyl-benzylsulfanyl)-5-(1-phenyl-5-trifluoromethyl-1H-pyrazol-4-yl)-
4H-[1,2,4]triazole;
4-EthyI-3-(3-nitro-benzylsuIfanyl)-5-(1-phenyl-5-trifluoromethyl-1H-pyrazol-4-yl)-4H-
[1,2,4]triazole;
4-[4-Ethyl-5-(1-phenyl-5-trifluoromethyl-1H-pyrazol-4-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]- benzoic acid methyl etser; 3-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-5-(1-phenyl-5-trifluoromethyl-1 .-pyrazol-4-yl)-4H-
[1 ,2,4]triazole;
3-(4-Benzyloxy-benzylsulfanyl)-4-ethyl-5-(1-phenyI-5-trifluoromethyl-1H-pyrazol-4-yl)-4H-
[1 ,2,4]triazole; 4-Ethyl-3-(4-methyl-benzylsulfanyl)-5-(1 -phenyI-5-trifluoromethyl-1 --pyrazol-4-yl)-4H-
[1 ,2,4]triazole;
N-{4-[4-Ethyl-5-(1 -phenyl-5-trifluoromethyI-1 H-pyrazol-4-yl)-4H-[1 ,2,4]triazol-3- ylsulfanylmethyl]-phenyl}-acetamide;
4-Ethyl-3-(5-methyl-2-nitro-benzylsuIfanyl)-5-(1-phenyI-5-trifluoromethyl-1/.-pyrazol-4-yl)-4H- [1,2,4]triazole;
4-Ethyl-3-(2-nitro-benzylsulfanyl)-5-(1-phenyl-5-trifluoromethyl-1/--pyrazol-4-yl)-4H-
[1 ,2,4]triazole;
3-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-5-(1-phenyl-5-trifluoromethyI-1H-pyrazol-4-yl)-4H-
[1 ,2,4]triazole; 3-(2-Chloro-benzylsulfanyl)-5-(3-chloro-4-methyl-thiophen-2-yl)-4-ethyl-4 --[1,2,4]triazole;
4-[5-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl]- benzonitrile;
3-(3-Chloro-4-methyl-thiophen-2-yl)-5-(3,4-dichloro-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazole;
4-{4-[5-(3-Chloro-4-methyI-thiophen-2-yl)-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-phenyl}- [1,2,3]thiadiazole;
3-(3-Chloro-4-methyl-thiophen-2-yl)-5-cyclohexylmethyIsulfanyl-4-ethyl-4H-[1,2,4]triazole;
3-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-5-(4-trifluoromethoxy-benzylsulfanyl)-4H-
[1,2,4]triazole;
3-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyI-5-(4-trifluoromethyl-benzylsulfanyl)-4H- [1 ,2,4]triazole;
3-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-5-(3-nitro-benzylsuIfanyl)-4H-[1,2,4]triazole;
4-[5-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-4H-[1,2,4]triazol-3-yIsulfanylmethyl]-benzoic acid methyl etser;
3-(3-Chloro-4-methyl-thiophen-2-yl)-5-(2,6-dichloro-benzylsuIfanyl)-4-ethyl-4H-[1,2,4]triazole; 3-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-5-(4-methyl-benzylsulfanyl)-4H-[1,2,4]triazole;
3-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-
[1 ,2,4]triazole;
3-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4/-/-
[1,2,4]triazole; 3-(3-ChIoro-4-methyl-thiophen-2-yl)-4-ethyl-5-(2-nitro-benzylsulfanyl)-4H-[1,2,4]triazole;
4-(4-Ethyl-5-pyridin-2-yl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile; 2-[5-(6-Chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-4 .-[1 ,2,4]triazol-3-yl]-pyridine
2-[5-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-4 -/-[1,2,4]triazol-3-yl]-pyridine;
2-[5-(4-Bromo-benzylsulfanyI)-4-ethyl-4H-[1,2,4]triazol-3-yl]-pyridine;
2-[4-Ethyl-5-(4-[1,2,3]thiadiazol-4-yl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine; 2-[5-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yI]-pyridine;
2-[4-Ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine;
2-[4-Ethyl-5-(4-methanesulfonyl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine;
2-[4-EthyI-5-(3-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yI]-pyridine;
4-(4-Ethyl-5-pyridin-2-yl-4fY-[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzoic acid methyl etser; 2-[4-Ethyl-5-(4-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine;
2-[5-(4-Benzyloxy-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-pyridine;
2-[4-Ethyl-5-(4-methyl-benzyIsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine;
2-[4-Ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine;
2-[4-Ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine; 2-[4-Ethyl-5-(2-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine;
3-[5-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-4 --[1,2,4]triazol-3-yl]-2-methylsulfanyl-pyridine;
3-[4-Ethyl-5-(4-[1,2,3]thiadiazol-4-yl-benzylsulfanyl)-4r.-[1,2,4]triazol-3-yl]-2-methylsulfanyl- pyridine;
3-(5-Cyclohexylmethylsulfanyl-4-ethyl-4H-[1,2,4]triazol-3-yl)-2-methylsulfanyl-pyridine; 3-[4-Ethyl-5-(4-trifluoromethoxy-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-2-methylsulfanyl- pyridine;
3-[5-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-2-methyIsulfanyl-pyridine;
3-[4-EthyI-5-(4-trifluoromethyl-benzylsuIfanyl)-4 --[1,2,4]triazol-3-yI]-2-methylsulfanyl-pyridine;
3-(5-Benzylsulfanyl-4-ethyl-4 y-[1,2,4]triazol-3-yl)-2-methylsulfanyI-pyridine; 3-[4-EthyI-5-(4-methanesulfonyl-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-2-methylsulfanyl- pyridine;
4-[4-Ethyl-5-(2-methylsulfanyl-pyridin-3-yl)-4 -/-[1,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser;
3-[5-(2,6-DichIoro-benzylsulfanyl)-4-ethyl-4ry-[1,2,4]triazol-3-yl]-2-methylsulfanyI-pyridine; 3-[5-(4-Benzyloxy-benzyIsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-2-methylsulfanyl-pyridine;
3-[4-Ethyl-5-(4-methyl-benzylsulfanyl)-4 -/-[1 ,2,4]triazol-3-yl]-2-methylsulfanyl-pyridine;
3-[4-Ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-2-methylsulfanyl- pyridine;
N-{4-[4-Ethyl-5-(2-methylsulfanyl-pyridin-3-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}- acetamide;
3-[4-EthyI-5-(5-methyl-2-nitro-benzylsulfanyl)-4 --[1,2,4]triazoI-3-yl]-2-methylsulfanyl-pyridine; 3-[4-EthyI-5-(2-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-2-methylsulfanyl-pyridine;
3-(2-Chloro-benzylsulfanyl)-4-ethyl-5-(5-methyl-thiophen-2-yl)-4/-y-[1,2,4]triazole;
4-[4-Ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazol-3-ylsuIfanyImethyl]-benzonitrile;
3-(6-Chloro-benzo[1,3]dioxol-5-yImethylsulfanyl)-4-ethyl-5-(5-methyl-thiophen-2-yl)-4rV- [1 ,2,4]triazole;
3-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-5-(5-methyl-thiophen-2-yl)-4/-/-[1 ,2,4]triazoIe;
4-{4-[4-Methyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyi}-
[1 ,2,3]thiadiazole;
3-Cyclohexylmethylsulfanyl-4-ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazole; 4-Ethyl-3-(5-methyl-thiophen-2-yI)-5-(4-trifluoromethoxy-benzylsulfanyl)-4 --[1,2,4]triazole;
3-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-5-(5-methyl-thiophen-2-yl)-4 --[1,2,4]triazole;
4-Ethyl-3-(5-methyl-thiophen-2-yl)-5-(4-trifluoromethyl-benzylsulfanyl)-4 --[1,2,4]triazole;
3-Benzylsulfanyl-4-ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazoie;
4-Ethyl-3-(4-methanesulfonyl-benzylsulfanyl)-5-(5-methyl-thiophen-2-yl)-4 -.-[1 ,2,4]triazole; 4-Ethyl-3-(5-methyl-thiophen-2-yl)-5-(3-nitro-benzylsulfanyl)-4 -/-[1,2,4]triazole;
4-[4-Ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser;
4-Ethyl-3-(5-methyl-thiophen-2-yl)-5-(4-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazole;
3-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazole; 4-Ethyl-3-(4-methyl-benzylsulfanyl)-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazole;
N-{4-[4-Ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}- acetamide;
4-Ethyl-3-(4-methoxy-benzylsulfanyl)-5-(5-methyl-thiophen-2-yl)-4 -/-[1,2,4]triazole;
4-Ethyl-3-(5-methyl-thiophen-2-yl)-5-(2-nitro-benzylsulfanyl)-4H-[1,2,4]triazole; 3-(2,4-Dichloro-benzylsuifanyl)-4-ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazole;
4-[5-(5-Chloro-thiophen-2-yl)-4-ethyI-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
3-(5-Chloro-thiophen-2-yl)-5-(3,4-dichloro-benzyIsulfanyl)-4-ethyl-4H-[1,2,4]triazole;
3-(4-Bromo-benzylsulfanyl)-5-(5-chloro-thiophen-2-yl)-4-ethyl-4H-[1,2,4]triazole;
4-{4-[5-(5-Chloro-thiophen-2-yl)-4-ethyI-4 -/-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyI}- [1,2,3]thiadiazole;
3-(5-Chloro-thiophen-2-yI)-5-cyclohexylmethylsulfanyl-4-ethyl-4H-[1,2,4]triazole;
3-(5-Chloro-thiophen-2-yl)-4-ethyl-5-(4-trifluoromethoxy-benzyIsulfanyl)-4 --[1,2,4]triazole;
3-(5-Chloro-thiophen-2-yl)-5-(3,5-dimethoxy-benzyIsulfanyl)-4-ethyl-4/-/-[1,2,4]triazole;
3-(5-ChIoro-thiophen-2-yl)-4-ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4/--[1,2,4]triazoIe; 3-(5-Chloro-thiophen-2-yl)-4-ethyI-5-(3-nitro-benzylsulfanyl)-4 -/-[1,2,4]triazole; 4-[5-(5-Chloro-thiophen-2-yl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser;
3-(5-Chloro-thiophen-2-yl)-5-(2,6-dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazole;
3-(5-Chloro-thiophen-2-yl)-4-ethyl-5-(4-methyl-benzylsulfanyl)-4H-[1,2,4]triazole; 3-(5-Chloro-thiophen-2-yl)-4-ethyl-5-(3-trifluoromethoxy-benzylsulfanyI)-4H-[1,2,4]triazoIe;
N-{4-[5-(5-Chloro-thiophen-2-yl)-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-phenyl}- acetamide;
3-(5-Chloro-thiophen-2-yl)-4-ethyl-5-(4-methoxy-benzylsulfanyl)-4H-[1,2,4]triazole;
3-(5-Chloro-thiophen-2-yl)-4-ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1,2,4]triazole; 3-(5-Chloro-thiophen-2-yl)-4-ethyl-5-(2-nitro-benzylsulfanyl)-4 .-[1,2,4]triazole;
3-(5-Chloro-thiophen-2-yl)-5-(2,4-dichIoro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazole;
4-[4-Ethyl-5-(1ry-indol-3-ylmethyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
3-[5-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-4/-/-[1,2,4]triazol-3-ylmethyl]-1H-indole;
3-[5-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazoI-3-ylmethyl]-1H-indole; 3-[4-Ethyl-5-(4-methanesulfonyl-benzylsulfanyl)-4 --[1 ,2,4]triazol-3-ylmethyl]-1 H-indole;
3-[4-Ethyl-5-(3-nitro-benzylsulfanyI)-4ry-[1,2,4]triazol-3-ylmethyl]-1H-indole;
3-[4-Ethyl-5-(4-nitro-benzylsulfanyI)-4 -/-[1,2,4]triazol-3-ylmethyl]-1H-indole;
3-[5-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-ylmethyl]-1H-indole;
3-[5-(4-Benzyloxy-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-ylmethyl]-1H-indole; 3-[4-Ethyl-5-(3-trifluoromethoxy-benzyIsulfanyl)-4H-[1 ,2,4]triazol-3-ylmethyl]-1 H-indole;
N-{4-[4-Ethyl-5-(1H-indol-3-ylmethyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-acetamide;
3-[4-Ethyl-5-(4-methoxy-benzylsulfanyl)-4H-[1,2,4]triazol-3-ylmethyl]-1W-indole;
3-[4-Ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-ylmethyl]-1H-indole;
3-[4-Ethyl-5-(2-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-ylmethyl]-1H-indole; 3-[5-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazol-3-ylmethyl]-1 H-indole;
2-[5-(6-Chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazol-3-yl]-phenoI;
2-[4-Ethyl-5-(4-[1,2,3]thiadiazol-4-yl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol;
2-(5-Cyclohexylmethylsulfanyl-4-ethyl-4/- -[1,2,4]triazol-3-yl)-phenol;
2-[5-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-phenol; 2-[4-Ethyl-5-(4-trifluoromethyI-benzylsulfanyI)-4/-/-[1,2,4]triazol-3-yl]-phenol;
2-(5-Benzylsulfanyl-4-ethyl-4H-[1 ,2,4]triazol-3-yl)-phenol;
2-[4-Ethyl-5-(4-methanesulfonyl-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-phenol;
2-[4-Ethyl-5-(3-nitro-benzylsulfanyl)-4/--[1,2,4]triazol-3-yl]-phenol;
4-[4-Ethyl-5-(2-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser; 2-[4-Ethyl-5-(4-nitro-benzylsulfanyl)-4 .-[1,2,4]triazol-3-yl]-phenol;
2-[5-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-4/-.-[1,2,4]triazol-3-yl]-phenol; 2-[4-Ethyl-5-(4-methyl-benzylsulfanyl)-4/.-[1 ,2,4]triazol-3-yl]-phenol;
2-[4-EthyI-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-phenol;
N-{4-[4-Ethyl-5-(2-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-acetamide;
2-[4-Ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4 -/-[1 ,2,4]triazol-3-yl]-phenol; 2-[4-Ethyl-5-(2-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yI]-phenol;
2-[5-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazol-3-yl]-phenol;
5-[5-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-4/--[1 ,2,4]triazol-3-yl]-4-methyl-[1,2,3]thiadiazole;
5-[5-(4-Bromo-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazol-3-yl]-4-methyl-[1 ,2,3]thiadiazole;
5-(5-Cyclohexylmethylsulfanyl-4-ethyl-4H-[1 ,2,4]triazol-3-yl)-4-methyl-[1 ,2,3]thiadiazole; 5-[5-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-4/-.-[1 ,2,4]triazol-3-yl]-4-methyl-[1 ,2,3]thiadiazole;
5-(5-BenzyIsulfanyl-4-ethyl-4H-[1 ,2,4]triazol-3-yl)-4-methyl-[1 ,2,3]thiadiazole;
5-[4-Ethyl-5-(3-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-4-methyl-[1 ,2,3]thiadiazole;
4-[4-Ethyl-5-(4-methyl-[1 ,2,3]thiadiazol-5-yl)-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser; 5-[4-Ethyl-5-(4-nitro-benzylsulfanyl)-4ry-[1 ,2,4]triazol-3-yl]-4-methyl-[1 ,2,3]thiadiazole;
5-[5-(4-Benzyloxy-benzylsulfanyl)-4-ethyl-4/--[1 ,2,4]triazol-3-yl]-4-methyl-[1 ,2,3]thiadiazole;
5-[4-Ethyl-5-(4-methyl-benzylsulfanyl)-4ry-[1 ,2,4]triazol-3-yl]-4-methyl-[1 ,2,3]thiadiazole;
5-[4-Ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-4-methyl-
[1 ,2,3]thiadiazole; 5-[4-Ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4/--[1 ,2,4]triazol-3-yl]-4-methyl-
[1 ,2,3]thiadiazole;
5-[5-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-4-methyl-[1,2,3]thiadiazole;
4-(5-Benzyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile;
3-BenzyI-5-(3,4-dichloro-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazole; 4-[4-(5-Benzyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyI)-phenyl]-[1 ,2,3]thiadiazole;
3-Benzyl-5-(3,5-dimethoxy-benzylsulfanyl)-4-ethyl-4/- -[1 ,2,4]triazole;
3-Benzyl-4-ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4 - -[1 ,2,4]triazole;
3-Benzyl-5-benzyIsulfanyI-4-ethyl-4H-[1 ,2,4]triazole;
3-Benzyl-5-(2,6-dichloro-benzylsulfanyl)-4-ethyl-4/- -[1 ,2,4]triazole; 3-Benzyl-4-ethyl-5-(4-methyl-benzylsulfanyl)-4H-[1 ,2,4]triazole;
3-Benzyl-4-ethyl-5-(4-methoxy-benzylsulfanyl)-4H-[1,2,4]triazole;
3-Benzyl-4-ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4ry-[1 ,2,4]triazole;
3-Benzyl-4-ethyl-5-(2-nitro-benzylsulfanyI)-4H-[1 ,2,4]triazole;
3-Benzyl-5-(2,4-dichloro-benzylsulfanyl)-4-ethyI-4H-[1 ,2,4]triazole; 3-(2-Bromo-phenyl)-5-(2-chloro-benzylsulfanyl)-4-ethyl-4 .-[1 ,2,4]triazole;
4-[5-(2-Bromo-phenyl)-4-ethyl-4/-/-[1 ,2,4]triazol-3-ylsuIfanylmethyl]-benzonitrile; 3-(2-Bromo-phenyl)-5-(6-chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-4/--[1,2,4]triazole;
3-(2-Bromo-phenyl)-5-(3,4-dichloro-benzylsulfanyl)-4-ethyl-4r.-[1,2,4]triazole;
3-(2-Bromo-phenyl)-5-cyclohexylmethylsulfanyl-4-ethyl-4r -[1,2,4]triazole;
3-(2-Bromo-phenyl)-4-ethyl-5-(4-trifluoromethoxy-benzylsulfanyl)-4 --[1,2,4]triazole; 3-(2-Bromo-phenyl)-5-(3,5-dimethoxy-benzylsulfanyl)-4-ethyl-4/-/-[1 ,2,4]triazole;
3-(2-Bromo-phenyl)-4-ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1,2,4]triazole;
3-(2-Bromo-phenyl)-4-ethyl-5-(3-nitro-benzylsulfanyl)-4ry-[1,2,4]triazole;
3-(4-Benzyloxy-benzylsulfanyl)-5-(2-bromo-phenyl)-4-ethyI-4H-[1,2,4]triazole;
3-(2-Bromo-phenyl)-4-ethyl-5-(4-methoxy-benzylsulfanyl)-4H-[1,2,4]triazole; 3-(2-Bromo-phenyl)-4-ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1,2,4]triazole;
3-(2-Bromo-phenyl)-5-(2,4-dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazole;
2-[4-(3-Methoxy-propyl)-5-(1-methyl-piperidin-2-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]- benzonitrile;
2-[4-(3-Methoxy-propyl)-5-(1-methyl-piperidin-2-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]- pyridine;
2-[5-(2-Methoxy-ethylsulfanyl)-4-(3-methoxy-propyl)-4H-[1,2,4]triazol-3-yl]-1-methyl-piperidine;
2-[4-(2-Methoxy-ethyl)-5-(1-methyl-piperidin-2-yl)-4 -/-[1,2,4]triazol-3-ylsulfanylmethyl]- benzonitrile;
2-[4-(2-Methoxy-ethyl)-5-(1-methyl-piperidin-2-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-pyridine; 2-[4-(2-Methoxy-ethyl)-5-(2-methoxy-ethylsulfanyl)-4 --[1,2,4]triazol-3-yl]-1-methyl-piperidine;
2-[4-Cyclopropyl-5-(1-methyl-piperidin-2-yl)-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
2-[4-Cyclopropyl-5-(1-methyl-piperidin-2-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-pyridine;
2-[4-Cyclopropyl-5-(2-methoxy-ethylsulfanyl)-4H-[1,2,4]triazol-3-yl]-1-methyl-piperidine;
2-[5-(1-Methyl-piperidin-2-yl)-4-(2-piperidin-1-yl-ethyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]- benzonitrile;
2-[5-(1-Methyl-piperidin-2-yl)-4-(2-piperidin-1-yl-ethyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]- pyridine;
2-[4-Cyclopropylmethyl-5-(1-methyl-piperidin-2-yl)-4/-/-[1,2,4]triazol-3-ylsulfanylmethyl]- benzonitrile; 2-[4-CyclopropylmethyI-5-(1 -methyl-piperidin-2-yl)-4/-/-[1 ,2,4]triazol-3-ylsulfanylmethyl]- pyridine;
2-[4-Cyclopropylmethyl-5-(2-methoxy-ethylsulfanyl)-4ry-[1,2,4]triazol-3-yl]-1-methyl-piperidine;
2-[5-(2-Hydroxy-phenyl)-4-(3-methoxy-propyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]- benzonitrile; 2-[4-(3-Methoxy-propyl)-5-(pyridin-2-ylmethylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol;
2-[5-(2-Methoxy-ethylsulfanyl)-4-(3-methoxy-propyl)-4H-[1,2,4]triazol-3-yl]-phenol; 2-[5-(2-Hydroxy-phenyl)-4-(2-methoxy-ethyl)-4/-/-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
2-[4-(2-Methoxy-ethyl)-5-(pyridin-2-ylmethylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol;
2-[4-(2-Methoxy-ethyl)-5-(2-methoxy-ethylsulfanyl)-4ry-[1,2,4]triazol-3-yl]-phenol;
2-[4-Cyclopropyl-5-(2-hydroxy-phenyl)-4fy-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile; 2-[4-Cyclopropyl-5-(pyridin-2-ylmethylsuIfanyI)-4H-[1,2,4]triazol-3-yl]-phenol;
2-[4-Cydopropyl-5-(2-methoxy-ethylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol;
2-[5-(2-Hydroxy-phenyl)-4-(2-piperidin-1-yl-ethyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyI]- benzonitrile;
2-[4-(2-Piperidin-1-yl-ethyl)-5-(pyridin-2-ylmethylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol; 2-[5-(2-Methoxy-ethylsulfanyl)-4-(2-piperidin-1-yl-ethyl)-4H-[1,2,4]triazol-3-yl]-phenol;
2-[4-Cyclopropylmethyl-5-(2-hydroxy-phenyl)-4H-[1 ,2,4]triazoI-3-ylsulfanylmethyl]-benzonitrile;
2-[4-Cyclopropylmethyl-5-(pyridin-2-ylmethylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol;
2-[4-Cyclopropylmethyl-5-(2-methoxy-ethylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol;
2-[5-(2-Methoxy-phenyI)-4-(3-methoxy-propyl)-4 -/-[1,2,4]triazol-3-ylsulfanyImethyl]- benzonitrile;
2-[5-(2-Methoxy-phenyl)-4-(3-methoxy-propyI)-4H-[1,2,4]triazol-3-ylsuIfanylmethyl]-pyridine;
3-(2-Methoxy-ethylsulfanyl)-5-(2-methoxy-phenyl)-4-(3-methoxy-propyI)-4H-[1,2,4]triazole;
2-[4-(2-Methoxy-ethyl)-5-(2-methoxy-phenyl)-4/-/-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
2-[4-(2-Methoxy-ethyl)-5-(2-methoxy-phenyl)-4 -/-[1,2,4]triazol-3-ylsulfanylmethyl]-pyridine; 4-(2-Methoxy-ethyl)-3-(2-methoxy-ethylsulfanyl)-5-(2-methoxy-phenyl)-4H-[1,2,4]triazole;
2-[4-Cyclopropyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
2-[4-Cyclopropyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-pyridine;
4-Cyclopropyl-3-(2-methoxy-ethylsulfanyl)-5-(2-methoxy-phenyl)-4 --[1,2,4]triazole;
2-[5-(2-Methoxy-phenyl)-4-(2-piperidin-1-yl-ethyl)-4H-[1,2,4]triazol-3-ylsulfanyImethyl]- benzonitrile;
2-[5-(2-Methoxy-phenyl)-4-(2-piperidin-1-yl-ethyl)-4ry-[1,2,4]triazol-3-ylsulfanylmethyl]-pyridine;
1-{2-[3-(2-Methoxy-ethylsulfanyl)-5-(2-methoxy-phenyl)-[1,2,4]triazol-4-yl]-ethyl}-piperidine;
2-[4-Cyclopropylmethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]- benzonitrile; 2-[4-Cyclopropylmethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-pyridine;
4-Cyclopropylmethyl-3-(2-methoxy-ethyIsulfanyl)-5-(2-methoxy-phenyl)-4H-[1,2,4]triazole;
2-[4-(3-Methoxy-propyl)-5-thiophen-2-yl-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
2-[4-(3-Methoxy-propyl)-5-thiophen-2-yl-4/--[1,2,4]triazol-3-ylsulfanylmethyl]-pyridine;
3-(2-Methoxy-ethylsulfanyl)-4-(3-methoxy-propyl)-5-thiophen-2-yl-4H-[1,2,4]triazole; 2-[4-(2-Methoxy-ethyl)-5-thiophen-2-yl-4r.-[1,2,4]triazol-3-ylsulfanylmethyI]-benzonitrile;
2-[4-(2-Methoxy-ethyl)-5-thiophen-2-yl-4H-[1,2,4]triazoI-3-ylsulfanylmethyl]-pyridine; 4-(2-Methoxy-ethyl)-3-(2-methoxy-ethylsulfanyl)-5-thiophen-2-yl-4H-[1 ,2,4]triazole; 2-(4-CyclopropyI-5-thiophen-2-yl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile; 2-(4-CycIopropyI-5-thiophen-2-yl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-pyridine; 4-Cyclopropyl-3-(2-methoxy-ethylsuIfanyl)-5-thiophen-2-yl-4H-[1 ,2,4]triazole; 2-[4-(2-Piperidin-1-yl-ethyl)-5-thiophen-2-yl-4/-.-[1 ,2,4]triazoI-3-ylsulfanylmethyl]-benzonitrile; 2-[4-(2-Piperidin-1-yl-ethyl)-5-thiophen-2-yl-4/-/-[1 ,2,4]triazol-3-yIsulfanylmethyl]-pyridine; 1-{2-[3-(2-Methoxy-ethyIsulfanyl)-5-thiophen-2-yl-[1 ,2,4]triazol-4-yl]-ethyl}-piperidine; 2-(4-Cyclopropylmethyl-5-thiophen-2-yl-4 -/-[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile; 2-(4-Cyclopropylmethyl-5-thiophen-2-yl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl)-pyridine; 4-Cyclopropylmethyl-3-(2-methoxy-ethylsulfanyl)-5-thiophen-2-yl-4/- -[1 ,2,4]triazole; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
The compounds of the present invention have asymmetric centers and may occur as racemates, racemic mixtures, and as individual enantiomers or diastereoisomers, with all isomeric forms being included in the present invention as well as mixtures thereof.
The present invention also encompasses pharmaceutically acceptable salts of the present compounds. Such salts include pharmaceutically acceptable acid addition salts, pharmaceutically acceptable base addition salts, pharmaceutically acceptable metal salts, ammonium and alkylated ammonium salts. Acid addition salts include salts of inorganic acids as well as organic acids. Representative examples of suitable inorganic acids include hydrochloric, hydrobromic, hydroiodic, phosphoric, sulfuric, nitric acids and the like. Representative examples of suitable organic acids include formic, acetic, trichloroacetic, trifluoroacetic, propionic, benzoic, cinnamic, citric, fumaric, glycolic, lactic, maleic, malic, malonic, mandelic, oxalic, picric, pyruvic, salicylic, succinic, methanesulfonic, ethanesulfonic, tartaric, ascorbic, pamoic, bismethylene salicylic, ethanedisulfonic, gluconic, citraconic, aspartic, stearic, palmitic, EDTA, glycolic, p-aminobenzoic, glutamic, benzenesulfonic, p- toluenesulfonic acids, sulphates, nitrates, phosphates, perchlorates, borates, acetates, benzoates, hydroxynaphthoates, glycerophosphates, ketoglutarates and the like. Further examples of pharmaceutically acceptable inorganic or organic acid addition salts include the pharmaceutically acceptable salts listed in J. Pharm. Sci., 66, 2 (1977), which is incorporated herein by reference. Examples of metal salts include lithium, sodium, potassium, barium, calcium, magnesium, zinc, calcium salts and the like. Examples of amines and organic amines include ammonium, methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, propylamine, butylamine, tetramethylamine, ethanolamine, diethanolamine, triethanolamine, meglumine, ethylenediamine, choline, N,N'-dibenzylethylenediamine, N- benzylphenylethylamine, N-methyl-D-glucamine, guanidine and the like. Examples of cationic amino acids include lysine, arginine, histidine and the like.
Further, some of the compounds of the present invention may form solvates with water or common organic solvents. Such solvates are encompassed within the scope of the invention.
The pharmaceutically acceptable salts are prepared by reacting a compound of the present invention with 1 to 4 equivalents of a base such as sodium hydroxide, sodium methoxide, sodium hydride, potassium tert-butoxide, calcium hydroxide, magnesium hydroxide and the like, in solvents like ether, THF, methanol, tert-butanol, dioxane, isopropanol, ethanol etc. Mixtures of solvents may be used. Organic bases like lysine, arginine, diethanolamine, choline, guandine and their derivatives etc. may also be used. Alternatively, acid addition salts wherever applicable are prepared by treatment with acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, p- toluenesulphonic acid, methanesulfonic acid, acetic acid, citric acid, maleic acid salicylic acid, hydroxynaphthoic acid, ascorbic acid, palmitic acid, succinic acid, benzoic acid, benzenesulfonic acid, tartaric acid and the like in solvents like ethyl acetate, ether, alcohols, acetone, THF, dioxane etc. Mixture of solvents may also be used.
The stereoisomers of the compounds forming part of this invention may be prepared by using reactants in their single enantiomeric form in the process wherever possible or by conducting the reaction in the presence of reagents or catalysts in their single enantiomer form or by resolving the mixture of stereoisomers by conventional methods. Some of the preferred methods include use of microbial resolution, enzymatic resolution, resolving the diastereomeric salts formed with chiral acids such as mandelic acid, camphorsulfonic acid, tartaric acid, lactic acid, and the like wherever applicable or chiral bases such as brucine, (/ .)- or (S)-phenylethylamine, cinchona alkaloids and their derivatives and the like. Commonly used methods are compiled by Jaques et al. in "Enantiomers, Racemates and Resolution" (Wiley Interscience, 1981). More specifically the compound of the present invention may be converted to a 1 :1 mixture of diastereomeric amides by treating with chiral amines, aminoacids, aminoalcohols derived from aminoacids; conventional reaction conditions may be employed to convert acid into an amide; the diastereomers may be separated either by fractional crystallization or chromatography and the stereoisomers of compound of formula I may be prepared by hydrolysing the pure diastereomeric amide.
Various polymorphs of the compounds forming part of this invention may be prepared by crystallization of said compounds under different conditions. For example, using different solvents commonly used or their mixtures for recrystallization; crystallizations at different temperatures; and various modes of cooling, ranging from very fast to very slow cooling during crystallizations. Polymorphs may also be obtained by heating or melting the compound followed by gradual or fast cooling. The presence of polymorphs may be determined by solid probe NMR spectroscopy, IR spectroscopy, differential scanning calorimetry, powder X-ray diffraction or such other techniques. The invention also encompasses prodrugs of the present compounds, which on administration undergo chemical conversion by metabolic processes before becoming active pharmacological substances. In general, such prodrugs will be functional derivatives of the present compounds, which are readily convertible in vivo into the required compound of the present invention. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in "Design of Prodrugs", ed. H. Bundgaard, Elsevier, 1985.
It is a well known problem in drug discovery that compounds, such as enzyme inhibitors, may be very potent and selective in biochemical assays, yet be inactive in vivo. This lack of so-called bioavailability may be ascribed to a number of different factors such as lack of or poor absorption in the gut, first pass metabolism in the liver and/or poor uptake in cells. Although the factors determining bioavailability are not completely understood, there are many examples in the scientific literature, well known to those skilled in the art, of how to modify compounds, which are potent and selective in biochemical assays but show low or no activity in vivo, into drugs that are biologically active. It is within the scope of the invention to modify the compounds of the present invention, termed the "original compound", by attaching chemical groups that will improve the bioavailability of said compounds in such a way that the uptake in cells or mammals is facilitated.
Examples of said modifications, which are not intended in any way to limit the scope of the invention, include changing of one or more carboxy groups to esters (for instance methyl esters, ethyl esters, tert-butyl, acetoxymethyl, pivaloyloxymethyl esters or other acyloxymethyl esters). Compounds of the invention, original compounds, such modified by attaching chemical groups are termed "modified compounds".
The invention also encompasses active metabolites of the present compounds. The compounds according to the invention alters, and more specifically, reduces the level of active intracellular glucocorticoid and are accordingly useful for the treatment, prevention and/or prophylaxis of disorders and diseases in which such a modulation or reduction is beneficial.
Accordingly, the present compounds may be applicable for the treatment, prevention and/or prophylaxis of the metabolic syndrome, insulin resistance, dyslipidemia, hypertension, obesity, type 2 diabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), Latent Autoimmune Diabetes in the Adult (LADA), type 1 diabetes, diabetic late complications including cardiovascular diseases, cardiovascular disorders, disorders of lipid metabolism, neurodegenerative and psychiatric disorders, dysregulation of intraocular pressure including glaucoma, immune disorders, inappropriate immune responses, musculo-skeletal disorders, gastrointestinal disorders, polycystic ovary syndrome (PCOS), reduced hair growth or other diseases, disorders or conditions that are influenced by intracellular glucocorticoid levels, adverse effects of increased blood levels of active endogenous or exogenous glucocorticoid, and any combination thereof, adverse effects of increased plasma levels of endogenous active glucocorticoid, Cushing's disease, Cushing's syndrome, adverse effects of glucocorticoid receptor agonist treatment of autoimmune diseases, adverse effects of glucocorticoid receptor agonist treatment of inflammatory diseases, adverse effects of glucocorticoid receptor agonist treatment of diseases with an inflammatory component, adverse effects of glucocorticoid receptor agonist treatment as a part of cancer chemotherapy, adverse effects of glucocorticoid receptor agonist treatment for surgical/post-surgical or other trauma, adverse effects of glucocorticoid receptor agonist therapy in the context of organ or tissue transplantation or adverse effects of glucocorticoid receptor agonist treatment in other diseases, disorders or conditions where glucocorticoid receptor agonists provide clinically beneficial effects.
More specifically the present compounds may be applicable for the treatment, prevention and/or prophylaxis of the metabolic syndrome, type 2 diabetes, diabetes as a consequence of obesity, insulin resistance, hyperglycemia, prandial hyperglycemia, hyperinsulinemia, inappropriately low insulin secretion, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), increased hepatic glucose production, type 1 diabetes, LADA, pediatric diabetes, dyslipidemia, diabetic dyslipidemia, hyperlipidemia, hypertriglyceridemia, hyperiipoproteinemia, hypercholesterolemia, decreased HDL cholesterol, impaired LDLJ HDL ratio, other disorders of lipid metabolism, obesity, visceral obesity, obesity as a consequence of diabetes, increased food intake, hypertension, diabetic late complications, micro- / macroalbuminuria, nephropathy, retinopathy, neuropathy, diabetic ulcers, cardiovascular diseases, arteriosclerosis, atherosclerosis, coronary artery disease, cardiac hypertrophy, myocardial ischemia, heart insufficiency, congestional heart failure, stroke, myocardial infarction, arrythmia, decreased blood flow, erectile dysfunction (male or female), myopathy, loss of muscle tissue, muscle wasting, muscle catabolism, osteoporosis, decreased linear growth, neurodegenerative and psychiatric disorders, Alzheimers disease, neuronal death, impaired cognitive function, depression, anxiety, eating disorders, appetite regulation, migraine, epilepsia, addiction to chemical substances, disorders of intraocular pressure, glaucoma, polycystic ovary syndrome (PCOS), inappropriate immune responses, inappropriate T heIper-1/T helper-2 polarisation, bacterial infections, mycobacterial infections, fungal infections, viral infections, parasitic infestations, suboptimal responses to immunizations, immune dysfunction, partial or complete baldness, or other diseases, disorders or conditions that are influenced by intracellular glucocorticoid levels and any combination thereof, adverse effects of glucocorticoid receptor agonist treatment of allergic- inflammatory diseases such as asthma and atopic dermatitis, adverse effects of glucocorticoid receptor agonist treatment of disorders of the respiratory system e.g. asthma, cystic fibrosis, emphysema, bronchitis, hypersensitivity, pneumonitis, eosinophilic pneumonias, pulmonary fibrosis, adverse effects of glucocorticoid receptor agonist treatment of inflammatory bowel disease such as Crohn's disease and ulcerative colitis; adverse effects of glucocorticoid receptor agonist treatment of disorders of the immune system, connective tissue and joints e.g. reactive arthritis, rheumatoid arthritis, Sjόgren's syndrome, systemic lupus erythematosus, lupus nephritis, Henoch-Schόnlein purpura, Wegener's granulomatosis, temporal arteritis, systemic sclerosis, vasculitis, sarcoidosis, dermatomyositis-polymyositis, pemphigus vulgaris; adverse effects of glucocorticoid receptor agonist treatment of endocrinological diseases such as hyperthyroidism, hypoaldosteronism, hypopituitarism; adverse effects of glucocorticoid receptor agonist treatment of hematological diseases e.g. hemolytic anemia, thrombocytopenia, paroxysmal nocturnal hemoglobinuria; adverse effects of glucocorticoid receptor agonist treatment of cancer such as spinal cord diseases, neoplastic compression of the spinal cord, brain tumours, acute lymphoblastic leukemia, Hodgkin's disease, chemotherapy-induced nausea, adverse effects of glucocorticoid receptor agonist treatment of diseases of muscle and at the neuro-muscular joint e.g. myasthenia gravis and heriditary myopathies (e.g. Duchenne muscular dystrophy), adverse effects of glucocorticoid receptor agonist treatment in the context of surgery & transplantation e.g. trauma, post- surgical stress, surgical stress, renal transplantation, liver transplantation, lung transplantation, pancreatic islet transplantation, blood stem cell transplantation, bone marrow transplantation, heart transplantation, adrenal gland transplantation, tracheal transplantation, intestinal transplantation, corneal transplantation, skin grafting, keratoplasty, lens implantation and other procedures where immunosuppression with glucocorticoid receptor agonists is beneficial; adverse effects of glucocorticoid receptor agonist treatment of brain absess, nausea/vomiting, infections, hypercalcemia, adrenal hyperplasia, autoimmune hepatitis, spinal cord diseases, saccular aneurysms; or adverse effects to glucocorticoid receptor agonist treatment in other diseases, disorders and conditions where glucocorticoid receptor agonists provide clinically beneficial effects. Accordingly, in a further aspect the invention relates to a compound according to the invention for use as a pharmaceutical composition. The invention also relates to pharmaceutical compositions comprising, as an active ingredient, at least one compound according to the invention together with one or more pharmaceutically acceptable carriers or diluents.
The pharmaceutical composition is preferably in unit dosage form, comprising from about 0.05 mg/day to about 2000 mg/day, preferably from about 1 mg/day to about 500 mg/day of a compound according to the invention.
In another embodiment, the patient is treated with a compound according to the invention for at least about 1 week, for at least about 2 weeks, for at least about 4 weeks, for at least about 2 months or for at least about 4 months. In yet another embodiment, the pharmaceutical composition is for oral, nasal, transdermal, pulmonal or parenteral administration.
Furthermore, the invention relates to the use of a compound according to the invention for the preparation of a pharmaceutical composition for the treatment, prevention and/or prophylaxis of disorders and diseases wherein a modulation or an inhibition of the activity of 110-HSD1 is beneficial.
The invention also relates to a method for the treatment, prevention and/or prophylaxis of disorders and diseases wherein a modulation or an inhibition of the activity of 11 ?-HSD1 is beneficial, the method comprising administering to a subject in need thereof an effective amount of a compound according to the invention. In a preferred embodiment of the invention the present compounds are used for the preparation of a medicament for the treatment, prevention and/or prophylaxis of any diseases and conditions that are influenced by intracellular glucocorticoid levels as mentioned above. Thus, in a preferred embodiment of the invention the present compounds are used for the preparation of a medicament for the treatment, prevention and/or prophylaxis of conditions and disorders where a decreased level of active intracellular glucocorticoid is desirable, such as the conditions and diseases mentioned above.
In yet a preferred embodiment of the invention the present compounds are used for the preparation of a medicament for the treatment, prevention and/or prophylaxis of the metabolic syndrome including insulin resistance, dyslipidemia, hypertension and obesity. In yet another preferred embodiment of the invention the present compounds are used for the preparation of a medicament for the treatment, prevention and/or prophylaxis of type 2 diabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG).
In yet another preferred embodiment of the invention the present compounds are used for the preparation of a pharmaceutical composition for the delaying or prevention of the progression from IGT to type 2 diabetes. In yet another preferred embodiment of the invention the present compounds are used for the preparation of a pharmaceutical composition for the delaying or prevention of the progression of the metabolic syndrome into type 2 diabetes.
In still another preferred embodiment of the invention the present compounds are used for the preparation of a pharmaceutical composition for the treatment, prevention and/or prophylaxis of diabetic late complications including cardiovascular diseases; arteriosclerosis; atherosclerosis.
In a further preferred embodiment of the invention the present compounds are used for the preparation of a pharmaceutical composition for the treatment, prevention and/or prophylaxis of neurodegenerative and psychiatric disorders.
In yet a further preferred embodiment of the invention the present compounds are used for the preparation of a pharmaceutical composition for the treatment, prevention and/or prophylaxis of adverse effects of glucocorticoid receptor agonist therapy.
In another embodiment of the present invention, the route of administration may be any route which effectively transports a compound according to the invention to the appropriate or desired site of action, such as oral, nasal, buccal, transdermal, pulmonal, or parenteral.
In still a further aspect of the invention the present compounds are administered in combination with one or more further active substances in any suitable ratios. Such further active substances may e.g. be selected from antiobesity agents, antidiabetics, agents modifying the lipid metabolism, antihypertensive agents, glucocorticoid receptor agonists, agents for the treatment and/or prevention of complications resulting from or associated with diabetes and agents for the treatment and/or prevention of complications and disorders resulting from or associated with obesity. > Thus, in a further aspect of the invention the present compounds may be administered in combination with one or more antiobesity agents or appetite regulating agents.
Such agents may be selected from the group consisting of CART (cocaine amphetamine regulated transcript) agonists, NPY (neuropeptide Y) antagonists, MC4 (melanocortin 4) agonists, orexin antagonists, TNF (tumor necrosis factor) agonists, CRF (corticotropin releasing factor) agonists, CRF BP (corticotropin releasing factor binding protein) antagonists, urocortin agonists, β3 agonists, MSH (melanocyte-stimulating hormone) agonists, MCH (melanocyte-concentrating hormone) antagonists, CCK (cholecystokinin) agonists, serotonin re-uptake inhibitors, serotonin and noradrenaline re-uptake inhibitors, mixed serotonin and noradrenergic compounds, 5HT (serotonin) agonists, bombesin agonists, galanin antagonists, growth hormone, growth hormone releasing compounds, TRH (thyreotropin releasing hormone) agonists, UCP 2 or 3 (uncoupling protein 2 or 3) modulators, leptin agonists, DA agonists (bromocriptin, doprexin), lipase/amylase inhibitors, PPAR (peroxisome proliferator-activated receptor) modulators, RXR (retinoid X receptor) modulators, TR β agonists, AGRP (Agouti related protein) inhibitors, H3 histamine antagonists, opioid antagonists (such as naltrexone), exendin-4, GLP-1 and ciliary neurotrophic factor.
In one embodiment of the invention the antiobesity agent is leptin; dexamphetamine or amphetamine; fenfluramine or dexfenfluramine; sibutramine; orlistat; mazindol or phentermine.
Suitable antidiabetic agents include insulin, insulin analogues and derivatives such as those disclosed in EP 792 290 (Novo Nordisk A S), eg NεB29-tetradecanoyl des (B30) human insulin, EP 214 826 and EP 705 275 (Novo Nordisk A/S), eg AspB28 human insulin, US 5,504,188 (Eli Lilly), eg LysB28 Pro629 human insulin, EP 368 187 (Aventis), eg Lantus, which are all incorporated herein by reference, GLP-1 (glucagon like peptide-1) and GLP-1 derivatives such as those disclosed in WO 98/08871 to Novo Nordisk A/S, which is incorporated herein by reference as well as orally active hypoglycaemic agents.
The orally active hypoglycaemic agents preferably comprise sulphonylureas, biguanides, meglitinides, glucosidase inhibitors, glucagon antagonists such as those disclosed in WO 99/01423 to Novo Nordisk A/S and Agouron Pharmaceuticals, Inc., GLP-1 agonists, potassium channel openers such as those disclosed in WO 97/26265 and WO 99/03861 to Novo Nordisk A/S which are incorporated herein by reference, DPP-IV (dipeptidyl peptidase- IV) inhibitors, inhibitors of hepatic enzymes involved in stimulation of gluconeogenesis and/or glycogenolysis, glucose uptake modulators, compounds modifying the lipid metabolism such as antihyperlipidemic agents and antilipidemic agents as PPARσ modulators, PPARc. modulators, cholesterol absorption inhibitors, HSL (hormone-sensitive lipase) inhibitors and HMG CoA inhibitors (statins), nicotinic acid, fibrates, anion exchangers, compounds lowering food intake, bile acid resins, RXR agonists and agents acting on the ATP-dependent potassium channel of the β-cells.
In one embodiment, the present compounds are administered in combination with insulin or an insulin analogue or derivative, such as NεB29-tetradecanoyl des (B30) human insulin, AspB28 human insulin, LysB28 ProB29 human insulin, Lantus®, or a mix-preparation comprising one or more of these.
In a further embodiment the present compounds are administered in combination with a sulphonylurea e.g. tolbutamide, glibenclamide, glipizide or glicazide.
In another embodiment the present compounds are administered in combination with a biguanide e.g. metformin. In yet another embodiment the present compounds are administered in combination with a meglitinide e.g. repaglinide or senaglinide.
In still another embodiment the present compounds are administered in combination with a thiazolidinedione e.g. troglitazone, ciglitazone, pioglitazone, rosiglitazone or compounds disclosed in WO 97/41097 such as 5-[[4-[3-Methyl-4-oxo-3,4-dihydro-2-quinazo- linyl]methoxy]phenyl-methyl]thiazolidine-2,4-dione or a pharmaceutically acceptable salt thereof, preferably the potassium salt.
In yet another embodiment the present compounds may be administered in combination with the insulin sensitizers disclosed in WO 99/19313 such as (-) 3-[4-[2- Phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or a pharmaceutically acceptable salts thereof, preferably the arginine salt.
In a further embodiment the present compounds are administered in combination with an α-glucosidase inhibitor e.g. miglitol or acarbose.
In another embodiment the present compounds are administered in combination with an agent acting on the ATP-dependent potassium channel of the β-cells e.g. tolbutamide, glibenclamide, glipizide, glicazide or repaglinide.
Furthermore, the present compounds may be administered in combination with nateglinide.
In still another embodiment the present compounds are administered in combination with an antihyperlipidemic agent or antilipidemic agent e.g. cholestyramine, colestipol, clofibrate, gemfibrozil, fenofibrate, bezafibrate, tesaglitazar, EML-4156, LY-818, MK-767, atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin, acipimox, probucol, ezetimibe or dextrothyroxine.
In a further embodiment the present compounds are administered in combination with more than one ofthe above-mentioned compounds e.g. in combination with a sulphonylurea and metformin, a sulphonylurea and acarbose, repaglinide and metformin, insulin and a sulphonylurea, insulin and metformin, insulin, insulin and lovastatin, etc.
Further, the present compounds may be administered in combination with one or more antihypertensive agents. Examples of antihypertensive agents are β-blockers such as alprenolol, atenolol, timolol, pindolol, propranolol, metoprolol, bisoprololfumerate, esmolol, acebutelol, metoprolol, acebutolol, betaxolol, celiprolol, nebivolol, tertatolol, oxprenolol, amusolalul, carvedilol, labetalol, ?2-receptor blockers e.g. S-atenoloI, OPC-1085, ACE (angiotensin converting enzyme) inhibitors such as quinapril, lisinopril, enalapril, captopril, benazepril, perindopril, trandolapril, fosinopril, ramipril, cilazapril, delapril, imidapril, moexipril, spirapril, temocapril, zofenopril, S-5590, fasidotril, Hoechst-Marion Roussel: 100240 (EP 00481522), omapatrilat, gemopatrilat and GW-660511 , calcium channel blockers such as nifedipine, felodipine, nicardipine, isradipine, nimodipine, diltiazem, amlodipine, nitrendipine, verapamil, lacidipine, lercanidipine, aranidipine, cilnidipine, clevidipine, azelnidipine, barnidipine, efonodipine, iasidipine, iemildipine, iercanidipine, manidipine, nilvadipine, pranidipine, furnidipine, α-blockers such as doxazosin, urapidil, prazosin, terazosin, bunazosin and OPC-28326, diuretics such as thiazides/sulphonamides (e.g. bendroflumetazide, chlorothalidone, hydrochlorothiazide and clopamide), loop-diuretics (e.g. bumetanide, furosemide and torasemide) and potassium sparing diuretics (e.g. amiloride, spironolactone), endothelin ET-A antagonists such as ABT-546, ambrisetan, atrasentan, SB-234551 , CI-1034, S-0139 and YM-598, endothelin antagonists e.g. bosentan and J-104133, renin inhibitors such as aliskiren, vasopressin V1 antagonists e.g. OPC-21268, vasopressin V2 antagonists such as tolvaptan, SR-121463 and OPC-31260, B-type natriuretic peptide agonists e.g. Nesiritide, angiotensin II antagonists such as irbesartan, candesartancilexetil, losartan, valsartan, telmisartan, eprosartan, candesartan, CL-329167, eprosartan, iosartan, olmesartan, pratosartan, TA-606, and YM-358, 5-HT2 agonists e.g. fenoldopam and ketanserin, adenosine A1 antagonists such as naftopidil, N-0861 and FK-352, thromboxane A2 antagonists such as KT2-962, endopeptidase inhibitors e.g. ecadotril, nitric oxide agonists such as LP-805, dopamine D1 antagonists e.g. MYD-37, dopamine D2 agonists such as nolomirole, n-3 fatty acids e.g. omacor, prostacyclin agonists such as treprostinil, beraprost, PGE1 agonists e.g. ecraprost, Na+/K+ ATPase modulators e.g. PST-2238, Potassium channel activators e.g. KR-30450, vaccines such as PMD-3117, Indapamides, CGRP-unigene, guanylate cyclase stimulators, hydralazines, methyldopa, docarpamine, moxonidine, CoAprovel, MondoBiotech- 811.
Further reference can be made to Remington: The Science and Practice of Pharmacy, 19th Edition, Gennaro, Ed., Mack Publishing Co., Easton, PA, 1995.
Furthermore, the present compounds may be administered in combination with one or more glucocorticoid receptor agonists. Examples of such glucocorticoid receptor agonists are betametasone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, beclomethasone, butixicort, clobetasol, flunisolide, flucatisone (and analogues), momethasone, triamcinolonacetonide, triamcinolonhexacetonide GW-685698, NXC-1015, NXC-1020, NXC-1021, NS-126, P-4112, P-4114, RU-24858 and T-25 series.
It should be understood that any suitable combination of the compounds according to the invention with one or more of the above-mentioned compounds and optionally one or more further pharmacologically active substances are considered to be within the scope of the present invention. PHARMACEUTICAL COMPOSITIONS
The compounds of the present invention may be administered alone or in combination with pharmaceutically acceptable carriers or excipients, in either single or multiple doses as part of combination therapy comprising antihypertensive agents. The pharmaceutical compositions according to the invention may be formulated with pharmaceutically acceptable carriers or diluents as well as any other known adjuvants and excipients in accordance with conventional techniques such as those disclosed in Remington: The Science and Practice of Pharmacy, 19th Edition, Gennaro, Ed., Mack Publishing Co., Easton, PA, 1995.
The pharmaceutical compositions may be specifically formulated for administration by any suitable route such as the oral, rectal, nasal, pulmonary, topical (including buccal and sublingual), transdermal, intracisternal, intraperitoneal, vaginal and parenteral (including subcutaneous, intramuscular, intrathecal, intravenous and intradermal) route, the oral route being preferred. It will be appreciated that the preferred route will depend on the general condition and age of the subject to be treated, the nature of the condition to be treated and the active ingredient chosen.
Pharmaceutical compositions for oral administration include solid dosage forms such as hard or soft capsules, tablets, troches, dragees, pills, lozenges, powders and granules. Where appropriate, they can be prepared with coatings such as enteric coatings or they can be formulated so as to provide controlled release of the active ingredient such as sustained or prolonged release according to methods well-known in the art.
Liquid dosage forms for oral administration include solutions, emulsions, suspensions, syrups and elixirs.
Pharmaceutical compositions for parenteral administration include sterile aqueous and non- aqueous injectable solutions, dispersions, suspensions or emulsions as well as sterile powders to be reconstituted in sterile injectable solutions or dispersions prior to use. Depot injectable formulations are also contemplated as being within the scope of the present invention.
Other suitable administration forms include suppositories, sprays, ointments, cremes, gels, inhalants, dermal patches, implants etc. A typical oral dosage is in the range of from about 0.001 to about 100 mg/kg body weight per day, preferably from about 0.01 to about 50 mg/kg body weight per day, and more preferred from about 0.05 to about 10 mg/kg body weight per day administered in one or more dosages such as 1 to 3 dosages. The exact dosage will depend upon the frequency and mode of administration, the sex, age, weight and general condition of the subject treated, the nature and severity of the condition treated and any concomitant diseases to be treated and other factors evident to those skilled in the art. The formulations may conveniently be presented in unit dosage form by methods known to those skilled in the art. A typical unit dosage form for oral administration one or more times per day such as 1 to 3 times per day may contain from 0.05 to about 2000 mg, e.g. from about 0.1 to about 1000 mg, from about 0.5 mg to about 500 mg., from about 1 mg to about 200 mg, e.g. about 100 mg.
For parenteral routes, such as intravenous, intrathecal, intramuscular and similar administration, typically doses are in the order of about half the dose employed for oral administration.
The compounds of this invention are generally utilized as the free substance or as a pharmaceutically acceptable salt thereof. Examples are an acid addition salt of a compound having the utility of a free base and a base addition salt of a compound having the utility of a free acid. The term "pharmaceutically acceptable salts" refers to non-toxic salts ofthe compounds for use according to the present invention which are generally prepared by reacting the free base with a suitable organic or inorganic acid or by reacting the acid with a suitable organic or inorganic base. When a compound for use according to the present invention, contains a free base such salts are prepared in a conventional manner by treating a solution or suspension of the compound with a chemical equivalent of a pharmaceutically acceptable acid. When a compounds for use according to the present invention, contains a free acid such salts are prepared in a conventional manner by treating a solution or suspension of the compound with a chemical equivalent of a pharmaceutically acceptable base. Physiologically acceptable salts of a compound with a hydroxy group include the anion of said compound in combination with a suitable cation such as sodium or ammonium ion. Other salts which are not pharmaceutically acceptable may be useful in the preparation of compounds for use according to the present invention and these form a further aspect of the present invention. For parenteral administration, solutions of the present compounds in sterile aqueous solution, aqueous propylene glycol or sesame or peanut oil may be employed. Such aqueous solutions should be suitable buffered if necessary and the liquid diluent first rendered isotonic with sufficient saline or glucose. The aqueous solutions are particularly suitable for intravenous, intramuscular, subcutaneous and intraperitoneal administration. The sterile aqueous media employed are all readily available by standard techniques known to those skilled in the art. Suitable pharmaceutical carriers include inert solid diluents or fillers, sterile aqueous solution and various organic solvents. Examples of suitable carriers are water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, peanut oil, olive oil, syrup, phospholipids, gelatine, lactose, terra alba, sucrose, cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin, acacia, stearic acid or lower alkyl ethers of cellulose, silicic acid, fatty acids, fatty acid amines, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid esters, polyoxyethylene, hydroxymethylcellulose and polyvinylpyrrolidone. Similarly, the carrier or diluent may include any sustained release material known in the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax. The formulations may also include wetting agents, emulsifying and suspending agents, preserving agents, sweetening agents or flavouring agents.
The pharmaceutical compositions formed by combining the compounds of the invention and the pharmaceutically acceptable carriers are then readily administered in a variety of dosage forms suitable for the disclosed routes of administration. The formulations may conveniently be presented in unit dosage form by methods known in the art of pharmacy. Formulations of the present invention suitable for oral administration may be presented as discrete units such as capsules or tablets, each containing a predetermined amount of the active ingredient, and which may include a suitable excipient. These formulations may be in the form of powder or granules, as a solution or suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion. Compositions intended for oral use may be prepared according to any known method, and such compositions may contain one or more agents selected from the group consisting of sweetening agents, flavouring agents, colouring agents, and preserving agents in order to provide pharmaceutically elegant and palatable preparations. Tablets may contain the active ingredient in admixture with non-toxic pharmaceutically-acceptable excipients which are suitable for the manufacture of tablets. These excipients may be for example, inert diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example corn starch or alginic acid; binding agents, for example, starch, gelatine or acacia; and lubricating agents, for example magnesium stearate, stearic acid or talc. The tablets may be uncoated or they may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate may be employed. They may also be coated by the techniques described in U.S. Patent Nos. 4,356,108; 4,166,452; and 4,265,874, incorporated herein by reference, to form osmotic therapeutic tablets for controlled release. Formulations for oral use may also be presented as hard gelatine capsules where the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or a soft gelatine capsule wherein the active ingredient is mixed with water or an oil medium, for example peanut oil, liquid paraffin, or olive oil.
Aqueous suspensions may contain the active compounds in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients are suspending agents, for example sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents may be a naturally-occurring phosphatide such as lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example, heptadecaethyl-eneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan monooleate. The aqueous suspensions may also contain one or more colouring agents, one or more flavouring agents, and one or more sweetening agents, such as sucrose or saccharin.
Oily suspensions may be formulated by suspending the active ingredient in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as a liquid paraffin. The oily suspensions may contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol. Sweetening agents such as those set forth above, and flavouring agents may be added to provide a palatable oral preparation. These compositions may be preserved by the addition of an anti-oxidant such as ascorbic acid.
Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water provide the active compound in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified by those already mentioned above. Additional excipients, for example, sweetening, flavouring, and colouring agents may also be present.
The pharmaceutical compositions comprising a compound for use according to the present invention may also be in the form of oil-in-water emulsions. The oily phase may be a vegetable oil, for example, olive oil or arachis oil, or a mineral oil, for example a liquid paraffin, or a mixture thereof. Suitable emulsifying agents may be naturally-occurring gums, for example gum acacia or gum tragacanth, naturally-occurring phosphatides, for example soy bean, lecithin, and esters or partial esters derived from fatty acids and hexitol anhydrides, for example sorbitan monooleate, and condensation products of said partial esters with ethylene oxide, for example polyoxyethylene sorbitan monooleate. The emulsions may also contain sweetening and flavouring agents.
Syrups and elixirs may be formulated with sweetening agents, for example glycerol, propylene glycol, sorbitol or sucrose. Such formulations may also contain a demulcent, preservative, flavouring and colouring agents. The pharmaceutical compositions may be in the form of a sterile injectable aqueous or oleaginous suspension. This suspension may be formulated according to the known methods using suitable dispersing or wetting agents and suspending agents described above. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally-acceptable diluent or solvent, for example as a solution in 1 ,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are conveniently employed as solvent or suspending medium. For this purpose, any bland fixed oil may be employed using synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables.
The compositions may also be in the form of suppositories for rectal administration ofthe compounds of the present invention. These compositions can be prepared by mixing the drug with a suitable non-irritating excipient which is solid at ordinary temperatures but liquid at the rectal temperature and will thus melt in the rectum to release the drug. Such materials include cocoa butter and polyethylene glycols, for example.
For topical use, creams, ointments, jellies, solutions of suspensions, etc., containing the compounds of the present invention are contemplated. For the purpose of this application, topical applications shall include mouth washes and gargles. The compounds for use according to the present invention may also be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles, and multilamellar vesicles. Liposomes may be formed from a variety of phospholipids, such as cholesterol, stearylamine, or phosphatidylcholines.
In addition, some ofthe compounds for use according to the present invention may form solvates with water or common organic solvents. Such solvates are also encompassed within the scope of the present invention.
Thus, in a further embodiment, there is provided a pharmaceutical composition comprising a compound and antihypertensive agent(s) for use according to the present invention, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and one or more pharmaceutically acceptable carriers, excipients, or diluents. if a solid carrier is used for oral administration, the preparation may be tabletted, placed in a hard gelatine capsule in powder or pellet form or it can be in the form of a troche or lozenge. The amount of solid carrier will vary widely but will usually be from about 25 mg to about 1 g. If a liquid carrier is used, the preparation may be in the form of a syrup, emulsion, soft gelatine capsule or sterile injectable liquid such as an aqueous or non-aqueous liquid suspension or solution.
A typical tablet which may be prepared by conventional tabletting techniques may contain: Core: Active compound (as free compound or salt thereof) 5.0 mg
Lactosum Ph. Eur. 67.8 mg Cellulose, microcryst. (Avicel) 31.4 mg AmberliteφIRP88* 1.0 mg Magnesii stearas Ph. Eur. q.s.
Coating:
Hydroxypropyl methylcellulose approx.9 mg Mywacett 9-40 T** approx.0.9 mg
Polacrillin potassium NF, tablet disintegrant, Rohm and Haas. * Acylated monoglyceride used as plasticizer for film coating.
The compounds of the invention may be administered to a patient which is a mammal, especially a human. Such mammals include animals, both domestic animals, e.g. household pets, and non-domestic animals such as wildlife.
PHARMACOLOGICAL METHODS
Materials:
3H-cortisone, 3H-cortisol and scintillation proximity assay (SPA) beads were purchased from Amersham Pharmacia Biotech, β-NADPH and β-NAO were from Sigma Chemical Co, rabbit anti-cortisol antibodies were from Fitzgerald and sheep-anti-11-dehydrocorticosterone antibodies were from Chemicon International INC. Hepes and phosphate-buffered saline were purchased from Life Technologies. The test compounds were dissolved in DMSO (10 mM). All dilutions were performed in a buffer containing 50 mM TRIS-HCI (Sigma Chemical Co) , 4 mM EDTA (Sigma Chemical Co), 0.1% BSA (Sigma Chemical Co), 0.01% Tween-20 (Sigma Chemical Co) and 0.005% bacitracin (Novo Nordisk A/S), pH=7.4. Optiplate 96 wells plates were supplied by Packard. The amount of radioligand bound to the SPA beads was measured on TopCount NXT, Packard.
Experimental procedures in vitro:
11ff-HSD1 enzymatic activity assay:
An extract of yeast transformed with h-11 β HSD1 (Hult et al., FEBS Lett., 441, 25 (1998)) was used as the source of enzyme. Enzyme preparation, 120 nM 3H-cortisone, 4 mM 7-NADPH, rabbit-anti cortisol antibody (1:200), serial dilutions of test compound and anti-rabbit Ig coated SPA particles (2 mg/well) were added to the wells. The reaction was initiated by mixing the different components and was allowed to proceed under shaking for 60 min at 30°C. The reaction was stopped be the addition of 10 fold excess of a stopping buffer containing 500 μ M carbenoxolone and 1.0 μM cortisone. Data was analysed using GraphPad Prism software.
Selectivity vs. h-11/?HSD2:
Baby hamster kidney (BHK) cells were transfected with full-length h-11 ?HSD2. The cells were sonicated in phosphate-buffered saline containing 10 mM HEPES (Life Technologies). The cell lysate was used as the source of enzyme. Enzyme preparation, 50 nM 3H-cortisol, 4 mM β -NAD, antibody (1 :40), serial dilutions of test compound and anti-sheep Ig coated SPA particles (1 mg/well) were added to the wells of 96-well plates. The reaction was initiated by mixing the different components and was allowed to proceed under shaking for 30 min at 30°C. The reaction was stopped be the addition of 10 fold excess of a stopping buffer containing 5 μM carbenoxolone. Data was analysed using GraphPad Prism software.
Animal studies
Pharmacological activity may be determined in an in vivo test procedure in rats as follows:
Spontaneously hypertensive rats (SHR) are allowed to acclimatise for at least 2 weeks after which a telemetry-transducer is surgically implanted in the aorta according to the manufacturer's instructions. The rats are allowed to restitute for at least 4 weeks, and acclimatise to the test facility. Throughout the experiment, the rats are kept in their home cages at a standard 12 hour light - 12 hour dark cycle at 20 ± 2°C with free access to standard laboratory rat chow and drinking water. The combination according to the present invention or the active ingredients alone are dissolved in a vehicle appropriate for the chosen route of administration and administered in fixed amounts alone or in combination to the test animals. At predetermined time-points blood pressure is determined. Synergy versus additivity is tested at each of the doses used in combination, using a contrast between the mean from the combination group and the sum of the means from each monotherapy group.
While the invention has been described and illustrated with reference to certain particular embodiments thereof, those skilled in the art will appreciate that various adaptations, changes, modifications, substitutions, deletions, or additions of procedures and protocols may be made without departing from the spirit and scope of the invention. All references cited herein are hereby incorporated by reference in their entirety.

Claims

1. A combination therapy which comprises an 1 λβ -hydroxysteroid dehydrogenase type 1 (11 ?-HSD1) inhibitor and an antihypertensive agent.
2. The combination according to claim 1 wherein the 11β-HSDI inhibitor is of the formula (I):
Figure imgf000170_0001
Formula (I)
wherein
R1 and R2 independently are hydrogen, halo, C(=0)NR6R7, C02R15, NR6C(=0)R11, OR12 or SR12;
R3and R5 independently are hydrogen, NR13R14, trihalomethyl, trihalomethoxy, CrC6aIkyl, C2- C6alkenyl, C2-C6alkynyl, CrC6alkyloxy, CrC6alkylthio, aryl, aryld-Cealkyl, hetaryl or hetaryld-Cealkyl, wherein alkyl, alkynyl, alkenyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R8;
R4 is hydrogen, cyano, halo, C02R15, C(=0)NR6R7, CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrC6alkyl, hydroxy, CrC6alkyloxy, arylCrC6alkyloxy, hetarylCrCealkyloxy, or CrCealkyloxyCrCealkyl, wherein the alkyl, alkynyl, alkenyl, cycloalkyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R9;
R6 and R7 independently are CrC6alkyl, C3-C10cycloalkyl, hetC3-C10cycloalkyl, arylCrC6alkyl or hetarylCrC6alkyl, wherein the alkyl, cycloalkyl, hetcycloalkyl, arylalkyl, and hetarylalkyl groups independently are optionally substituted with one or more of R10; or
R6 and R7 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C6alkyl, aryl, hetaryl, arylCrCealkyl, halo, hydroxy, oxo, CrC6alkyloxy, aryld-C6alkyloxy, hetaryld-Cealkyloxy, d-Cealkyloxyd- C6alkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetaryld- C6alkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, aryld-C6alkylcarboxy or hetarylCrC6aIkylcarboxy;
R8 and R9 independently are hydrogen, halo, hydroxy, oxo, cyano, nitro, C3-Cι0cycloalkyl, C3- Ciohetocydoalkyl, CrC6alkyl, C C6alkyloxy, trihalomethyl, trihalomethoxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrC6alkylcar- bonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy, hetarylCrC6alkylcarboxy, CrC6alkylcarbonylamino or aryICrC6alkylcarbonyl- amino;
R10 is hydrogen, halo, cyano, nitro, hydroxy, oxo, C3-C10cycloalkyl, C3-Cι0hetcycloalkyl, d-C6- alkyl, CrC6alkyloxy, trihalomethyl, trihalometh dialkylamino oxy, arylCrCealkyloxy, hetaryld- C6alkyloxy, CrC6alkyIcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R11 is d-Cealkyl, C2-C6alkenyl, C2-C6alkynyl, arylCrC6alkyl, hetarylCrC6alkyl, d-C6alkyl- carbonyld-C6aIkyI, d-C6alkyloxy, aryloxy, CrC6alkyloxy, arylcarbonyl, arylCrCealkylcarbonyl, hetarylcarbonyICrC6alkyl, wherein the alkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R9;
R12 is d-CealkylcarbonylaminoCrCealkyl, arylcarbonylaminoCrC6aIkyl or arylCrC6alkyl- carbonylaminoCrC6alkyl;
R13and R14 independently are hydrogen, oxo, C3-C10cycloalkyl, CrC6alkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrC6alkylcarbonyl, hetarylCrC6alkylcarbonyl;
R15 is hydrogen, C3-Cι0cycloalkyl, CrC6alkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrCealkyl, CrC6alkyloxyalkyl or arylCrC6alkyIoxyalkyl; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
3. The combination according to claim 2 wherein the 11 ?-HSD1 inhibitor is of the formula (I) wherein R1 and R2 independently are hydrogen, halo, C(=0)NR6R7, NC(=0)R11, OR12 or SR12;
R3and R5 independenly are hydrogen, NR13R14 trihalomethyl, trihalomethoxy, CrC6aIkyl, C2- C6alkenyl, C2-C6alkynyl, CrC6alkyloxy, CrC6alkylthio, aryl, arylCrC6alkyl, hetaryl or hetarylCrC6alkyl, wherein alkyl, alkynyl, alkenyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R8;
R4 is hydrogen, cyano, halo, C02R15, C(=0)NR6R7, CrCealkyl, C2-C6alkenyl, C2-C6alkynyl, aryl, hetaryl, aryICrC6alkyl, hetarylCrC6alkyl, hydroxy, CrC6alkyloxy, arylCrCealkyloxy, hetaryld-Cealkyloxy, or CrCealkyloxyCrCealkyl, wherein the alkyl, alkynyl, alkenyl, cycloalkyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R9;
R6 and R7 independently are d-Cealkyl, C3-C 0cycloalkyl, hetC3-C10cycloalkyl, arylCrC6alkyl or hetarylCrCealkyl, wherein the alkyl, cycloalkyl, hetcycloalkyl, arylalkyl, and hetarylalkyl groups independently are optionally substituted with one or more of R10; or
R6 and R7, together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, arylCrC6alkyl, halo, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, d-Cβalkyloxyd- , C6alkyl, d-C6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetaryld- C6alkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy or hetarylCrC6alkylcarboxy;
R8 and R9 independently are hydrogen, halo, hydroxy, oxo, cyano, nitro, C3-C10cycloalkyl, C3- dohetocycloalkyl, d-Cealkyl, CrC6alkyloxy, trihalomethyl, trihalomethoxy, arylCrC6alkyloxy, hetarylCrC6alkyloxy, CrC6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy, hetarylCrC6alkylcarboxy, CrC6alkyIcarbonylamino or aryld-C6aIkyl- carbonylamino;
R10 is hydrogen, halo, cyano, nitro, hydroxy, oxo, C3-C 0cycloalkyl, C3-C10hetcycloalkyl, CrCealkyl, CrC6alkyloxy, trihalomethyl, trihalometh dialkylamino oxy, aryICrC6alkyloxy, hetaryld- C6alkyloxy, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R11 is C C6alkyl, C2-C6alkenyl, C2-C6alkynyl, aryld-Cealkyl, hetarylCrCealkyl, d-C6alkyl- carbonylCrC6alkyl, CrC6alkyl, arylcarbonyl, arylCrCealkylcarbonyl, hetarylcarbonylCι-C6- alkyl, wherein the alkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R9;
R12 is d-CealkylcarbonylaminoCrCealkyl; arylcarbonylaminoCrC6aIkyl or arylCι-C6alkyl- carbonylaminoCrC6alkyl;
R13and R14 independently are hydrogen, oxo, C3-C10cycloalkyl, CrC6alkyl, CrC6alkyloxy, trihalomethyl, trihalomethoxy, aryld-Cealkyloxy, hetaryld-Cealkyloxy, d-C6alkyIcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrC6alkyl- carboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy;
R15 is hydrogen, C3-Cι0cycloalkyl, CrC6alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, CrC6alkyloxyalkyl or arylCrC6alkyloxyalkyl; or
, a salt thereof with a pharmaceutically acceptable acid or base, or optical isomer, mixture of optical isomers, racemic mixture, or tautomeric form thereof.
4. The combination according to claim 2 or 3 wherein the 11 ?-HSD1 inhibitor is selected from the group: (3-Bromo-5-thiophen-2-yI-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(2,6-dimethyl- piperidin-1 -yl-)-methanone;
(3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(2-ethyl-piperidin-1- yl-)-methanone;
(5-Thiophen-2-yI-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(1 ,3,3-trimethyl-6-aza- bicyclo[3.2.1]oct-6-yl)-methanone;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(2-methyl-piperidin-
1-yl-)-methanone;
5-Methyl-7-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexylamide;
Azepan-1-yl-(3-chloro-5-thiophen-2-yI-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)- methanone; Azepan-1-yl-(3-chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)- methanone;
(2,6-Dimethyl-piperidin-1-yl-)-(3-chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-3-yl) methanone; 3-Bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-carboxylic acid cyclohexylamide;
(7-Methyl-5-phenyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(4-methyl-piperidin-1-yl-methanone;
5-(4-Methoxy-phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid benzyl- methyl-amide; [5-(4-Ethoxy-phenyI-7-methyl-pyrazolo[1 ,5-a]pyrimidine-2-yl)]-piperidin-1 -yl-methanone;
Azepan-1-yl-(3-bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone;
5-Benzo[1 ,3]dioxol-5-yl-7-trifluoromethyI-pyrazolo[1 ,5-a]pyrimidine-3-carboxyIic acid cyclohexyl-methyl-amide;
(3,4-Dihydro-1H-isoquinolin-2-yl)-[5-(-4-Methoxy-phenyl-7-trifluoromethyl-pyrazolo[1 ,5- a]pyrimidin-3-yl]-methanone;
Azepan-1 -yl-[5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-methanone
Azepan-1 -yl-(5,7-diphenyl)-pyrazolo[1,5-a]pyrimidin-3-yl)-methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-(2-methyl-piperidin-1-yl)- methanone; (5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(2-methyl-piperidin-1-ylj- methanone;
(2,6-Dimethyl-piperidin-1-yl-)-[7-(4-ethoxy-phenyl)-5-methyl-pyrazolo[1,5-a]pyrimidin-2- yljmethanone;
5-(4-Ethoxy-phenyl)-7-methyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexylamide; Piperidin-1-yl-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(2-methyl-piperidin-1-yl)- methanone;
(2-Methyl-piperidin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)- methanone; Azepan-1 -yl-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl]- methanone;
5-Thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxyIic acid benzyl-methyl- amide;
5-p-Tolyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid (1 , 3-di methyl- 1.7- pyrazol-4-ylmethyl)-methyl-amide;
5-MethyI-7-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl-amide; 7-Methyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl-amide; (5-Phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone; 5-Naphthalen-1-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl- methyl-amide; 5-Naphthalen-1 -yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexylamide;
(5-Naphthalen-1-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone (2-Methyl-piperidin-1-yl)-(5-naphthalen-1-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone; 5,7-Diphenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexylamide;
5,7-Diphenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl-amide; (5,7-Diphenyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(2-methyl-piperidin-1-yl)-methanone; (5,7-Diphenyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone; 5-Methyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexylamide; (5-Methyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone;
5-Methyl-7-trifluoromethyI-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl- amide;
(2-Methyl-piperidin-1-yl)-(5-methyl-7-trifluoromethyl-pyrazoIo[1 ,5-a]pyrimidin-2-yl)-methanone; 5-Phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a!]pyrimidine-2-carboxylic acid cyclohexylamide; (5-Phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-piperidin-1 -yl-methanone;
7-Phenyl-5-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl- amide;
5-Phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid cyclohexylamide; and (5-Phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-piperidin-1 -yl-methanone; or
a salt thereof with a pharmaceutically acceptable acid or base, or optical isomer, mixture of optical isomers, racemic mixture, or tautomeric form thereof.
5. The combination according to claim 2 or 3 wherein the 11β-HSD1 inhibitor is selected from the group of
5-Methyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid methyl ester;
5-Methyl-7-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid methyl ester;
7-Methyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid methyl ester;
(5-methyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)- (piperidin-1 -yl)methanone; (5-methyl-7-phenyI-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl amide;
7-Methyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl-amide; 7-Phenyl-5-trifluoromethyl-pyrazoIo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl- amide;
(5-Phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone;
(2-Methyl-piperidin-1-yl)-(5-methyl-7-trifluoromethyI-pyrazolo[1 ,5-a]pyrimidin-2-yl)-methanone; 5-Methyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxyIic acid cyclohexyl-methyl- amide;
(5-Methyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone;
(5,7-Diphenyl-pyrazoIo[1 ,5-a]pyrimidin-2-yl)-piperidin-1 -yl-methanone;
(5,7-Diphenyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(2-methyl-piperidin-1-yI)-methanone; 5,7-Diphenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl-amide;
(2-Methyl-piperidin-1-yl)-(5-naphthalen-1-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)- methanone;
(5-Naphthalen-1-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone;
5-NaphthaIen-1-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid cyclohexyl- methyl-amide;
[7-(4-Ethoxy-phenyl)-5-methyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(1,3,3-trimethyl-6-aza- bicyclo[3.2.1 ]oct-6-yl)-methanone;
(2-Methyl-piperidin-1-yl)-(7-phenyl-5-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone; (5-Methyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(1 ,3,3-trimethyl-6-aza- bicyclo[3.2.1]oct-6-yl)-methanone;
(5-Phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(1 ,3,3-trimethyl-6-aza- bicyclo[3.2.1 ]oct-6-yl)-methanone;
(6-Bromo-3-chloro-pyrazolo[1,5-a]pyrimidin-2-yl)-morpholin-4-yl-methanone;
(5-Phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yI)-piperidin-1 -yl-methanone; MorphoIin-4-yl-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone;
(6-Bromo-pyrazoIo[1 ,5-a]pyrimidin-2-yl)-piperidin-1 -yl-methanone;
(6-Bromo-pyrazolo[1,5-a]pyrimidin-2-yl)-morpholin-4-yl-methanone;
(3,6-Dibromo-pyrazolo[1 ,5-a]pyrimidin-2-yl)-morpholin-4-yl-methanone;
(3-Bromo-5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone; (3-Bromo-5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-morpholin-4-yl-methanone;
(3-ChIoro-5-phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-piperidin-1-yl-methanone;
(3-Chloro-5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-morpholin-4-yl-methanone;
(3,6-Dibromo-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1 -yl-methanone;
[4-(4-Fluoro-phenyl)-piperazin-1-yl]-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin- 2-yl)-methanone; 5-Thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl- methyl-amide;
(5-Benzo[1,3]dioxol-5-yl-7-trifluoromethyI-pyrazolo[1,5-a]pyrimidin-2-yl)-(4-methyl-piperazin-1- yl)-methanone; [5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(2-methyl-piperidin-1- yl)-methanone;
3-Chloro-5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid methyl-(2-pyridin-2-yl-ethyl)-amide;
[3-Chloro-5-(4-chloro-phenyI)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(3,4-dihydro-2 -/- quinolin-1 -yl)-methanone;
[5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-[4-(2-methoxy-phenyl)- piperazin-1 -yl]-methanone; (4-Benzoyl-piperazin-1 -yl)-[3-chIoro-5-(4-chloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5- a]pyrimidin-2-yl]-methanone;
4-(5-Benzo[1,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carbonyl)-piperazine-
1 -carboxylic acid ethyl ester;
(5-Benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(6,7-dimethoxy-1 - methyl-3,4-dihydro-1 H-isoquinoIin-2-yl)-methanone;
[4-(Furan-2-carbonyl)-piperazin-1-yl]-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-2-yl]-methanone;
(3-Chloro-5-thiophen-2-yI-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-[4-(2-methoxy- phenyl)-piperazin-1 -ylj-methanone; [5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-piperidin-1 -yl- methanone;
(3,4-Dihydro-2H-quinolin-1-yl)-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone;
(3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(2,6-dimethyl- piperidin-1-yl)-methanone;
(3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(2-ethyl-piperidin-1- yl)-methanone;
3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl-amide; [5-(4-Bromo-phenyl)-3-chloro-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-pyrrolidin-1-yl- methanone; (3-Chloro-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-[4-(4-fluoro-phenyl)- piperazin-1 -ylj-methanone;
(3-Chloro-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(4-phenyl-piperazin-1- yl)-methanone; [3-Chloro-5-(4-chloro-phenyI)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(4-me.thyl- piperazin-1 -yl)-methanone;
Azepan-1 -yl-[3-chloro-5-(4-chloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]- methanone;
[3-Chloro-5-(3,4-dimethoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-pyrrolidin- 1 -yl-methanone;
[5-(4-Chloro-phenyI)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(2-methyl-piperidin-1-yl)- methanone;
(5-Thiophen-2-yl-7-trifluoromethyl-pyrazoIo[1 ,5-a]pyrimidin-2-yl)-(1 ,3,3-trimethyl-6-aza- bicyclo[3.2.1]oct-6-yl)-methanone; [4-(2-Chloro-phenyl)-piperazin-1-yl]-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-
2-yl)-methanone;
(3,4-Dihydro-1H-isoquinolin-2-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- yl)-methanone;
(4-Methyl-piperazin-1-yl)-[5-(4-nitro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]- methanone;
[5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-thiomorpholin-4-yl- methanone;
(3-Bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(3,4-dihydro-2ry- quinolin-1 -yl)-methanone; (5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-pyrrolidin-1 -yl-methanone;
[4-(Furan-2-carbonyl)-piperazin-1-yl]-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5- , a]pyrimidin-2-yl]-methanone;
[5-(4-Nitro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-1-yl-methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-pyrrolidin-1 -yl-methanone; (4-Methyl-piperidin-1-yl)-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone;
(3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-[4-(4-fluoro-phenyl)- piperazin-1 -ylj-methanone;
[4-(4-Fluoro-phenyl)-piperazin-1-yl]-(5-phenyl-7-trifluoromethyl-pyrazoIo[1,5-a]pyrimidin-2-yl)- methanone; [4-(4-Fluoro-phenyI)-piperazin-1-yl]-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-
2-yl)-methanone; [3-Bromo-5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone;
[4-(4-Fluoro-phenyl)-piperazin-1-yl]-(7-methyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidin-2-yI)- methanone; (4-Benzoyl-piperazin-1-yl)-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(4-phenyl-piperazin-
1-yl)-methanone;
(2-Ethyl-piperidin-1-yl)-(5-phenyI-7-trifluoromethyl-pyrazolo[1,5-ajpyrimidin-2-yl)-methanone; (5,7-Diphenyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(4-methyl-piperazin-1-yl)-methanone;
(4-Benzyl-piperazin-1-yl)-(3-chloro-5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(4-methyl-piperazin-
1-yl)-methanone; (4-Phenyl-piperazin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-pyrrolidin-1-yl-methanone;
(5,7-Diphenyl-pyrazolo[1,5-a]pyrimidin-2-yl)-pyrrolidin-1-yl-methanone;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(2-ethyl-piperidin-1- yl)-methanone;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yI)-(2-methyl-piperidin-
1-yl)-methanone;
5-Methyl-7-phenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl-amide;
(3-ChIoro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-morphoIin-4-yl- methanone;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-[4-(4-fluoro-phenyl)- piperazin-1 -ylj-methanone;
(3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(4-methyl-piperazin-
1-yl)-methanone; (7-Methyl-5-phenyI-pyrazolo[1 ,5-a]pyrimidin-2-yl)-piperidin-1 -yl-methanone;
Azepan-1-yl-(3-chIoro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone;
Azepan-1-yl-[3-bromo-5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]- methanone; 3-Bromo-5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl-amide; (2,6-Dimethyl-piperidin-1-yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-
2-yl]-methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(4-methyl-piperazin-1-yl)- methanone; 5-Phenyl-7-trifluoromethyl-pyrazolo[1 ,5-ajpyrimidine-2-carboxylic acid benzyl-methyl-amide;
[5-(4-Ethoxy-phenyl)-7-methyl-pyrazoIo[1,5-a]pyrimidin-2-ylj-(4-phenyl-piperazin-1-yl)- methanone;
(3,4-Dihydro-1H-isoquinolin-2-yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-2-yl]-methanone; Morpholin-4-yl-[5-(4-nitro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-ylj-methanone;
(Hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- yl)-methanone;
(Hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-ajpyrimidin-2- yl)-methanone; (Hexahydro-pyrrolo[1 ,2-a]pyrazin-2-yI)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5- a]pyrimidin-2-yl)-methanone;
(3-Chloro-5-phenyl-7-trifluoromethyI-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(hexahydro-pyrroIo[1,2- a]pyrazin-2-yl)-methanone;
[5-(4-Fluoro-phenyl)-7-methyI-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yl-methanone; (5,7-Diphenyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(2-methyl-piperidin-1 -yl)-methanone;
5-Phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid (1 ,3-dimethyl-1 H- pyrazol-4-ylmethyl)-methyl-amide;
5-Thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid (1 ,5-dimethyl-
1 H pyrazol-4-ylmethyl)-methyl-amide; 5-Thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid methyl-(1 ,3,5- trimethyl-1H-pyrazol-4-ylmethyI)-amide;
3-Chloro-5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid
(1 ,3-dimethyl-1 H-pyrazol-4-ylmethyl)-methyl-amide;
5-(4-Chloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid (1 ,3- dimethyl-1 H-pyrazol-4-ylmethyl)-methyl-amide;
5-(3,4-Dimethoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxyIic acid (1 ,3- dimethyl-1 -/-pyrazol-4-ylmethyI)-methyl-amide;
(2,5-Dimethyl-piperidin-1-yl)-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone; 5-Furan-2-yI-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid methyl-(1 ,3,5- trimethyl-1H-pyrazol-4-ylmethyl)-amide; 5-(4-Chloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid (1 ,5- dimethyl-1H-pyrazol-4-ylmethyl)-methyl-amide;
(2,4-Dimethyl-piperidin-1-yl)-(5-phenyl-7-trifluoromethyI-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone; (3-Bromo-5-phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(hexahydro-pyrrolo[1 ,2- ajpyrazin-2-yl)-methanone;
[5-(3,4-Dimethoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(hexahydro- pyrrolo[1,2-a]pyrazin-2-yl)-methanone;
(3-Chloro-5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(hexahydro-pyrrolo[1,2- a]pyrazin-2-yl)-methanone;
(3-Bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1-yl- methanone;
(3-Chloro-5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-pyrrolidin-1-yl-methanone;
(7-Methyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(4-methyl-piperidin-1-yl)-methanone; (4-Methyl-piperazin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone;
[3-Bromo-5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-1-yl- methanone;
(4-Methyl-piperazin-1-yl)-(5-phenyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone; [4-(4-Fluoro-phenyl)-piperazin-1-yl]-(5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- yl)-methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone;
(3,4-Dihydro-2/.-quinolin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone;
(3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-morpholin-4-yl- methanone;
Azepan-1-yl-(3-chloro-5-phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-methanone;
(4-Benzoyl-piperazin-1-yl)-[5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]- methanone;
(4-Benzyl-piperazin-1-yl)-[5-(4-bromo-phenyl)-3-chloro-7-trifluoromethyl-pyrazolo[1 ,5- a]pyrimidin-2-yl]-methanone;
[5-(4-Bromo-phenyl)-3-chloro-7-trifluoromethyI-pyrazolo[1,5-a]pyrimidin-2-yl]-(4-methyI- piperazin-1 -yl)-methanone; Azepan-1-yl-[5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazoIo[1,5-a]pyrimidin-2-yl]-methanone; [3-Bromo-5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-ylj-(3,4-dihydro-2 -/- quinolin-1 -yl)-methanone;
[5-(3,4-Dimethoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone; (3-Bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yI)-(4-methyl-piperazin-1- yl)-methanone;
(4-Benzoyl-piperazin-1-yl)-(3-bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2- yl)-methanone;
(3-Bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(3,4-dihydro-2 -- quinolin-1 -yl)-methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-1-yl-methanone;
[5-(4-Ethoxy-phenyl)-7-methyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-1-yl-methanone;
[5-(4-Ethoxy-phenyl)-7-methyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yI-methanone;
Azepan-1-yl-(3-bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-methanone; (3,4-Dihydro-1H-isoquinolin-2-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- yl)-methanone;
(4-Benzyl-piperazin-1-yl)-(3-bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- yl)-methanone;
Azepan-1 -yl-[5-(4-bromo-phenyl)-3-chloro-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]- methanone;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(3,4-dihydro-1H- isoquinolin-2-yl)-methanone;
(5-Benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-piperidin-1 -yl- methanone; Azepan-1 -yl-(5,7-diphenyl-pyrazolo[1 ,5-ajpyrimidin-2-yl)-methanone;
Azepan-1 -yl-(5-benzo[1 ,3]dioxoI-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)- methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone; [3-Bromo-5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-ajpyrimidin-2-yl]-morpholin-4-yl- methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-thiomorphoIin-4-yl- methanone;
[5-(4-Bromo-phenyl)-3-chloro-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-1-yl- methanone; (5-Benzo[1 ,3]dioxol-5-yl-7-trifluoromethyI-pyrazoIo[1,5-a]pyrimidin-2-yl)-(3,4-dihydro-2H- quinolin-1 -yl)-methanone;
(5-Benzo[1,3]dioxoI-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(4-benzyl-piperazin-1- yl)-methanone; (5-Benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-morpholin-4-yl- methanone;
[5-(4-Bromo-phenyI)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-[4-(2-methoxy-phenyI)- piperazin-1 -ylj-methanone;
[3-Bromo-5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(4-methyl- piperazin-1 -yl)-methanone;
Azepan-1 -yl-[5-(4-methoxy-phenyI)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]- methanone;
(2,6-Dimethyl-piperidin-1-yl)-[7-(4-ethoxy-phenyI)-5-methyl-pyrazolo[1,5-a]pyrimidin-2-ylj- methanone; (3,4-Dihydro-2 --quinolin-1 -yl)-(5,7-diphenyl-pyrazo!o[1 ,5-a]pyrimidin-2-yl)-methanone;
(3,6-Dibromo-pyrazolo[1 ,5-ajpyrimidin-2-yl)-piperidin-1 -yl-methanone;
(3-Bromo-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-piperidin-1 -yl- methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-thiomorpholin-4-yI- methanone;
[5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-thiomorpholin-4-yl- methanone;
(3,4-Dihydro-1H-isoquinolin-2-yl)-[5-(4-nitro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-
2-yl]-methanone; Azepan-1 -yl-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-ylj- methanone;
Azepan-1 -yl-[5-(4-nitro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-methanone;
[5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone; Azepan-1 -yl-[5-(3,4-dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-ylj- methanone;
(3,4-Dihydro-1H-isoquinolin-2-yl)-(5-phenyl-7-trifluoromethyl-pyrazoIo[1,5-a]pyrimidin-2-yl)- methanone;
[5-(4-Bromo-phenyl)-3-chloro-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-pyrrolidin-1-yl- methanone;
5,7-Diphenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxyIic acid cyclohexyl-methyl-amide; (3,4-Dihydro-1H-isoquinolin-2-yl)-(5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)- methanone;
(4-Benzyl-piperazin-1-yl)-(3-chloro-5-furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)- methanone; [3-Chloro-5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-1 -yl- methanone;
(3-Chloro-5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(4-methyl-piperazin-1-yl)- methanone;
(3-Chloro-5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(4-phenyl-piperazin-1-yl)- methanone;
[3-Chloro-5-(3,4-dimethoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-1- yl-methanone;
[4-(4-Fluoro-phenyl)-piperazin-1-yl]-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)- methanone; (4-Phenyl-piperazin-1 -yl)-(5-p-tolyl-7-trifluoromethyI-pyrazoIo[1 ,5-a]pyrimidin-2-yl)-methanone;
Morpholin-4-yI-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone;
(4-Benzyl-piperazin-1-yl)-(5-p-tolyI-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-methanone;
[5-(4-Chloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-(4-methyl-piperazin-1 -ylj- methanone; [5-(4-Chloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone;
(4-Benzyl-piperazin-1-yl)-[5-(4-chloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-ajpyrimidin-2-yl]- methanone;
[5-(4-Fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-morpholin-4-yl- methanone;
[5-(4-Fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-1-yI-methanone;
(3,4-Dihydro-2H-quinolin-1-yl)-[5-(4-fluoro-phenyI)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- yl]-methanone;
Azepan-1 -yl-[5-(3,4-dimethoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-ylj- methanone;
(4-Benzyl-piperazin-1-yl)-[5-(4-methoxy-phenyI)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- ylj-methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-pyrrolidin-1 -yl- methanone; (5-Benzo[1,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-pyrrolidin-1 -yl- methanone; (3,4-Dihydro-2H-quinolin-1-yl)-[5-(4-nitro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- yl]-methanone;
[3-Chloro-5-(4-methoxy-phenyI)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(4-methyl- piperidin-1 -yl)-methanone; [3-Chloro-5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-(3,4-dihydro-
2H-quinolin-1-yl)-methanone;
3-Chloro-5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid cyclohexyl-methyl-amide;
[3-Chloro-5-(4-fluoro-phenyl)-7-trifluoromethyl-pyrazoIo[1,5-a]pyrimidin-2-yl]-(4-methyl- piperazin-1 -yl)-methanone;
(3-Chloro-5-p-tolyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-morpholin-4-yl-methanone;
Azepan-1-yl-(3-chIoro-5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone;
Azepan-1-yl-[3-chloro-5-(3,4-dimethoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- yl]-methanone; [5-(3,4-Dichloro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-(4-methyl-piperazin-1 - yI)-methanone;
5,7-Diphenyl-pyrazolo[1 ,5-a]pyrimidine-2-carboxylic acid benzyl-methyl-amide;
(5,7-Diphenyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-(4-phenyl-piperazin-1 -yl)-methanone;
Morpholin-4-yl-(5-phenyl-7-trifluoromethyl-pyrazoIo[1 ,5-a]pyrimidin-2-yl)-methanone; Morpholin-4-yl-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-methanone;
Piperidin-1-yl-(5-thiophen-2-yI-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methanone;
[3-Bromo-5-(4-bromo-thiophen-2-yl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-piperidin-
1 -yl-methanone;
(3-Bromo-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-(3,4-dihydro-2H- , quinolin-1 -yl)-methanone;
(3-Chloro-5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-piperidin-1 -yl- methanone;
(7-Methyl-5-phenyl-pyrazolo[1,5-a]pyrimidin-2-yl)-morpholin-4-yl-methanone;
(7-Methyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidin-2-yl)-pyrrolidin-1 -yl-methanone; 7-Methyl-5-phenyl-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid benzyl-methyl-amide;
(2,6-Dimethyl-piperidin-1-yl)-[5-(4-fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2- yl]-methanone;
Azepan-1 -yl-[5-(4-fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-2-yl]-methanone;
[5-(4-Fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yl]-(4-methyl-piperazin-1-yl)- methanone; [5-(4-Fluoro-phenyl)-7-trifluoromethyI-pyrazolo[1 ,5-a]pyrimidin-2-yl]-(4-phenyl-piperazin-1-yl)- methanone;
(2-Ethyl-piperidin-1-yl)-[5-(4-fluoro-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-2-yI]- methanone;
(5-Phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-piperidin-1-yl-methanone;
(5-Methyl-7-phenyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
(5-Thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-(1 ,3,3-trimethyl-6-aza- bicyclo[3.2.1]oct-6-yl)-methanone;
(4-Phenyl-piperazin-1 -yl)-pyrazolo[1 ,5-a]pyrimidin-3-yl-methanone;
Pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid benzyl-(2-hydroxy-ethyl)-amide;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl]-(3,4-dihydro-1 H- isoquinolin-2-yl)-methanone; (5,7-Dimethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-[4-(4-methoxy-phenyl)-piperazin-1 -ylj-methanone;
(3,4-Dihydro-2H-quinolin-1-yl)-[5-(4-fluoro-phenyI)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3- ylj-methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-piperidin-1 -yl-methanone;
Azepan-1-yl-[7-trifluoromethyl-5-(3,4,5-trimethoxy-phenyl)-pyrazolo[1 ,5-a]pyrimidin-3-ylj- methanone;
(5-Benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-pyrrolidin-1 -yl- methanone;
Azepan-1 -yl-(5,7-diphenyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-methanone;
4-(5,7-Dimethyl-pyrazolo[1 ,5-a]pyrimidine-3-carbonyl)-piperazine-1 -carboxylic acid ethyl ester; (3,4-Dihydro-1 H-isoquinolin-2-yl)-(5,7-dimethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-methanone;
[4-(3-Chloro-phenyl)-piperazin-1-yl]-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)- methanone;
(4-Methyl-piperidin-1-yl)-pyrazolo[1 ,5-a]pyrimidin-3-yl-methanone;
[4-(2-Methoxy-phenyl)-piperazin-1-yl]-pyrazolo[1 ,5-a]pyrimidin-3-yl-methanone; (3,4-Dihydro-2H-quinolin-1 -yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5- a]pyrimidin-3-yl]-methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl]-thiomorpholin-4-yl- methanone;
(5-Furan-2-yI-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-(2-methyl-piperidin-1 -yl)- methanone;
(4-BenzyI-piperazin-1-yl)-(5,7-dimethyl-pyrazoIo[1 ,5-a]pyrimidin-3-yl)-methanone; [5-(4-Bromo-phenyl)-7-trifluoromethyI-pyrazolo[1 ,5-a]pyrimidin-3-yl]-morpholin-4-yI- methanone;
(5,7-Dimethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-piperidin-1-yl-methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-[4-(2-methoxy-phenyl)-piperazin- 1 -ylj-methanone;
(5-Phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-piperidin-1 -yl-methanone;
Azepan-1 -yl-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-methanone;
(2,6-Dimethyl-piperidin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)- methanone; [5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-(4-methyl-piperazin-1- yl)-methanone;
(4-Methyl-piperazin-1-yl)-(5-thiophen-2-yI-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)- methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-(4-methyl-piperazin-1-yl)- methanone;
(Hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3- yl)-methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-(hexahydro-pyrrolo[1,2- a]pyrazin-2-yl)-methanone; [5-(3,4-Dimethoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-ajpyrimidin-3-yl]-(hexahydro- pyrrolo[1,2-a]pyrazin-2-yl)-methanone;
1-[5-(3-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carbonyl]-piperidine-4- carboxylic acid ethyl ester;
4-[5-(3-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carbonyl]-piperazine-1- carboxylic acid ethyl ester;
(3,4-Dihydro-2H-quinolin-1 -yl)-[5-(3-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5- a]pyrimidin-3-yl]-methanone;
[4-(4-Fluoro-phenyl)-piperazin-1-yl]-[5-(3-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-3-yl]-methanone; 5-p-Tolyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid (1 ,3-dimethyl-1 H- pyrazol-4-yImethyl)-methyl-amide;
5-p-ToIyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxyIic acid methyl-(1 ,3,5-trimethyl-
1 H-pyrazol-4-ylmethyl)-amide;
[7-Difluoromethyl-5-(4-methoxy-phenyl)-pyrazolo[1,5-a]pyrimidin-3-yl]-(2-ethyl-imidazol-1-yl)- methanone; [7-Difluoromethyl-5-(4-methoxy-phenyl)-pyrazolo[1 ,5-a]pyrimidin-3-yl]-morpholin-4-yl- methanone;
1 -[7-Difluoromethyl-5-(4-methoxy-phenyl)-pyrazolo[1 ,5-a]pyrimidine-3-carbonylj-1 --indole-3- carboxylic acid methyl ester; [4-(4-Chloro-phenyl)-piperazin-1 -yl]-[7-difluoromethyl-5-(4-methoxy-phenyl)-pyrazoIo[1 ,5- a]pyrimidin-3-yl]-methanone;
[7-Difluoromethyl-5-(4-methoxy-phenyl)-pyrazolo[1,5-a]pyrimidin-3-yl]-(2-ethyl-piperidin-1-yl)- methanone;
7-Difluoromethyl-5-p-tolyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid (1-ethyl-5-methyl-1H- pyrazol-4-ylmethyl)-methyl-amide;
1-(7-Difluoromethyl-5-methyl-pyrazolo[1 ,5-a]pyrimidine-3-carbonyl)-piperidine-4-carboxylic acid amide;
(7-Difluoromethyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-(2-ethyI-imidazol-1-yl)-methanone;
(7-Difluoromethyl-5-phenyl-pyrazolo[1,5-a]pyrimidin-3-yl)-thiomorpholin-4-yl-methanone; (7-Difluoromethyl-5-p-tolyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-(4-pyridin-2-yl-piperazin-1-yl)- methanone;
[7-Difluoromethyl-5-(4-methoxy-phenyl)-pyrazolo[1,5-a]pyrimidin-3-yl]-[4-(furan-2-carbonyl)- piperazin-1 -ylj-methanone;
7-Difluoromethyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid (1 -ethyl-3-methyl-1 H- pyrazol-4-ylmethyl)-methyl-amide;
[7-Difluoromethyl-5-(4-methoxy-phenyl)-pyrazolo[1 ,5-a]pyrimidin-3-yl]-thiomorpholin-4-yl- methanone;
(7-Difluoromethyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-(3,4-dihydro-1H-isoquinolin-2-yl)- methanone; (7-Difluoromethyl-5-methyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-piperidin-1 -yl-methanone;
Azepan-1 -yl-(7-difluoromethyl-5-phenyl-pyrazoIo[1,5-a]pyrimidin-3-yl)-methanone;
7-Difluoromethyl-5-p-tolyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxy!ic acid methyl-(1 -methyl-1 /-/- pyrazol-4-ylmethyl)-amide;
(7-Difluoromethyl-5-p-tolyI-pyrazolo[1 ,5-a]pyrimidin-3-yl)-(3-methyl-piperidin-1-yl)-methanone; (7-Difluoromethyl-5-p-tolyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(4-ethyl-piperazin-1-yl)-methanone;
(7-Difluoromethyl-5-p-tolyl-pyrazolo[1 ,5-ajpyrimidin-3-yl)-morpholin-4-yl-methanone;
7-Difluoromethyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid methyl-(1 ,3,5-trimethyl-
1 H-pyrazol-4-yImethyl)-amide;
(7-Difluoromethyl-5-phenyl-pyrazolo[1,5-a]pyrimidin-3-yl)-[4-(2-methyl-2H-pyrazole-3- carbonyl)-piperazin-1 -ylj-methanone;
7-DifluoromethyI-5-p-tolyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid benzyl-methyl-amide; 7-Difluoromethyl-5-(4-methoxy-phenyl)-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid (1-ethyl-3- methyl-1 --pyrazol-4-ylmethyl)-methyl-amide;
7-Difluoromethyl-5-phenyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid methyl-(4-pyrazol-1-yl- benzyl)-amide; Azepan-1 -yl-(5-cyclopropyl-7-difluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-methanone;
(4-Benzyl-piperazin-1-yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3- ylj-methanone;
(3,4-Dihydro-2 -/-quinoIin-1-yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-3-yl]-methanone; 5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid benzyl- methyl-amide;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(4-methyl-piperazin-1-yl)- methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-thiomorpholin-4-yl-methanone; [5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-ajpyrimidin-3-yl]-morpholin-4-yl- methanone;
(4-Benzyl-piperazin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yI)- methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-morpholin-4-yl- methanone;
Azepan-1 -yl-(5-benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)- methanone;
(5-Benzo[.1,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-(3,4-dihydro-2H- quinolin-1 -yl)-methanone; 5-Benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid cyclohexyl-methyl-amide;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-(3,4-dihydro-2/--quinolin-
1-yI)-methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-ajpyrimidin-3-yl]-piperidin-1 -yl-methanone; Azepan-1 -yl-(5-furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-methanone;
(5-Benzo[1,3]dioxol-5-yI-7-trifluoromethyl-pyrazoIo[1 ,5-a]pyrimidin-3-yl)-pyrrolidin-1 -yl- methanone;
(5-Benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(4-methyl-piperazin-1- yl)-methanone; (3,4-Dihydro-1 ry-isoquinolin-2-yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5- a]pyrimidin-3-yl]-methanone; Azepan-1 -yl-[5-(4-bromo-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-methanone;
(3,4-Dihydro-2H-quinolin-1-yl)-(5,7-diphenyl-pyrazolo[1,5-a]pyrimidin-3-yl)-methanone;
Azepan-1-yl-(5,7-diphenyl-pyrazolo[1,5-a]pyrimidin-3-yl)-methanone;
(5-Benzo[1,3]dioxol-5-yl-7-trifluoromethyl-pyrazoIo[1,5-a]pyrimidin-3-yl)-(4-benzyl-piperazin-1- yl)-methanone;
(4-Benzyl-piperazin-1-yl)-(5,7-diphenyl-pyrazolo[1,5-a]pyrimidin-3-yl)-methanone;
(5,7-Diphenyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-(4-methyl-piperazin-1 -yl)-methanone;
[5-(4-Bromo-phenyl)-7-trifluoromethyl-pyrazoIo[1,5-a]pyrimidin-3-yl]-(2-methyl-piperidin-1-yl)- methanone; (3,4-Dihydro-2/--quinolin-1-yl)-(5-furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)- methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(2-methyl-piperidin-1-yl)- methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yI]-piperidin-1-yI- methanone; .
(5-Benzo[1,3]dioxol-5-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-morpholin-4-yl- methanone;
(5-Benzo[1 ,3]dioxol-5-yl-7-trifluoromethyl-pyrazoIo[1 ,5-a]pyrimidin-3-yl)-piperidin-1 -yl- methanone; Morpholin-4-yl-[7-trifluoromethyl-5-(3,4,5-trimethoxy-phenyl)-pyrazolo[1 ,5-a]pyrimidin-3-ylj- methanone;
(4-Benzyl-piperazin-1 -yl)-[7-trifluoromethyI-5-(3,4,5-trimethoxy-phenyl)-pyrazolo[1 ,5- ajpyrimidin-3-yl]-methanone;
(3,4-Dihydro-2/-/-quinolin-1 -yl)-[7-trifluoromethyl-5-(3,4,5-trimethoxy-phenyl)-pyrazolo[1 ,5- a]pyrimidin-3-yl]-methanone;
(4-Methyl-piperazin-1 -yl)-[7-trif luoromethyl-5-(3,4,5-trimethoxy-phenyl)-pyrazolo[1 ,5- a]pyrimidin-3-yl]-methanone;
Azepan-1-yl-[7-trifluoromethyl-5-(3,4,5-trimethoxy-phenyl)-pyrazolo[1,5-a]pyrimidin-3-yl]- methanone;, [5-(4-Methoxy-phenyI)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl]-piperidin-1 -yl- methanone;
[5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl]-pyrrolidin-1 -yl- methanone;
Piperidin-1-yl-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-methanone; (4-Benzyl-piperazin-1-yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3- ylj-methanone; (3,4-Dihydro-2H-quinolin-1-yl)-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1,5- a]pyrimidin-3-yl]-methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-(2-methyl-piperidin-1-yl)- methanone; (5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-morpholin-4-yl-methanone;
(5-Furan-2-yl-7-trifluoromethyI-pyrazolo[1,5-a]pyrimidin-3-yl)-thiomorpholin-4-yl-methanone;
[4-(4-Fluoro-phenyl)-piperazin-1-yl]-(5-thiophen-2-yI-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-
3-yl)-methanone;
(4-Methyl-piperidin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yI)- methanone;
(5-Furan-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-(4-methyl-piperazin-1 -yl)- methanone;
(4-Benzyl-piperazin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)- methanone; [5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-ylj-morpholin-4-yl- methanone;
Piperidin-1-yl-[7-trifluoromethyl-5-(3,4,5-trimethoxy-phenyl)-pyrazolo[1,5-a]pyrimidin-3-yl]- methanone;
(2-Methyl-piperidin-1-yl)-(5-thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)- methanone;
Azepan-1 -yl-[5-(4-methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-ylj- methanone;
5-Thiophen-2-yl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid benzyl-methyl- amide; [5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl]-pyrrolidin-1 -yl- methanone;
[5-(4-Chloro-phenyl)-2-methyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-piperidin-1-yl- methanone;
Azepan-1-yl-[5-(4-chloro-phenyl)-2-methyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-ylj- methanone;
[5-(4-Chloro-phenyl)-2-methyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-(4-methyl- piperazin-1 -yl)-methanone;
Morpholin-4-yl-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yI)-methanone;
(4-Benzyl-piperazin-1-yl)-(5-p-tolyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidin-3-yl)-methanone; 5-(4-Methoxy-phenyl)-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidine-3-carboxylic acid benzyl- methyl-amide; (4-Benzyl-piperazin-1-yl)-(5-phenyl-7-trifluoromethyl-pyrazoloii,5-a]pyrimidin-3-yl)- methanone;
Morpholin-4-yl-(5-phenyl-7-trifluoromethyl-pyrazolo[1 ,5-a]pyrimidin-3-yl)-methanone; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
6. The combination according to claim 1 wherein the 11 HSD1 inhibitor is of the Formula (II):
Figure imgf000192_0001
wherein
R1 is C3-Ci0cycloalkyl, C3-C10hetcycloalkyl, d-C8aIkyl, aryl, hetaryl, aryld-Cealkyl or hetarylCrCealkyl, wherein the cycloalkyl, hetcycloalkyl, alkyl, arylalkyl and hetarylalkyl groups independently are optionally substituted with one or more of R4.
R2 is hydrogen, CrC8alkyl, aryl, hetaryl, arylCrCealkyl, d-docycloalkyld-Cealkyl, CrCealkylcarboxyCrCealkyl wherein the alkyl, aryl and cycloalkyl groups independently are optionally substituted with one or more of R5; or
R1 and R2 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC8alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, aryld-Cealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C6alkyIcarbonyl, hetarylCrCealkylcarbonyl, d-C6alkylcarboxy, arylcarboxy or arylCr C6aIkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R14;
R3 is d-C8alkyl, CrC6alkenyl, CrC6alkynyl, C3-C10cycloalkyl, C3-Cι0hetcycloalkyl, aryl, hetaryl, aryICrC6alkyl, CrC6alkyloxyCrC6alkyI, hetarylCrCealkyl, aryl-R6-CrC6alkyl, hetaryl- R6-C C6alkyl or arylCrCealkyl-R6-CrC6alkyl wherein the alkyl, cycloalkyl, hetcycloalkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R7;
R4 and R5 independently are hydrogen, hydroxy, oxo, cyano, halo, methylendioxo, NR8R9, d- C8alkyl, CrCealkyloxy, trihalomethyl, trihalomethyloxy, C3-C10cycloalkyl, C3-C10hetcycloalkyl, C3-Ci0cycloalkenyl, aryl, hetaryl, hetarylSOn, arylCrCealkyloxy, hetarylCrCealkyloxy, d- C6alkyl-R6-CrC6alkyl, arylCι-C6alkyl-R6-CrC6alkyl, CrCealkylcarbonyl, arylcarbonyl, aryld- C6alkylcarbonyl, hetarylcarbonyl, hetarylCrC6alkyl-carbonyl, CrC6alkylSOn, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy or hetarylCrC6alkylcarboxy wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one ore more of R15;
R6 is oxygen, sulphur, SOn or NR16;
R7 is hydrogen, halo, hydroxy, cyano, nitro, COOR17, d-C8alkyl, C3-Cι0cycloalkyl, C3-Cι0het- cycloalkyl, methylendioxo, trihalomethyl, trihalomethyloxy, aryl, arylCrC6alkyl, CrC6alkyloxy, CrCealkyloxyCrCealkyl, aryloxy, arylCrCealkyloxy, aryloxyCrC6alkyl, arylCrC6alkyloxyCr C6alkyl, hetaryl, hetarylCrCealkyl, hetaryloxy, hetarylCrCealkyloxy, hetaryloxyCrC6alkyl, hetarylCrC6alkyl-oxyCrC6alkyl, NR8R9, S02NR8R9, NR4R5carbonyld-C6alkyl, arylthio, hetarylthio, R18carbonylNR8, arylSOn, hetarylSOn, R19SOmNR8, arylthiod-C6alkyl, hetarylthioCrC6alkyl or arylCrC6alkylR6CrC6alkyl; wherein the aryl and hetaryl groups independently are optionally substituted with one or more R10;
R8 and R9 independently are hydrogen, d-C8alkyl, aryl, hetaryl, aryld-Cealkyl or hetaryld- Cealkyl wherein the alkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R11; or
R8 and R9 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one halo, cyano, CrC8aIkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrCealkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, hetaryld- Cealkyloxy, CrCealkyloxyCrCealkyl, CrC6alkyl-carbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrC6alkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy or hetarylCrC6alkylcarboxy; R10 and R11 independently are hydrogen, hydroxy, oxo, halo, cyano, nitro, d-C8alkyl, d- C6alkyloxy, NR12R13, methylendioxo, trihalomethyl or trihalomethyloxy;
R12 and R13 independently are hydrogen, C C8alkyl or arylCrCealkyl;
R14 is hydrogen, halo, hydroxy, oxo, nitro, cyano, CrC8aIkyl, d-C6alkyloxy or aryloxy;
R15 is hydrogen, halo, hydroxy, oxo, nitro, cyano, CONR8R9 or COOR17;
R16 is hydrogen, CrC8alkyl, C3-C10cycloalkyl, C3-Cι0hetcycloalkyl, aryl, arylCrCealkyl, hetaryl, hetarylCrC6alkyl, alkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, aryloxyd-C6alkyl, hetaryloxyCrCealkyl, arylthioCrC6alkyl or hetarylthioCrC6alkyl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R10;
R is hydrogen, CrC8alkyl, aryl or arylCrC6alkyI;
R18 is CrC6alkyl, C2-C6alkenyl, aryl, aryICrC6alkyl, hetaryl, hetarylCrCealkyl, C3-Cι0cycloalkyl, C3-Ci0hetcycloalkyl, CrC6alkyloxy, aryloxy, arylCrCealkyloxy, arylCrCealkyloxyCrCealkyl, hetaryloxy, hetarylCrCealkyloxy, hetarylCrCealkyloxyCrCealkyl or R8R9NCrC6alkyl wherein the alkyl, alkenyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups are optionally substituted with R15;
R19 is d-Cealkyl, C3-C10cycloalkyl, C3-Cι0hetcycloalkyl, aryl, arylCrC6alkyl, hetaryl, hetaryld- Cealkyl;
m is 1 or 2;
n is 0, 1 or 2; or
a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
7. The combination according to claim 6 wherein the 11β-HSD1 inhibitor is of formula (II) wherein R1 is C3-C10cycloalkyl, C3-Cι0hetcycloalkyl, C C8alkyl, aryl, hetaryl, aryld-C6alkyl or hetarylCrCealkyl, wherein the cycloalkyl, hetcycloalkyl, alkyl, arylalkyl and hetarylalkyl groups independently are optionally substituted with one or more of R4;
R2 is hydrogen, C C8aIkyl, aryl, hetaryl, aryld-Cealkyl, d-docycIoalkyld-Cealkyl, C C6alkylcarboxyCrC6aIkyl wherein the alkyl, aryl and cycloalkyl groups independently are optionally substituted with one or more of R5; or
R1 and R2 are together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C8alkyI, aryl, hetaryl, arylCrC6alkyl, hetarylCrC6alkyl, hydroxy, oxo, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyd-Cealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylC C6aIkylcarbonyl, hetarylCrC6alkylcarbonyI, CrCealkylcarboxy, arylcarboxy or aryld-
6aIkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R14;
R3 is CrC8alkyl, d-C6alkenyl, CrC6alkynyl, C3-Cι0cycloalkyl, C3-C10hetcycloalkyl, aryl, hetaryl, arylCrC6alkyl, CrCealkyloxyd-Cealkyl, hetaryld-Cealkyl, aryl-R6-CrC6alkyl, hetaryi- R6-CrC6alkyl or arylCrC6alkyl-R6-CrC6alkyl wherein the alkyl, cycloalkyl, hetcycloalkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R7;
R4 and R5 independently are hydrogen, hydroxy, oxo, cyano, halo, methylendioxo, NR8R9, d- C8alkyl, CrC6alkyloxy, trihalomethyl, trihalomethyloxy, C3-Cι0cycloalkyl, C3-C10hetcycloalkyl, C3-Ci0cycloalkenyl, aryl, hetaryl, hetaryISOn, arylCrCealkyloxy, hetarylCrCealkyloxy, C C6alkyl-R6-CrCealkyl, arylCι-C6alkyl-R6-Cι-Cealkyl, CrC6alkylcarbonyl, arylcarbonyl, aryld- C6alkylcarbonyl, hetarylcarbonyl, hetarylCrC6alkyl-carbonyl, CrC6alkylSOn, CrC6alkyl- carboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy or hetarylCrC6alkylcarboxy wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one ore more of R 5;
R6 is oxygen, sulphur, SOn, NR16 R7 is hydrogen, halo, hydroxyl, cyano, nitro, COOR17, CrC8aIkyl, C3-C10cycloalkyl, C3-C10het- cycloalkyl, methylendioxo, trihalomethyl, trihalomethyloxy, aryl, arylCrCealkyl, CrC6alkyloxy, CrCealkyloxyCrCealkyl, aryloxy, aryloxyCrC6alkyl, arylCrCealkyloxyCrCealkyl, hetaryl, hetarylCrCealkyl, hetaryloxy, hetarylCrCealkyloxy, hetaryloxyCrCealkyl, hetarylCrC6alkyI- oxyd-Cealkyl, NR8R9, S02NR8R9, NR4R5carbonylalkyl, arylcarbonylNR8, arylthio, hetarylthio, arylSOm, hetarylSOm, arylSOmNR8, arylthioCrCealkyl, hetarylthioC C6alkyl or arylC CeaIkylR6CrC6alkyl; wherein the aryl and hetaryl groups independently are optionally substituted with one or more R10;
R8 and R9 independently are hydrogen, d-Cealkyl, aryl, hetaryl, arylCrC6alkyl or hetaryld- C6alkyl wherein the alkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R11; or
R8 and R9 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one d-C8aIkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrC6alkyl, hydroxy, oxo, CrC6aIkyloxy, arylCrC6alkyloxy, hetarylCrC6alkyloxy, d- CealkyloxyCrdialkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C6alkylcarbonyl, hetarylCrC6alkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, aryld-C6alkyl-carboxy or hetarylCrC6alkylcarboxy;
R10 and R11 independently are hydrogen, hydroxy, oxo, halo, cyano, nitro, d-C6alkyl, d- C6alkyloxy, NR12R13, methylendioxo, trihalomethyl or trihalomethyloxy;
R12 and R 3 independently are hydrogen, d-C8alkyl or aryld-Cealkyl;
R14 is hydrogen, halo, hydroxy, oxo, nitro, cyano, d-C8alkyl, d-C6alkyloxy or aryloxy;
R15 is hydrogen, halo, hydroxy, oxo, nitro, cyano or COOR17;
R16 is hydrogen, CrC8alkyl, C3-Cι0cycloalkyl, C3-C 0hetcycloalkyl, aryl, arylCrC6alkyl, hetaryl, hetarylCrCealkyl, alkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, aryloxyd-Cealkyl, hetaryloxyCrCealkyl, arylthioCrC6alkyl or hetarylthioCrC6alkyl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R10; R17 is hydrogen, CrC8alkyl, aryl or arylCrCealkyl;
m is 1 or 2;
n is 0, 1 or 2; or
a salt thereof with a pharmaceutically acceptable acid or base, or optical isomer, mixture of optical isomers, racemic mixture, or tautomeric form thereof.
8. The combination according to claim 6 or 7 wherein the 11/.-HSD1 inhibitor is selected from the group:
3-(10,11-Dihydro-dibenzo[b,f]azepin-5-yl)-1-[4-(1 H-imidazol-4-yl)-piperidin-1-yl]-propan-1-one;
4-(10,11-Dihydro-dibenzo[b,f]azepin-5-yl)-1-[4-(3H-imidazol-4-yl)-piperidin-1-yl]-butan-1-one; 2,4-Bis-benzyloxy-benzamide;
(1H-lndol-4-yl)-piperidin-1 -yl-methanone;
N-(1 ,4-Dioxo-1 ,4-dihydro-naphthalen-2-yl)-benzamide;
N-(2,3-Dihydroxy-propyl)-2-(2-phenyl-adamantan-2-yl)-acetamide;
(6-Fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-phenyl-methanone; (2-Chloro-phenyI)-(6-fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-methanone;
3-Cyclopentyl-1-(6-fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-propan-1-one;
(3-Chloro-thieno[2,3-b]thiophen-2-yl)-thiomorpholin-4-yl-methanone;
2-[2-(4-Chloro-phenyl)-adamantan-2-yl]-1-[4-(4-methoxy-phenyl)-piperazin-1-yl]-ethanone;
1-(4-Benzyl-piperazin-1-yl)-2-[2-(4-chloro-phenyI)-adamantan-2-ylj-ethanone; 2-[2-(4-Chloro-phenyl)-adamantan-2-yl]-1 -(4-methyI-piperazin-1 -yl)-ethanone;
1-[4-(6-Chloro-pyridin-2-yI)-piperazin-1-yl]-2-(2-phenyl-adamantan-2-yl)-ethanone;
4-Chloro-N-(1 ,7,7-trimethyl-bicyclo[2.2.1]hept-2-yI)-benzamide;
3-Chloro-benzo[b]thiophene-2-carboxylic acid (2-cyano-ethyl)-cyclohexyl-amide;
2-[2-(Bicyclo[2.2.1]hept-5-en-2-ylamino)-4-oxo-4,5-dihydro-thiazol-5-yl]-N-(2-chloro-phenyl)- acetamide;
[3-(4-sec-Butyl-phenoxy)-phenyl]-piperidin-1-yI-methanone;
3-(6-Chloro-pyridin-2-yloxy)-N-ethyl-benzamide;
N-Benzyl-2,4-dichIoro-N-pyridin-2-yl-benzamide;
2-[Benzoyl-(3-chloro-4-fluoro-phenyl)-amino]-propionic acid butyl ester; 2-[Benzoyl-(3-chloro-4-fluoro-phenyl)-amino]-propionic acid pentyl ester;
3-(4-Fluoro-phenyl)-1-(4-phenyl-piperidin-1-yl)-but-2-en-1-one; N-(1 ,7,7-Trimethyl-bicyclo[2.2.1]hept-2-yl)-benzamide;
1-(3-Cyclopentyl-propionyl)-piperidine-3-carboxylic acid ethyl ester;
4-Phenyl-1-phenylacetyl-piperidine-4-carbonitrile;
1-Octanoyl-4-phenyl-piperidine-4-carbonitrile; 2,2-Dimethyl-1-(1 ,3,3-trimethyI-6-aza-bicyclo[3.2.1]oct-6-yl)-propan-1-one;
(4-Chloro-phenyl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
N-[1-(4-Methanesulfonyl-phenyl)-ethyl]-N-(tetrahydro-furan-2-ylmethyl)-benzamide;
2-(2-Amino-phenylsulfanyl)-1-(5-fluoro-2,3-dihydro-indol-1-yl)-ethanone;
N-(1-Methyl-2,3-dihydro-1 H-indol-5-ylmethyl)-N-(tetrahydro-furan-2-ylmethyl)-benzamide; 1-Benzoyl-piperidine-2-carboxylic acid ethyl ester;
N-(2-Chloro-phenyl)-2-(1 ,2,3,4-tetrahydro-isoquinolin-1-yl)-acetamide;
(Decahydro-naphthalen-1-yl)-(4-methyl-piperazin-1-yl)-methanone;
(4-Methyl-piperazin-1-yl)-(2-p-tolylsulfanyl-phenyl)-methanone;
Adamantane-1 -carboxylic acid (3-benzyloxy-2-ethyl-6-methyl-pyridin-4-yl)-amide; (6-Fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-(3,4,5-trimethoxy-phenyl)-methanone;
N-Bicyclo[2.2.1 ]hept-2-yl-3-cyclopentyl-propionamide;
(2-Benzo[1 ,2,5]oxadiazol-5-yl-thiazol-4-yl)-piperidin-1-yl-methanone;
Thiophene-2-carboxylic acid [4-(4-fluoro-phenyl)-4-hydroxy-butyl]-isopropyl-amide;
N-Cyclohexyl-3-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-yl)-propionamide; 2-[(Adamantane-1-carbonyl)-amino]-3-(1 H-indol-3-yl)-propionic acid methyl ester;
Adamantane-1 -carboxylic acid [3-(1 H-benzoimidazol-2-ylsulfanyl)-5-nitro-phenyl]-amide;
N-Benzyl-N-(1-cyclopropyl-ethyl)-4-fluoro-benzamide;
Thiophene-2-carboxylic acid 2-[2-(2-phenyl-adamantan-2-yl)-acetylamino]-ethyl ester;
N-(4-Acetyl-phenyI)-2-(2-phenyl-adamantan-2-yl)-acetamide; 2-[2-(4-Chloro-phenyl)-adamantan-2-yl]-N-(2-hydroxy-ethyl)-acetamide;
(4-Benzoyl-piperidin-1-yl)-thiophen-2-yl-methanone;
N-(2-Benzoyl-4-methyl-phenyl)-3-phenyl-acryIamide;
N-(2-Benzoyl-4-methyl-phenyl)-2-fluoro-benzamide;
Adamantane-1 -carboxylic acid (4-ethoxy-benzothiazol-2-yI)-amide; Adamantane-1 -carboxylic acid (5-benzoyl-4-phenyl-thiazol-2-yl)-amide;
3-(2-Hydroxy-phenyI)-1 ,3-di-piperidin-1-yl-propan-1-one;
N-(1-Methyl-2-phenyl-ethyl)-3-phenyl-propionamide;
4-Oxo-4-piperidin-1-yl-butyric acid 4-tert-butyl-cyclohexyl ester;
N-tert-Butyl-N-(4-methoxy-benzyl)-4-nitro-benzamide; {4-[(Adamantane-1-carbonyI)-aminoj-phenoxy}-acetic acid;
2-(4-lsobutyl-phenyl)-N-(1-phenyl-ethyl)-propionamide; Adamantane-1 -carboxylic acid 4-[(adamantane-1 -carbonyl)-amino]-2,6-dimethyl-pyridin-3-yl ester;
2-Phenyl-1 -(3-phenyl-pyrrolidin-1 -yl)-ethanone;
Adamantane-1 -carboxylic acid 4-[(adamantane-1 -carbonyl)-amino]-2-ethyl-6-methyl-pyridin-3- yl ester;
N-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-N-(4-hydroxy-phenyl)-benzamide;
Biphenyl-4-yl-piperidin-1-yl-methanone;
Azepan-1-yl-(3,5-dichloro-phenyl)-methanone;
Azepan-1-yl-biphenyl-4-yl-methanone; Azepan-1 -yl-(4-chloro-phenyl)-methanone;
3-Heptylcarbamoyl-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid;
Adamantan-1 -yl-azepan-1 -yl-methanone;
N,N-Dibenzyl-3,4-dimethoxy-benzamide;
N-Benzyl-N-isopropyl-4-nitro-benzamide; N-[2-(1 H-lndol-3-yl)-1-methyl-ethyl]-2-(4-isobutyI-phenyl)-propionamide;
N-tert-Butyl-2-(4-isobutyl-phenyl)-propionamide;
Adamantane-1 -carboxylic acid (2-acetyl-phenyl)-amide;
N-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-N-(4-fluoro-phenyl)-benzamide;
(Octahydro-quinolin-l-yl)-phenyl-methanone; (7-Hydroxy-octahydro-quinolin-1-yI)-phenyl-methanone;
N-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-ylmethyl)-N-p-tolyl-benzamide;
N,N-Dibenzyl-4-methyI-benzamide;
(2-Chloro-phenyl)-(2-methyl-piperidin-1-yl)-methanone;
[4-Bromo-3-(piperidine-1-sulfonyl)-phenyl]-piperidin-1-yl-methanone; 2-Chloro-N-(3,4-dimethyI-phenyl)-benzamide;
1 -Azepan-1 -yl-2-(3,3-dimethyl-3,4-dihydro-2H-isoquinolin-1-ylidene)-ethanone;
N-Cyclohexyl-4-(2,4-dichloro-phenoxy)-butyramide;
N-Benzo[1 ,3]dioxol-5-yl-2-chloro-benzamide;
(4-Benzyl-piperidin-1-yl)-(2-chloro-phenyl)-methanone; 2-(Benzothiazol-2-ylsulfanyl)-N-cyclohexyl-acetamide;
Cyclohexanecarboxylic acid (7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-quinazolin-2-yl)-amide;
2,4-Dichloro-N-ethyl-N-o-tolyl-benzamide;
(4-Benzyl-piperidin-1-yl)-(4-fluoro-phenyl)-methanone;
N-Cyclohexyl-4-(2,4-dichloro-phenoxy)-N-methyl-butyramide; 3-[2-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-yl)-ethyl]-adamantane-1 -carboxylic acid;
MorphoIin-4-yl-(3-p-tolyl-adamantan-1-yl)-methanone; N-Benzyl-2,4-dichloro-N-methyl-benzamide;
Thiophene-2-carboxylic acid dibenzylamide;
Azepan-1-yl-(2-bromo-phenyl)-methanone;
(3,4-Dichloro-phenyl)-(4-methyI-piperidin-1-yl)-methanone; N,N-Dibenzyl-3,4-dichloro-benzamide;
4-(2,4-Dichloro-phenoxy)-1 -piperidin-1 -yl-butan-1 -one;
N,N-Dibenzyl-2-fluoro-benzamide;
(2-Chloro-phenyl)-piperidin-1-yl-methanone;
2-Chloro-N-(3-trifluoromethyl-phenyl)-benzamide; N-Benzyl-N-ethyI-2-phenyl-acetamide;
(3,4-Dihydro-2H-quinolin-1-yl)-p-tolyI-methanone;
Thiophene-2-carboxylic acid benzyl-ethyl-amide;
N-Adamantan-1-yl-2-dibenzylamino-acetamide;
N-Cyclohexyl-2-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-yl)-3-phenyl-propionamide; Thiophene-2-carboxyIic acid cycloheptylamide;
N-Cyclohexyl-3-diethylsulfamoyl-4-methyl-benzamide;
4-Benzoyl-N-methyl-N-phenyl-benzamide;
N-Benzyl-2-bromo-N-methyl-benzamide;
2-Chloro-N-methyl-N-phenyl-benzamide; 4-Chloro-N-ethyl-N-o-tolyl-benzamide;
N-Benzyl-4,N-dimethyl-benzamide;
2-(4-Chloro-3,5-dimethyl-phenoxy)-N-cyclohexyl-N-methyI-acetamide;
N-Benzyl-2-bromo-N-isopropyl-benzamide;
3-(2-Chloro-phenyl)-N-cyclohexyl-N-methyl-acrylamide; N-Phenyl-N-(2,2,5-trimethyl-hex-4-enyl)-acetamide;
N-m-Tolyl-N-(2,2,5-trimethyl-hex-4-enyl)-acetamide;
(3-Chloro-benzo[b]thiophen-2-yl)-(4-methyl-piperazin-1-yl)-methanone;
Adamantane-1 -carboxylic acid (5-methyl-pyridin-2-yl)-amide;
3-Bromo-N-[2-methyl-1-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-butylj- benzamide;
4-Chloro-N-[2-methyl-1-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-butyIj- benzamide;
4-Methyl-N-[2-methyl-1 -(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-butylj- benzamide; Cyclohexanecarboxylic acid [2-methyl- 1-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6- carbonyl)-butyl]-amide; 3-Cyclopentyl-N-[2-methyl-1 -(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-butylj- propionamide;
2-Chloro-N-[2-(4-ethyl-benzoylamino)-ethyl]-N-(4-fluoro-phenyI)-benzamide;
N-{1-Benzyl-2-[4-(3-cyclopentyl-propionyl)-piperazin-1-yl]-2-oxo-ethyl}-3-cycIopentyl- propionamide;
N-Bicyclo[2.2.1]hept-5-en-2-ylmethyl-3-cyclopentyl-N-[2-(1H-indol-3-yl)-ethyl]-propionamide;
N-Bicyclo[2.2.1 ]hept-5-en-2-ylmethyl-2,4-dichloro-N-[2-(1 H-indol-3-yl)-ethyl]-benzamide;
Naphthalene-2-carboxylic acid (2-oxo-azepan-3-yl)-thiophen-3-ylmethyl-amide;
3,4,5-Trimethoxy-N-(4-methyl-benzyl)-N-[6-(pyridin-2-ylamino)-hexyl]-benzamide; 3-Cyclopentyl-N-(4-methyl-benzyl)-N-[6-(pyridin-2-ylamino)-hexyl]-propionamide;
N-(3,4-Dimethoxy-benzyl)-3-methoxy-N-[6-(pyridin-2-ylamino)-hexyl]-benzamide;
N,N-Dimethyl-2-[3-(4-nitro-phenyl)-adamantan-1-yl]-acetamide;
Adamantane-1 -carboxylic acid [4-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-yl)-butyl]-p-tolyl-amide;
2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-N-(2-trifluoromethyl-phenyl)-butyramide; 2-(4-Chloro-2-methyl-phenoxy)-N-(2-trifluoromethyl-phenyl)-propionamide;
4-(2,4-Dichloro-phenoxy)-1 -[4-(4-fluoro-phenyl)-piperazin-1 -yl]-butan-1 -one;
(3,4-Dihydro-2H-quinolin-1-yl)-[3-(piperidine-1-sulfonyl)-phenylj-methanone;
Acetic acid 4-(azepane-1-carbonyl)-phenyl ester;
N-Adamantan-1 -ylmethyl-benzamide; [3-(4-Nitro-phenyl)-adamantan-1 -yl]-piperidin-1 -yl-methanone;
N-(1 ,1-Dimethyl-hexyl)-2-morpholin-4-yl-acetamide;
Adamantyl-1 -carboxylic acid (2-methoxy-ethyl)-amide;
N-(4-Adamantan-1 -yl-2-methyl-phenyl)-acetamide;
3-p-Tolyl-adamantane-1 -carboxylic acid (2,5-dichloro-phenyl)-amide; (3-Chloro-adamantan-1 -yl)-pyrrolidin-1 -yl-methanone;
2-Amino-5-cyclohexylcarbamoyl-4-methyl-thiophene-3-carboxylic acid ethyl ester;
N-(2-Chloro-phenyl)-2-{3-[(2-chloro-phenylcarbamoyl)-methyl]-adamantan-1-yl}-acetamide;
3-p-Tolyl-adamantane-1 -carboxylic acid (2,4-difluoro-phenyl)-amide;
Adamantyl-1 -carboxylic acid tert-butylamide; 2-Adamantan-1 -yl-N-tert-butyl-acetamide;
N-Methyl-N-phenyl-4-(pyrrolidine-1-sulfonyl)-benzamide;
N-(1 -Adamantan-1 -yl-ethyl)-2-fluoro-benzamide;
Adamantane-1 -carboxylic acid [2-(3,4-dimethoxy-phenyl)-ethyl]-amide;
Adamantane-1 -carboxylic acid dimethylamide; N-Benzyl-4-chloro-N-(1-cyclopropyl-vinyl)-benzamide;
3,5-Dimethyl-adamantane-1 -carboxylic acid benzylamide; 2,4-Dichloro-N-cycIohexyl-N-(2-hydroxy-ethyl)-benzamide;
N-Adamantan-1-yl-2,4-dichloro-N-ethyl-benzamide;
2-[(3-p-Tolyl-adamantane-1-carbonyl)-amino]-propionic acid methyl ester;
N-Adamantan-1-yl-3-morpholin-4-yl-propionamide; 3-p-Tolyl-adamantane-1 -carboxylic acid isopropylamide;
N-Adamantan-1 -yI-2-benzyIamino-acetamide; - -
N-BenzyI-2,4-dichloro-N-(1-cyclopropyl-ethyl)-5-methyl-benzamide;
2-[(Adamantane-1-carbonyl)-amino]-benzoic acid ethyl ester;
N-Benzyl-N-isopropyl-4-methyl-3-nitro-benzamide; (3,4-Dihydro-2H-quinolin-1-yl)-(2-fluoro-phenyl)-methanone;
N-Ethyl-2-fluoro-N-phenyl-benzamide;
2-Phenethyl-N-(2-trifluoromethyI-phenyl)-benzamide;
1-(3,4-Dihydro-2H-quinolin-1-yl)-2-o-tolyloxy-ethanone;
2-(1 -Benzyl-1 H-imidazol-2-yIsulfanyl)-N-cyclohexyl-acetamide; Cyclohexanecarboxylic acid (2-propoxy-phenyl)-amide;
2-{3-[4-(2-Chloro-phenyl)-piperazin-1-yl]-3-oxo-propyl}-isoindole-1,3-dione;
N-Cyclopentyl-2-(2,4-dichloro-phenoxy)-propionamide;
Adamantane-1 -carboxylic acid (2-trifluoromethyl-phenyl)-amide;
(4-ChIoro-3-nitro-phenyl)-(2,6-dimethyl-piperidin-1-yl)-methanone; 4-(2-Ethyl-phenyl)-4-aza-tricyclo[5.2.2.02'6jundec-8-ene-3,5-dione;
2-Phenyl-N-(2-trifluoromethyl-phenyl)-butyramide;
N-Adamantan-1 -yI-4-chloro-2-nitro-benzamide;
3-p-Tolyl-adamantane-1 -carboxylic acid (2,3-dimethyl-phenyl)-amide;
N-Benzyl-3-methyl-4-p-tolyl-butyramide; N-(2-Cyclohex-1 -enyl-ethyl)-2-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-yl)-propionamide;
(4-tert-Butyl-phenyl)-(3,4-dihydro-1H-isoquinolin-2-yl)-methanone;
2-[1-(4-Chloro-benzenesulfonyl)-1H-benzoimidazol-2-ylsulfanyl]-N-thiophen-2-ylmethyl- acetamide;
2-Phenoxy-1-[4-(2-trifluoromethyl-benzyl)-piperazin-1-yl]-ethanone; Cyclohexanecarboxylic acid [5-(2-fluoro-benzylsulfanylmethyl)-[1 ,3,4]thiadiazol-2-yl]-amide;
4-Methyl-2-phenyl-thiazole-5-carboxylic acid naphthalen-1 -ylamide;
4-Fluoro-N-[4-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenylj- benzenesulfonamide;
(3-Methoxy-phenyl)-(4-o-tolyl-piperazin-1-yl)-methanone; N-Adamantan-1 -yl-3-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-yl)-propionamide;
N-Cyclooctyl-2-methoxy-3-methyl-benzamide; 2-[4-(2,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]-isoindole-1 ,3-dione;
(2,3-Diphenyl-quinoxalin-6-yl)-(2,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
Adamantan-1-yl-(1 ,3,4,5-tetrahydro-pyrido[4,3-b]indol-2-yl)-methanone;
N-{4-[1-(Naphthalene-2-sulfonyl)-piperidin-3-yl]-butyl}-N'-p-tolyl-oxalamide; N-Benzyl-N-(2-oxo-2-pyrroIidin-1-yl-ethyl)-benzenesulfonamide;
(4-Amino-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
1-[4-(4-Fluoro-phenyl)-piperazin-1-yl]-2-(2-isopropyl-5-methyl-phenoxy)-ethanone;
Adamantane-1 -carboxylic acid benzyl-pyridin-2-yl-amide;
Adamantan-1 -yl-piperidin-1 -yl-methanone; Adamantan-1 -yl-pyrrolidin-1 -yl-methanone;
(3,4-Dihydro-2H-quinolin-1-yl)-o-tolyl-methanone;
Adamantyl-1 -carboxylic acid benzylamide;
Pyridine-2-carboxylic acid adamantan-2-ylamide;
(3-Chloro-adamantan-1 -yl)-piperidin-1 -yl-methanone; Adamantan-1 -yl-(4-methyl-piperidin-1-yl)-methanone;
2-[3-(Azepane-1 -carbonyl)-phenyl]-isoindole-1 ,3-dione;
2-[3-(Piperidine-1 -carbonyl)-phenyl]-isoindole-1 ,3-dione;
4-(Benzyl-methanesulfonyl-amino)-N-furan-2-ylmethyl-benzamide;
(4-Nitro-phenyl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; 1-Cyclohexyl-5-oxo-pyrrolidine-3-carboxylic acid (4-chloro-3-nitro-phenyl)-amide;
N-(2-Chloro-phenyl)-2-(2-oxo-2-phenyl-ethylsulfanyl)-acetamide;
3-(4-Hydroxy-phenyl)-N-isochroman-1-ylmethyl-3-phenyl-propionamide;
(4-Ethoxy-phenyl)-(2-methyl-piperidin-1-yl)-methanone;
1 -Cyclohexyl-5-oxo-pyrroIidine-3-carboxylic acid (3-chloro-phenyl)-amide; N-[4-(Benzyl-isopropyl-sulfamoyl)-phenyl]-acetamide;
N-(3,4-Dimethyl-phenyl)-N-[4-(piperidine-1-carbonyl)-benzyl]-methanesulfonamide;
2-(5-Phenyl-1 H-imidazoI-2-ylsulfanyl)-N-(1 ,1 ,3,3-tetramethyl-butyl)-acetamide;
2-(Benzothiazol-2-ylsulfanyl)-N-(1 ,1,3,3-tetramethyl-butyl)-acetamide;
2-(Benzooxazol-2-ylsulfanyl)-N-(1 , 1 ,3,3-tetramethyI-butyl)-acetamide; 2-(Naphthalen-2-ylcarbamoylmethylsulfanyl)-N-(1 , 1 ,3,3-tetramethyI-butyl)-acetamide;
Acetic acid 4-(3,5-dimethyl-piperidine-1-carbonyl)-phenyI ester;
(4-ChIoro-3-nitro-phenyl)-(2,6-dimethyl-piperidin-1-yl)-methanone;
[1-(4-Chloro-benzenesulfonyI)-piperidin-3-yl]-(octahydro-quinolin-1-yI)-methanone;
2,4-Dichloro-N-cyclohexyI-N-(2-hydroxy-ethyl)-benzamide; (4-Fluoro-phenyl)-(3,4,4a,8a-tetrahydro-2H-quinolin-1-yl)-methanone;
N-Adamantan-1-yl-2-ethoxy-acetamide; 2-(2-Oxo-2-phenothiazin-10-yl-ethyl)-hexahydro-isoindole-1 ,3-dione;
Adamantane-1 -carboxylic acid (tetrahydro-furan-2-ylmethyl)-amide;
2-Bromo-N-cycloheptyl-benzamide;
Bicyclo[2.2.1 ]hept-2-yl-[4-(2-ethoxy-phenyl)-piperazin-1 -ylj-methanone; N-Furan-2-ylmethyl-2-phenyI-2-phenylsulfanyl-acetamide;
Adamantane-1 -carboxylic acid benzyl-methyl-amide;
1-(3,4-Dihydro-2H-quinolin-1-yl)-3-(4-fluoro-phenyl)-propenone;
Adamantan-1 -yl-(2,6-dimethyl-piperidin-1 -yl)-methanone;
4-Methyl-N-homoadamantyl-3-yl-benzamide; (3,5-Dimethyl-piperidin-1-yl)-(3-methyl-4-nitro-phenyl)-methanone;
Quinoline-2-carboxylic acid cyclooctylamide;
Adamantane-1 -carboxylic acid [2-(2,4-dimethoxy-phenyl)-ethyl]-amide;
(3,4-Dihydro-1H-isoquinolin-2-yl)-o-tolyl-methanone;
(3,6-Dichloro-benzo[b]thiophen-2-yl)-(4-methyl-piperazin-1-yl)-methanone; 3-(1 -Benzyl-1 H-imidazol-2-ylsulfanyl)-N-cydohexyl-propionamide;
Propionic acid 2-amino-4-methyl-5-p-tolylcarbamoyl-thiophen-3-yl ester;
2-Cyclohexyl-N-(2,6-dimethyl-phenyl)-N-furan-2-ylmethyl-acetamide;
(3-Methoxy-phenyl)-(2,2,4-trimethyl-4-phenyl-3,4-dihydro-2H-quinolin-1-yl)-methanone;
1-[4-(2,3,3-Trimethyl-6-aza-bicyclo[3.2.1joctane-6-carbonyl)-phenyI]-pyrrolidine-2,5-dione; 1 -(3,4-Dihydro-2H-quinolin-1-yl)-2-(1 -naphthalen-1 -yl-1 H-tetrazol-5-ylsulfanyl)-ethanone;
[4-(2,3-Dimethyl-phenyl)-piperazin-1-yl]-o-tolyl-methanone;
(4-Benzyl-piperidin-1 -yl)-(4-methyl-3-nitro-phenyl)-methanone;
N-(2-Cyano-phenyl)-2-(9-ethyl-9H-1,3,4,9-tetraaza-fluoren-2-ylsulfanyl)-acetamide;
N-(2-Cyano-phenyl)-2-(9-methyl-9H-1 ,3,4,9-tetraaza-fluoren-2-ylsulfanyl)-acetamide; 1 -(Thiophene-2-carbonyl)-2,3-dihydro-1 H-quinolin-4-one;
(3-Chloro-6-nitro-benzo[b]thiophen-2-yl)-piperidin-1 -yl-methanone;
(4-Bromo-phenyl)r(3,5-dimethyl-piperidin-1-yl)-methanone;
2-Morpholin-4-yl-N-(1-phenyl-cyclopentylmethyl)-acetamide;
9-Oxo-9H-fluorene-1 -carboxylic acid (3-methyl-butyl)-amide; [4-(2,5-Dimethyl-pyrrol-1 -yl)-phenyl]-(4-methyl-piperidin-1 -yl)-methanone;
N-Cycloheptyl-3-diethylsulfamoyl-benzamide;
(4-Methoxy-phenyl)-(3-phenyl-piperidin-1-yl)-methanone;
3-Amino-N-cycIohexyl-N-methyl-benzamide;
N-Ethyl-3,4-dimethyl-N-phenyI-benzamide; N-Benzyl-3,4,N-trimethyl-benzamide;
(4-FIuoro-phenyl)-(3-phenyl-piperidin-1-yl)-methanone; [4-(2,3-Dimethyl-phenyl)-piperazin-1-yl]-(3-methoxy-phenyl)-methanone;
Furan-2-carboxylic acid [4-(4-methyl-piperidine-1 -sulfonyl)-phenyl]-amide;
N-(2-Cyclohex-1-enyl-ethyl)-2-o-tolyloxy-acetamide;
5-(2-Chloro-phenoxymethyl)-furan-2-carboxylic acid (1-bicyclo[2.2.1]hept-2-yl-ethyI)-amide; 3-(2-ChIoro-phenyl)-1 -[4-(2,3-dimethyl-phenyl)-piperazin-1 -ylj-propenone;
N-[3-(Azepane-1-carbonyl)-phenyl]-benzamide;
[3-(Piperidine-1 -carbonyl)-pyrazol-1 -ylj-o-tolyl-methanone;
N-(1-Phenyl-cyclopentylmethyl)-2-piperidin-1-yl-propionamide;
2-Morpholin-4-yl-N-(1-phenyl-cyclopentylmethyl)-propionamide; N-[4-(Azepane-1-sulfonyl)-phenyl]-2,2,2-trifluoro-acetamide;
2,3-Dihydro-benzo[1 ,4]dioxine-6-carboxylic acid (1 -adamantan-1 -yl-ethyl)-amide;
N-Adamantan-1-yl-2-(3-methoxy-phenoxy)-acetamide;
3-Chloro-benzo[b]thiophene-2-carboxylic acid (2-cyano-ethyl)-phenyl-amide;
[4-(4-Nitro-benzyl)-piperidin-1-yl]-phenyl-methanone; [4-(2-Nitro-benzyl)-piperidin-1-yl]-phenyl-methanone;
3-[5-(4-Fluoro-phenyl)-furan-2-yl]-1 -(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-propenone;
2-(3-Fluoro-benzoylamino)-4-methyl-5-(piperidine-1-carbonyl)-thiophene-3-carboxylic acid methyl ester;
N-(2-Ethyl-phenyl)-2-(3-methyl-piperidin-1 -yl)-acetamide; 2-(2-Methoxy-benzoylamino)-4-methyl-5-(piperidine-1 -carbonyl)-thiophene-3-carboxylic acid methyl ester;
1 -Phenyl-cyclopentanecarboxylic acid (4-phenyl-tetrahydro-pyran-4-ylmethyl)-amide;
4-(2,4-Dichloro-phenoxy)-1-(4-phenyl-piperazin-1-yl)-butan-1-one;
Naphthalene-1 -carboxylic acid cycloheptylamide; N-lndan-5-yl-2-methyl-3-nitro-benzamide;
N-Cyclohexyl-3-(2,2,2-trifluoro-ethoxymethyl)-benzamide;
2-Methoxy-N-(1-phenyl-cyclopentylmethyl)-benzamide;
[5-(2,5-Dichloro-phenoxymethyl)-furan-2-yl]-(2,6-dimethyl-morpholin-4-yl)-methanone;
[5-(2-Bromo-phenoxymethyl)-furan-2-yl]-(2-methyl-piperidin-1-yl)-methanone; 5-(2-Methoxy-phenoxymethyl)-furan-2-carboxylic acid cycloheptylamide;
(3,4-Dihydro-1H-isoquinolin-2-yl)-[1-(2-nitro-benzenesulfonyl)-piperidin-3-yl]-methanone;
N-Cyclooctyl-2-(4-methoxy-phenoxy)-acetamide;
N-(2,3-Dimethyl-phenyl)-4-[methyl-(toluene-4-sulfonyl)-amino]-butyramide;
N-Phenyl-N-[4-(piperidine-1-carbonyl)-benzylj-benzenesulfonamide; N-[4-(3,4-Dihydro-1H-isoquinoline-2-carbonyl)-benzyl]-N-(3,4-dimethyl-phenyl)- methanesulfonamide; 2,3-Dihydro-benzo[1 ,4]dioxine-2-carboxylic acid bicyclo[2.2.1]hept-2-ylamide;
4,5,6,7-Tetrahydro-benzo[b]thiophene-3-carboxylic acid cycloheptylamide;
N-(2-Azepan-1-yI-2-oxo-ethyl)-N-benzyl-4-fluoro-benzenesulfonamide;
1-(2,6-Dimethyl-morpholin-4-yl)-3,3-diphenyl-propan-1-one; N-Bicyclo[2.2.1 ]hept-2-yl-4-morpholin-4-yImethyl-benzamide;
[3-(2-Chloro-6-nitro-phenoxy)-phenylj-piperidin-1-yl-methanone;
N-Adamantan-1-yl-2-(4-methyl-quinolin-2-ylsulfanyl)-acetamide;
Cyclohexanecarboxylic acid (2-phenylsulfanyl-phenyl)-amide;
(4-Hydroxy-4-phenyl-octahydro-quinolin-1-yl)-phenyl-methanone; 3-Cyclohexyl-N-(3-phenyl-propyl)-propionamide;
2-[1-(2,5-Dimethyl-phenyl)-1H-tetrazol-5-ylsulfanyl]-N-isopropyl-N-phenyI-acetamide;
N-{2-[4-(3,4-Dihydro-1H-isoquinoline-2-sulfonyl)-phenyl]-ethyl}-acetamide;
N-Benzyl-N-[2-oxo-2-(4-phenyl-piperazin-1-yl)-ethyl]-benzenesulfonamide;
[4-(2-ChIoro-6-nitro-phenoxy)-phenyl]-piperidin-1 -yl-methanone; N-Cydoheptyl-3-phenyI-propionamide;
(3-Chloro-6-methyl-benzo[b]thiophen-2-yl)-piperidin-1 -yl-methanone;
N-Cycloheptyl-2,4-dimethoxy-benzamide;
N-(3-Chloro-phenyl)-2-(8,11,11-trimethyl-3,4,6-triaza-tricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-5- ylsulfanyl)-acetamide; N-(2-Nitro-phenyl)-2-(8,11 ,11-trimethyl-3,4,6-triaza-tricyclo[6.2.1.02'7]undeca-2(7),3,5-trien-5- ylsulfanyl)-acetamide;
N-Phenyl-2-(8,11 ,11-trimethyl-3,4,6-triaza-tricycIo[6.2.1.02'7]undeca-2(7),3,5-trien-5- ylsulfanyl)-acetamide;
N-Ethyl-3-methyl-N-o-tolyl-benzamide; N-[5-(2,4-Dichloro-benzylsulfanyl)-[1,3,4]thiadiazol-2-yl]-2,2-dimethyl-propionamide;
4-FIuoro-N-[4-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-phenylj- benzenesulfonamide;
4-Bromo-1-ethyl-1 H-pyrazole-3-carboxylic acid (2-methylsulfanyI-phenyl)-amide;
5-Benzoyl-furan-2-carboxylic acid diisopropylamide; 2-[3-(Piperidine-1 -carbonyl)-phenyl]-isoindole-1 ,3-dione;
N-{2-[2-(4-Bromo-phenyl)-2-oxo-ethylsulfanyl]-benzothiazol-6-yl}-acetamide;
2-(6-Amino-benzothiazol-2-ylsulfanyl)-N-cycIohexyl-acetamide;
N-(2-Cyclohexylcarbamoylmethylsulfanyl-benzothiazol-6-yl)-2-methoxy-benzamide;
Benzofuran-2-yl-(4-phenyl-piperidin-1-yl)-methanone; 1-(2-Nitro-phenyl)-piperidine-3-carboxylic acid diethylamide;
1-(4-Nitro-phenyl)-piperidine-3-carboxylic acid diethylamide; 5-Bromo-furan-2-carboxylic acid adamantan-2-ylamide;
3,3-Dimethyl-pentanedioic acid bis-[(2,4-difluoro-phenyl)-amidej;
2-(3-Bromo-benzylsulfanyl)-1-(4-phenyl-piperazin-1-yl)-ethanone;
N-(2-Azepan-1-yl-2-oxo-ethyl)-N-benzyl-4-bromo-benzenesulfonamide; 1-(2,3-Dihydro-indol-1-yl)-2-p-tolylsulfanyl-ethanone;
[4-(4-Bromo-benzenesulfonyl)-piperazin-1-yl]-furan-2-yl-methanone;
[5-(2-Bromo-phenoxymethyl)-furan-2-yl]-(2,6-dimethyl-morpholin-4-yl)-methanone;
5-(2-Chloro-phenoxymethyl)-furan-2-carboxylic acid diethylamide;
5-(2-Bromo-phenoxymethyl)-furan-2-carboxylic acid diethylamide; 5-(2-Chloro-phenoxymethyl)-furan-2-carboxylic acid methyl-phenyl-amide;
[5-(2-Chloro-phenoxymethyI)-furan-2-yl]-(4-methyl-piperidin-1-yl)-methanone;
[3-(2,5-Dichloro-phenoxymethyl)-phenyl]-pyrrolidin-1-yl-methanone;
[5-(4-Ethoxy-phenoxymethyl)-furan-2-yl]-(4-methyl-piperidin-1-yl)-methanone;
3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-N-(2-methyl-cyclohexyl)-propionamide; 3-(3,4-Dihydro-2H-quinoline-1-carbonyl)-N-phenyl-benzenesulfonamide;
[3-(2,3-Dihydro-indole-1-sulfonyl)-phenyl]-(3,4-dihydro-2H-quinolin-1-yl)-methanone;
[3-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-(4-methyl-piperidin-1-yl)-methanone;
N-Cyclohexyl-3-(2-hydroxy-4-methyl-phenyl)-3-phenyl-propionamide;
2-Diethylamino-N-(1-phenyl-cydopentylmethyl)-propionamide; (6-Fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-(3-trifluoromethyl-phenyl)-methanone;
(2,6-Dimethyl-morpholin-4-yl)-[4-(naphthalen-1-yloxymethyl)-phenyl]-methanone;
N-Benzyl-4-bromo-N-ethyl-benzamide;
(3-Methyl-piperidin-1-yl)-[4-(naphthalen-1-yloxymethyl)-phenyl]-methanone;
Azepan-1-yl-[5-(2-chloro-phenoxymethyl)-furan-2-yl]-methanone; (4-Methyl-piperidin-1-yl)-[4-(naphthalen-1-yIoxymethyl)-phenyl]-methanone;
Azepan-1 -yl-[5-(2,4-dichloro-phenoxymethyl)-furan-2-yl]-methanone;
N-CycloheptyI-4-(4-methoxy-2-methyl-phenyI)-butyramide;
2-(4-Benzothiazol-2-yl-piperazin-1-yl)-N-cyclohexyl-acetamide;
N-Cycloheptyl-2-(2,6-dimethyl-phenoxy)-acetamide; (3,4-Dihydro-2H-quinolin-1-yl)-(3-iodo-phenyl)-methanone;
N-Cycloheptyl-3-(2,2,2-trifluoro-ethoxymethyl)-benzamide;
Azepan-1-yI-[4-(2-chloro-phenoxymethyl)-phenyl]-methanone;
(2,6-Dimethyl-morpholin-4-yl)-[4-(naphthalen-2-yloxymethyl)-phenyl]-methanone;
Azepan-1-yl-[3-(4-ethoxy-phenoxymethyl)-phenyl]-methanone; Benzo[b]thiophene-3-carboxylic acid (1,2,3,4-tetrahydro-naphthalen-1-yl)-amide;
2-(4-Chloro-2-methyl-phenoxy)-N-cycloheptyl-acetamide; 2,4-Dichloro-N-cyclohexyl-N-methyl-benzamide;
N-Cyclooctyl-2-p-tolyloxy-acetamide;
(3,5-Dimethyl-piperidin-1-yl)-(4-methyl-3-nitro-phenyl)-methanone;
Biphenyl-4-yl-(2,6-dimethyI-piperidin-1-yl)-methanone; N-Cyclohexyl-4-fluoro-N-methyl-benzamide;
N-[4-(Azepane-1-carbonyl)-phenyl]-N-methyl-benzenesulfonamide;
N-Cycloheptyl-2-fluoro-benzamide;
N-Cycloheptyl-4-methyl-benzamide;
(3-Methyl-piperidin-1-yl)-p-tolyl-methanone; [2-(3,4-Dimethoxy-phenylcarbamoyl)-piperidin-1-yl]-acetic acid benzyl ester;
N-[4-(2-Methyl-piperidine-1-sulfonyl)-phenyl]-acetamide;
2-(2,4-Dichloro-phenoxy)-N-(2-methyl-butyl)-propionamide;
[4-(2-Chloro-6-nitro-phenyl)-piperazin-1-yl]-(4-methoxy-phenyl)-methanone;
N-CyclohexyI-4-(4-methoxy-3-methyl-phenyl)-butyramide; (3-Chloro-6-methoxy-benzo[b]thiophen-2-yl)-(3,4-dihydro-1H-isoquinolin-2-yl)-methanone;
2-(4-Methyl-benzylsulfanyl)-1 -piperidin-1 -yl-ethanone;
N-Cyclohexyl-N-[(4-phenyl-thiazol-2-ylcarbamoyl)-methyl]-benzamide;
N-(2-Azepan-1-yl-2-oxo-ethyl)-N-(4-isopropyl-phenyl)-methanesulfonamide;
N-Adamantan-1-yl-3-p-tolylsulfanyl-propionamide; 6-(2,4-Dichloro-phenylcarbamoyI)-3,4-dimethyl-cyclohex-3-enecarboxylic acid;
(4-Butyl-cyclohexyl)-morpholin-4-yl-methanone;
(3,4-Dichloro-phenyl)-(3,4-dihydro-2H-quinolin-1-yl)-methanone;
N-(2-Cyclohex-1-enyl-ethyl)-3-methoxy-benzamide;
N-Adamantan-2-yl-3-(1 ,5-dimethyl-1 H-pyrazol-4-yl)-acrylamide; N-Adamantan-1 -yl-N-methyl-4-(4-nitro-pyrazol-1 -ylmethyl)-benzamide;
5-(4-Chloro-3,5-dimethyl-pyrazol-1 -ylmethyl)-furan-2-carboxylic acid adamantan-2-ylamide;
2-(4-Chloro-phenoxy)-N-(2-fluoro-5-methyl-phenyl)-2-methyl-propionamide;
N-Adamantan-1-yl-2-(4-chloro-3,5-dimethyl-phenoxy)-acetamide;
2-[(3-Carboxy-bicyclo[2.2.1]heptane-2-carbonyl)-amino]-5,6-dihydro-4H- cyclopenta[b]thiophene-3-carboxylic acid propyl ester;
2-Adamantan-1 -yl-N-[1 -(2,5-dimethyl-phenyl)-ethyl]-acetamide;
3-Methyl-thiophene-2-carboxylic acid cyclooctylamide;
N-p-Tolyl-2-(8,11 ,11-trimethyl-3,4,6-triaza-tricyclo[6.2.1.02,7]undeca-2,4,6-trien-5-ylsulfanyl)- propionamide; Azepan-1 -yl-[5-(4-chloro-5-methyl-3-nitro-pyrazol-1 -ylmethyl)-furan-2-yl]-methanone;
N-Adamantan-2-yl-3-(4-bromo-3-nitro-pyrazoI-1-yImethyl)-benzamide; N-Bicyclo[2.2.1 ]hept-2-y!-2-chloro-benzamide;
[5-(3-Chloro-phenoxymethyl)-furan-2-yl]-piperidin-1-yl-methanone;
1-(4-Ethyl-benzoyl)-6-methoxy-2-methyl-2,3-dihydro-1H-quinolin-4-one;
6-Fluoro-2-methyl-1 -{3-[4-(propane-1 -sulfonyl)-phenoxymethyl]-benzoyl}-2,3-dihydro-1 H- quinolin-4-one;
N-Cycloheptyl-2-(naphthalen-1-yloxy)-acetamide;
N-Cyclohexyl-4-o-tolyloxy-butyramide;
(2-Benzylsulfanyl-phenyl)-morpholin-4-yl-methanone;
(2-Chloro-5,6-difluoro-3-methyl-phenyl)-(4-methyl-piperidin-1-yl)-methanone; (3-Bromo-phenyl)-[4-(4-chloro-2-nitro-phenyl)-piperazin-1 -ylj-methanone;
2-Bromo-N-(1 ,1 ,3,3-tetramethyl-butyl)-benzamide;
N-Adamantan-1 -yl-2-(2-benzoyl-5-methoxy-phenoxy)-acetamide;
N-Cyclohexyl-3-methyl-4-p-tolyl-butyramide;
[5-(4-Methyl-2-nitro-phenoxymethyl)-furan-2-ylj-thiomorpholin-4-yl-methanone; [5-(2,5-Dichloro-phenoxymethyl)-furan-2-yl]-thiomorpholin-4-yl-methanone;
5-(4-Chloro-2-nitro-phenoxymethyl)-furan-2-carboxylic acid adamantan-1 -ylamide;
4,5,6,7-Tetrahydro-benzo[b]thiophene-3-carboxylic acid cyclohexylamide;
4-Chloro-1 ,5-dimethyl-1 H-pyrazole-3-carboxylic acid adamantan-1 -yl-methyl-amide;
4-(4-Methoxy-3-methyl-phenyl)-N-(2-methyl-cyclohexyl)-butyramide; 3-Benzo[1 ,3]dioxol-5-yl-1 -(3,4-dihydro-1 H-isoquinolin-2-yl)-propenone;
N-Bicyclo[2.2.1 ]hept-2-yl-3-phenylsulfanyl-propionamide;
Azepan-1 -yl-[5-(2-nitro-phenoxymethyl)-furan-2-yl]-methanone;
N-Benzyl-2-(4-chloro-phenylsulfanyl)-N-methyI-acetamide;
1-(4-Benzyl-piperidin-1-yl)-2-benzylsulfanyl-ethanone; 2-(4-tert-Butyl-phenoxy)-1 -(4-ethyl-piperazin-1 -yl)-ethanone;
[4-(4-Ethoxy-phenoxymethyl)-phenyl]-(4-methyl-piperidin-1-yl)-methanone;
5-(4-Bromo-3,5-dimethyl-pyrazol-1 -ylmethyl)-furan-2-carboxylic acid adamantan-2-ylamide;
1 -Azepan-1 -yl-3-(4-chloro-phenylsulfanyl)-propan-1 -one;
N-Bicyclo[2.2.1jhept-2-yl-2-(2-chloro-benzylsuIfanyl)-acetamide; 2-(2-Methyl-benzylsulfanyl)-1 -(4-phenyl-piperazin-1 -yl)-ethanone;
N-[2-(1-Benzo[1,3]dioxol-5-yl-3-furan-2-yl-3-oxo-propylsulfanyl)-phenyl]-acetamide;
(3,5-Dimethyl-piperidin-1-yl)-(3-iodo-phenyl)-methanone;
[5-(2-Bromo-phenoxymethyl)-furan-2-yl]-(6-fluoro-2-methyI-3,4-dihydro-2H-quinolin-1-yl)- methanone; N-Benzyl-N-cycIohex-1 -enyl-isonicotinamide;
1-[4-(4-Fluoro-phenyl)-piperazin-1-yl]-2-(2-methyl-benzylsulfanyl)-ethanone; 2-(2-Bromo-4-methyl-phenoxy)-N-(2-cyclohex-1-enyl-ethyl)-acetamide;
2-[5-(2-Hydroxy-phenyl)-[1 ,3,4]oxadiazol-2-ylsulfanyl]-1 -piperidin-1 -yl-ethanone;
5-(4-Nitro-pyrazol-1 -ylmethyl)-f uran-2-carboxyIic acid adamantan-2-ylamide;
3-Benzo[1 ,3]dioxol-5-yl-3-(2-methoxy-phenyl)-1 -pyrrolidin-1 -yl-propan-1 -one; N-Adamantan-2-yl-3,4-dichloro-benzamide;
Benzo[b]thiophen-3-yl-(6-fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-methanone;
2-Adamantan-1-yI-1-(3,4-dihydro-1H-isoquinolin-2-yl)-ethanone;
4,5,6,7-Tetrahydro-benzo[b]thiophene-3-carboxylic acid (2-cyclohex-1 -enyl-ethyl)-amide;
Benzo[b]thiophene-3-carboxylic acid (3,3,5-trimethyl-cyclohexyl)-amide; 2-(2,6-Dimethyl-phenoxy)-N-(2-isopropyl-phenyl)-acetamide;
4-Bromo-N-[3-(piperidine-1-carbonyl)-phenyl]-benzamide;
N-Benzo[1,3]dioxol-5-ylmethyl-2-(2-cyano-phenylsulfanyl)-benzamide;
N-Adamantan-1 -yl-2-(naphthalen-2-yloxy)-acetamide;
[4-(4-Chloro-phenylsulfanylmethyl)-phenyl]-morpholin-4-yl-methanone; Thiophene-2-carboxylic acid (3,3,5-trimethyl-cyclohexyl)-amide;
Benzo[1,3]dioxol-5-yl-(3,4-dihydro-2H-quinolin-1-yl)-methanone;
3-Chloro-benzo[b]thiophene-2-carboxylic acid cyclooctylamide;
2-[2-Morpholin-4-yl-1-(4-nitro-benzyl)-2-oxo-ethyl]-isoindole-1 ,3-dione;
2-Hydroxy-4,4-dimethyl-6-oxo-cyclohex-1 -enecarboxylic acid phenylamide; (2,4-Dichloro-phenyl)-(2,6-dimethyl-piperidin-1-yl)-methanone;
Adamantane-1 -carboxylic acid furan-2-ylmethyl-p-tolyl-amide;
Azocan-1-yl-(4-tert-butyl-phenyl)-methanone;
3-Chloro-benzo[b]thiophene-2-carboxylic acid benzyl-methyl-amide;
Adamantane-1 -carboxylic acid (2-fluoro-phenyl)-amide; 2-(Piperidine-1 -carbonyl)-5-piperidin-1 -yl-oxazole-4-carbonitrile;
N-(4,6-Dimethyl-5-nitro-pyridin-3-yI)-benzamide;
Adamantan-1-yl-[4-(2-methoxy-phenyl)-piperazin-1 -ylj-methanone;
(2-Methyl-piperidin-1-yl)-o-tolyl-methanone;
N-Benzyl-4-chloro-N-isopropyI-3-nitro-benzamide; N-(3-Hexylsulfanyl-[1,2,4]thiadiazol-5-yl)-3-methyl-butyramide;
4,N-Dimethyl-N-[4-(piperidine-1-carbonyl)-phenyIj-benzenesulfonamide;
Azepan-1 -yl-(5-tert-butyl-2H-pyrazol-3-yl)-methanone;
2-Amino-4-methyl-5-(piperidine-1-carbonyl)-thiophene-3-carboxylic acid ethyl ester;
5-MethyI-furan-2-carboxylic acid (1 -adamantan-1 -yl-ethyl)-amide; (3-Chloro-6-methyl-benzo[b]thiophen-2-yl)-(3,4-dihydro-1H-isoquinolin-2-yl)-methanone;
N-Adamantan-1-yI-2-trifluoromethyl-benzamide; (3-Bromo-phenyl)-(2,2,4-trimethyI-4-phenyl-3,4-dihydro-2H-quinolin-1-yl)-methanone;
Benzo[1 ,3]dioxole-5-carboxylic acid dipropylamide;
N-(3,3-Diphenyl-propyl)-4-methoxy-benzamide;
[4-(2-Chloro-6-nitro-phenyl)-piperazin-1-ylj-p-tolyl-methanone; Furan-2-yl-[4-(toluene-4-sulfonyl)-piperazin-1 -ylj-methanone;
3-(2-Chloro-6-fluoro-phenyl)-1-(3,4-dihydro-2H-quinolin-1-yl)-propenone;
2-Chloro-N-cycloheptyl-benzamide;
1-[4-(4-Nitro-phenyl)-piperazin-1-yl]-3-phenyl-propan-1-one;
(3,4-Dihydro-1H-isoquinolin-2-yl)-(3,4-dimethyl-phenyl)-methanone; (1 -Adamantan-1 -yl-4-bromo-1H-pyrazol-3-yl)-morpholin-4-yl-methanone;
2-Phenyl-cyclopropanecarboxylic acid cyclooctylamide;
3-[4-(2-Ethoxy-phenyl)-piperazine-1-carbonylj-isochromen-1-one;
[3-(4-Bromo-pyrazol-1-ylmethyl)-phenyl]-(4-methyl-piperidin-1-yl)-methanone;
2-Azepan-1-yI-N-biphenyl-2-yl-acetamide; N-[5-(3,4-Dimethoxy-benzyl)-[1 ,3,4]thiadiazol-2-yl]-3-methyl-butyramide;
Adamantan-1 -yl-(4-phenyl-piperidin-1-yl)-methanone;
N-(2-Azepan-1-yl-2-oxo-ethyI)-N-(4-ethoxy-phenyl)-4-methylsulfanyl-benzenesulfonamide;
1 -Adamantan-1 -yl-4-bromo-1 H-pyrazole-3-carboxylic acid diethylamide;
(6-Fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-(2-fluoro-phenyl)-methanone; 3-[4-(2,3-Dimethyl-phenyl)-piperazine-1 -carbonyl]-isochromen-1 -one;
N-Cyclooctyl-2-(2-methoxy-phenoxy)-acetamide;
N-Cyclohexyl-N-methyl-2-nitro-benzamide;
Adamantane-1 -carboxylic acid (1 ,1-dioxo-tetrahydro-thiophen-3-yl)-amide;
N-Adamantan-2-yl-2-(4-chloro-phenyl)-acetamide; (2,4-Dichloro-phenyl)-(3-methyl-piperidin-1 -yl)-methanone;
2-(4-tert-Butyl-phenoxy)-N-cyclooctyl-acetamide;
(4-Hydroxy-4-phenyl-octahydro-quinolin-1-yl)-phenyl-methanone;
(2-Chloro-phenyl)-(2-methyI-piperidin-1-yl)-methanone;
(10,11-Dihydro-dibenzo[b,fjazepin-5-yl)-(2-methoxy-phenyl)-methanone; (3-Chloro-phenyl)-(2-methyl-piperidin-1 -yl)-methanone;
(3-Chloro-6-nitro-benzo[b]thiophen-2-yl)-(3-methyl-piperidin-1-yl)-methanone;
(2,5-Dichloro-phenyl)-(4-methyl-piperidin-1-yl)-methanone;
N-[5-(3,4-Dichloro-benzyl)-[1,3,4]thiadiazol-2-yl]-2,2-dimethyl-propionamide;
4-(4-Chloro-2-methyl-phenoxy)-1-(3,4-dihydro-2H-quinolin-1-yl)-butan-1-one; (3,4-Dichloro-phenyI)-[4-(2,3-dimethyI-phenyl)-piperazin-1-yl]-methanone;
Cyclooctanecarboxylic acid [1 -(naphthalene-2-sulfonyI)-pyrrolidin-2-yl]-amide; 1-Butyl-pyrrolidine-2-carboxylic acid benzo[1 ,3jdioxol-4-ylamide;
5-Methyl-furan-2-carboxylic acid dibenzylamide;
(3,4-Dihydro-2H-quinolin-1-yl)-[3-(4-phenyl-piperazine-1-sulfonyl)-phenyl]-methanone;
Bicyclo[2.2.1]hept-2-yl-[4-(2,3-dimethyl-phenyl)-piperazin-1 -ylj-methanone; N-Adamantan-1 -yl-2-benzoyl-benzamide;
[5-(2-Chloro-phenoxymethyl)-furan-2-yl]-(3-methyl-piperidin-1-yI)-methanone;
(3,5-Dimethyl-piperidin-1-yl)-(2-iodo-phenyl)-methanone;
1-Benzenesulfonyl-pyrrolidine-2-carboxylic acid cyclooctylamide;
(3,4-Dimethoxy-phenyl)-(6-fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-methanone; 3-(2,6-Dichloro-phenyI)-1-(2-ethyl-piperidin-1-yl)-propenone;
N-(3,4-Difluoro-phenyl)-2,6-difluoro-benzamide;
2,6-Difluoro-N-naphthalen-1-yI-benzamide;
(4-Chloro-phenyl)-(3,5-dimethyl-piperidin-1-yl)-methanone;
N-[4-(2,6-Dimethyl-piperidine-1-carbonyl)-phenyl]-2-(naphthalen-2-yloxy)-acetamide; (2-Chloro-phenyl)-(3-methyl-piperidin-1-yl)-methanone;
N-{2-[4-(Piperidine-1-sulfonyl)-phenyl]-ethyl}-acetamide;
N-Biphenyl-2-yl-2-(pyridin-2-yIsulfanyl)-acetamide;
Azepan-1 -yl-[5-(4-chloro-3,5-dimethyl-pyrazol-1-ylmethyl)-furan-2-yl]-methanone;
Acetic acid 4-(4-methyl-piperidine-1-carbonyl)-phenyl ester; Acetic acid 4-(4-benzyl-piperidine-1-carbonyl)-phenyl ester;
Benzo[1 ,3]dioxole-5-carboxyIic acid cycloheptylamide;
2-(2,4-Dimethyl-phenoxy)-1-(6-fluoro-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-ethanone;
Acetic acid 4-(3,4-dihydro-2H-quinoline-1-carbonyl)-phenyl ester;
Azepan-1 -yl-(3,5-dibromo-phenyl)-methanone; (3,5-Dibromo-phenyl)-[4-(2-methoxy-phenyl)-piperazin-1 -ylj-methanone;
N-CyclooctyI-4-isopropyl-benzamide;
N-Cyclooctyl-2-(4-methoxy-phenyl)-acetamide;
(4-tert-Butyl-piperidin-1-yl)-phenyl-methanone;
N-(4-tert-Butyl-3-nitro-phenyl)-acetamide; (2,6-DimethyI-piperidin-1-yl)-[5-(2,3,5,6-tetrafluoro-phenoxymethyl)-furan-2-yl]-methanone;
2-(4-Chloro-3,5-dimethyl-phenoxy)-N-cyclohexyl-N-methyl-acetamide;
N-Cyclohexyl-3-(1 ,3-dioxo-1 ,3-dihydro-isoindol-2-yl)-N-methyl-propionamide;
2-(4-Chloro-3-methyl-phenoxy)-N-cycIohexyl-N-methyl-acetamide;
N-Cyclopentyl-3-(3,4-dihydro-2H-quinoline-1-carbonyl)-benzenesulfonamide; (3,4-Dihydro-1 H-isoquinolin-2-yl)-(3-dimethylamino-phenyl)-methanone;
3-Cydohexylcarbamoyl-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid isopropyl ester; 1-(3,4-Dihydro-1H-isoquinolin-2-yl)-2-(2-methoxy-phenyl)-ethanone;
N-Benzyl-N-cyclohex-1 -enyl-benzamide;
[1-(Thiophene-2-sulfonyl)-piperidin-4-yl]-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone; N-Adamantan-1 -yl-2-(1 -phenyl- 1 H-tetrazol-5-ylsulfanyl)-acetamide;
(3,4-Dihydro-2H-quinolin-1-yl)-[4-(morpholine-4-suIfonyl)-phenyl]-methanone;
(3,4-Dihydro-2H-quinolin-1-yI)-[4-(pyrroIidine-1-sulfonyl)-phenyl]-methanone;
(3,4-Dihydro-2H-quinolin-1 -yl)-[1 -(thiophene-2-sulfonyI)-piperidin-4-yl]-methanone;
(1-Benzenesulfonyl-piperidin-3-yl)-(3,4-dihydro-1H-isoquinolin-2-yl)-methanone; 6,7-Dimethyl-4-oxa-tricyclo[4.3.0.03,7]nonane-3-carboxylic acid cyclohexylamide;
6,7-DimethyI-4-oxa-tricyclo[4.3.0.03,7]nonane-3-carboxylic acid (2-chIoro-phenyl)-amide;
(6,7-Dimethyl-4-oxa-tricyclo[4.3.0.03,7]non-3-yl)-piperidin-1 -yl-methanone;
2-[(Adamantane-1-carbonyl)-amino]-3-(1H-indol-3-yI)-propionic acid methyl ester;
2-(5,6-Dimethyl-4-oxo-3,4-dihydro-thieno[2,3-d]pyrimidin-2-ylsulfanyl)-N-furan-2-ylmethyl- acetamide;
N-Allyl-2-(5,6-dimethyl-4-oxo-3,4-dihydro-thieno[2,3-d]pyrimidin-2-ylsulfanyl)-acetamide;
N-Adamantan-1-yl-2-(5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidin-4-ylsulfanyl)- acetamide;
1-(3,4-Dihydro-2H-quinoline-1-carbonyl)-4,7,7-trimethyl-2-oxa-bicyclo[2.2.1]heptan-3-one; 1-(3,4-Dihydro-1 H-isoquinoline-2-carbonyl)-4,7,7-trimethyl-2-oxa-bicyclo[2.2.1]heptan-3-one;
Azepan-1 -yl-(6,7-dimethyl-4-oxa-tricyclo[4.3.0.03,7]non-3-yl)-methanone;
2,5-Dimethyl-furan-3-carboxylic acid (1 -adamantan-1 -yl-ethyl)-amide;
1 -Cyclohexyl-5-oxo-pyrrolidine-3-carboxylic acid (3-cyano-4,5,6,7-tetrahydro- benzo[b]thiophen-2-yl)-amide; 6-(2,4-Dichloro-phenylcarbamoyl)-3,4-dimethyl-cyclohex-3-enecarboxylic acid;
2-(2-Cyano-phenylsulfanyl)-N-cyclopentyl-benzamide;
[5-(2-Methoxy-4-propyl-phenoxymethyl)-furan-2-yl]-(3-methyl-piperidin-1-yl)-methanone;
(4-tert-Butyl-phenyI)-(3,5-dimethyl-piperidin-1-yl)-methanone;
[4-(2-Methoxy-naphthalen-1-ylmethyl)-piperazin-1-yl]-(4-methoxy-phenyl)-methanone; (3,4-Dichloro-phenyl)-(3,5-dimethyl-piperidin-1-yl)-methanone;
(4-Ethoxy-phenyI)-(4-methyl-piperidin-1-yl)-methanone;
2-Phenethyl-N-(tetrahydro-furan-2-ylmethyI)-benzamide;
N-Cycloheptyl-2-phenoxy-benzamide;
Adamantane-1 -carboxylic acid (2-ethoxy-phenyI)-amide; N-Adamantan-2-yl-2-o-tolyloxy-acetamide;
(2-Chloro-phenyl)-(3,5-dimethyI-piperidin-1-yl)-methanone; 1-Morpholin-4-yl-2-[3-(4-nitro-phenyl)-adamantan-1-yl]-ethanone;
2-Dimethylamino-N-(2-nitro-phenyl)-benzamide;
N-Benzyl-2-(4,4,6-trimethyl-1-p-tolyI-1,4-dihydro-pyrimidin-2-ylsuIfanyl)-acetamide;
[4-(3,5-Dinitro-phenoxy)-phenyl]-(2-ethyl-piperidin-1-yl)-methanone; 1-(4-Chloro-benzoyl)-2,3-dihydro-1 H-benzo[g]quinolin-4-one;
2-[(Adamantane-1-carbonyl)-amino]-3-phenyl-propionic acid methyl ester;
[Benzyl-(4-nitro-benzoyl)-amino]-acetic acid ethyl ester;
9-Oxo-9H-fluorene-3-carboxylic acid methyl-(4-nitro-phenyl)-amide;
Adamantane-1 -carboxylic acid [2-(4-methoxy-phenyl)-ethyl]-amide; (10,11-Dihydro-dibenzo[b,fjazepin-5-yl)-(4-fluoro-phenyl)-methanone;
2-Benzylsulfanyl-N-[2-(2-methoxy-phenoxy)-ethyl]-acetamide;
N-Adamantan-1 -yl-2-(2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide;
2-Bromo-N-tricyclo[3.2.1.02,4]oct-6-ylmethyl-benzamide;
Adamantane-1 -carboxylic acid (2,6-dimethoxy-pyrimidin-4-yl)-amide; Hexanedioic acid (2,7,7-trimethyl-bicyclo[2.2.1Jhept-1-yl)-amide (1 ,7,7-trimethyl- bicyclo[2.2.1 ]hept-2-yl)-amide;
2-Chloro-N-(2-cyclohexyl-ethyl)-benzamide;
2-[3-(2-Ethyl-piperidin-1-yl)-3-oxo-propyl]-isoindole-1 ,3-dione;
N-Adamantan-1 -yl-2-(2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide; N-Adamantan-1 -yl-2-hydroxy-2,2-diphenyl-acetamide;
Adamantane-1 -carboxylic acid (naphthalen-1 -ylmethyl)-amide;
Adamantane-1 -carboxylic acid (benzo[1 ,3jdioxol-5-ylmethyl)-amide;
1 -(Azepane-1 -carbonyl)-fluoren-9-one;
2-(Quinolin-2-ylsuIfanyl)-N-p-tolyl-acetamide; 2,4-Dichloro-N-[3-(piperidine-1-carbonyl)-phenylj-benzamide;
2-Chloro-4,5-difluoro-N-(3,3,5-trimethyl-cyclohexyl)-benzamide;
2-(2-Chloro-benzylsulfanyl)-N-p-tolyl-acetamide;
[4-(4-Chloro-phenylsulfanylmethyl)-phenyl]-pyrrolidin-1-yl-methanone;
N-Adamantan-1 -yl-N-methyl-isonicotinamide; Azepan-1-yl-[4-(4-chloro-phenylsulfanylmethyl)-phenyl]-methanone;
(2-ChIoro-phenyl)-(1,5,7-trimethyl-3,7-diaza-bicyclo[3.3.1]non-3-yl)-methanone;
(3-Chloro-benzo[b]thiophen-2-yl)-(4-methyl-piperidin-1-yl)-methanone;
Benzoic acid 1-benzoyl-decahydro-quinolin-4-yl ester;
2-(3-Bromo-benzylsuIfanyl)-1-[4-(2-methoxy-phenyl)-piperazin-1-yl]-ethanone; 4-Methyl-N-[2-(phenoxazine-10-carbonyl)-phenyl]-benzenesuIfonamide;
2-[1 -(Azepane-1 -carbonyl)-2-methyl-propyl]-isoindole-1 ,3-dione; 2-(3-Bromo-benzylsulfanyl)-1 -piperidin-1 -yl-ethanone;
1-[3-(4-Bromo-phenyl)-1-furan-2-yl-3-oxo-propyl]-pyrrolidin-2-one;
2-Chloro-N-cyclooctyl-4,5-difluoro-benzamide;
2,4-Dichloro-N-(2-furan-2-yImethyl-cyclohexyl)-benzamide; N-(4-Benzoyl-furazan-3-yl)-2-fluoro-benzamide;
N-Adamantan-1-yl-2-(3-cyano-4-methoxymethyl-6-methyl-pyridin-2-ylsulfanyl)-acetamide;
4-tert-Butyl-N-cyclooctyl-benzamide;
N-Adamantan-1-yl-2-phenyl-butyramide;
(3-Chloro-6-methoxy-benzo[b]thiophen-2-yl)-piperidin-1-yl-methanone; (3,7-Dichloro-6-methoxy-benzo[b]thiophen-2-yl)-piperidin-1 -yl-methanone;
Acetic acid 1-benzoyl-decahydro-quinolin-4-yl ester;
2-Bromo-N-methyl-N-phenyl-benzamide;
N-Benzo[1 ,3]dioxol-5-yl-2,4-dichloro-benzamide;
(3-Chloro-6-fluoro-benzo[b]thiophen-2-yl)-piperidin-1-yl-methanone; N-(1 ,2,3,5,6,7-Hexahydro-s-indacen-1-yl)-2-piperidin-1-yl-acetamide;
2-[(Adamantane-1-carbonyl)-amino]-3-(1H-indol-3-yl)-propionic acid methyl ester;
2-[2-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-yl)-3-phenyl-propionyIamino]-3-methyl-butyric acid methyl ester;
2-(6-Oxo-6-piperidin-1 -yl-hexyl)-isoindole-1 ,3-dione; 2-[2-(1 ,3-Dioxo-1 ,3-dihydro-isoindol-2-yl)-3-phenyl-propionylamino]-3-methyl-butyric acid methyl ester;
Adamantane-1 -carboxylic acid (2,6-dihydroxy-pyrimidin-4-yl)-amide;
Adamantane-1 -carboxylic acid [3-(1 H-benzoimidazol-2-ylsulfanyl)-5-nitro-phenyl]-amide;
Adamantane-1 -carboxylic acid methyl-phenyl-amide; 3-Chloro-benzo[b]thiophene-2-carboxylic acid dibenzylamide;
N-Adamantan-1-yl-2-(3-cyano-6-methyl-4-trifluoromethyl-pyridin-2-ylsulfanyl)-acetamide;
2-(3-Oxo-3-phenyl-propenyl)-isoindole-1 ,3-dione;
Adamantane-1 -carboxylic acid (4-ethoxy-benzothiazol-2-yl)-amide;
N-[5-(5-Chloro-benzooxazol-2-yl)-2-methyl-phenyl]-2-methoxy-benzamide; N-[2-(2-Bromo-phenyl)-benzooxazol-5-yl]-2-methoxy-benzamide;
2-(4-Chloro-phenoxy)-N-(4-chloro-3-trifluoromethyl-phenyl)-acetamide;
2,2-Dimethyl-N-(5-propyl-[1,3,4]thiadiazol-2-yl)-propionamide;
2-[2-(2,6-Dimethyl-morpholin-4-yl)-1-methyl-2-oxo-ethyl]-isoindole-1 ,3-dione;
2-(2-Cyano-phenylsulfanyl)-N-(2-trifluoromethyl-phenyl)-benzamide; Azepan-1 -yl-(3,6-dichloro-benzo[b]thiophen-2-yl)-methanone;
Benzo[1 ,3]dioxol-5-yl-(4-benzyl-piperidin-1 -yl)-methanone; Azepan-1-yl-(3-chloro-6-methyl-benzo[b]thiophen-2-yl)-methanone;
N-(5-Hexyl-[1,3,4]thiadiazol-2-yl)-isobutyramide;
(3-Chloro-phenyl)-(10,11-dihydro-dibenzo[b,fjazepin-5-yl)-methanone;
(2-Chloro-phenyl)-(10,11 -dihydro-dibenzo[b,fjazepin-5-yl)-methanone; 2-Amino-5-(azepane-1-carbonyl)-4-methyl-thiophene-3-carboxylic acid ethyl ester;
Adamantan-1 -yl-(4-cyclopropyl-1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-methanone;
Adamantan-1-yl-(4-trifluoromethyl-1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-methanone;
Adamantan-1 -yl-[4-(1 H-benzoimidazol-2-ylsulfanyl)-piperidin-1 -ylj-methanone;
Adamantan-1-yl-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-methanone; [4-(1H-lmidazol-4-yl)-piperidin-1-yl]-(4-pentyl-phenyl)-methanone;
3-Cyclohexyl-1-[4-(1H-imidazol-4-yI)-piperidin-1-yl]-propan-1-one;
1 -(4-Propyl-piperazin-1 -yl)-3-(4-trifluoromethyl-phenyl)-propan-1 -one;
N-(2-Hydroxy-benzyl)-3-thiophen-3-yl-N-(2-thiophen-2-yl-ethyl)-acrylamide;
N-(1 ,3-DimethyI-pentyl)-2-(3-fluoro-phenyl)-N-(4-hydroxy-benzyl)-acetamide; N-Cyclobutyl-2-(3-fluoro-phenyl)-N-(4-hydroxy-benzyI)-acetamide;
N-Cyclobutyl-N-(4-hydroxy-benzyl)-4-trifluoromethyl-benzamide;
N-(3-Hydroxy-benzyl)-2-methyl-3-nitro-N-(4-sulfamoyl-benzyl)-benzamide;
N-(4-Bromo-benzyl)-N-(4-hydroxy-benzyl)-2-naphthalen-1-yl-acetamide;
6-(2-Bromo-phenylsulfanyl)-hexanoic acid (3-amino-2,2-dimethyl-propyl)-amide; N-(3-Amino-2,2-dimethyl-propyl)-4-[2-(2-isopropyl-phenylsulfanyl)-ethyl]-benzamide;
N-(3-Amino-2,2-dimethyl-propyl)-4-[4-(4-chloro-phenyl)-pyrimidin-2-ylsulfanylmethyl]-3-nitro- benzamide;
4-(4-Bromo-phenyl)-N-(2-hydroxy-benzyl)-4-oxo-N-thiophen-2-yImethyl-butyramide;
N-[2-(2,4-Dichloro-phenyl)-ethyl]-N-(4-hydroxy-benzyl)-2-thiophen-3-yl-acetamide; N-(2-Chloro-benzyl)-N-(4-hydroxy-benzyl)-2-thiophen-2-yl-acetamide;
Heptanoic acid benzyl-(4-hydroxy-benzyl)-amide;
N-(4-Fluoro-benzyl)-N-(4-hydroxy-benzyl)-2-thiophen-3-yl-acetamide;
4-Methyl-pentanoic acid (4-fluoro-benzyl)-(4-hydroxy-benzyl)-amide;
N-Allyl-2-(4-chloro-phenyl)-N-(4-hydroxy-benzyl)-acetamide; N-Allyl-2-benzo[b]thiophen-3-yl-N-(4-hydroxy-benzyl)-acetamide;
Heptanoic acid (3-ethoxy-propyl)-(4-hydroxy-benzyl)-amide;
Dec-3-enoic acid (4-hydroxy-benzyl)-(4-trifluoromethyl-benzyl)-amide;
6-Oxo-6-phenyl-hexanoic acid (4-hydroxy-benzyl)-(4-trifluoromethyl-benzyl)-amide;
2-(3,4-Difluoro-phenyl)-N-(4-hydroxy-benzyl)-N-thiophen-2-ylmethyl-acetamide; 2-MethyI-pent-4-enoic acid (3-hydroxy-benzyl)-[2-(2-methoxy-phenyl)-ethyl]-amide;
Heptanoic acid (3-hydroxy-benzyl)-(4-isopropyl-benzyl)-amide; 5-(2,6-Dichloro-phenylsulfanyl)-pentanoic acid (naphthalen-1 -ylmethyl)-amide;
N-(6,6-Dimethyl-bicyclo[3.1.1]hept-2-ylmethyl)-4-[2-(5-methyl-1H-benzoimidazol-2-ylsulfanyl)- ethylj-benzamide;
N-(6,6-Dimethyl-bicyclo[3.1.1jhept-2-ylmethyl)-4-[2-(4-phenoxy-pyrimidin-2-ylsulfanyl)-ethylj- benzamide;
N-(6,6-DimethyI-bicyclo[3.1.1jhept-2-ylmethyl)-4-[2-(4-fluoro-phenylsulfanyl)-ethylj-benzamide;
4-(2,6-Dichloro-phenylsulfanyl)-N-(6,6-dimethyl-bicyclo[3.1.1]hept-2-ylmethyl)-butyramide;
N-(6,6-Dimethyl-bicyclo[3.1.1]hept-2-ylmethyl)-4-[2-(5-methyl-1H-benzoimidazol-2-ylsulfanyi)- ethylj-benzamide; N-(6,6-Dimethyl-bicyclo[3.1.1]hept-2-ylmethyl)-4-[2-(4-fluoro-phenylsulfanyl)-ethyl]-benzamide;
5-(3-Methylsulfanyl-[1 ,2,4]thiadiazol-5-ylsulfanyl)-pentanoic acid (6,6-dimethyl- bicyclo[3.1.1 ]hept-2-ylmethyl)-amide;
5-(2,6-Dichloro-phenylsulfanyl)-pentanoic acid [2-(3-trifluoromethyl-phenyl)-ethyl]-amide;
4-[2-(2,6-Dichloro-phenylsulfanyl)-ethyl]-N-[2-(2-fluoro-phenyl)-ethyl]-benzamide; 2-Cyclohexylamino-thiazole-4-carboxylic acid (1,2,3,4-tetrahydro-naphthalen-1-yl)-amide;
2-Cyclohexylamino-thiazole-4-carboxylic acid (3-chloro-4-hydroxy-phenyl)-amide;
2-Cyclohexylamino-thiazole-4-carboxylic acid (1 ,2-dimethyI-propyl)-amide;
2-Cyclohexylamino-thiazole-4-carboxylic acid (1 -ethyl-propyl)-amide;
2-Cyclohexylamino-thiazole-4-carboxylic acid [3-(1 -hydroxy-ethyl)-phenyl]-amide; 2-Cyclohexylamino-thiazole-4-carboxylic acid (l-ethynyl-cyclohexyl)-amide;
2-Cyclohexylamino-thiazole-4-carboxylic acid (2-methoxy-dibenzofuran-3-yl)-amide;
2-Cyclohexylamino-thiazole-4-carboxylic acid [2-(4-hydroxy-phenyl)-ethyl]-amide;
2-Cyclohexylamino-thiazole-4-carboxylic acid (4-hydroxy-cyclohexyl)-amide;
2-(2,6-Difluoro-benzyIamino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-acetamide; 4-{4-[2-(4-Dimethylamino-phenyl)-acetyl]-piperazin-1-yl}-3-(2-phenyl-propylamino)-benzamide;
2-(2-Ethyl-phenylsulfanyl)-3-[methyl-(2-pyridin-4-yl-ethyl)-amino]-N-prop-2-ynyI-propionamide;
4-Methyl-cyclohexanecarboxylic acid {[2-(2-chloro-6-fluoro-benzylsulfanyl)-ethylcarbamoylj- methyl}-prop-2-ynyl-amide;
2-Benzylsulfanyl-N-{[2-(2-chloro-6-fluoro-benzylsulfanyl)-ethylcarbamoyl]-methyl}-N-(2- methoxy-ethyl)-acetamide;
4-[2-(5-CyclopropylmethylsuIfanyl-[1,3,4Jthiadiazol-2-ylsulfanyl)-ethyl]-N-(6,6-dimethyl- bicyclo[3.1.1]hept-2-ylmethyl)-benzamide;
N-(6,6-Dimethyl-bicyclo[3.1.1]hept-2-ylmethyl)-4-[2-(4-phenoxy-pyrimidin-2-ylsulfanyl)-ethylj- benzamide; N-(6,6-Dimethyl-bicyclo[3.1.1]hept-2-ylmethyl)-2-p-toIyloxy-acetamide;
Bicyclo[2.2.1 ]hept-5-ene-2-carboxylic acid [4-(2,5-difluoro-phenoxy)-butyl]-amide; 4-Trifluoromethyl-cyclohexanecarboxylic acid [6-(2,6-difluoro-phenoxy)-hexyl]-amide;
N-Cyclopropyl-3-methoxy-N-(2-piperidin-4-yl-ethyl)-5-(pyridine-2-carbonyl)-benzamide;
3-Methoxy-N-(2-methoxy-ethyl)-N-(2-piperidin-4-yl-ethyl)-5-(pyridine-2-carbonyl)-benzamide;
3-Methoxy-N-(2-piperidin-4-yl-ethyl)-5-(pyridine-2-carbonyl)-N-(tetrahydro-furan-2-ylmethyl)- benzamide;
3-Methoxy-N-(2-oxo-azepan-3-yl)-N-(2-piperidin-4-yl-ethyl)-5-(pyridine-2-carbonyl)- benzamide;
3-Methoxy-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-N-(2-piperidin-4-yl-ethyl)-5-(pyridine-2- carbonyl)-benzamide; 3-Methoxy-N-methyl-N-(2-piperidin-4-yl-ethyl)-5-(pyridine-2-carbonyl)-benzamide;
[2-({Cyclopropyl-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-methyl)-phenoxy]-acetic acid;
(2-{[[3-Methoxy-5-(pyridine-2-carbonyI)-benzoyl]-(3-methyl-butyl)-amino]-methyl}-phenoxy)- acetic acid; [2-({Cyclopentyl-[3-methoxy-5-(pyridine-2-carbonyI)-benzoyl]-amino}-methyl)-phenoxy]-acetic acid;
[2-({(2-Methoxy-ethyl)-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-methyl)-phenoxyj- acetic acid;
[2-({Carbamoylmethyl-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-methyl)-phenoxyj- acetic acid;
[2-({[3-Methoxy-5-(pyridine-2-carbonyl)-benzoyl]-pyridin-4-yl-amino}-methyl)-phenoxy]-acetic acid;
[2-({Cyclopropylmethyl-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-methyl)-phenoxyj- acetic acid; [2-({[3-Methoxy-5-(pyridine-2-carbonyl)-benzoyl]-methyl-amino}-methyl)-phenoxy]-acetic acid;
[4-(4-Hydroxy-benzyl)-piperazin-1-yl]-[3-methoxy-5-(pyridine-2-carbonyI)-phenylj-methanone;
{Carbamoylmethyl-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-acetic acid;
{(3-lmidazol-1-yl-propyl)-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-acetic acid;
{[3-Methoxy-5-(pyridine-2-carbonyl)-benzoyl]-pyridin-4-yl-amino}-acetic acid; [[3-Methoxy-5-(pyridine-2-carbonyl)-benzoyl]-(2-oxo-azepan-3-yl)-amino]-acetic acid;
3-Methoxy-N-(2-methoxy-ethyl)-N-piperidin-3-ylmethyl-5-(pyridine-2-carbonyl)-benzamide;
4-[3-Methoxy-5-(pyridine-2-carbonyl)-benzoylaminoj-piperidine-1 -carboxylic acid ethyl ester;
3-Methoxy-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-5-(pyridine-2-carbonyl)-benzamide;
3-({Carbamoylmethyl-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-methyl)-benzoic acid; 3-({(3-lmidazol-1-yl-propyl)-[3-methoxy-5-(pyridine-2-carbonyl)-benzoyl]-amino}-methyl)- benzoic acid;
4-Amino-N-(3-hydroxy-benzyl)-N-indan-2-yl-2-propionylamino-butyramide;
5-Amino-2-propionylamino-pentanoic acid (3-hydroxy-benzyl)-indan-2-yl-amide; N-EthyI-2-hexylamino-N-(4-hydroxy-benzyl)-acetamide;
2-Hexylamino-N-(4-hydroxy-benzyl)-N-methyl-acetamide;
1 -[1 -(6-Phenyl-hexanoyl)-piperidin-4-ylj-1 ,3-dihydro-benzoimidazol-2-one;
1 -[1 -(3-Cyclohexyl-propionyl)-piperidin-4-yl]-1 ,3-dihydro-benzoimidazol-2-one;
N-(2-Hydroxy-benzyl)-N-isobutyl-benzamide; N-(2-Hydroxy-benzyl)-2-(4-hydroxy-phenyl)-N-isobutyl-acetamide;
N-(2-Hydroxy-benzyl)-N-(3-methyl-butyI)-benzamide;
N-(4-Hydroxy-benzyI)-N-isobutyl-benzamide;
4-Hydroxy-N-(4-hydroxy-benzyl)-N-isobutyl-benzamide;
N-(4-Hydroxy-benzyl)-2-(4-hydroxy-phenyl)-N-isobutyl-acetamide; N-(4-Hydroxy-benzyl)-N-(3-methyl-butyl)-benzamide;
N-(2-Ethoxy-ethyl)-4-hydroxy-N-(4-hydroxy-benzyl)-benzamide;
N-(4-Hydroxy-benzyl)-N-(3-isopropoxy-propyl)-benzamide;
N-(3-Hydroxy-benzyl)-N-(4-methyl-pentyl)-benzamide;
N-(3-Hydroxy-benzyl)-2-(4-hydroxy-phenyl)-N-(4-methyl-pentyl)-acetamide; N-(3-Hydroxy-benzyl)-N-(3-isopropoxy-propyl)-benzamide;
N-(2-Hydroxy-benzyl)-N-(3-methyl-butyl)-4-propyl-benzamide;
N-(4-Hydroxy-benzyl)-N-(6-hydroxy-hexyl)-4-propyl-benzamide;
N-(4-Hydroxy-benzyl)-N-(3-methyl-butyl)-4-propyl-benzamide; and
N-[2-(4-Fluoro-benzylamino)-thiazol-4-ylmethyl]-N-phenethyl-butyramide; or
a salt thereof with a pharmaceutically acceptable acid or base, or an optical isomer, mixture of optical isomers, racemic mixture, or tautomeric form thereof.
9. The combination according to claim 6 or 7 wherein the 11 ?-HSD1 inhibitor is selected from the group ::
(4-Tetrazol-1 -yl-phenyl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone; N-Cyclohexyl-N-methyl-2-phenoxymethyl-benzamide; 4-Amino-N-cyclohexyl-N-methyl-benzamide; N-Cycloheptyl-N-methyl-2-phenoxymethyI-benzamide; N-Cydohexyl-N-methyl-benzamide; 2-Chloro-N-cyclohexyl-6-fluoro-N-methyl-benzamide;
N-Cyclohexyl-N-methyl-4-trifluoromethoxy-benzamide;
N-Cyclohexyl-2,3,N-trimethyl-benzamide;
3,5-Dichloro-N-cyclohexyl-N-methyl-benzamide;
N-CycIohexyl-N-methyl-2-phenoxy-benzamide;
2,4-Bis-benzyloxy-N-cycIohexyl-N-methyl-benzamide;
2-Benzyloxy-N-cyclohexyl-N-methyl-benzamide;
N-Cyclohexyl-N-methyl-4-phenoxy-benzamide;
4-Benzyloxy-N-cyclohexyl-N-methyl-benzamide;
N-Cyclohexyl-N-methyl-4-phenoxymethyl-benzamide;
2-Chloro-N-cyclohexyl-N-ethyl-4-nitro-benzamide;
4-Chloro-N-cyclohexyl-N-ethyl-3-nitro-benzamide;
6-Fluoro-4H-benzo[1 ,3]dioxine-8-carboxylic acid cyclohexyl-methyl-amide;
Azepan-1-yl-(2-chloro-phenyl)-methanone;
Azepan-1-yl-(3-chloro-phenyl)-methanone;
Azepan-1 -yl-phenyl-methanone;
2-(Biphenyl-4-yloxy)-N-cyclohexyl-N-methyl-benzamide;
N-Cyclohexyl-2-(3,5-dimethoxy-phenoxy)-N-methyl-benzamide;
N-Cyclohexyl-2-(2,3-dimethoxy-phenoxy)-N-methyl-benzamide;
2,4-Dichloro-N-(3,3-dimethyl-1,5-dioxa-spiro[5.5]undec-9-yl)-N-methyl-benzamide;
2,4-Dichloro-N-methyl-N-(4-oxo-cyclohexyl)-benzamide;
N-Cyclohexyl-2-hydroxy-N-methyl-benzamide;
N-Cyclohexyl-3-methoxy-N-methyl-benzamide;
Benzo[1 ,3]dioxole-5-carboxylic acid cyclohexyl-methyl-amide;
3-Benzyloxy-N-cyclohexyl-N-methyl-benzamide;
N-CyclohexyI-3-hydroxy-N-methyl-benzamide;
[4-(Morpholine-4-sulfonyl)-phenyl]-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
N-Benzyl-3-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-benzenesulfonamide;
[4-Fluoro-3-(morpholine-4-sulfonyl)-phenyl]-(1 ,3,3-trimethyl-6-aza-bicycIo[3.2.1 ]oct-6-yl)- methanone;
Thiophene-2-sulfonic acid [4-(1 ,3,3-trimethyI-6-aza-bicyclo[3.2.1]octane-6-carbonyl)- phenylj-amide;
N-Phenyl-4-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-benzenesulfonamide;
(4-Phenoxy-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
N-(2,4-Dimethyl-phenyl)-3-(1,3,3-trimethyI-6-aza-bicyclo[3.2.1]octane-6-carbonyI)- benzenesulfonamide;
(2-Phenoxymethyl-phenyI)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
4-(3-Aza-bicyclo[3.2.2]nonane-3-carbonyl)-N,N-dipropyl-benzenesulfonamide;
2-Bromo-N-cyclohexyl-N-methyl-benzamide;
N-[4-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]-acetamide;
(4-Dimethylamino-phenyI)-(1 ,3,3-trimethyl-6-aza-bicycIo[3.2.1 ]oct-6-yl)-methanone;
(4-Pyrrol-1-yl-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(4-lmidazol-1-yl-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(4-Amino-2-methoxy-phenyl)-(trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(4-Methanesulfonyl-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(3-Methanesulfonyl-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(4-Benzenesulfonyl-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
Azepan-1 -yl-[4-(3,4-dihydro-1H-isoquinolin-2-ylmethyl)-phenyl]-methanone;
Azepan-1-yl-(4-morpholin-4-ylmethyl-phenyl)-methanone;
[4-(3-Trifluoromethyl-pyrazol-1-yl)-phenyl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
(4-[1,2,4]Triazol-1-yl-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(4-Pyrazol-1-yl-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
2-Benzyloxymethyl-N-cyclohexyl-N-methyl-benzamide;
N-Cyclohexyl-N-methyl-4-(3-methyl-5-oxo-4,5-dihydro-pyrazol-1-yl)-benzamide;
5-Methyl-2-[4-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyI)-phenyl]-2,4-dihydro- pyrazol-3-one;
(9H-Carbazol-3-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
[4-(3,5-Dimethyl-pyrazol-1 -yl)-phenyl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 joct-6-yl)- methanone;
Phenyl-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
Azepan-1-yl-(2-bromo-phenyl)-methanone;
(3-Aza-bicyclo[3.2.2]non-3-yI)-(2-bromo-phenyl)-methanone;
(4-Benzyl-piperidin-1-yl)-quinolin-2-yl-methanone;
(2-Methyl-piperidin-1-yl)-quinolin-2-yl-methanone;
(3-Aza-bicyclo[3.2.2jnon-3-yl)-quinolin-2-yl-methanone;
Quinoline-2-carboxylic acid cyclohexyl-methyl-amide;
Quinolin-2-yl-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
1-[4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]-pyrrolidine-2,5-dione;
Pyridin-3-yl-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; Pyridin-4-yl-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone;
Pyridin-2-yl-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone;
(6-Pyrazol-1-yl-pyridin-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-benzoic acid; lmidazo[2, 1 -b]thiazol-6-yl-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone; 8-(4-Dimethylamino-benzoyl)-8-aza-bicyclo[3.2.1 ]octan-3-one; (4-Dimethylamino-phenyl)-(3-hydroxy-8-aza-bicyclo[3.2.1]oct-8-yl)-methanone; (4-Dimethylamino-phenyI)-(3-hydroxy-3-methyl-8-aza-bicyclo[3.2.1joct-8-yl)-methanone; Trifluoro-acetic acid 8-(4-dimethyIamino-benzoyl)-8-aza-bicyclo[3.2.1]oct-3-yl ester; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
10. The combination according to claim 6 or 7 wherein the 11 ?-HSD1 inhibitor is of the Formula (lla):
Figure imgf000222_0001
(lla) wherein
R1 is aryl, arylCrC6alkyl, hetaryl or hetarylCrC6aIkyI optionally substituted with one or more of R6 independently;
R2 is halo, CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C10cycloalkyl, C3-CιocycloalkylCrC6alkyl, trihalomethyl, aryl, arylCrCealkyl, CrCealkyloxyCrCealkyl, arylCrCealkyloxyCrCealkyl, d-C6- alkylNR5CrC6alkyl, arylCrC6alkylNR5CrC6aIkyl, hetaryl or hetaryld-Cealkyl wherein the alkyl, alkenyl, alkynyl, cycloalkyl and aryl groups independently are optionally substituted with one or more R7;
R3 is d-Cealkyl optionally substituted with one or more of R8;
R4 is Ce-docycloalkyl, C6-C10hetcycloalkyl, C6-CιocycloalkylCrC6alkyl or C6-C 0hetcyclo- alkyld-C6alkyl wherein the alkyl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R8; or R3 and R4 together with the nitrogen to which they are attached, are forming a saturated or partially saturated bicydic/bridge ring system containing from 7 to 12 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, arylCrCealkyl, hetaryl- CrC6alkyl, hydroxy, oxo, CrC6alkyloxy, aryld-Cealkyloxy or hetarylCrCealkyloxy, wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R9;
R5 is CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C10cycloalkyl, C3-Cι0hetcycloalkyl, C3-C10- cycloalkylCrC6alkyl, C3-CιohetcycloalkylCrC6alkyl, aryl, hetaryl, arylCrC6alkyl or hetaryld- C6alkyl wherein the alkyl, alkenyl, alkynyl, aryl, hetaryl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R9;
R6 and R7 independently are hydrogen, hydroxy, oxo, halo, nitro, cyano, CrC6alkyl, CrCealkyloxy, trihalomethyl, trihalomethoxy, NR R , aryld-Cealkyloxy, hetaryld-Cealkyloxy, C C6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, CrCealkyloxycarbonyl, aryloxycarbonyl, arylCrCealkyloxycarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R8 and R9 independently are hydrogen, CrC6alkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrC6- alkyl, hydroxy, oxo, cyano, NR10R11, CrC6alkyloxy, aryloxy, arylCrCealkyloxy, hetaryloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R10 and R11 independently are hydrogen, CrC8alkyl, aryl, hetaryl, arylCrCealkyl, C3-C10- cycloalkyl, C3-C10hetcycloalkyl, Qrdocycloalkyld-Cealkyl, CrCealkylcarbonyl, C C6aIkylcarboxyCrC6alkyl; or
R10 and R11 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C8alkyl, aryl, hetaryl, aryld-C6aIkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, C C6aIkyloxy, aryld-Cealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylC C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or aryld-e- alkylcarboxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
11. The combination according to claim 10 wherein the 11 ?-HSD1 inhibitor is of the Formula (lla)wherein:
R is aryl or hetaryl optionally substituted with one or more R6 independently;
R2is halo, d-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-Cι0cycloalkyl, Cs-docycloalkylCi-Cealkyl, aryl, aryld-C6alkyl, CrCealkyloxyd-Cealkyl, arylCrCealkyloxyCrCealkyl, Cι-C6alkylNR5Cr C6alkyl, arylCrC6alkylNR5Cι-C6alkyl, hetaryl or hetarylCrC6alkyl wherein the alkyl, alkenyl, alkynyl, cycloalkyl and aryl groups independently are optionally substituted with one or more R7;
R3 is CrC6alkyl optionally substituted with one or more of R8;
R4 is Ce-docycloalkyl, C6-Cι0hetcycloalkyl, C6-CιocycloalkylCrC6alkyl or C6-C10hetcyclo- alkylCrC6alkyl wherein the alkyl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R8;
R5 is Ci-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C10cycloalkyl, C3-dohetcycloalkyl, C3-Cι0- cycloalkylCrC6alkyl, C3-CιohetcycloalkylCrCealkyl, aryl, hetaryl, arylCrC6alkyl or hetaryld- C6alkyl wherein the alkyl, alkenyl, alkynyl, aryl, hetaryl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R9;
R6 and R7 independently are hydrogen, hydroxy, oxo, halo, nitro, cyano, d-Cealkyl, CrCealkyloxy, trihalomethyl, trihalomethoxy, NR10R11, arylCrCealkyloxy, hetarylCrCealkyloxy, C C6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, CrCealkyloxycarbonyl, aryloxycarbonyl, arylCrCealkyloxycarbonyl, CrC6alkylcarboxy, arylcarboxy or aryld-C6alkyl- carboxy;
R8 and R9 independently are hydrogen, CrC6alkyl, aryl, hetaryl, arylCrC6aIkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, NR 0R11, CrC6alkyloxy, aryloxy, arylCrCealkyloxy, hetaryloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrC6alkyl-carbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrC6alkyl-carbonyI, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy; R10 and R11 independently are hydrogen, CrC8alkyl, aryl, hetaryl, arylCrC6aIkyl, C3-C10- cycloalkyl, C3-Cι0hetcycloalkyl, C3-CιocycloalkylCrCealkyl, CrCealkylcarboxyCrCealkyl; or
R10 and R11 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC8alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, d-C6alkyIoxy, arylCrCealkyloxy, hetaryl CrC6alkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrC6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCr6- alkylcarboxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, a prodrug thereof, or any tautomeric forms.
12. The combination according to claim 10 or 11 wherein the 11 ?-HSD1 inhibitor is selected from:
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic acid cyclohexyl-methyl-amide; 1-(4- Chloro-phenyl)-5-trifluoromethyl-1 H-pyrazole-4-carboxylic acid cyclohexyl-methyl-amide;
[1-(4-Methoxy-phenyl)-5-methyl--/H-pyrazol-4-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone; 1 [1-(4-Chloro-phenyl)-5-propyl-1H-pyrazol-4-yl]-(1 ,3,3-trimethyl-6-aza- bicyclo[3.2.1 ]oct-6-yl)-methanone;
[1-(3,5-Dichloro-phenyl)-5-propyl-1 .-pyrazol-4-yl]-(1 ,3,3-trimethyl-6-aza-bicyc[o[3.2.1]oct-6- yl)-methanone;
1 -(Phenyl)-5-methyl-1 H-pyrazole-4-carboxylic acid cyclohexyl-methyl-amide;
1 -(4-Fluoro-phenyl)-5-methyl-1 H-pyrazole-4-carboxylic acid cyclohexyl-methyl-amide;
1 -(4-Methoxy-phenyI)-5-methyl-1 H-pyrazole-4-carboxylic acid cyclohexyl-methyl-amide;
1-(4-Chloro-phenyl)-5-methyl-1 H-pyrazole-4-carboxylic acid cyclohexyl-methyl-amide; 1 -(2-Methyl-phenyl)-5-methyl-1 H-pyrazole-4-carboxylic acid cyclohexyl-methyl-amide;
1 -(4-Amino-phenyl)-5-methyl-1 /-/-pyrazole-4-carboxylic acid cyclohexyl-methyl-amide;
1 -(2-Pyridyl)-5-methyl-1 --pyrazole-4-carboxylic acid cyclohexyl-methyl-amide;
1-(2-Pyridyl)-5-propyl-1r/-pyrazole-4-carboxylic acid cyclohexyl-methyl-amide; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
13. The combination according to claim 6 or 7 wherein the 1 β -HSD1 inhibitor is of the Formula (lib)
Figure imgf000226_0001
(lib) wherein
R1 is hydrogen, trihalomethyl, d-Cealkyl, d-C6alkyloxy, CrC6alkylthio, aryl, aryld-Cealkyl, hetaryl or hetaralkyl, wherein the alkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R8;
R2 , R3, R4 and R5 independently are hydrogen, halo, nitro, cyano, hydroxy, NR9R10, trihalomethyl, CrC6alkyl, CrC6alkyloxy, CrC6alkylthio, aryl, arylCrC6alkyl, hetaryl or hetaralkyl, wherein the alkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R8; or
R2 together with R3 are forming a saturated or partially saturated cyclic ring system containing from 3 to 6 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrCealkyl, hydroxy, oxo, CrC6alkyloxy, aryloxy, aryld- Cealkyloxy or hetarylCrCealkyloxy; or
R3 together with R4 are forming a saturated or partially saturated cyclic ring system containing from 3 to 6 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, CrC6aIkyloxy, aryloxy, aryld- C6alkyloxy or hetarylCrCealkyloxy; or
R4 together with R5 are forming a saturated or partially saturated cyclic ring system containing from 3 to 6 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, CrC6alkyloxy, aryloxy, aryld- Cealkyloxy or hetarylCrCealkyloxy; R6 is aryl, hetaryl, arylCrC6alkyl, C3-C10cycloalkyl, C3-Cι0hetcycloalkyl, C3-Cι0cycloalkyICr C6alkyl, CrCealkylcarboxyCrCealkyl, wherein the alkyl, aryl and cycloalkyl groups independently are optionally substituted with one or more of R11;
R7 is CrC8alkyl, aryl, hetaryl, aryld-Cealkyl, C3-Cι0cycloalkyl, C3-Cι0hetcycloalkyl, C3- C10cycloalkylCrC6alkyl, CrCealkylcarboxyCrCealkyl, wherein the alkyl, aryl and cycloalkyl groups independently are optionally substituted with one or more of R11; or
R6 and R7, together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC8alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, d-C6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld-
C6alkylcarbonyl, hetarylCrCealkylcarbonyl, d-Cealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R8;
R9 and R10 independently are hydrogen, d-C8alkyl, aryl, hetaryl, arylCrC6alkyl, C3-Cι0- cycloalkyl, C3-C10hetcycloalkyl, C3-C10cycloalkylCrC6alkyl, CrCealkylcarboxyCrCealkyl, wherein the alkyl, aryl and cycloalkyl groups independently are optionally substituted with one or more of R11; or
R9 and R10, together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC8alkyl, aryl, hetaryl, arylCrC6alkyl, hetaryld-Cealkyl, hydroxy, oxo, cyano, d-C6alkyloxy, aryld-Cealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld-
C6aIkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R8;
R8 and R11 independently are hydrogen, halo, hydroxy, oxo, nitro, cyano, d-C8alkyl, CrCealkyloxy or aryloxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
14. The combination according to claim 13 wherein the 11 ?-HSD1 inhibitor is selected frm the group: pyrazolo[1,5-a]pyridin-3-yl-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; (2-Methyl-pyrazolo[1 ,5-a]pyridin-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; Pyrazolo[1 ,5-a]pyridine-3-carboxylic acid cyclohexyl-methyl-amide; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
15. The combination according to claim 6 or 7 wherein the 1 β -HSD1 inhibitor is of the Formula (lie):
Figure imgf000228_0001
(He) wherein
R1 is hydrogen, d-Cealkyl, CrCealkyloxyCrCealkyl, aryl, hetaryl, arylCrC6alkyl, hetaryld- Cealkyl, CrC6S02, arylS02, hetarylS02, aryICrC6alkylS02 or hetarylC C6alkylS02 all of which is optionally substituted with one or more R8;
R2 and R5 independently are hydrogen, halo, nitro, cyano, trihalomethyl, CrC6alkyl, aryl, aryICrC6alkyl, hetaryl or hetarylCrCealkyl wherein the alkyl, aryl, arylalkyl, hetaryl and hetarylalkyl groups independently are substituted with one or more R9; and
either R3 is hydrogen; and R4 is C(0)NR7R8; or R3 is C(0)NR7R8; and R4 is hydrogen; and
R6 is hydrogen, halo, cyano, trihalomethyl, NR12R13, d-Cealkyl, aryl, arylCrC6alkyl, hetaryl or hetarylCrC6alkyl wherein the alkyl, aryl, arylalkyl, hetaryl and hetarylalkyl groups independently are substituted with one or more R9; and R7 and R8 independently are d-C8alkyl, C3-C10cycloalkyl, C3-C10hetcycloalkyl, C3-Cι0cyclo- alkylCrC6alkyl, wherein the alkyl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R10; or
R7 and R8 together with the nitrogen to which they are attached, are forming a saturated or partially saturated bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of CrC8alkyl, arylCrCealkyl, hetarylCrC6alkyl, hydroxy, cyano, CrC6alkyloxy, aryld-Cealkyloxy, hetarylCrC6alkyloxy, CrC6alkyloxyCr C6alkyl, CrC6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetaryld- C6alkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R11;
R9 is hydrogen, hydroxy, oxo, halo, nitro, cyano, d-Cealkyl, CrCealkyloxy, trihalomethyl, trihalomethoxy, NR12R13, C(0)NR12R13, arylCrCealkyloxy, d-Cealkylcarbonyl, arylcarbonyl, aryld-Cealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R10 and R11 independently are hydrogen, halo, oxo, hydroxy, CrC6alkyl, aryl, aryld-Cealkyl, hetaryl or hetarylalkyl;
R12 and R13 independently are hydrogen, d-C8alkyl, aryl, hetaryl, arylCrC6alkyl, C3-Cι0- cycloalkyl, C3-Cι0hetcycloalkyl, C3-CιocycloalkylCrC6alkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, hetarylcarbonyl, hetarylCrC6alkylcarbonyl, Cι-C6alkylcarboxyCr C6alkyl; or
R12 and R13 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC8alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, d-Cealkyl-oxyd-Cealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrC6alkyl-car- bonyl, hetarylCrC6alkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or aryId-C6aIkylcarboxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, a prodrug thereof, or any tautomeric forms.
16. The combination according to claim 15 wherein the 11/ff-HSDI inhibitor is of the Formula (lid)
Figure imgf000230_0001
(lid) wherein
R1 is hydrogen, CrC8alkyl, aryl, hetaryl, arylCrCealkyl or hetarylCrCealkyl optionally substituted with one or more R8;
R2 and R5 independently are hydrogen, halo, nitro, cyano, trihalomethyl, CrCβalkyl, aryl, arylCrC6alkyl, hetaryl or hetarylCrCealkyl wherein the alkyl, aryl, arylalkyl, hetaryl and hetarylalkyl groups independently are substituted with one or more R8; and
either R3 is hydrogen; and R4 is C(0)NR6R7; or R3 is C(0)NR6R7; and R4 is hydrogen;
R6 and R7 independently are CrC8alkyl, C3-Cι0cycloalkyl, C3-Cι0hetcycloalkyl, C3-C10cyclo- alkylCrC6alkyl, wherein the alkyl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R9; or
R6 and R7 together with the nitrogen to which they are attached, are forming a saturated or partially saturated bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of CrC8aIkyl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, cyano, d-C6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, d-Cealkyloxyd- C6alkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetaryld- C6alkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R10;
R8 is hydrogen, hydroxy, oxo, halo, nitro, cyano, CrC6alkyl, CrC6alkyIoxy, trihalomethyl, trihalomethoxy, NR11R12, arylCrCealkyloxy, CrCealkylcarbonyl, arylcarbonyl, arylCrC6alkyl- carbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrC6alkyIcarboxy; R9 and R10 independently are hydrogen, halo, oxo, hydroxy, d-Cealkyl, aryl, arylCrC6alkyl, hetaryl or hetarylalkyl;
R11 and R12 independently are hydrogen, CrC8alkyl, aryl, hetaryl, arylCrCealkyl, C3-C10- cycloalkyl, C3-Cι0hetcycloalkyl, C3-CιocycloalkylCrCealkyl, CrCealkyl-carboxyCrCealkyl; or
R11 and R12 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C8alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, aryld-C6alkyloxy, hetarylCrCealkyloxy, Cι-C6alkyl-oxyCrC6alkyl, CrC6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrC6alkyI-car- bonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrC6alkylcarboxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
17. The combination according to claim 15 or 16 wherein the 11 ?-HSD1 inhibitor is selected from the group:
1H-Benzoimidazole-5-carboxylic acid cyclohexyl-methyl-amide; 1 -Benzyl-1 H-benzoimidazole-5-carboxylic acid cyclohexyl-methyl-amide;
(1/- -Benzoimidazol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; lsopropyl-2-trifluoromethyl-1 H-benzoimidazole-5-carboxylic acid cyclohexyl-methyl-amide;
1 -Benzyl-1 H-benzoimidazole-5-carboxylic acid cyclohexyl-methyl-amide;
2-Methyl-1 H-benzoimidazole-5-carboxylic acid cyclohexyl-methyl-amide; 2-Hydroxymethyl-1 /-/-benzoimidazole-5-carboxylic acid cyclohexyl-methyl-amide;
2-(4-Amino-phenyl)-1 H-benzoimidazole-5-carboxylic acid cyclohexyl-methyl-amide;
(1ry-Benzoimidazol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(2-Methyl-1 H-benzoimidazol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone;
(2-Amino-1fy-benzoimidazol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; (2-Benzo[1 ,3]dioxol-5-yl- . H-benzoimidazol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
3-[5-(1 ,3,3-Trimethyl-6-aza-bicycIo[3.2.1]octane-6-carbonyl)-^H-benzoimidazol-2-yl]-benzoic acid methyl ester;
(2-Thiophen-2-yl- . H-benzoimidazol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone; [2-(2-Nitro-phenyl)- . H-benzoimidazol-5-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanon; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, a prodrug thereof, or any tautomeric forms.
18. The combination according to claim 6 or 7 wherein the 11/.-HSD1 inhibitor is of the Formula (Ile)
Figure imgf000232_0001
(Ile) wherein X is oxygen or (CR1R2)n;
R1, R2, R3, and R4 independently are hydrogen, d-C6alkyl, aryl, aryld-Cealkyl, hetaryl or hetarylCrCealkyl optionally substituted with one or more R8 independently; or
R1 and either R3 or R4 together are forming a saturated or partially saturated ring system containing from 4 to 8 carbon atoms, the ring system optionally being substituted with at least one of CrC6alkyl, hydroxy, oxo, aryl, hetaryl, arylCrC6alkyl or hetarylCrC6alkyl; or
R1 and either R3 or R4 together with the single bond are forming a carbon-carbon double bond;
R5 is CrC8alkyl optionally substituted with one or more of R9;
R6 is C3-Ci0cycloalkyl, C3-Cι0hetcycloalkyl, C3-CιocycloalkylCrC6alkyl, wherein the alkyl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R9; or
R5 and R6 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6aIkyl, aryl, hetaryl, arylCrC6alkyl, hetaryld-Cealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetaryld-Cealkyloxy, CrCealkyloxyd-Cealkyl, d-Cealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylC C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylC C6alkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R10;
R7 is hydrogen, halo, nitro, NR12R13, cyano, trihalomethyl, CrC6alkyl, aryl, aryld-Cealkyl, d- C6aIkyloxy, aryloxy, arylCrC6alkyloxy, hetaryl, hetarylCrC6alkyl, hetaryloxy or hetarylCrCealkyloxy optionally substituted with one or more R11 independently;
R8 and R9 independently are hydrogen, hydroxy, oxo, halo, nitro, cyano, CrC6alkyl, CrCealkyloxy, trihalomethyl, trihalomethoxy, NR12R13, arylCrCealkyloxy, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R10 is hydrogen, CrC8alkyl, aryld-Cealkyl, hetarylCrCealkyl, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy;
R11 is hydrogen, halo, hydroxy, oxo, nitro, cyano, d-C8alkyl, CrC6alkyloxy, aryloxy or hetaryloxy;
R12 and R13 independently are hydrogen, CrC8alkyl, aryl, hetaryl, arylCrC6alkyl, C3-Cι0cydo- alkyl, C3-Cι0hetcycloalkyl, d-C6alkylcarbonyl, arylCrCealkylcarbonyl, C3-C10cycloalkylCrC6- alkyl, CrCealkyloxycarbonyl; or
R12 and R13 are together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, arylCrCealkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetaryld- C6alkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryIC C6alkylcarbonyl, hetarylCrCealkylcarbonyl, d-C6alkylcarboxy, arylcarboxy or aryld- ealkylcarboxy;
n is 1 or 2; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, a prodrug thereof, or any tautomeric forms.
19. The combination according to claim 18 wherein the 11^-HSD1 inhibitor is selected from the group:
2,3-DimethyI-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
2,5-Dimethyl-3-phenyl-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
2,2-Dimethyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide; 2-Methyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
(2,3-Dimethyl-2,3-dihydro-benzofuran-7-yl)-(2,4,4-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
4-Methoxy-2-methyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
2-Methyl-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide; (2-Methyl-2,3-dihydro-benzofuran-7-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
Benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
2,3-Dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
3,3-Dimethyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide; Chroman-8-carboxylic acid cyclohexyl-methyl-amide; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
20. The combination according to claim 18 wherein the 11β-HSD1 inhibitor is selected from the group:
2,3-Dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
Benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
2-Methyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
2-Methyl-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide; 3,3-Dimethyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
(2,3-Dimethyl-2,3-dihydro-benzofuran-7-yl)-(2,4,4-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
4-Methoxy-2-methyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide;
2,2-Dimethyl-2,3-dihydro-benzofuran-7-carboxylic acid cyclohexyl-methyl-amide; (2-Methyl-2,3-dihydro-benzofuran-7-yl)-(1,3,3-trimethyl-6-aza-bicycIo[3.2.1]oct-6-yl)- methanone; Chroman-8-carboxylic acid cyclohexyl-methyl-amide; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, a prodrug thereof, or any tautomeric forms.
21. The combination according to claim 6 or 7 wherein the 11 ?-HSD1 inhibitor is of the Formula (llf)
Figure imgf000235_0001
(llf) wherein
R1 is hydrogen, d-C8alkyl, hetaryl, arylCrC6alkyl or hetarylCrCealkyl optionally substituted with one or more R9;
R2, R3, R4, R5 and R6 independently are hydrogen, halo, nitro, cyano, trihalomethyl, carboxy, N(R12R13), C(0)NR7R8, d-C8alkyl, C3-C10cycloalkyl, C3-Cι0hetcycloalkyl, N(R12R13)d-C6alkyl, CrC6alkyloxy, CrC6alkyloxyCrC6alkyl, aryl, arylCrC6alkyl, aryloxy, aryIoxyd-C6alkyl, aryld- C6alkyloxy, arylCrCealkyloxyCrCealkyl, CrC6alkylcarboxy, arylcarboxy, arylCrCealkylcarboxy, hetaryl, hetarylCrCealkyl, hetaryld-Cealkyloxy, hetaryloxyCrC6alkyl or hetaryld- CealkyloxyCrCealkyl wherein wherein the alkyl, aryl, arylalkyl, hetaryl and hetarylalkyl groups independently are substituted with one or more R9;
R7 is hydrogen or d-C8alkyl optionally substituted with one or more of R10;
R8 is Crdocycloalkyl, C3-Cι0hetcycloalkyl, C3-CιocycloalkylCrC6alkyI, wherein the cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R10; or
R7 and R8 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of d-C8alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyl- oxy, CrCealkyloxyCrCealkyl, d-C6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R11;
R9 is hydrogen, hydroxy, oxo, halo, nitro, cyano, d-Cealkyl, CrC6alkyloxy, trihalomethyl, trihalomethoxy, NR12R13, arylCrCealkyloxy, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R10 and R11 independently are hydrogen, halo, oxo, hydroxy, d-C6alkyl, aryl, arylCrC6alkyl, hetaryl or hetarylalkyl;
R12 and R13 independently are hydrogen, C C8alkyl, aryl, hetaryl, arylCrC6alkyl, C3-Cι0- cycloalkyl, C3-C10hetcycloalkyl, C3-CιocycloalkylCrC6alkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, C3-C10cycloalkylcarbonyl, C3-Cι0hetcycloalkylcarbonyl or C3-C10cyclo- alkylCrC6alkylcarbonyl wherein the alkyl and aryl groups independently are optionally substituted with one or more of R11, wherein R11 is as defined above; or
R12 and R13 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-C8alkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, aryld-Cealkyloxy, hetarylCrCealkyloxy, CrCealkyl-oxyCrCealkyl, d-Cealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrC6alkyl- carbonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
22. The combination according to claim 21 wherein the 11^-HSD1 inhibitor is of the Formula (llf) wherein
R1 is hydrogen, CrC8alkyl, hetaryl, aryld-Cealkyl or hetarylCrCealkyl optionally substituted with one or more R9; R2 and R5 independently are hydrogen, halo, nitro, cyano, trihalomethyl, CrC6alkyI, CrCealkyloxy, CrCealkyloxyCrCealkyl, aryl, arylCrC6alkyl, aryloxy, aryloxyd-Cealkyl, arylCrCealkyloxy, arylCrCealkyloxyCrCealkyl, hetaryl or hetarylCrCealkyl wherein the alkyl, aryl, arylalkyl, hetaryl and hetarylalkyl groups independently are substituted with one or more R9; and
either R3 is C(0)NR7R8, and R4 is hydrogen; or R3 is hydrogen, and R4 is C(0)NR7R8;
R6 is d-C8alkyl, C3-d0cycloalkyl, C3-Cι0hetcycloaikyl, N(R1 R13)CrC6alkyl, Cι-C6alkyloxyCr C6alkyl, aryloxyCrC6alkyl, arylCrCealkyloxy or aryld-Cealkyloxyd-Cealkyl;
R7 is CrC8alkyl optionally substituted with one or more of R10;
R8 is C3-Cιocycloalkyl, C3-Cι0hetcycloalkyl, CrdocycloalkylCrCealkyl, wherein the cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R10; or
R7 and R8 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of C C8alkyI, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, d-C6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R11;
R9 is hydrogen, hydroxy, oxo, halo, nitro, cyano, d-Cealkyl, CrC6alkyloxy, trihalomethyl, trihalomethoxy, NR12R13, aryld-Cealkyloxy, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R10 and R11 independently are hydrogen, halo, oxo, hydroxy, CrC6alkyl, aryl, aryld-Cealkyl, hetaryl or hetarylalkyl;
R12 and R13 independently are hydrogen, CrC8alkyl, aryl, hetaryl, arylCrC6alkyl, C3-Cι0- cycloalkyl, C3-Cι0hetcycloalkyl, CrCiocycloalkylCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, C3-C10cycloalkylcarbonyl, C3-C10hetcycloalkylcarbonyl or C3-Cι0cyclo- alkylCrC6alkyIcarbonyl; or
R12 and R13 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC8alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, d-Cealkyl-oxyd-Cealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrC6alkyl- carbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
23. The combination according to claim 21 or 22 wherein the 11 -HSD1 inhibitor is selected from the group:
(1H-lndol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
1H-lndole-6-carboxyIic acid cyclohexyl-methyl-amide;
(1 .-lndol-7-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; (1 H-lndol-6-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
1H-lndole-6-carboxylic acid adamantan-2-ylamide;
(6-Aza-bicyclo[3.2.1]oct-6-yl)-(1H-indol-6-yI)-methanone;
1H-lndole-6-carboxylic acid (8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-amide;
1H-lndole-5-carboxylic acid adamantan-2-yIamide; (6-Aza-bicyclo[3.2.1]oct-6-yl)-(1 H-indol-5-yl)-methanone;
(1 .-lndol-4-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(1 -/-lndol-3-yl)-(1,3,3-trimethyi-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(1H-lndol-2-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(1 -Methyl-1 H-indol-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone; (3-Aza-bicyclo[3.2.2]non-3-yl)-(1 H-indoI-3-yl)-methanone;
1 -Methyl-1 H-indole-3-carboxyIic acid cycloheptylamide;
1 -Methyl-1 H-indole-3-carboxyIic acid adamantan-1 -ylamide;
(3-Aza-bicyclo[3.2.2]non-3-yl)-(1-methyl-1/-/-indol-3-yl)-methanone;
(1 -Methyl-1 -/-indol-3-yl)-(4-methyI-piperazin-1 -yl)-methanone; 1 -Methyl-1 H-indole-3-carboxylic acid (3-hydroxy-adamantan-1 -yl)-amide;
1 -Methyl-1 H-indoIe-3-carboxylic acid azepan-1 -ylamide; 1 -Methyl-1 /--indole-3-carboxylic acid (2-oxo-azepan-3-yl)-amide;
(4-Benzyl-piperidine-1-yl)-(1 -methyl-1 H-indol-3-yl)-methanone;
1 -Methyl-1 H-indole-3-carboxylic acid (2,6-dimethyl-piperidin-1-yl)-amide;
1 -Methyl-1 - -indole-3-carboxylic acid (2-methyl-piperidin-1 -yl)-amide; (1-Cyclopropylmethyl-6-fluoro-1 .-indol-3-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
Azepan-1 -yl-(1 -methyl-1 H-indol-3-yl)-methanone;
(5-BenzyIoxy-1ry-indol-3-yl)-(1,3,3-trimethyI-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(5 .-[1,3]Dioxolo[4,5]indol-7-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; (5-Chloro-1/-/-indol-3-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(6-Trifluoromethyl-1/--indol-3-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(6-Methyl-1H-indol-3-yl)-(1,3,3-trimethyl-6-aza-bicydo[3.2.1]oct-6-yl)-methanone;
(6-Nitro-1H-indol-3-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(5-Methoxy-1 H-indol-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; (6-Fluoro-1H-indol-3-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(6-Methoxy-1H-indol-3-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(7-Nitro-1H-indol-3-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(1/-/-lndol-4-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
2-(1H-lndol-3-yl)-1-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-ethanone; 1 -(3-Aza-bicyclo[3.2.2]non-3-yl)-2-(1 H-indol-3-yl)-ethanone;
1-(3-Aza-bicyclo[3.2.2]non-3-yl)-2-(1 -methyl-1 H-indol-3-yl)-ethanone;
2-(1 -Methyl-1 ry-indol-3-yl)-1-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-ethanone;
[3-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 --indol-6-yloxy]-acetic acid tert- butyl ester; 6-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 -/-indole-3-carboxylic acid;
6-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-1 H-indole-3-carboxylic acid ethyl ester;
5-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1joctane-6-carbonyl)-1H-indole-3-carboxylic acid;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indole-3-carboxylic acid ethyl ester;
4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indole-3-carboxylic acid;
4-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 -.-indole-3-carboxylic acid ethyl ester;
5-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 --indole-3-carboxylic acid; 5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1/--indole-3-carboxyIic acid ethyl ester; 4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 --indole-3-carboxylic acid;
4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indole-3-carboxylic acid ethyl ester;
[3-(Piperidine-1-carbonyl)-1H-indol-5-yI]-(1,3,3-trimethyI-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
5-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 --indole-3-carboxylic acid cyanomethyl-amide;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 /-/-indole-3-carboxylic acid benzylamide; 5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1/--indole-3-carboxylic acid dimethylamide;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-1 --indole-3-carboxylic acid allylamide;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 H-indole-3-carboxylic acid (2- dimethylamino-ethyl)-methyl-amide;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-1 --indole-3-carboxylic acid (2- methoxy-ethyl)-amide;
5-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 -/-indole-3-carboxylic acid 4- methoxy-benzylamide; 5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 --indole-3-carboxylic acid
(tetrahydro-furan-2-ylmethyl)-amide;
[3-(2-Methoxymethyl-pyrrolidine-1-carbonyl)-1H-indol-5-yl]-(1,3,3-trimethyl-6-aza-bicyclo-
[3.2.1]oct-6-yl)-methanone;
[3-(2,6-Dimethyl-morphoIine-4-carbonyl)-1H-indol-5-yl]-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct- 6-yl)-methanone;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-1 H-indole-3-carboxylic acid (1,1- dioxo-tetrahydro-thiophen-3-yl)-amide;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indole-3-carboxylic acid [3-(4- methyl-piperazin-1-yl)-propyl]-amide; 5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-1 /--indole-3-carboxylic acid 4- trifluoromethyl-benzylamide;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-1 H-indole-3-carboxylic acid (furan-
2-ylmethyl)-amide;
[3-(2,3,5,6-Tetrahydro-[1,2,]bipyrazinyI-4-carbonyl)-.H-indol-5-yl]-(1 ,3,3-trimethyl-6-aza- bicyclo[3.2.1]oct-6-yl)-methanone; 5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indole-3-carboxylic acid (2H- tetrazol-5-ylmethyI)-amide;
[3-(1 ,3,3-Trimethyl-6-aza-bicycIo[3.2.1 ]octane-6-carbonyl)-1 H-indol-5-yl]-(1 ,3,3-trimethyl-6- aza-bicyclo[3.2.1]oct-6-yl)-methanone; 3-{[5-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indole-3-carbonyl]-amino}- propionic acid ethyl ester;
5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indole-3-carboxylic acid (4- methoxy-phenyl)-amide;
3-{[5-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indole-3-carbonyl]-amino}- propionic acid;
Azepan-1 -yl-(1 -.-indol-5-yl)-methanone;
1H-lndole-5-carboxylic acid dibenzylamide;
(3-Aza-bicyclo[3.2.2]non-3-yl)-(. H-indol-5-yI)-methanone;
(4-Benzyl-piperidin-1 -yl)-(1 H-indol-5-yl)-methanone; 8-(1H-lndole-5-carbonyl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one;
[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-(1H-indol-5-yl)-methanone;
1 -[1 -(1 H-lndole-5-carbonyl)-piperidin-4-yl]-1 ,3-dihydro-benzoimidazol-2-one;
(4-ter_-Butyl-piperidin-1 -yl)-(1 H-indol-5-yl)-methanone;
1 -(1 ry-lndole-5-carbonyl)-4-phenyl-piperidine-4-carbonitrile; (1H-lndol-5-yl)-(4-phenyl-piperidin-1-yl)-methanone;
(5-Benzyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-(1H-indol-5-yl)-methanone;
(1H-lndol-5-yl)-(4-pyrrolidin-1-yl-piperidin-1-yI)-methanone;
1 H-lndole-5-carboxylic acid (5-hydroxy-1 ,3,3-trimethyl-cyclohexylmethyl)-amide;
1 H-lndole-5carboxylic acid (3,4-dihydrospiro(1 H-indene-1 ,4-piperidine)-amide; (3-Methanesulfonylmethyl-1 H-indol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
(3-Dimethylaminomethyl-1H-indol-6-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
1-{3-Acetyl-2-[5-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indol-3-yl]-2,3- dihydro-imidazol-1 -yl}-ethanone;
1 -Ethyl-3-[5-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-1 H-indol-3-yl]-pyrrolidine-
2,5-dione;
(3-Thiazol-2-yl-1/-/-indol-5-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(3-lodo-1H-indol-5-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; 6-(1,3,3-TrimethyI-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1H-indole-3-carbonitrile;
5-(1 ,3,3-TrimethyI-6-aza-bicyclo[3.2.1 ]octane-6-carbonyl)-1 H-indole-3-carbonitrile; 6-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1 H-indole-3-carboxylic acid amide;
[3-(2H-Tetrazol-5-yl)-1H-indoI-6-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; V-[3-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-1ry-indol-7-yl]-acetamide;
(1-Benzenesulfonyl-1/-/-indol-5-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; (1-Benzenesulfonyl-2-methyl-1H-indoI-5-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
(1 -methyl-1 H-indol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)-methanone;
(1 -Benzyl-1 H-indol-5-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
[6-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-indol-1-yl]-acetic acid ethyl ester; [1-(2-Ethoxy-ethyl)-1H-indol-6-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
{1 -[2-(2-Methoxy-ethoxy)-ethyl]-1 H-indol-6-yl}-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6-yl)- methanone;
3-[5-(1 ,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-indol-1-yl]-propionic acid ethyl ester; (1-Phenethyl-1/-/-indol-5-yl)-(1,3,3-trimethyI-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
[1-(Tetrahydro-furan-2-ylmethyl)-1ry-indol-5-yl]-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
2-[5-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-indol-1-yl]-acetamide;
[1-(4-Trifluoromethoxy-benzyl)-1H-indol-5-yl]-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1joct-6-yl)- methanone;
3-[5-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-indol-1-ylmethyl]-benzoic acid methyl ester;
4-[5-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-indol-1-ylmethylj-benzonitrile; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
24. The combination according to claim 6 or 7 wherein the 11/?-HSD1 inhibitor is of the Formula (llg)
Figure imgf000242_0001
wherein
X is NR4, S or O; R1 and R2 independently are hydrogen, halo, cyano, trihalomethyl, d-C6alkyl or CrCealkyloxy, wherein the alkyl groups independently are optionally substituted with one or more of R7;
R3 is hydrogen, CrC6alkyI, C3-Cι0cycloalkyl, CrC6alkyIoxy, CrC6alkyIthio, aryl, arylCrC6alkyl, hetaryl or hetarylalkyl, wherein the alkyl, cycloalkyl, aryl, hetaryl and hetarylalkyl groups independently are optionally substituted with one or more of R7;
R4 is hydrogen, CrC8alkyl, CrCealkyloxyd-Cealkyl, aryl, hetaryl, hetaryld-Cealkyl, arylC C6alkyl, arylCrCealkyloxyCrCealkyl, C3-Cι0cycloalkyl, C3-Cι0hetcycloalkyl, C3-Cι0cyclo- alkylCrC6alkyl, CrCealkylcarboxyCrCealkyl wherein the alkyl, aryl, hetaryl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R7;
R5 is hydrogen, and R6 is adamantyl optionally substituted with hydroxy, d-C6alkyloxy, aryl, arylCrC6alkyl, aryloxy, arylCrCealkyloxy, hetaryl, hetaryloxy or hetarylCrCealkyloxy wherein the alkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R7; or
R5 and R6 are together with the nitrogen to which they are attached, forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, arylCrC6alkyl, hetarylalkyl, hydroxy, oxo, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetaryld-Cealkyloxy, d- C6alkyloxyCrC6alkyI, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or aryld-
C6alkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R7;
R7 are independently hydrogen, halo, hydroxy, oxo, nitro, NR9R10, cyano, COOR8, CONR9R10, CrC8alkyl, CrC6alkyloxy, aryloxy, arylCrCealkyloxy, hetaryloxy or hetarylCrCealkyloxy;
R8 is hydrogen, d-Cealkyl, aryl, arylCrC6alkyl, hetarylalkyl, wherein the alkyl, aryl and hetarylalkyl groups independently are optionally substituted with one or more of R7; R9 and R10 independently are hydrogen, C C8alkyl, C3-C10cycloalkyl, C3-C10hetcycloalkyl, C3- C ocycloalkylCrC6alkyI, wherein the alkyl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R7; or
R9 and R10 together with the nitrogen to which they are attached, are forming a saturated or partially saturated bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen or oxygen, the ring system optionally being substituted with at least one of C C8alkyl, aryld-Cealkyl, hetaryld-Cealkyl, hydroxy, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, d-Cealkyloxyd- Cealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetaryld- C6alkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R11;
R11 is hydrogen, halo, oxo, hydroxy, CrC6alkyl, aryl, arylCrCealkyl, hetaryl or hetarylalkyl;
provided that hetcycloalkyl is not 7-aza[2,2,1]bicycleheptane; or
a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
25. The combination according to claim 24 wherein the 11 ?-HSD1 inhibitor is of the Formula (llg) wherein
X is NR4, S or O;
R1 and R2 independently are hydrogen, halo, cyano, trihalomethyl, d-C6alkyI or CrCealkyloxy, wherein the alkyl groups independently are optionally substituted with one or more of R7;
R3 is hydrogen, CrC6alkyl, C3-C10cycloalkyl, CrC6alkyloxy, CrC6aIkylthio, aryl, arylCrC6alkyl, hetaryl or hetarylalkyl, wherein the alkyl, cycloalkyl, aryl, hetaryl and hetarylalkyl groups independently are optionally substituted with one or more of R7;
R4 is hydrogen, CrC8alkyl, CrCealkyloxyCrCealkyl, aryl, hetaryl, arylCrCealkyl, arylC C6alkyloxyCrC6alkyl, C3-Cι0cycloalkyl, C3-Cι0hetcycloalkyl, C3-C10cycloalkylCι-C6alkyl, C Cealkylcarboxyd-Cealkyl wherein the alkyl, aryl, hetaryl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R7;
R5 is hydrogen, and R6 is adamantyl optionally substituted with hydroxy, CrC6alkyloxy, aryl, arylCrC6alkyl, aryloxy, aryld-Cealkyloxy, hetaryl, hetaryloxy or hetarylCrCealkyloxy wherein the alkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R7; or
R5 and R6 are together with the nitrogen to which they are attached, forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 5 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, arylCrCealkyl, hetarylalkyl, hydroxy, oxo, cyano, CrC6alkyloxy, arylCrCealkyloxy, hetarylCrCealkyloxy, d- Cealkyloxyd-Cealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, aryld- C6alkylcarbonyl, hetarylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or aryld-
C6alkyIcarboxy wherein the alkyl and aryl groups independently are optionally substituted with one ore more of R7;
R7 are independently hydrogen, halo, hydroxy, oxo, nitro, NR5R6, cyano, COOR8, CONR5R6, d-C8alkyI, d-C6alkyloxy, aryloxy or hetaryloxy;
R8 is hydrogen, d-Cealkyl, aryl, arylCrC6alkyl, hetarylalkyl, wherein the alkyl, aryl and hetarylalkyl groups independently are optionally substituted with one or more of R7;
provided that hetcycloalkyl is not 7-aza[2,2,1]bicycleheptane; or
a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
26. The combination according to claim 24 or 25 wherein the 11j--HSD1 inhibitor is selected from the group
(4-MethyI-2-phenyl-thiazol-5-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone ;
(2,4-Dimethyl-thiazol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone;
(4-Methyl-2-pyrazin-2-yl-thiazol-5-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; [4-MethyI-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1 ]oct-6- yl)-methanone; (3-Aza-bicyclo[3.2.2]non-3-yl)-(2,4-dimethyl-thiazol-5-yI)-methanone;
(1 H-lmidazol-4-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone ;
(3-Aza-bicyclo[3.2.2]non-3-yl)-(4-methyI-2-phenyl-thiazol-5-yl)-methanone ;
2,4-Dimethyl-thiazole-5-carboxyIic acid cycloheptylamide; Azepan-1 -yl-(2,4-dimethyl-thiazol-5-yl)-methanone;
2,4-Dimethyl-thiazole-5-carboxylic acid adamantan-1 -ylamide;
(3-Aza-bicyclo[3.2.2]non-3-yl)-(1H-imidazol-4-yI)-methanone;
2,4-Dimethyl-thiazole-5-carboxylic acid (3-hydroxy-adamantan-1 -yl)-amide;
(1 -Methyl-1 H-imidazol-4-yl)-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone; [1-(6-Methyl-pyridin-2-yl)-1 H-imidazol-4-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone;
[1-(4-Chloro-benzyl)-5-methyl-1 H-imidazol-4-yl]-(1 ,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)- methanone; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
27. The combination according to claim 1 wherein the 11 ?-HSD1 inhibitor is of the Formula (III):
Figure imgf000246_0001
Formula (III) wherein
R1 is C5-Ci0cycloalkyl, C5-C10hetcycloalkyl, aryl, hetaryl, aryld-Cealkyl or hetarylCrCealkyl, wherein the cycloalkyl, hetcycloalkyl, aryl, hetaryl and arylalkyl groups independently are optionally substituted with one or more of R7;
R2 and R3 independently are hydrogen, d-Cealkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, aryloxy, hetaryloxy, aryld-C6alkyloxy or hetaryld-Cealkyloxy wherein the alkyl, aryl, hetaryl, arylalkyl and hetarylalkyl groups independently are optionally substituted with one or more of R8; or
R2 and R3 together with the carbon atom to which they are attached, are forming a saturated or partially saturated cyclic ring system containing from 3 to 6 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCrCealkyl, hydroxy, oxo, CrC6alkyloxy, aryloxy, aryld-Cealkyloxy or hetarylCrCealkyloxy;
R4 and R5 independently are hydrogen, halo, hydroxy, d-Cealkyl, C2-C6alkenyl, C2-C6alkynyl, CrCealkyloxy, aryl, hetaryl, aryloxyCrC6alkyl, aryloxyaryl, hetaryloxyaryl, aryloxyhetaryl, hetaryloxyhetaryl or arylCrC6alkyIoxyCrCealkyl wherein the alkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R9; or
R4 and R5 together with the carbon atoms to which they are attached, are forming a saturated, partially saturated or aromatic ring system containing from 5 to 8 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, aryld-C6alkyl, NR10R11, halo, trihalomethyl, trihalomethoxy, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, d-C6alkyloxy- CrC6alkyl, CrC6alkylcarbonyl, arylcarbonyl, arylCrC6alkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy; or
R4 and either R2 or R3 together are forming a saturated or partially saturated bridge containing from 1 to 4 carbon atoms, the bridge can optionally be substituted with at least one of d- C6alkyl, aryl, hetaryl, aryICrC6alkyl or hetaryld-Cealkyl;
R6 is hydrogen, d-C6alkyl, aryl, hetaryl, aryld-Cealkyl or hetarylCrCealkyl; or
R6 and either R4 or R5 together with the carbon atoms to which they are attached, are forming a saturated, partially saturated or aromatic ring system containing from 5 to 8 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrCβalkyl, aryl, arylCrC6alkyl, NR10R11, halo, trihalomethyl, trihalomethoxy, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, C C6alkyIcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R7 and R8 independently are hydrogen, halo, hydroxy, cyano, nitro, d-C6alkyl, CrC6alkyloxy, trihalomethyl, trihalomethoxy, aryloxy, hetaryloxy, aryld-C6alkyloxy, hetaryld-Cealkyloxy, C Cealkyloxyd-Cealkyl, aryloxyd-Cealkyl, arylCrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrC6alkylcarboxy or hetarylCrC6alkylcarboxy; R9 is hydrogen, halo, hydroxy, cyano, CrC6alkyl, methylendioxo, trihalomethyl, trihalomethoxy, aryl, aryld-C6alkyl, aryloxy, NR10R11 or aryloxyCrC6alkyl, wherein the aryl group is optionally substituted with one or more of R12;
R10 and R11 independently are hydrogen, CrC6alkyl, aryl or arylCrC6alkyl wherein the alkyl and aryl groups independently are optionally substituted with one or more of R13; or
R10 and R11 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, aryld-C6alkyl, hydroxy, oxo, d-C6alkyloxy, arylCrCealkyloxy, CrC6alkyloxyCrC6alkyl, CrC6alkyIcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCι-C6alkyl-carboxy;
R12 is oxo or halo;
R13 is halo, hydroxy, cyano, CrC6alkyl, CrC6alkyloxy, NR14R15, methylendioxo, trihalomethyl, or trihalomethoxy;
R14 and R15 independently are hydrogen, CrC6alkyl, aryl, hetaryl, arylCrC6alkyl or hetaryld- Cealkyl;
A is a single, double or triple bond;
X is a chemical bond, (CR16R17)n or NR10, wherein R16 and R17 independently are hydrogen, oxo or CrC6alkyl, or
X, together with either R2 or R3, is a double bond;
Y is CR18 or nitrogen, wherein R18 is hydrogen, CrC6alkyl, aryl, hetaryl, arylCrC6alkyl or hetarylCrCealkyl; or
R18 and either R2 or R3 together are forming a saturated or partially saturated cyclic ring system containg from 1 to 4 carbon atoms, the ring system can optionally be substituted with at least one of CrC6alkyl, aryl, hetaryl, arylCrC6alkyl or hetarylCrC6alkyl; or R18 with either R2 or R3 and either R4 or R5 together are forming a saturated or partially saturated cyclic ring system having one common carbon atom containing from 8 to 12 carbon atoms, the ring system can optionally be substituted with at least one of CrC6alkyl, aryl, hetaryl, arylCrC6alkyl or hetarylCrC6alkyl;
n is 0, 1 or 2; or
a salt thereof with a pharmaceutically acceptable acid or base, or optical isomer, mixture of optical isomers, racemic mixture, or tautomeric form thereof.
28. The combination according to claim 27 wherein the 11 ?-HSD1 inhibitor is selected from the group: 3-(2-Bromo-phenyl)-6,7,8,9-tetrahydro-5H-[1 ,2,4]triazolo[4,3-a]azepine;
3-Phenyl-[1 ,2,4]triazolo[3,4-a]isoquinoline;
(2-Methoxy-benzyl)-(3-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-amine;
3-(2-Fluoro-phenyl)-5-(4-methoxy-phenoxy)-[1 ,2,4]triazolo[4,3-c]quinazoline;
3-Phenyl-6,7,8,9-tetrahydro-5H-[1 ,2,4]triazolo[4,3-a]azepine; 3-(4-Chloro-phenyl)-6,7,8,9-tetrahydro-5H-[1 ,2,4]triazolo[4,3-a]azepine;
3-(3-Chloro-phenyl)-6,7,8,9-tetrahydro-5H-[1 ,2,4]triazolo[4,3-a]azepine;
3-(3,4-Dichloro-phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine;
5,5-Dimethyl-3-thiophen-2-yl-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoline;
3-(2-Chloro-phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine; 5,5-Dimethyl-3-(3,4,5-trimethoxy-phenyl)-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoline;
3-Furan-2-yl-5,5-dimethyl-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoline;
3-(3-Bromo-phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine;
3-(4-Bromo-phenyl)-5,5-dimethyl-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoline;
4-(5,5-DimethyI-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-phenol; 3-(4-Methoxy-phenyl)-5,5,8,9-tetramethyl-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoline;
5,5-Dimethyl-3-phenyI-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoline;
3-(5,5-DimethyI-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-phenol;
5,5-Dimethyl-3-p-tolyl-5,6-dihydro-[1 ,2,4]triazolo[3,4-a]isoquinoline;
5,5-Dimethyl-3-thiophen-2-yl-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinoIine; 7,10-Dimethoxy-5,5-dimethyl-3-phenyI-5,6-dihydro-[1,2,4]triazoIo[3,4-a]isoquinoline;
3-(2,4-Dichloro-phenyl)-6,6-dimethyl-5,6,7,8-tetrahydro-[1 ,2,4]triazolo[4,3-a]pyrimidine; 2-(6,6-Dimethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrimidin-3-yl)-phenol; 3-(2-Chloro-phenyl)-6,6-dimethyl-5,6,7,8-tetrahydro-[1,2,4jtriazolo[4,3-a]pyrimidine; 4-Benzyl-3,5-di-p-toIyl-4H-[1,2,4jtriazole; 3-p-Tolyl-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine; 3-(4-Methoxy-phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine; 3-Pyridin-4-yl-6,7,8,9-tetrahydro-5H-[1,2,4jtriazolo[4,3-a]azepine; 3-(4-Bromo-phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine; 3-Furan-2-yl-5,5,8,9-tetramethyl-5,6-dihydro-[1 ,2,4]triazolo[3,4-a]isoquinoline; 6,6-Dimethyl-3-(2-nitro-phenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrimidine; and 3-(2,4-Dichloro-phenyl)-5,5-dimethyl-5,6-dihydro-[1 ,2,4]triazolo[3,4-a]isoquinoline; or
a salt thereof with a pharmaceutically acceptable acid or base, or optical isomer, mixture of optical isomers, racemic mixture, or tautomeric form thereof.
29. The combination according to claim 27 wherein the 11 ?-HSD1 inhibitor is of the Formula (Ilia)
Figure imgf000250_0001
wherein R1 is aryl or hetaryl, wherein the aryl and hetaryl groups independently are optionally substituted with one or more of R7;
R2 and R3 together with the atoms to which they are connected forms a C5-C10cycloalkyl or C5- Ciohetcycloalkyl, wherein the cycloalkyl and hetcycloalkyl rings independently are optionally substituted with one or more of R8; or
R2 and R3 are connected to one of the following ring systems at the carbon atoms marked with an asterix (*)
Figure imgf000251_0001
Figure imgf000251_0002
wherein the ring systems independently are optionally substituted with one or more R8;
R7 is hydrogen, halo, hydroxy, cyano, nitro, C C6alkyl, CrC6alkyloxy, trihalomethyl, trihalomethoxy, aryloxy, hetaryloxy, NR9R10, arylCrCealkyloxy, hetarylCrCealkyloxy, d- Cealkyloxyd-Cealkyl, aryloxyCrC6alkyl, arylCrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrCealkylcarboxy or hetarylCrC6alkylcarboxy;
R8 is hydrogen, CrC6alkyl, halo, aryl, hetaryl, aryld-Cealkyl, NR9R10, trihalomethyl, trihalomethoxy, hydroxy, oxo, CrC6alkyloxy, aryloxy, aryICrC6alkyloxy, hetarylCrC6alkyloxy, CrC6alkyloxyCrC6alkyl, CrC6alkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, d- C6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R9 and R10 independently are hydrogen, CrC6alkyl, aryl or arylCrC6alkyl wherein the alkyl and aryl groups independently are optionally substituted with one or more of R11; or
R9 and R10 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, aryld-Cealkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R11 is d-Cealkyl, oxo or halo;
X is (CR12R13)n, wherein R12 and R13 independently are hydrogen, oxo, hydroxy or d-C6alkyI; and n is 1 or 2; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
30. The combination according to claim 27 wherein the 11 ? -HSD1 inhibitor is of the Formula (Illb)
Figure imgf000252_0001
wherein R1 is aryl or hetaryl, wherein the aryl and hetaryl groups independently are optionally substituted with one or more of R7;
R7 is hydrogen, halo, hydroxy, cyano, nitro, CrC6alkyl, CrCealkyloxy, trihalomethyl, trihalomethoxy, aryloxy, hetaryloxy, NR9R10, arylCrCealkyloxy, hetaryld-Cealkyloxy, d- CealkyloxyCrCealkyl, aryloxyCrC6alkyl, arylCrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, hetarylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetarylcarboxy, arylCrC6alkylcarboxy or hetarylCrC6alkylcarboxy;
R9 and R10 independently are hydrogen, d-Cealkyl, aryl or aryld-Cealkyl wherein the alkyl and aryl groups independently are optionally substituted with one or more of R11; or
R9 and R10 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, arylCrCealkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrC6a- alkylcarboxy;
R11 is CrC6alkyl, oxo or halo;
a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
31. The combination according to claim 29 or 30 wherein the 110-HSD1 inhibitor is selected from the group: 3-(2-Bromo-phenyl)-6,7,8,9-tetrahydro-5H-[1 ,2,4]triazolo[4,3-a]azepine; 3-(2-Phenoxymethyl-phenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]azepin-9-one;
3-(2-Phenoxymethyl-phenyl)-6,7,8,9,10,11-hexahydro-5r7-5,9:7,11-dimethano[1 ,2,4]tria- zolo[4.3-a]azonine;
3-(5-Bromo-pyridin-3-yl)-6,7,8,9-tetrahydro-5H-[1 ,2,4]triazolo[4,3-a]azepine;
3-(5-Hex-1-ynyl-pyridin-3-yl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine; 3-(6-Chloro-pyridin-3-yl)-6,7,8,9-tetrahydro-5H-[1 ,2,4]triazolo[4,3-a]azepine;
3-(6-Morpholin-4-yl-pyridin-3-yl)-6,7,8,9-tetrahydro-5/.-[1 ,2,4]triazolo[4,3-a]azepine;
3-Pyridin-3-yl-6,7,8,9-tetrahydro--H-[1 ,2,4]triazolo[4,3-a]azepine;
3-(2-Benzyloxymethyl-phenyl)-6,7,8,9-tetrahydro-5H-5,9-methano[1,2,4]triazolo[4.3-ajazepine;
3-Phenyl-[1 ,2,4]triazolo[3,4-a]isoquinoline; or salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
32. The combination according to claim 1 wherein the 11 ?-HSD1 inhibitor is of the Formula (IV):
Figure imgf000253_0001
wherein
R1 and R2 independently are hydrogen, d-C6alkyl, C3-C10cycloalkyl, C3-Cι0 het-cycloalkyl, aryl, hetaryl, arylC C6alkyl or hetarylCrCealkyl, wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R6; or
R1 and R2 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic or bicyclic ring system containing from 4 to 8 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, CrC6alkyl-oxy, arylCrCealkyloxy, hetarylCrCealkyloxy, CrCealkyloxyd-Cealkyl, CrC6alkyl-carbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, C C6alkylcarboxy, arylcarboxy, hetarylcarboxy or arylCrCealkylcarboxy; R3 and R4 independently are hydrogen, C C6alkyI, CrC6alkenyl, CrC6alkynyl, aryl, hetaryl, arylCrC6alkyl or hetarylCrCealkyl, wherein the alkyl, alkenyl, alkynyl, aryl, and hetaryl groups independently are optionally substituted with one or more of R7;
R5 is C3-Cιocycloalkyl, C3-Cι0hetcycloalkyl, aryl or hetaryl, wherein the aryl, hetaryl, cycloalkyl and hetcycloalkyl groups independently are optionally substituted with one or more of R8; or
R3 and R5 together with the carbon atoms to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, hetaryl, aryld- C6alkyl, hetarylCrC6alkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, CrC6alkyIoxyCr C6alkyl, d-Cealkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, d-C6alkyl- carboxy, aryl-carboxy, hetarylcarboxy or arylCrCealkylcarboxy; or
R2, R3 and R5 together with the atoms to which they are attached, are forming a saturated or partially saturated bicyclic or tricyclic ring system containing from 6 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, CrC6alkyl-oxy, aryld-Cealkyloxy, CrC6alkyloxyCrC6alkyl, d- dalkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy, hetaryl-carboxy or arylCrC6alkylcarboxy;
R6 is hydrogen, hydroxy, oxo, halo, adamantyl, d-C6alkyl, CrC6alkyloxy, trihalomethyl, trihalomethoxy, NR9R10, aryld-Cealkyloxy, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, Cι-C6alkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R7 and R8 independently are hydrogen, hydroxy, oxo, halo, cyano, nitro, NR9R10, d-C6alkyl, CrC6alkyloxy, aryl, hetaryl, arylCrC6alkyloxy, hetaryld-Cealkyloxy, CrC6alkyIcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrC6alkylcarbonyl, CrC6alkyl-carboxy, arylcarboxy or arylCrCealkylcarboxy, wherein the aryl and hetaryl groups independently are optionally substituted with C3-Cι0cycloalkyl or C3-C 0hetcycloalkyl;
R9 and R10 independently are hydrogen, CrC6aIkyl, C3-Cι0cycloalkyl, C3-Cι0 hetcycloalkyl, aryl, hetaryl, arylCrC6alkyl or hetaryld-Cealkyl; or R9 and R10 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 5 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulfur, the ring system optionally being substituted with at least one d-Cealkyl, aryl, hetaryl, arylCrC6alkyl, hetarylCrCealkyl, hydroxy, oxo, d-C6alkyloxy, aryld-Cealkyloxy, CrCealkyloxyCrCealkyl, C C6alkylcarbonyl, arylcarbonyl, hetarylcarbonyl, arylCrCealkylcarbonyl, CrC6alkylcarboxy, arylcarboxy, hetarylcarboxy or arylCrCealkylcarboxy; or
a salt thereof with a pharmaceutically acceptable acid or base, or optical isomer, mixture of optical isomers, racemic mixture, or tautomeric form thereof.
33. The combination according to claim 32 wherein the 11 7-HSD1 inhibitor is selected from the group: 1 -Adamantan-1 -yl-2-morpholin-4-yl-ethanone;
1 -Adamantan-1 -yl-2-benzylamino-propan-1 -one;
1 -Adamantan-1 -yl-2-benzylamino-ethanone;
2-Pyrrolidin-1-yl-1-(3-p-tolyl-adamantan-1-yl)ethanone;
1 -Adamantan-1 -yl-2-morpholin-4-yl-propan-1 -one; 1-[4-(5-Adamantan-1-yl-[1 ,2,3]triazol-1-yl)-phenyl]-2-phenylamino-ethanone;
6-Benzo[1 ,3]dioxol-5-yl-8-benzyl-8-aza-bicyclo[3.2.1 joctan-2-one;
2-tet_-Butylamino-1 -(3-p-tolyl-adamantan-1 -yl)ethanone;
2-Morpholin-4-yl-1 -(3-p-tolyl-adamantan-1 -yl)ethanone; and
1 -Adamantan-1 -yl-2-[4-(4-nitro-phenyl)-piperazin-1 -yljethanone; or
a salt thereof with a pharmaceutically acceptable acid or base, or optical isomer, mixture of optical isomers, racemic mixture, or tautomeric form thereof.
34. The combination according to claim 1 wherein the 1 \β -HSD1 inhibitor is of the Formula (V):
Figure imgf000255_0001
Formula (V) wherein X is O or S;
R1 is hydrogen, d-Cealkyl, C2-C6alkenyl, C2-C6alkynyl, C3-Cι0cycloalkyl, arylCrC6alkyl, hetarylCrCealkyl, R R5NcarbonyICrC6alkyl, arylcarbonylCrC6alkyl, hetarylcarbonylCrC6alkyl; wherein the alkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R6;
R2 is CrC6alkyl, CrC6alkenyl, arylCrC6alkyl, C3-C10cycloalkyl or hetarylC C6alkyl; wherein the alkyl, alkenyl, cycloalkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R7;
R3 is C3-C10cycloalkyl, C3-Cι0hetcycloalkyl, aryl, hetaryl, aryICrC6alkyl, hetarylCrCealkyl, arylR8CrC6alkyl or hetarylR8CrC6alkyl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R9;
R4 and R5 independently are hydrogen, CrC6alkyl, C3-C10cycloalkyl, C5-C8hetcycloalkyl, aryl, hetaryl, aryld-C6alkyl or hetarylCrCealkyl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R11; or
R4 and R5 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, arylCrC6alkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrC6alkyl-carbonyl, CrCealkylcarboxy, arylcarboxy or arylCrCealkylcarboxy;
R6, R7, R9 and R11 independently are hydrogen, halo, N02, NH2, cyano, NR4R5, CONR4R5, trihalomethyl, trihalomethoxy, hydroxy, oxo, CrC6aIkyl, C3-C10cycloalkyl, C3-C10hetcycloalkyl, aryl, hetaryl, aryld-Cealkyl, hetarylCi -C6alkyl, CrC6alkylS02, R15R16NS02) d-C6alkyloxy, aryloxy, hetaryloxy, arylCrC6alkyloxy, CrCealkylcarbonyl, arylcarbonyl, aryld- C6alkylcarbonyl, arylcarbonylNR15, carboxyCrC6alkyl or carboxyarylCι-C6alkyl;
R8 is oxygen, NR10, C(=0)NR1° or SOnNR10; wherein n is 1 or 2;
R10 is hydrogen, CrC6alkyl, aryl, hetaryl, aryld-C6alkyl or hetarylCrCealkyl; R15 and R16 independently are hydrogen, CrC6alkyl, C3-Cι0cycloalkyl, C5-C8hetcycloalkyI, aryl or hetaryl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl or hetaryl groups independently are optionally substituted with one or more of R11; or
R15 and R16 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 8 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of CrC6alkyl, aryl, arylCrC6alkyl, hydroxy, oxo, CrC6alkyloxy, aryld-Cealkyloxy, CrCealkyloxyCrCealkyl, d-Cealkylcarbonyl, arylcarbonyl, arylCrC6alkylcarbonyl, CrC6alkylcarboxy, arylcarboxy or aryld-C6alkyl-carboxy; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
35. The combination according to claim 34 wherein the 11 ?-HSD1 inhibitor is of the Formula (V) wherein X is O or S;
R1 is hydrogen, CrC6alkyl, C2-C6alkenyl, C2-C6alkynyl, aryld-Cealkyl, hetarylCrCealkyl,
NR R5carbonylCrC6alkyl, arylcarbonylCrC6alkyl, hetarylcarbonylCrC6alkyl; wherein the alkyl, alkenyl, alkynyl, aryl and hetaryl groups independently are optionally substituted with one or more of R6;
R2 is d-Cealkyl, CrC6alkenyl, arylCrC6alkyl or hetarylCrCealkyl; wherein the alkyl, alkenyl, aryl and hetaryl groups independently are optionally substituted with one or more of R7;
R3 is C5-C8cycloalkyl, C5-C8hetcycloalkyl, aryl, hetaryl, arylCrC6alkyl, hetaryld-Cealkyl, arylR8CrC6alkyl or hetarylR8CrC6alkyl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl and hetaryl groups independently are optionally substituted with one or more of R9;
R4 and R5 independently are hydrogen, d-C6alkyl, C5-C 0cycloalkyl, C5-C8hetcycloalkyl, aryl, hetaryl, aryld-Cealkyl or hetaryld-Cealkyl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl, hetaryl, arylalkyl or hetarylalkyl groups independently are optionally substituted with one or more of R11; or R4 and R5 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 10 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, aryld-Cealkyl, hydroxy, oxo, d-C6alkyIoxy, aryld-Cealkyloxy, CrCealkyloxyCrCealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, d-C6alkylcarboxy, arylcarboxy or arylCi-Cealkyl-carboxy;
R6, R7, R9 and R11 independently are hydrogen, halo, N02, NH2, cyano, trihalomethyl, trihalo- methoxy, hydroxy, oxo, d-Cealkyl, aryl, hetaryl, aryld-Cealkyl, hetaryld-Cealkyl, S02NR 5R16, CrC6alkyloxy, aryloxy, hetaryloxy, arylCrCealkyloxy, d-Cealkylcarbonyl, arylcarbonyl, aryld- C6alkylcarbonyI, arylcarbonylNR15, carboxyCrC6alkyl or carboxyarylCrC6alkyl;
R8 is oxygen, NR10, C(=0)NR10 or SOnNR10; wherein n is 1 or 2;
R10 is hydrogen, CrC6alkyl, aryl, hetaryl, arylCrC6alkyl or hetarylCrCealkyl;
R15 and R16 independently are hydrogen, CrC6alkyl, C5-Cι0cycloalkyl, C5-C8hetcycloalkyl, aryl or hetaryl; wherein the alkyl, cycloalkyl, hetcycloalkyl, aryl or hetaryl groups independently are optionally substituted with one or more of R11; or
R 5 and R16 together with the nitrogen to which they are attached, are forming a saturated or partially saturated cyclic, bicyclic or tricyclic ring system containing from 4 to 8 carbon atoms and from 0 to 2 additional heteroatoms selected from nitrogen, oxygen or sulphur, the ring system optionally being substituted with at least one of d-Cealkyl, aryl, arylCrC6alkyl, hydroxy, oxo, CrC6alkyloxy, arylCrCealkyloxy, CrCealkyloxyd-Cealkyl, CrCealkylcarbonyl, arylcarbonyl, arylCrCealkylcarbonyl, CrCealkylcarboxy, arylcarboxy or arylCrC6alkyl-carboxy; or
a salt thereof with a pharmaceutically acceptable acid or base, optical isomer, mixture of optical isomers, racemic mixture, or tautomeric form thereof.
36. The combination according to claim 34 or 35 wherein the 11 ?-HSD1 inhibitor is selected from the group:
3-(4-Allyl-5-mercapto-4H-[1 ,2,4]triazol-3-yl)-1 -(2,4-dichloro-benzyl)-1 H-pyridin-2-one; 4-Methyl-3-(4-methyl-2-phenyl-thiazol-5-yl)-5-prop-2-ynyIsulfanyl-4H-[1 ,2,4]triazole; N-{1-[5-(4-tert-Butyl-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-ethyl}-4-chloro- benzenesulfonamide;
4-Methyl-3-methylsulfanyl-5-[3-(3-trifluoromethyl-benzyIoxy)-thiophen-2-yl]-4H-[1 ,2,4]triazole;
N-(4-Chloro-phenyl)-2-(4-methyl-5-thiophen-3-ylmethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)- acetamide;
2-[4-Methyl-5-(2-oxo-2-phenyl-ethyIsuIfanyI)-4H-[1,2,4]triazol-3-ylmethyl]-4H- benzo[1 ,4]thiazin-3-one;
3-(4-Fluoro-benzylsulfanyI)-5-(2-fluoro-phenyl)-4-methyl-4H-[1,2,4]triazole;
3-(2-Fluoro-phenyl)-4-methyl-5-(4-methyl-benzylsulfanyl)-4H-[1,2,4]triazole; 4-Methyl-3-(4-methyl-benzylsulfanyl)-5-(3-trifluoromethyl-phenyl)-4H-[1,2,4]triazole;
3-(2,4-Dichloro-phenyl)-4-furan-2-ylmethyl-5-methylsulfanyl-4H-[1,2,4]triazole;
3-(4-tert-Butyl-phenyl)-5-(2,6-dichloro-benzylsulfanyl)-4-furan-2-ylmethyl-4H-[1,2,4]triazole;
4-Methyl-3-(4-methyl-benzyIsulfanyl)-5-(5-methyl-isoxazol-3-yl)-4H-[1,2,4]triazole;
3-(3-Methoxy-benzyIsulfanyl)-4-methyl-5-thiophen-2-yl-4H-[1,2,4]triazole; 3-(4-Fluoro-benzylsulfanyl)-4-methyl-5-thiophen-2-yI-4H-[1 ,2,4]triazole;
3-(4-tert-Butyl-benzylsulfanyl)-4-methyl-5-thiophen-2-yl-4H-[1,2,4]triazole;
4-Methyl-3-(2-methyl-benzylsulfanyl)-5-thiophen-2-yl-4H-[1 ,2,4]triazoIe;
2-(5-Benzylsulfanyl-4-methyl-4H-[1,2,4]triazol-3-ylmethyl)-4H-benzo[1,4]thiazin-3-one;
2-[5-(4-Chloro-benzylsulfanyl)-4-methyl-4H-[1,2,4jtriazol-3-ylmethyl]-4H-benzo[1,4]thiazin-3- one;
5-[5-(2,6-DichIoro-benzylsulfanyl)-4-methyl-4H-[1 ,2,4]triazol-3-yl]-benzo[1,2,5]oxadiazole;
1-(4-Chloro-phenyl)-2-[4-methyl-5-(4-trifluoromethyl-pyridin-3-yl)-4H-[1,2,4]triazol-3-ylsulfanylj- ethanone;
3-[5-(4-Chloro-benzylsulfanyl)-4-methyI-4H-[1,2,4]triazol-3-yl]-2-methyl-imidazo[1,2-a]pyridine; 3-[5-(2,4-Dichloro-benzyIsulfanyl)-4-methyl-4H-[1 ,2,4]triazol-3-yl]-2,8-dimethyl-imidazo[1,2- ajpyridine;
4-Allyl-5-(2,4-dichloro-phenyl)-4H-[1 ,2,4]triazole-3-thiol;
3-(5-Allylsulfanyl-4-methyl-4H-[1 ,2,4]triazol-3-yl)-1 -benzyl-1 H-pyridin-2-one;
3-(4-AllyI-5-methylsulfanyl-4H-[1,2,4]triazol-3-yl)-1-(2,4-dichIoro-benzyl)-1H-pyridin-2-one; 3-(4-Allyl-5-mercapto-4H-[1 ,2,4]triazoI-3-yl)-1 -(4-chloro-benzyl)-1 H-pyridin-2-one;
3-(4-Allyl-5-prop-2-ynylsulfanyl-4H-[1,2,4]triazol-3-yl)-1-(4-chloro-benzyl)-1H-pyridin-2-one;
3-(5-AllylsulfanyI-4-ethyl-4H-[1,2,4]triazol-3-yl)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
1-(2,4-Dichloro-benzyl)-3-[4-ethyl-5-(2-oxo-2-phenyl-ethyIsulfanyl)-4H-[1,2,4]triazol-3-ylj-1H- pyridin-2-one; 3-(4-Allyl-5-prop-2-ynylsulfanyl-4H-[1 ,2,4jtriazol-3-yl)-1 -(3,4-dichloro-benzyl)-1 H-pyridin-2-one;
4-Allyl-5-(4-methyl-2-phenyl-thiazol-5-yI)-4H-[1,2,4]triazole-3-thiol; 3-Allylsulfanyl-4-methyI-5-(4-methyl-2-phenyl-thiazol-5-yl)-4H-[1 ,2,4]triazole;
4-Allyl-5-[2-(3,4-dimethoxy-phenyl)-thiazol-4-yl]-4H-[1,2,4]triazoIe-3-thioI;
N-[5-(4-tert-Butyl-benzylsulfanyl)-4-methyl-4H-[1 ,2,4]triazol-3-yImethyl]-4-methyl- benzenesulfonamide; 4-Methyl-3-[3-(4-methyl-benzyloxy)-thiophen-2-yl]-5-methylsulfanyl-4H-[1,2,4]triazole;
5-[3-(2,4-Dichloro-benzyloxy)-thiophen-2-yl]-4-methyl-4H-[1,2,4]triazole-3-thiol;
3-[3-(2,4-Dichloro-benzyloxy)-thiophen-2-yl]-4-methyl-5-methylsulfanyl-4H-[1,2,4]triazole;
4-Methyl-5-[3-(3-trifluoromethyl-benzyloxy)-thiophen-2-yl]-4H-[1,2,4]triazole-3-thiol;
2-(5-Benzyl-4-methyl-4H-[1,2,4jtriazol-3-yIsulfanyl)-N-(4-iodo-phenyl)-acetamide; 3-(5-Allylsulfanyl-4-methyl-4H-[1 ,2,4]triazol-3-yl)-2,7-dimethyl-imidazo[1 ,2-a] pyridine;
3-(5-Benzylsulfanyl-4-methyl-4H-[1,2,4]triazol-3-yl)-2,7-dimethyl-imidazo[1,2-a]pyridine;
3-(5-Benzylsulfanyl-4-methyl-4H-[1,2,4]triazol-3-yl)-2-methyl-imidazo[1,2-a]pyridine;
4-Butyl-5-(3-chloro-phenyl)-4H-[1,2,4]triazole-3-thiol;
4-Allyl-5-(3-chloro-phenyl)-4H-[1,2,4]triazole-3-thiol; N-(5-{2-[5-(4-Methoxy-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl]-2-oxo-ethylsulfanyl}-4- methyl-4H-[1,2,4]triazol-3-ylmethyl)-benzamide;
N-(5-{2-[3,5-Bis-(4-methoxy-phenyl)-4,5-dihydro-pyrazol-1-yl]-2-oxo-ethylsulfanyl}-4-methyl-
4H-[1,2,4]triazol-3-ylmethyl)-3-methoxy-benzamide;
N-(5-{2-[5-(4-Methoxy-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl]-2-oxo-ethylsulfanyl}-4- methyl-4H-[1 ,2,4]triazol-3-ylmethyl)-4-(pyrrolidine-1 -sulfonyl)-benzamide;
N-(5-{2-[5-(4-Methoxy-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl]-2-oxo-ethylsulfanyl}-4- methyl-4H-[1,2,4]triazol-3-ylmethyl)-4-(piperidine-1-sulfonyl)-benzamide;
N-(5-{2-[5-(4-Methoxy-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl]-2-oxo-ethylsulfanyl}-4- methyl-4H-[1,2,4]triazol-3-ylmethyl)-4-(morpholine-4-sulfonyl)-benzamide; 4-Benzyl-3-(4-f luoro-naphthalen-1 -ylmethylsulfanyl)-5-phenyl-4H-[1 ,2,4]triazole;
2-[4-Allyl-5-(4-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1 -naphthalen-1 -yl-ethanone;
1 -(4-Fluoro-phenyl)-4-(4-methyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsuIfanyl)-butan-1 -one
2-(4-Methyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-(5,6,7,8-tetrahydro-naphthalen-2-yl)- ethanone; 5-(2-Carbazol-9-yl-ethyl)-4-(2-methyl-allyl)-4H-[1,2,4]triazole-3-thiol;
1-(4-Methoxy-phenyl)-2-[4-(2-methyl-alIyl)-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-ethanone;
2-{2-[4-Allyl-5-(3-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetylamino}-benzoic acid methyl ester;
5-(2,4-Dichloro-phenyl)-4-(2-methyl-allyl)-4H-[1,2,4]triazoIe-3-thiol; 4-Allyl-3-(4-methoxy-benzylsulfanyl)-5-(3-methoxy-phenyl)-4H-[1,2,4]triazole;
2-[4-AIIyI-5-(3-methoxy-phenyl)-4H-[1,2,4]triazoI-3-ylsulfanylj-1-(9H-fluoren-2-yl)-ethanone; 3-(4-Methoxy-benzylsulfanyl)-4-methyl-5-phenyl-4H-[1,2,4]triazole;
2-[4-Allyl-5-(3-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-1-(4-ethyl-phenyl)-ethanone;
2-(4-Allyl-5-phenyI-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(4-chloro-phenyl)-acetamide;
2-[4-Allyl-5-(4-tert-butyl-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-1-(4-chloro-phenyl)-ethanone; 2-(4-Allyl-5-phenylaminomethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2,4-difluoro-phenyl)- acetamide;
2-(4-Allyl-5-phenoxymethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-(4-methoxy-phenyl)-ethanone;
2-(4-Allyl-5-phenoxymethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-(4-bromo-phenyl)-ethanone;
(4-Allyl-5-benzylsulfanyl-4H-[1,2,4]triazol-3-ylmethyl)-phenyl-amine; 2-(4-Allyl-5-benzotriazol-1 -yimethyI-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1 -(4-methoxy-phenyl)- ethanone;
2-(4-Allyl-5-phenylaminomethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-chloro-phenyl)-acetamide;
1-(4-Methoxy-phenyl)-2-[4-(2-methyl-allyl)-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-ethanone;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H7[1 ,2,4]triazol-3-ylsulfanyl]-N-(4-methyl-3-nitro-phenyl)- acetamide;
[5-(2-Methoxy-phenyl)-4-methyl-4H-[1 ,2,4]triazoI-3-ylsulfanyl]-acetic acid isopropyl ester;
N-(4-Chloro-phenyl)-2-[4-ethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetamide;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(4-methoxy-phenyl)- acetamide; N-(3-Cyano-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-2-[4-ethyl-5-(2-methoxy-phenyl)-4H-
[1,2,4]triazol-3-ylsulfanyl]-acetamide;
N-(4-Acetyl-phenyl)-2-[4-ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-acetamide;
4-[5-(2,6-Dichloro-benzylsulfanyl)-4-furan-2-ylmethyl-4H-[1 ,2,4]triazol-3-ylj-pyridine;
N-(4-Methyl-3-nitro-phenyl)-2-[4-methyl-5-(3,4,5-trimethoxy-phenyl)-4H-[1 ,2,4]triazol-3- ylsulfanylj-acetamide;
N-(3-Cyano-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-2-(4-furan-2-ylmethyl-5-pyridin-4-yl-4H-
[1,2,4]triazol-3-yIsulfanyl)-acetamide;
2-[2-(4-Ethyl-5-m-tolyl-4H-[1 ,2,4jtriazol-3-ylsulfanyl)-acetylamino]-benzoic acid methyl ester;
2-(4-Methyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-thiazol-2-yl-acetamide; N-(4-Chloro-phenyl)-2-(4-ethyl-5-m-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(4-Ethoxy-phenyI)-2-(4-ethyl-5-m-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(4-Ethyl-5-m-tolyl-4H-[1,2,4]triazoI-3-ylsulfanyl)-N-(2-nitro-phenyl)-acetamide;
2-(5-Benzyl-4-methyl-4H-[1,2,4]triazoI-3-ylsulfanyl)-N-(4-bromo-phenyl)-acetamide;
2-{5-[(2,6-Dimethyl-phenylamino)-methyl]-4-methyl-4H-[1,2,4]triazoI-3-yIsulfanyl}-1-phenyl- ethanone;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-fluoro-phenyl)-acetamide; 2-[4-EthyI-5-(4-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyI]-1-(4-methoxy-phenyl)- ethanone;
N-(4-lodo-2-methyl-phenyI)-2-[5-(2-methoxy-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanylj- acetamide; 2-(5-Benzyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-(3,4-dihydro-2H-quinolin-1-yl)-ethanone;
N-(2-Bromo-4-methyl-phenyl)-2-(4-furan-2-ylmethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3- ylsulfanyl)-acetamide;
N-(4-Chloro-phenyl)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsuIfanyl)-acetamide;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsuIfanyl]-N-(3-trifluoromethyl-phenyl)- acetamide;
2-[5-[(4-Fluoro-phenylamino)-methyl]-4-(tetrahydro-furan-2-ylmethyl)-4H-[1,2,4]triazol-3- ylsulfanyl]-1 -p-tolyl-ethanone;
2-(5-Methyl-4-phenethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-naphthaIen-1-yl-acetamide;
N-(5-Ethyl-[1,3,4]thiadiazol-2-yl)-2-(5-methyl-4-phenethyl-4H-[1,2,4]triazol-3-ylsulfanyl)- acetamide;
2-(5-Methyl-4-phenethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-phenyl-acetamide;
[5-(4-Bromo-phenyl)-4-methyl-4H-[1 ,2,4]triazoI-3-ylsulfanyl]-acetic acid cyclohexyl ester;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(3-chloro-phenyl)-acetamide;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1,2,4jtriazol-3-ylsulfanyl]-N-(4-chloro-phenyl)-acetamide; 2-[5-(2-Bromo-phenyI)-4-ethyl-4H-[1,2,4jtriazol-3-ylsulfanyl]-N-m-tolyl-acetamide;
N-(3-Cyano-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-2-[5-(4-hydroxy-phenyl)-4-methyl-4H-
[1,2,4]triazol-3-ylsulfanyl]-acetamide;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-methyl-4-nitro-phenyl)-acetamide;
3-Benzylsulfanyl-4-methyl-5-phenyl-4H-[1 ,2,4]triazole; 3-ButylsulfanyI-5-(4-methoxy-phenyl)-4-methyl-4H-[1,2,4]triazole;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(4-ethoxy-phenyl)-acetamide;
N-(4-Acetyl-phenyl)-2-(4-benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2,4-dimethyl-phenyl)-acetamide;
N-(3-Nitro-phenyl)-2-(4-phenethyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-yIsulfanyl)-acetamide; 2-(4-Phenethyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-phenyl-acetamide;
N-Naphthalen-1-yl-2-(4-phenethyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsuIfanyl)-acetamide;
(4-Benzyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetic acid cyclohexyl ester;
1-(3,4-Dihydro-2H-quinolin-1-yl)-2-(4-ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-ethanone;
N-(3-Cyano-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-2-(4-ethyl-5-phenyl-4H-[1,2,4]triazol-3- ylsulfanyl)-acetamide;
2-[5-(4-Methoxy-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1-phenyl-ethanone; 3-Benzylsulfanyl-5-(4-methoxy-phenyl)-4-methyl-4H-[1 ,2,4]triazole;
2-(4,5-Dibenzyl-4H-[1 ,2,4]triazol-3-ylsuIfanyl)-N-thiazol-2-yl-acetamide;
2-(4-Phenethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsuIfanyl)-N-m-tolyl-acetamide;
2-(4-Phenethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsuIfanyl)-N-phenyl-propionamide; 3-(5-Benzylsulfanyl-4-phenethyl-4H-[1 ,2,4]triazol-3-yl)-pyridine;
(4-PhenethyI-5-pyridin-3-yI-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetic acid ethyl ester;
2-(4-Phenethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1-phenyl-ethanone;
2-(4-Phenethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-p-tolyl-propionamide;
1-(3,4-Dihydro-2H-quinolin-1-yl)-2-{4-ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1 ,2,4]triazol- 3-ylsulfanyl}-ethanone;
2-[5-(3,4-Dimethoxy-phenyl)-4-methyI-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1-p-tolyl-ethanone;
N-(3-Chloro-2-methyl-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1 ,2,4]triazoI-3-ylsulfanyl)-acetamide;
2-(4-Ethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N,N-diphenyl-propionamide;
2-(5-Cyclohexyl-4-ethyl-4H-[1 ,2,4]triazol-3-yIsuIfanyl)-N-(2-nitro-phenyl)-acetamide; 2-(5-Cyclohexyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(4-methyI-3-nitro-phenyl)-acetamide;
N-(2-Bromo-4-methyl-phenyI)-2-(4-ethyI-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-yIsulfanyl)- acetamide;
1-(3,4-Dihydro-2H-quinolin-1-yl)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)- ethanone; N-(4-Fluoro-phenyI)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsuIfanyl)-acetamide;
N-(4-Acetyl-phenyl)-2-(5-benzyl-4-ethyI-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(5-Benzyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(2-chloro-phenyl)-acetamide;
N-(3-Chloro-2-methyl-phenyl)-2-[4-ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanylj- acetamide; 2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(2-methyl-4-nitro-phenyI)- acetamide;
2-[5-(2-Methoxy-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-p-tolyl-propionamide;
[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-acetic acid ethyl ester;
2-(4-Methyl-5-o-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(3-nitro-phenyl)-acetamide; 2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-naphthalen-1 -yl- propionamide;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-p-tolyl-propionamide;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-phenyI-propionamide;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(4-phenyl-thiazol-2-yl)- acetamide;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-p-tolyl-acetamide; N-(3-Chloro-4-methyl-phenyI)-2-[4-ethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazoI-3-ylsulfanylj- acetamide;
2-[5-(4-Hydroxy-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-nitro-phenyl)-acetamide;
4-{2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-acetylamino}-benzoic acid ethyl ester;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4jtriazol-3-ylsulfanyl]-N-o-tolyl-acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-chloro-phenyl)-acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-methoxy-2-nitro-phenyl)- acetamide; 2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-methyI-4-nitro-phenyl)- acetamide;
1-(3,4-Dihydro-2H-quinolin-1-yl)-2-{5-[(2,4-dimethyl-phenylamino)-methyl]-4-ethyl-4H-
[1,2,4]triazol-3-ylsulfanyl}-ethanone;
N-(4-Chloro-3-nitro-phenyI)-2-[5-(4-chIoro-phenyl)-4-ethyl-4H-[1 ,2,4]triazoI-3-ylsulfanylj- acetamide;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1-(3,4-dihydro-2H-quinolin-1-yl)- ethanone;
2-(5-Benzyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-p-tolyl-ethanone;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-methoxy-phenyl)-acetamide; 2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazoI-3-ylsuIfanyl)-N-(2-chloro-phenyl)-acetamide;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(5-ethyl-[1,3,4jthiadiazol-2-yl)- acetamide;
4-{2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsuIfanyl]-acetylamino}-benzoic acid methyl ester; 2-(5-Benzyl-4-methyl-4H-[1,2,4]triazol-3-ylsuIfanyl)-N-(2-nitro-phenyl)-acetamide;
2-(5-Benzyl-4-methyl-4H-[1,2,4jtriazol-3-ylsulfanyl)-N-(3-cyano-4,5,6,7-tetrahydro- benzo[bjthiophen-2-yl)-acetamide;
2-[5-(4-Chloro-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-nitro-phenyl)-acetamide;
(5-Benzylsulfanyl-4-ethyl-4H-[1,2,4]triazol-3-ylmethyl)-(4-chloro-phenyl)-amine; N-(2-Methoxy-phenyl)-2-[5-(2-methoxy-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanylj- acetamide;
2-(4-Allyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3,4-dichloro-phenyl)-acetamide;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsuIfanyl)-N-p-tolyl-acetamide;
2-(5-Benzyl-4-methyI-4H-[1,2,4]triazol-3-ylsulfanyI)-N-(4-chloro-phenyl)-acetamide; 2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-methoxy-phenyl)-acetamide;
N-(5-Chloro-2-methyl-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide; N-(4-Methoxy-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(2,4-Dimethyl-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(4-Ethoxy-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
4-[2-(4-Methyl-5-o-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetylamino]-benzoic acid methyl ester; N-(4-Chloro-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
2-[5-(4-Hydroxy-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(4-phenyl-thiazol-2-yl)- acetamide;
2-(5-Benzyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-bromo-4-methyl-phenyl)-acetamide;
2-(5-Benzyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-phenyl-ethanone; 2-(5-BenzyI-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-nitro-phenyl)-acetamide;
2-(5-Cyclohexyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-p-toIyl-acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-ethoxy-phenyl)-acetamide;
2-(5-Cyclohexyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-naphthalen-1-yl-acetamide;
4-[5-(4-tert-Butyl-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-pyridine; 4-[5-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazoI-3-yl]-pyridine;
2-(5-Cyclohexyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-methyl-4-nitro-phenyl)-acetamide;
2-(5-Cyclohexyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3-trifluoromethyl-phenyl)-acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-fluoro-phenyl)-acetamide;
4-{2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-acetylamino}-benzoic acid methyl ester;
N-(3-Chloro-phenyl)-2-(5-cyclohexyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(5-CycIohexyI-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(4-ethoxy-phenyl)-acetamide;
2-{5-[(4-Chloro-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-N-(2-nitro-phenyl)- acetamide; 2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3-chloro-2-methyl-phenyl)-acetamide;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-phenyl-acetamide;
3-Benzyl-5-(2-chloro-6-fluoro-benzylsulfanyl)-4-methyl-4H-[1 ,2,4]triazole;
2-(5-Cyclohexyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-nitro-phenyl)-acetamide;
2-[5-(4-Hydroxy-phenyi)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-1-phenyl-ethanone; 4-[5-(4-Chloro-benzylsulfanyl)-4-methyl-4H-[1,2,4]triazol-3-yl]-phenol;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-fluoro-phenyl)-acetamide;
2-(5-Cyclohexyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-(4-methoxy-phenyI)-ethanone;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-bromo-phenyl)-acetamide;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-phenyl-acetamide; 2-(5-Cyclohexyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-nitro-phenyl)-propionamide;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-trifluoromethyl-phenyl)-acetamide; {5-[(3-Chloro-4-methyl-phenylamino)-methyl]-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl}-acetic acid cyclohexyl ester;
3-[5-(2,4-Dichloro-benzylsulfanyl)-4-methyl-4H-[1,2,4]triazol-3-yl]-pyridine;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4jtriazol-3-ylsulfanyl]-N-phenyl-acetamide; N-(3-Chloro-4-methyl-phenyl)-2-[5-(4-hydroxy-phenyl)-4-methyl-4H-[1,2,4jtriazoI-3-ylsulfanyl]- acetamide;
N-(4-Chloro-phenyl)-2-[5-(4-hydroxy-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanylj- acetamide;
3-Benzyl-5-(4-chloro-benzylsulfanyl)-4-methyl-4H-[1,2,4]triazole; 2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-nitro-phenyl)-acetamide;
N-(4-Ethoxy-phenyl)-2-[5-(4-hydroxy-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanylj- acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyI]-N-(4-methoxy-phenyl)- acetamide; {5-[(4-Chloro-phenylamino)-methyl]-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyI}-acetic acid cyclohexyl ester;
3-BenzylsuIfanyl-5-(2-methoxy-phenyl)-4-methyl-4H-[1,2,4]triazole;
N-(2-Chloro-phenyl)-2-(4-methyl-5-m-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(2-Methoxy-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide; 2-(5-Cyclohexyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-phenyl-acetamide;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(3-nitro-phenyl)-acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-1-(3,4-dihydro-2H-quinolin-1-yl)- ethanone;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-bromo-4-methyl-phenyl)-acetamide; N-(2-Chloro-phenyl)-2-[5-(2-methoxy-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanylj- acetamide;
(5-Benzylsulfanyl-4-ethyl-4H-[1,2,4]triazol-3-ylmethyl)-(3-trifluoromethyl-phenyl)-amine;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-1-(4-methoxy-phenyl)-ethanone;
[4-AIIyl-5-(3-bromo-benzylsulfanyl)-4H-[1,2,4]triazol-3-ylmethyl]-phenyl-amine; 2-(4-Furan-2-ylmethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-(3-nitro-phenyl)-ethanone;
1-(4-Bromo-phenyl)-2-(4-furan-2-ylmethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)- ethanone;
4-{5-[2-(2-Methoxy-phenoxy)-ethylsulfanyl]-4-methyl-4H-[1,2,4]triazol-3-yl}-phenylamine;
4-[5-(4-Chloro-benzylsulfanyl)-4-methyl-4H-[1,2,4]triazol-3-yl]-phenylamine; [4-Allyl-5-(1 ,3-dioxo-1 H,3H-benzo[de]isoquinolin-2-ylmethyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]- acetic acid ethyl ester; 2-{4-Allyl-5-[(4-chloro-phenylamino)-methyl]-4H-[1,2,4]triazol-3-ylsulfanyI}-1-phenyl-ethanone;
5-(3-Bromo-phenyl)-4-(2-methyl-allyl)-4H-[1 ,2,4]triazole-3-thioI;
2-(4-AIIyl-5-benzotriazol-1-ylmethyI-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-chloro-phenyl)- acetamide; 1 -(4-Fluoro-phenyl)-2-(4-methyl-5-phenyl-4H-[1 ,2,4jtriazoI-3-ylsulfanyl)-ethanone;
8-(4-Methyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-5-nitro-quinoline;
3-(2-Bromo-benzylsulfanyl)-4-methyl-5-(4-nitro-phenyl)-4H-[1,2,4]triazole;
2-[4-Allyl-5-(3-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-1-(2,4-dimethyl-phenyl)- ethanone; 1 -(4-Bromo-phenyl)-2-(5-furan-2-yl-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-ethanone;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(5-methyl-thiazol-2-yl)- acetamide;
2-[4-Ethyl-5-(p-tolylamino-methyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-1 -p-tolyl-ethanone;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-ethyl-phenyl)-acetamide; 2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-(4-methoxy-phenyl)-ethanone;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)-acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-1-p-tolyl-ethanone;
3-(2-Bromo-phenyl)-4-methyl-5-(4-nitro-benzylsulfanyl)-4H-[1,2,4]triazole;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(4-phenyl-thiazol-2-yl)- acetamide;
2-[5-(2-Bromo-phenyl)-4-methyI-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2,4-dimethyl-phenyl)- acetamide;
N-(4-Bromo-phenyl)-2-[5'-(2-bromo-phenyl)-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-acetamide;
2-{5-[(2,4-Dimethyl-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-1-(4-methoxy- phenyl)-ethanone;
2-{5-[(2,4-Dimethyl-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-1-p-tolyl- ethanone;
{5-[(2,4-Dimethyl-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-acetic acid cyclohexyl ester; 2-{5-[(4-Fluoro-phenylamino)-methyl]-4-methyI-4H-[1 ,2,4]triazol-3-ylsulfanyl}-1 -phenyl- ethanone;
2-{4-Ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1,2,4]triazol-3-ylsulfanyl}-1-(4-methoxy- phenyl)-ethanone;
[4-Ethyl-5-(4-methyl-benzylsulfanyl)-4H-[1,2,4]triazol-3-ylmethyl]-(4-fluoro-phenyl)-amine; (5-Benzylsulfanyl-4-ethyl-4H-[1,2,4]triazol-3-ylmethyl)-(4-fluoro-phenyl)-amine; {4-Ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1 ,2,4]triazol-3-ylsulfanyI}-acetic acid cyclohexyl ester;
N-(4-Chloro-phenyl)-2-[4-ethyI-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetamide;
N-(4-Acetyl-phenyl)-2-(5-cyclohexyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide; 2-[4-Ethyl-5-(4-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(4-methyl-3-nitro-phenyl)- acetamide;
N-CyclohexyI-2-(4-phenethyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(2,4-Dimethyl-phenyl)-2-[4-furan-2-ylmethyl-5-(4-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3- ylsulfanylj-acetamide; 4-[2-(5-Cyclohexyl-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetylamino]-benzoic acid ethyl ester;
2-[4-Furan-2-ylmethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-methyl-3-nitro- phenyl)-acetamide;
3-lsobutylsulfanyl-4-methyl-5-p-tolyl-4H-[1,2,4]triazole; 2-[2-(4-Methyl-5-m-tolyl-4H-[1 ,2,4]triazol-3-ylsuIfanyl)-acetylamino]-benzoic acid methyl ester;
2-{4-Ethyl-5-[4-(morpholine-4-sulfonyl)-phenyl]-4H-[1,2,4]triazol-3-ylsulfanyl}-1-p-tolyl- ethanone;
4-Methyl-3-phenethylsulfanyl-5-p-tolyl-4H-[1,2,4]triazole;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-p-tolyl-acetamide; 2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4jtriazol-3-ylsulfanyl)-N-(4-nitro-phenyl)-acetamide;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-phenyl-acetamide;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3-chloro-phenyl)-acetamide;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-nitro-phenyl)-propionamide;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2,5-dichloro-phenyl)-acetamide; N-(3-Chloro-phenyI)-2-(4-phenethyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(4-Nitro-phenyl)-2-(4-phenethyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-propionamide;
N-(2-Bromo-4-methyl-phenyl)-2-[5-(3,4-dimethoxy-phenyl)-4-methyI-4H-[1,2,4]triazol-3- ylsulfanylj-acetamide;
2-{4-Ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1,2,4jtriazol-3-ylsulfanyl}-N-(4-nitro-phenyl)- acetamide;
3-Benzylsulfanyl-5-cyclohexyl-4-ethyl-4H-[1 ,2,4]triazole;
[5-(4-Hydroxy-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanylj-acetic acid cyclohexyl ester;
2-(5-Cyclohexyl-4-ethyl-4H-[1,2,4jtriazol-3-ylsulfanyl)-N-(5-ethyl-[1,3,4]thiadiazol-2-yl)- acetamide; N-(3-Chloro-4-methyl-phenyl)-2-[4-ethyI-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanylj- acetamide; [4-Benzyl-5-(4-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyI]-acetic acid ethyl ester;
3-Benzylsulfanyl-4-methyl-5-(3,4,5-trimethoxy-phenyl)-4H-[1,2,4]triazole;
N-(2-Chloro-phenyl)-2-[4-ethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetamide;
N-(2,4-Dimethoxy-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide; 2-(5-Cyclohexyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-methyl-4-nitro-phenyl)- acetamide;
2-(5-Cyclohexyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyI)-1-phenyl-ethanone;
3-Cyclohexyl-4-methyl-5-(4-methyl-benzylsulfanyl)-4H-[1,2,4]triazole;
N-(2-Bromo-phenyl)-2-(5-cyclohexyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide; 2-(5-Cyclohexyl-4-methyl-4H-[1,2,4jtriazol-3-ylsulfanyI)-N-(4-iodo-2-methyl-phenyl)-acetamide;
N-(3-Cyano-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-2-(5-cyclohexyI-4-methyl-4H-
[1,2,4]triazoI-3-ylsuIfanyl)-acetamide;
N-(4-Acetyl-phenyl)-2-(5-cyclohexyl-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(5-Cyclohexyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-methoxy-phenyl)-acetamide; N-(4-Chloro-phenyl)-2-(5-cyclohexyl-4-methyl-4H-[1,2,4]triazol-3-yIsulfanyl)-acetamide;
2-(5-Cyclohexyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-phenyl-acetamide;
2-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1 ,2,4jtriazol-3-ylsulfanyl]-N-(2-methoxy-4-nitro-phenyl)- acetamide;
N-(3-Cyano-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-2-[5-(2-methoxy-phenyl)-4-methyl-4H- [1 ,2,4]triazol-3-ylsulfanyl]-acetamide;
N-(4-Bromo-phenyl)-2-(5-cyclohexyl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
2-[4-Ethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-phenyl-acetamide;
N-(3-Chloro-phenyI)-2-[4-ethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetamide;
N-(4-Acetyl-phenyl)-2-[4-ethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetamide; N-(4-Bromo-phenyI)-2-[4-ethyl-5-(4-hydroxy-phenyl)-4H-[1 ,2,4jtriazol-3-yIsulfanyl]-acetamide;
2-[4-Ethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-iodo-2-methyl-phenyl)- acetamide;
N-(2,4-DimethyI-phenyl)-2-[4-ethyl-5-(4-hydroxy-phenyl)-4H-[1 ,2,4]triazoI-3-ylsulfanylj- acetamide; 4-[5-(4-Chloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-phenol;
[4-Ethyl-5-(4-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-acetic acid cyclohexyl ester;
2-[5-(2-Methoxy-phenyl)-4-methyI-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-phenyl-thiazol-2-yl)- acetamide;
N-(3-Chloro-phenyl)-2-[4-ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-acetamide; 2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanylj-N-(2-nitro-phenyl)-acetamide;
2-[4-Methyl-5-(4-nitro-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-1-phenyl-ethanone; N-(4-Bromo-phenyl)-2-{4-ethyl-5-[(4-fluoro-phenylamino)-methyi]-4H-[1,2,4]triazoI-3- ylsulfanylj-acetamide;
N-(4-Chloro-phenyl)-2-{4-ethyl-5-[(4-fluoro-phenylamino)-methylj-4H-[1,2,4]triazol-3- ylsulfanyl}-acetamide; 2-{4-Ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1,2,4]triazol-3-ylsulfanyl}-N-(2-nitro-phenyl)- acetamide;
1-(4-Methoxy-phenyl)-2-[4-methyl-5-(4-nitro-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-ethanone;
[5-(4-Chloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-ylmethyl]-(4-fluoro-phenyI)-amine;
2-{4-Ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1,2,4]triazol-3-ylsulfanyl}-1-p-tolyI-ethanone; 2-{4-Ethyl-5-[(4-fluoro-phenylamino)-methyl]-4H-[1,2,4]triazol-3-ylsulfanyl}-N-(4-methyl-3-nitro- phenyl)-acetamide;
N-(2-Bromo-4-methyl-phenyl)-2-{4-ethyI-5-[(4-fluoro-phenylamino)-methyl]-4H-[1,2,4]triazol-3- ylsulfanylj-acetamide;
4-AIIyl-5-(3-bromo-phenyl)-4H-[1,2,4]triazole-3-thiol; N-(2-Nitro-phenyl)-2-(4-phenethyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
2-{4-Ethyl-5-[4-(piperidine-1-sulfonyl)-phenyl]-4H-[1 ,2,4]triazol-3-ylsulfanyI}-1-p-tolyl-ethanone;
2-{4-Ethyl-5-[4-(piperidine-1 -sulfonyl)-phenyl]-4H-[1 ,2,4]triazol-3-ylsulfanyl}-1 -phenyl- ethanone;
N-Biphenyl-2-yl-2-(4-ethyI-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide; 2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3-chloro-4-methyl-phenyl)- acetamide;
N-(2-Bromo-phenyl)-2-(4-ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
4-Benzyl-5-cyclohexyl-4H-[1,2,4]triazole-3-thiol;
2-(5-Cyclohexyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-phenyl-ethanone; 2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsuIfanylj-1 -phenyl-ethanone;
(5-Benzyl-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetic acid cyclohexyl ester;
4-Methyl-3-(4-nitro-benzylsulfanyl)-5-phenyl-4H-[1 ,2,4]triazole;
2-(4-Methyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-p-tolyl-ethanone;
2-(4-Methyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-phenyl-ethanone; 3-BenzyIsulfanyl-4-methyI-5-(naphthalen-2-yloxymethyl)-4H-[1 ,2,4]triazole;
2-(5-Cyclohexyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-p-tolyl-acetamide;
3-Benzylsulfanyl-5-cyclohexyl-4-methyl-4H-[1,2,4]triazole;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-chloro-3-nitro-phenyl)-acetamide;
2-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-methyl-3-nitro-phenyl)-acetamide; 2-(5-Benzyl-4-ethyI-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-methoxy-4-nitro-phenyl)-acetamide;
N-(2-Bromo-4-methyl-phenyI)-2-(4-methyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide; 3-Benzylsulfanyl-4-ethyl-5-(4-nitro-phenyl)-4H-[1 ,2,4]triazole;
4-Ethyl-3-(4-methyl-benzyIsulfanyl)-5-(4-nitro-phenyl)-4H-[1 ,2,4]triazole;
2-[4-Ethyl-5-(4-nitro-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1-p-tolyl-ethanone;
3-(4-Chloro-benzylsulfanyl)-4-ethyl-5-(4-nitro-phenyl)-4H-[1 ,2,4]triazole; 2-[4-Ethyl-5-(4-nitro-phenyI)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1 -phenyl-ethanone;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(3,4-dimethyl-phenyl)- acetamide;
(2,4-DimethyI-phenyI)-[4-ethyl-5-(4-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-ylmethyl]-amine
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(4-methyl-3-nitro-phenyl)- acetamide;
2-(4-Methyl-5-o-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(2-trifluoromethyl-phenyl)-acetamide;
2-[5-[(2,4-Dimethyl-phenylamino)-methyl]-4-(tetrahydro-furan-2-ylmethyl)-4H-[1 ,2,4]triazol-3- ylsulfanyl]-1 -p-tolyl-ethanone;
4-[5-(2,6-Dichloro-benzylsulfanyl)-4-(tetrahydro-furan-2-ylmethyl)-4H-[1,2,4]triazol-3-ylj- pyridine;
3-Benzylsulfanyl-5-(4-chloro-phenoxymethyl)-4-ethyl-4H-[1 ,2,4]triazole;
3-Butylsulfanyl-4-methyI-5-p-tolyl-4H-[1 ,2,4]triazole;
1-(5-Chloro-2-methoxy-phenyl)-2-(4-methyl-5-p-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-ethanone;
1-(4-Chloro-phenyl)-2-(4-methyl-5-p-tolyl-4H-[1 ,2,4Jtriazol-3-ylsulfanyl)-ethanone; N-(2,4-Dimethoxy-phenyl)-2-(4-ethyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(4-Ethyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(2-methyl-4-nitro-phenyl)-acetamide;
N-(4-Ethoxy-phenyl)-2-(4-ethyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(4-Ethyl-phenyl)-2-(4-ethyl-5-phenyl-4H-[1 ,2,4]triazol-3-yIsuIfanyl)-acetamide;
2-(4-Ethyl-5-phenyI-4H-[1 ,2,4]triazol-3-ylsulfanyI)-N-thiazol-2-yl-acetamide; 2-(4-Ethyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1 -phenyl-ethanone;
2-(4-Ethyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1-p-tolyl-ethanone;
2-(4-Ethyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(2-nitro-phenyl)-acetamide;
N-(3-Chloro-phenyl)-2-(4-ethyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(2-Chloro-phenyl)-2-(4-ethyl-5-phenyl-4H-[1 ,2,4jtriazol-3-ylsulfanyl)-acetamide; 2-[5-(2-Hydroxy-phenyI)-4-phenethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1-piperidin-1-yl-ethanone;
2-[5-(2-Morpholin-4-yl-ethylsuIfanyI)-4-phenethyl-4H-[1 ,2,4]triazol-3-yl]-phenol;
N-(2-Methyl-4-nitro-phenyl)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)- acetamide;
N-(2-Methyl-5-nitro-phenyl)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)- acetamide;
N-(4-Bromo-phenyI)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide; N-(3-Nitro-phenyl)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(4-Ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-fluoro-phenyl)-acetamide;
2-(4-Ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-methoxy-4-nitro-phenyl)-acetamide;
N-(2,5-Dichloro-phenyI)-2-[4-ethyI-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanylj- acetamide;
2-(5-Cyclohexyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3-nitro-phenyl)-acetamide;
2-[4-Benzyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-methyl-4-nitro-phenyl)- acetamide;
2-(4-Phenethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3-trifluoromethyl-phenyl)- acetamide;
[4-Furan-2-ylmethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetic acid cyclohexyl ester;
2-[4-Furan-2-ylmethyl-5-(4-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanylj-1-phenyl-ethanone;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-ethyl-phenyl)-acetamide; 2-(5-CycIohexyl-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3,4-dichloro-phenyl)-acetamide;
2-(5-Cyclohexyl-4-methyl-4H-[1,2,4jtriazol-3-ylsulfanyl)-1-(4-methoxy-phenyl)-ethanone;
2-(4-Benzyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-methoxy-2-nitro-phenyl)-acetamide;
2-(4-Benzyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(5-methyl-thiazol-2-yl)-acetamide;
2-(4-Benzyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-thiazol-2-yl-acetamide; 2-(4,5-Dibenzyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-nitro-phenyl)-acetamide;
2-(4-Benzyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-nitro-phenyl)-acetamide;
3-Benzylsulfanyl-5-(4-bromo-phenyl)-4-methyl-4H-[1,2,4]triazole;
2-[4-Ethyl-5-(4-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(4-methyl-3-nitro-phenyl)- acetamide; 2-[4-Ethyl-5-(4-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1 -phenyl-ethanone;
2-(4-Benzyl-5-methyl-4H-[1,2,4]triazol-3-ylsuIfanyl)-1-phenyl-ethanone;
2-(5-Methyl-4-phenethyl-4H-[1 ,2,4]triazol-3-yIsulfanyl)-N-p-tolyl-acetamide;
2-(5-Methyl-4-phenethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3-trifluoromethyl-phenyl)-acetamide;
N-(3-Chloro-phenyl)-2-(5-methyl-4-phenethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide; N-(4-Chloro-phenyl)-2-(5-methyl-4-phenethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
2-[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-methoxy-4-nitro-phenyl)- acetamide;
2-(5-Cyclohexyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(3-nitro-phenyl)-acetamide;
N-(2,3-Dichloro-phenyl)-2-[4-ethyl-5-(2-methoxy-phenyI)-4H-[1,2,4]triazol-3-ylsulfanylj- acetamide; N-(2,3-Dichloro-phenyl)-2-[4-ethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanylj- acetamide;
2-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1-(4-methoxy-phenyl)- ethanone; 2-[4-BenzyI-5-(2-hydroxy-phenyI)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-1 -piperidin-1 -yl-ethanone;
2-[4-Benzyl-5-(2-hydroxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-p-tolyl-acetamide;
2-{5-[(2,4-Dimethyl-phenylamino)-methyl]-4-furan-2-ylmethyI-4H-[1,2,4]triazol-3-ylsulfanyl}-1- phenyl-ethanone;
2-(4-Methyl-5-m-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-p-tolyl-acetamide; 4-{4-Ethyl-5-[4-(piperidine-1-sulfonyl)-phenyl]-4H-[1,2,4]triazol-3-ylsuIfanylmethyl}-benzonitrile;
N-(2-Methoxy-phenyl)-2-(4-methyl-5-m-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetamide;
N-(4-Acetyl-phenyl)-2-(4-ethyl-5-m-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide;
2-(4-Ethyl-5-m-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(4-methyl-3-nitro-phenyl)-acetamide;
2-[5-(4-Amino-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-1-(4-nitro-phenyl)-ethanone; N-{4-[5-(2-Chloro-benzylsulfanyl)-4-methyl-4H-[1,2,4]triazol-3-yl]-phenyl}-2-methoxy- benzamide;
2-(4-Allyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1-(4-fluoro-phenyl)-ethanone;
2-(4-Benzyl-5-pyridin-3-yl-4H-[1,2,4]triazol-3-ylsuIfanyl)-N-(4-fluoro-phenyl)-acetamide;
2-[5-(4-Amino-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-1-(4-nitro-phenyl)-ethanone; 2-(4-Allyl-5-thiophen-2-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-chloro-phenyl)-acetamide;
(4-Benzyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-acetic acid ethyl ester;
4-[5-(4-tert-Butyl-benzylsulfanyl)-4-methyl-4H-[1,2,4]triazol-3-yl]-pyridine;
2-{5-[(3-Chloro-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-1-phenyl- ethanone; {5-[(2-Chloro-phenylamino)-methyl]-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl}-acetic acid isopropyl ester;
2-[4-Ethyl-5-(4-methoxy-phenoxymethyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-1 -phenyl-ethanone;
1-(4-Chloro-phenyl)-2-{5-[(2-chloro-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3- ylsulfanylj-ethanone; 4-[5-(2-Chloro-6-fluoro-benzylsulfanyl)-4-methyl-4H-[1,2,4]triazol-3-yl]-pyridine
3-Benzyl-5-benzylsulfanyl-4-ethyl-4H-[1,2,4]triazoIe;
3-Benzylsulfanyl-4-methyl-5-o-tolyI-4H-[1,2,4]triazoIe;
N-(4-Chloro-3-nitro-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1,2,4]triazoI-3-ylsulfanyl)-acetamide;
2-(4-Methyl-5-o-tolyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-p-tolyl-ethanone; 1 -(4-Methoxy-phenyl)-2-(4-methyl-5-o-tolyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-ethanone;
[5-(2-Bromo-phenyl)-4-methyl-4H-[1,2,4]triazol-3-ylsuIfanyl]-acetonitrile; [5-(2-Hydroxy-phenyl)-4-phenethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-acetonitrile;
1-[5-(2-Hydroxy-phenyI)-4-phenethyl-4H-[1,2,4]triazol-3-ylsulfanyl]-propan-2-one;
N-(2,3-Dichloro-phenyI)-2-[4-furan-2-ylmethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3- ylsulfanylj-acetamide; N-(3-Chloro-phenyI)-2-[4-furan-2-ylmethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]- acetamide;
N-(4-Chloro-phenyl)-2-[4-furan-2-ylmethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanylj- acetamide;
2-[5-(4-Methoxy-phenoxymethyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyIj-1-phenyl-ethanone; 2-{5-[(2-ChIoro-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-1-piperidin-1-yl- ethanone;
2-[5-(4-Methoxy-phenoxymethyl)-4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl]-1-(4-methoxy- phenyl)-ethanone;
N-(2,3-Dichloro-phenyl)-2-[4-furan-2-ylmethyl-5-(4-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3- ylsulfanylj-acetamide;
2-[4-Furan-2-ylmethyl-5-(4-hydroxy-phenyl)-4H-[1,2,4jtriazol-3-ylsulfanyl]-1-(4-methoxy- phenyl)-ethanone;
{5-[(2-ChIoro-phenylamino)-methyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanyl}-acetic acid cyclohexyl ester; 2-(4-Phenethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-thiazol-2-yl-acetamide;
2-(4-Ethyl-5-m-tolyl-4H-[1 ,2,4jtriazoI-3-ylsulfanyl)-N-(4-nitro-phenyl)-acetamide;
2-(4-Ethyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-N-(2-methoxy-phenyl)-acetamide;
2-(4-Ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(2-trifluoromethyl-phenyl)-acetamide;
2-[4-Furan-2-ylmethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-N-(2-methyl-4-nitro- phenyl)-acetamide;
N-(3-Chloro-2-methyl-phenyl)-2-[4-furan-2-ylmethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3- ylsulfanylj-acetamide;
4-Allyl-5-m-toIyl-4H-[1,2,4]triazole-3-thiol;
4-(2-Methyl-allyl)-5-m-tolyl-4H-[1,2,4]triazole-3-thiol; 2-[4-AIIyl-5-(3-bromo-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyl]-N-(4-ethyl-phenyl)-acetamide;
4-Allyl-3-(3-bromo-phenyI)-5-(2-nitro-benzylsulfanyl)-4H-[1,2,4]triazole;
2-[4-Allyl-5-(3-bromo-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-1-biphenyl-4-yl-ethanone;
4-(2-Methyl-alIyl)-5-(3-nitro-phenyl)-4H-[1,2,4]triazole-3-thiol;
4-AIIyl-5-(2-carbazol-9-yI-ethyl)-4H-[1 ,2,4]triazole-3-thiol; 5-(4-Bromo-phenyl)-4-(2-methyl-allyl)-4H-[1,2,4]triazole-3-thiol;
4-(2-Methyl-allyl)-5-(3-methyl-2-nitro-phenyl)-4H-[1,2,4]triazole-3-thiol; 5-(4-Methoxy-phenyl)-4-(2-methyl-allyl)-4H-[1,2,4jtriazole-3-thiol; 2-(4-Allyl-5-benzotriazol-1-ylmethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(4-bromo-phenyl)- acetamide;
2-(4-Allyl-5-benzotriazol-1-ylmethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-pyridin-2-yl-acetamide; {4-Allyl-5-[3-(1 ,3-dioxo-1 H,3H-benzo[de]isoquinolin-2-yI)-propyl]-4H-[1 ,2,4]triazol-3-ylsulfanyI}- acetic acid ethyl ester; and 4-Allyl-5-(4-phenyl-piperazin-1-ylmethyl)-4H-[1,2,4]triazole-3-thiol; or
a salt thereof with a pharmaceutically acceptable acid or base, or optical isomer, mixture of optical isomers, racemic mixture, or tautomeric form thereof.
37. The combination according to claim 34 or 35 wherein the 11/?-HSD1 inhibitor is selected from the group:
4-[2-(4-Ethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yIsulfanyl)ethyl]morpholine; 1-Benzothiazol-2-yl-2-(4-ethyl-5-phenyI-4H-[1 ,2,4]triazol-3-ylsulfanyl)-ethanone;
Λ/-Cyclohexyl-2-(4-ethyl-5-phenyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-Λ/-methyl-acetamide;
2-(4-Ethyl-5-phenyl-4/--[1,2,4]triazol-3-ylsulfanyl)-1-phenyl-ethanone;
2-(4-Ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyI)-1-(4-methoxy-phenyl)-ethanone;
2-(4-Ethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-pyridin-3-yl-ethanone; 2-(4-Ethyl-5-phenyl-4 --[1,2,4]triazol-3-ylsulfanyl)-1-(4-methanesulfonyl-phenyl)-ethanone;
2-(4-Phenethyl-5-phenyI-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1-phenyl-ethanone;
1-(4-Methoxy-phenyl)-2-(4-phenethyl-5-phenyl-4/--[1,2,4]triazol-3-ylsulfanyl)-ethanone;
2-(4-Phenethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-pyridin-3-yl-ethanone;
1-(4-MethanesuIfonyl-phenyl)-2-(4-phenethyl-5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)- ethanone;
2-(4-Ethyl-5-pyridin-4-yl-4/--[1,2,4]triazol-3-ylsulfanyl)-1-phenyl-ethanone;
2-(4-Ethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-(4-methoxy-phenyl)-ethanone;
2-(4-Ethyl-5-pyridin-4-yI-4/--[1 ,2,4]triazol-3-ylsulfanyI)-1-pyridin-3-yl-ethanone;
2-(4-Ethyl-5-pyridin-4-yl-4/--[1,2,4]triazol-3-ylsulfanyl)-1-(4-methanesulfonyl-phenyl)-ethanone; 2-(4-Phenethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1 -phenyl-ethanone;
1-(4-Methoxy-phenyl)-2-(4-phenethyI-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-ethanone;
2-(4-Phenethyl-5-pyridin-4-yl-4 -/-[1,2,4]triazol-3-ylsulfanyl)-1-pyridin-3-yl-ethanone;
1-(4-Methanesulfonyl-phenyl)-2-(4-phenethyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)- ethanone; 2-(4-Ethyl-5-furan-2-yl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1 -phenyl-ethanone;
2-(4-Ethyl-5-furan-2-yl-4/--[1,2,4]triazol-3-ylsulfanyl)-1-(4-methoxy-phenyI)-ethanone; 2-(4-Ethyl-5-furan-2-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-pyridin-3-yl-ethanone;
2-(4-Ethyl-5-furan-2-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-1-(4-methanesulfonyl-phenyl)-ethanone;
2-(5-Furan-2-yl-4-phenethyl-4 -/-[1,2,4]triazol-3-ylsulfanyI)-1-phenyl-ethanone;
2-(5-Furan-2-yl-4-phenethyl-4W-[1,2,4]triazol-3-ylsulfanyl)-1-(4-methoxy-phenyl)-ethanone; 2-(5-Furan-2-yl-4-phenethyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-1 -pyridin-3-yl-ethanone;
2-(5-Furan-2-yl-4-phenethyl-4H-[1,2,4]triazol-3-ylsuIfanyl)-1-(4-methanesulfonyl-phenyl)- ethanone;
1 -Adamantan-1 -yl-2-(4-methyl-4H-[1 ,2,4]triazol-3-ylsulfanyl)-ethanone;
3-[5-(2-Chloro-benzylsulfanyI)-4-ethyl-4H-[1,2,4]triazol-3-ylj-propan-1-ol; 4-[4-Ethyl-5-(3-hydroxy-propyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
3-[5-(6-Chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-propan-1-ol;
3-[5-(3,4-DichIoro-benzylsulfanyl)-4-ethyl-4--[1,2,4]triazol-3-yl]-propan-1-ol;
3-(5-CyclohexylmethylsuIfanyl-4-ethyl-4H-[1,2,4]triazol-3-yl)-propan-1-ol;
3-[4-Ethyl-5-(4-trifluoromethyI-benzylsulfanyl)-4H-[1 ,2,4]triazoI-3-yl]-propan-1-ol; 3-(5-Benzylsulfanyl-4-ethyl-4 - -[1,2,4]triazol-3-yl)-propan-1-ol;
3-[4-Ethyl-5-(4-methanesulfonyl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yI]-propan-1-ol;
3-[4-Ethyl-5-(3-nitro-benzyIsulfanyl)-4H-[1,2,4jtriazol-3-yl]-propan-1-ol;
3-[5-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-propan-1-ol;
3-[4-Ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4/-/-[1,2,4]triazol-3-yl]-propan-1-ol; N-{4-[4-Ethyl-5-(3-hydroxy-propyl)-4ry-[1,2,4]triazol-3-ylsulfanylmethylj-phenyl}-acetamide;
3-[4-Ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4 --[1 ,2,4]triazol-3-yl]-propan-1-ol;
3-[4-Ethyl-5-(2-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-propan-1-ol;
4-[4-Ethyl-5-(4-hydroxy-phenyI)-4/-/-[1,2,4]triazol-3-ylsulfanylmethylj-benzonitrile;
4-[5-(6-Chloro-benzo[1 ,3]dioxol-5-ylmethyIsulfanyl)-4-ethyl-4 .-[1,2,4]triazol-3-yl]-phenoI; 4-[5-(4-Bromo-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-phenol;
4-[4-Ethyl-5-(4-trifluoromethyl-benzylsulfanyI)-4H-[1 ,2,4]triazol-3-yl]-phenol;
4-(5-Benzylsulfanyl-4-ethyl-4H-[1 ,2,4]triazol-3-yl)-phenoI;
4-[4-Ethyl-5-(4-methanesulfonyl-benzylsuIfanyl)-4H-[1,2,4]triazol-3-ylj-phenol;
4-[4-Ethyl-5-(3-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol; 4-[4-Ethyl-5-(4-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsuIfanylmethyl]-benzoic acid methyl etser;
4-[5-(4-Benzyloxy-benzylsuIfanyl)-4-ethyl-4/--[1,2,4]triazol-3-yI]-phenol;
N-{4-[4-Ethyl-5-(4-hydroxy-phenyI)-4/--[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-acetamide;
4-[4-Ethyl-5-(4-methoxy-benzylsulfanyl)-4 -/-[1,2,4jtriazol-3-yl]-phenol;
4-[4-Ethyl-5-(5-methyI-2-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol; 4-[4-Ethyl-5-(2-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol;
4-[5-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-phenol; 3-Benzo[1,3]dioxol-5-yl-5-(2-chloro-benzylsuIfanyl)-4-ethyl-4H-[1,2,4]triazole;
4-(5-Benzo[1,3jdioxol-5-yl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile;
3-Benzo[1,3]dioxol-5-yl-5-(6-chloro-benzo[1,3]dioxol-5-ylmethyIsulfanyl)-4-ethyl-4H-
[1 ,2,4]triazole; 3-Benzo[1 ,3]dioxol-5-yI-5-(4-bromo-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4jtriazole;
4-[4-(5-Benzo[1,3]dioxol-5-yl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-phenylj-
[1 ,2,3]thiadiazole;
3-Benzo[1,3]dioxol-5-yl-5-cyclohexylmethylsulfanyI-4-ethyl-4H-[1 ,2,4]triazole;
3-Benzo[1,3]dioxol-5-yl-4-ethyl-5-(4-trifluoromethoxy-benzylsulfanyl)-4ry-[1,2,4]triazole; 3-Benzo[1 ,3]dioxol-5-yl-5-(3,5-dimethoxy-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazole;
3-Benzo[1,3]dioxol-5-yl-4-ethyl-5-(4-methanesulfonyI-benzylsulfanyl)-4H-[1,2,4]triazole;
4-(5-Benzo[1 ,3]dioxol-5-yl-4-ethyl-4 --[1 ,2,4jtriazoI-3-ylsulfanylmethyl)-benzoic acid methyl etser;
3-Benzo[1,3]dioxol-5-yl-5-(2,6-dichloro-benzylsulfanyl)-4-ethyI-4 -/-[1 ,2,4]triazole; 3-Benzo[1 ,3]dioxol-5-yl-5-(4-benzyloxy-benzylsuIfanyl)-4-ethyl-4 --[1 ,2,4]triazole;
N-[4-(5-Benzo[1,3]dioxol-5-yl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-phenyl]-acetamide;
3-Benzo[1,3]dioxol-5-yl-4-ethyl-5-(4-methoxy-benzylsulfanyl)-4H-[1,2,4]triazole;
3-Benzo[1,3]dioxol-5-yl-4-ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1,2,4]triazole;
3-Benzo[1,3]dioxol-5-yI-4-ethyl-5-(2-nitro-benzylsulfanyl)-4H-[1,2,4]triazole; 3-Benzo[1 ,3]dioxol-5-yl-5-(2,4-dichloro-benzyIsulfanyl)-4-ethyI-4H-[1 ,2,4]triazole;
4-[4-Ethyl-5-(2-phenoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
3-(6-Chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-5-(2-phenoxy-phenyl)-4 -/-
[1 ,2,4]triazole;
3-(3,4-Dichloro-benzyIsulfanyl)-4-ethyl-5-(2-phenoxy-phenyl)-4ry-[1,2,4]triazole; 3-(4-Bromo-benzylsulfanyI)-4-ethyl-5-(2-phenoxy-phenyl)-4 -/-[1,2,4]triazole;
4-{4-[4-Ethyl-5-(2-phenoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-
[1 ,2,3]thiadiazole;
3-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-5-(2-phenoxy-phenyl)-4H-[1 ,2,4]triazole;
4-Ethyl-3-(2-phenoxy-phenyl)-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1,2,4]triazole; 4-Ethyl-3-(4-methanesulfonyl-benzylsulfanyl)-5-(2-phenoxy-phenyl)-4H-[1,2,4]triazole;
4-[4-Ethyl-5-(2-phenoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser;
3-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-5-(2-phenoxy-phenyl)-4H-[1 ,2,4]triazole;
3-(4-Benzyloxy-benzylsuIfanyl)-4-ethyl-5-(2-phenoxy-phenyl)-4H-[1,2,4]triazole; 4-EthyI-3-(4-methyl-benzylsulfanyl)-5-(2-phenoxy-phenyl)-4H-[1 ,2,4]triazole;
4-EthyI-3-(2-phenoxy-phenyl)-5-(3-trifluoromethoxy-benzylsulfanyl)-4 .-[1,2,4]triazole; 4-Ethyl-3-(4-methoxy-benzylsulfanyl)-5-(2-phenoxy-phenyl)-4 -.-[1 ,2,4]triazole;
4-Ethyl-3-(2-nitro-benzylsulfanyl)-5-(2-phenoxy-phenyl)-4r/-[1,2,4]triazole;
3-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-5-(2-phenoxy-phenyl)-4H-[1,2,4]triazole;
3-Cyclohexylmethylsulfanyl-4-ethyl-5-naphthalen-1-yl-4 -/-[1,2,4]triazole; 4-Ethyl-3-naphthalen-1 -yl-5-(4-trifluoromethyl-benzylsulfanyl)-4/--[1 ,2,4]triazole;
4-Ethyl-3-(4-methanesulfonyl-benzylsulfanyl)-5-naphthalen-1-yl-4H-[1,2,4]triazole;
4-Ethyl-3-naphthalen-1-yI-5-(3-nitro-benzylsulfanyl)-4 --[1,2,4]triazole;
4-(4-Ethyl-5-naphthalen-1-yl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzoic acid methyl etser;
4-Ethyl-3-naphthalen-1-yI-5-(4-nitro-benzylsulfanyl)-4/L-[1,2,4]triazole; 3-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-5-naphthalen-1 -yl-4/-.-[1 ,2,4]triazole;
4-Ethyl-3-(4-methyl-benzylsulfanyl)-5-naphthalen-1-yl-4r/-[1,2,4]triazole;
4-EthyI-3-(4-methoxy-benzyIsulfanyl)-5-naphthalen-1-yI-4H-[1,2,4]triazole;
4-Ethyl-3-(5-methyl-2-nitro-benzylsulfanyl)-5-naphthalen-1-yl-4H-[1,2,4]triazole;
3-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-5-naphthalen-1-yl-4H-[1,2,4]triazole; [4-(5-Cyclohexylmethylsulfanyl-4-ethyl-4H-[1,2,4]triazol-3-yl)-phenyI]-dimethyl-amine
{4-[5-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazol-3-yl]-phenyl}-dimethyl-amine
{4-[4-Ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4 --[1,2,4]triazol-3-yl]-phenyl}-dimethyl-amine
4-[5-(4-Dimethylamino-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser; {4-[4-Ethyl-5-(4-nitro-benzylsulfanyl)-4H-[1,2,4]triazoI-3-yl]-phenyl}-dimethyl-amine;
{4-[4-Ethyl-5-(4-methoxy-benzylsulfanyl)-4/--[1,2,4]triazol-3-yl]-phenyl}-dimethyl-amine;
{4-[4-Ethyl-5-(5-methyI-2-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenyl}-dimethyl-amine;
{4-[5-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-4r -[1,2,4]triazol-3-yl]-phenyl}-dimethyl-amine;
4-(4-Ethyl-5-thiophen-2-yl-4ry-[1,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile; 3-(6-Chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-5-thiophen-2-yl-4ry-[1,2,4jtriazole;
3-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-5-thiophen-2-yl-4 .-[1 ,2,4]triazole;
3-(4-Bromo-benzylsulfanyl)-4-ethyl-5-thiophen-2-yl-4/- -[1,2,4]triazole;
4-[4-(4-Ethyl-5-thiophen-2-yl-4H-[1,2,4]triazoI-3-ylsulfanylmethyl)-phenylj-[1,2,3]thiadiazole;
4-Ethyl-3-thiophen-2-yl-5-(4-trifluoromethoxy-benzylsulfanyl)-4H-[1,2,4]triazole; 3-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-5-thiophen-2-yl-4-/-[1,2,4]triazole;
4-Ethyl-3-thiophen-2-yl-5-(4-trifluoromethyl-benzylsuIfanyl)-4/-/-[1 ,2,4]triazole;
3-Benzylsulfanyl-4-ethyl-5-thiophen-2-yl-4H-[1,2,4]triazole;
4-Ethyl-3-(4-methanesulfonyI-benzylsulfanyl)-5-thiophen-2-yl-4H-[1,2,4]triazole;
4-(4-EthyI-5-thiophen-2-yl-4H-[1 ,2,4]triazol-3-ylsulfanyImethyl)-benzoic acid methyl etser; 4-Ethyl-3-(4-nitro-benzylsulfanyl)-5-thiophen-2-yl-4H-[1,2,4]triazole;
3-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-5-thiophen-2-yl-4H-[1,2,4]triazole; 4-Ethyl-3-(4-methyl-benzylsulfanyl)-5-thiophen-2-yl-4H-[1 ,2,4]triazole;
4-Ethyl-3-(4-methoxy-benzylsulfanyl)-5-thiophen-2-yl-4H-[1,2,4]triazole;
4-Ethyl-3-(5-methyl-2-nitro-benzylsulfanyl)-5-thiophen-2-yl-4H-[1,2,4]triazole;
3-(2-Chloro-benzylsulfanyl)-4-ethyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazoIe; 3-(6-Chloro-benzo[1,3]dioxol-5-ylmethylsuIfanyl)-4-ethyl-5-(2-methoxy-phenyl)-4H-
[1 ,2,4]triazole;
4-Ethyl-3-(2-methoxy-phenyl)-5-(4-trifluoromethoxy-benzylsulfanyl)-4H-[1 ,2,4]triazole;
3-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-5-(2-methoxy-phenyl)-4 -/-[1,2,4]triazole;
4-Ethyl-3-(2-methoxy-phenyl)-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1,2,4]triazole; 3-Benzylsulfanyl-4-ethyI-5-(2-methoxy-phenyl)-4/.-[1,2,4jtriazole;
4-Ethyl-3-(4-methanesulfonyl-benzylsulfanyl)-5-(2-methoxy-phenyl)-4 --[1,2,4]triazole;
4-[4-Ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazoI-3-ylsulfanylmethyI]-benzoic acid methyl etser;
4-EthyI-3-(2-methoxy-phenyl)-5-(4-nitro-benzylsulfanyl)-4 -/-[1,2,4]triazole; 3-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4jtriazole;
3-(4-Benzyloxy-benzylsulfanyl)-4-ethyl-5-(2-methoxy-phenyl)-4ry-[1,2,4]triazole;
4-EthyI-3-(2-methoxy-phenyl)-5-(4-methyl-benzylsulfanyl)-4 --[1,2,4]triazole;
4-Ethyl-3-(2-methoxy-phenyl)-5-(3-trifluoromethoxy-benzylsulfanyl)-4 .-[1,2,4]triazole;
4-Ethyl-3-(2-methoxy-phenyl)-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1,2,4]triazole; 4-Ethyi-3-(2-methoxy-phenyl)-5-(2-nitro-benzylsulfanyl)-4H-[1,2,4]triazoie;
3-(2-Chloro-benzylsulfanyl)-4-ethyl-5-(4-methoxy-phenyl)-4 --[1 ,2,4]triazole;
4-[4-EthyI-5-(4-methoxy-phenyl)-4/- -[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
3-(6-Chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-5-(4-methoxy-phenyl)-4H-
[1 ,2,4]triazole; 3-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-5-(4-methoxy-phenyl)-4H-[1 ,2,4]triazole;
3-(4-Bromo-benzylsulfanyl)-4-ethyl-5-(4-methoxy-phenyl)-4 --[1,2,4]triazole;
4-{4-[4-Ethyl-5-(4-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-
[1 ,2,3]thiadiazoIe;
3-CycIohexylmethylsulfanyl-4-ethyl-5-(4-methoxy-phenyl)-4H-[1,2,4]triazole; 4-Ethyl-3-(4-methoxy-phenyl)-5-(4-trifluoromethyl-benzylsulfanyl)-4 --[1,2,4]triazole;
4-Ethyl-3-(4-methanesulfonyl-benzylsulfanyl)-5-(4-methoxy-phenyl)-4H-[1,2,4]triazole;
4-[4-Ethyl-5-(4-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyImethyl]-benzoic acid methyl etser;
3-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-5-(4-methoxy-phenyl)-4r -[1 ,2,4]triazole; 3-(4-Benzyloxy-benzylsuIfanyl)-4-ethyl-5-(4-methoxy-phenyl)-4 .-[1,2,4]triazole;
4-Ethyl-3-(4-methoxy-phenyl)-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-[1,2,4]triazoIe; N-{4-[4-Ethyl-5-(4-methoxy-phenyl)-4 --[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-acetamide;
4-Ethyl-3-(4-methoxy-benzylsulfanyl)-5-(4-methoxy-phenyl)-4 --[1 ,2,4jtriazole;
4-EthyI-3-(4-methoxy-phenyl)-5-(2-nitro-benzyIsulfanyl)-4H-[1,2,4]triazole;
4-(4-Ethyl-5-pyridin-4-yl-4/--[1,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile; 4-[5-(4-Bromo-benzylsulfanyl)-4-ethyl-4/L/-[1 ,2,4]triazol-3-yl]-pyridine;
4-[5-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-pyridine;
4-[4-Ethyl-5-(4-methanesulfonyl-benzylsulfanyI)-4/--[1,2,4]triazol-3-yl]-pyridine;
4-(4-Ethyl-5-pyridin-4-yl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzoic acid methyl etser;
4-[4-Ethyl-5-(4-methyl-benzyIsulfanyl)-4H-[1,2,4jtriazol-3-yl]-pyridine; 4-[4-Ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4 -/-[1,2,4]triazol-3-yl]-pyridine;
4-[5-(2,4-Dichloro-benzylsulfanyI)-4-ethyl-4 -/-[1,2,4]triazol-3-yl]-pyridine;
3-[5-(2-Chloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-pyridine;
4-(4-Ethyl-5-pyridin-3-yI-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile;
3-[5-(6-Chloro-benzo[1 ,3]dioxol-5-ylmethylsulfanyl)-4-ethyI-4 -/-[1,2,4]triazol-3-yl]-pyridine; 3-[5-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazol-3-yl]-pyridine;
3-[5-(4-Bromo-benzylsulfanyl)-4-ethyl-4 -/-[1,2,4]triazol-3-yl]-pyridine;
3-[4-Ethyl-5-(4-[1,2,3]thiadiazol-4-yl-benzylsulfanyl)-4rV-[1,2,4]triazol-3-yl]-pyridine;
3-[4-Ethyl-5-(4-trifluoromethoxy-benzylsulfanyl)-4 --[1,2,4]triazol-3-yl]-pyridine;
3-[5-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-4H-[1,2,4jtriazol-3-yl]-pyridine; 3-[4-Ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1,2,4jtriazol-3-ylJ-pyridine;
3-(5-Benzylsulfanyl-4-ethyl-4H-[1 ,2,4]triazol-3-yl)-pyridine;
3-[4-Ethyl-5-(4-methanesulfonyI-benzylsulfanyl)-4 -.-[1,2,4]triazol-3-ylj-pyridine;
3-[4-EthyI-5-(3-nitro-benzylsuIfanyl)-4 -/-[1 ,2,4]triazoI-3-yl]-pyridine;
4-(4-Ethyl-5-pyridin-3-yl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzoic acid methyl etser; 3-[5-(2,6-DichIoro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-pyridine;
3-[5-(4-BenzyIoxy-benzylsulfanyl)-4-ethyl-4 --[1 ,2,4]triazol-3-yl]-pyridine;
3-[4-Ethyl-5-(4-methyl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine;
3-[4-Ethyl-5-(3-trifluoromethoxy-benzylsulfanyI)-4/--[1 ,2,4]triazol-3-yl]-pyridine;
N-[4-(4-Ethyl-5-pyridin-3-yl-4/--[1 ,2,4]triazol-3-ylsulfanylmethyl)-phenyl]-acetamide; 3-[4-Ethyl-5-(4-methoxy-benzylsulfanyl)-4/-/-[1,2,4]triazol-3-yl]-pyridine;
3-[4-Ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4/-/-[1 ,2,4]triazol-3-yl]-pyridine;
3-[4-Ethyl-5-(2-nitro-benzylsulfanyl)-4/- -[1,2,4]triazol-3-ylj-pyridine;
3-[5-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazoI-3-yl]-pyridine;
3-(2-Chloro-benzylsulfanyl)-5-(4-chloro-phenyl)-4-ethyI-4ry-[1 ,2,4]triazole; 4-[5-(4-Chloro-phenyl)-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
3-(4-Chloro-phenyl)-5-(3,4-dichloro-benzyIsulfanyl)-4-ethyl-4H-[1,2,4]triazole; 4-{4-[5-(4-Chloro-phenyl)-4-ethyI-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-
[1 ,2,3]thiadiazole;
3-(4-Chloro-phenyl)-4-ethyl-5-(4-methanesulfonyl-benzylsulfanyl)-4H-[1,2,4jtriazole;
3-(4-Chloro-phenyl)-4-ethyl-5-(3-nitro-benzylsulfanyl)-4H-[1,2,4]triazole; 4-[5-(4-Chloro-phenyl)-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser;
3-(4-Chloro-phenyl)-5-(2,6-dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazole;
3-(4-Benzyloxy-benzylsulfanyl)-5-(4-chloro-phenyl)-4-ethyl-4H-[1,2,4]triazole;
3-(4-Chloro-phenyl)-4-ethyl-5-(4-methyl-benzylsulfanyl)-4H-[1,2,4jtriazole;
3-(4-Chloro-phenyl)-4-ethyl-5-(3-trifluoromethoxy-benzylsulfanyI)-4H-[1,2,4]triazoIe; N-{4-[5-(4-Chloro-phenyl)-4-ethyl-4H-[1,2,4jtriazol-3-ylsulfanylmethyl]-phenyl}-acetamide;
3-(4-Chloro-phenyl)-4-ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4 --[1,2,4]triazole;
3-(4-Chloro-phenyl)-5-(2,4-dichloro-benzylsulfanyl)-4-ethyl-4/-/-[1,2,4]triazole;
5-[5-(2-Chloro-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazol-3-yl]-4-phenyl-[1,2,3]thiadiazole;
4-[4-Ethyl-5-(4-phenyl-[1,2,3]thiadiazol-5-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile; 5-[5-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-4 -/-[1,2,4]triazol-3-yl]-4-phenyl-[1,2,3]thiadiazole;
5-[4-Ethyl-5-(4-trifluoromethoxy-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-4-phenyl-
[1 ,2,3]thiadiazole;
5-[5-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyI-4/-/-[1,2,4]triazol-3-yl]-4-phenyl-[1,2,3]thiadiazole;
5-[4-Ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-4-phenyl- [1 ,2,3]thiadiazole;
5-(5-BenzylsulfanyI-4-ethyl-4H-[1,2,4]triazol-3-yl)-4-phenyl-[1,2,3]thiadiazole;
5-[4-Ethyl-5-(4-methanesulfonyl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-4-phenyl-
[1 ,2,3]thiadiazole;
5-[4-Ethyl-5-(4-nitro-benzyIsulfanyl)-4H-[1,2,4]triazol-3-yl]-4-phenyl-[1 ,2,3]thiadiazole; 5-[5-(2,6-Dichloro-benzylsuIfanyl)-4-ethyI-4H-[1,2,4]triazol-3-yl]-4-phenyl-[1 ,2,3]thiadiazole;
5-[4-Ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4ry-[1 ,2,4]triazol-3-yl]-4-phenyI-
[1 ,2,3]thiadiazole;
5-[4-Ethyl-5-(4-methoxy-benzyIsulfanyl)-4 -/-[1,2,4jtriazol-3-yl]-4-phenyl-[1,2,3]thiadiazole;
5-[4-Ethyl-5-(2-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-4-phenyl-[1 ,2,3]thiadiazole; 4-{5-[4-(2,5-Dimethyl-pyrrol-1 -yl)-phenyl]-4-ethyl-4/-/-[1 ,2,4]triazol-3-ylsulfanylmethyl}- benzonitrile;
3-(6-Chloro-benzo[1,3]dioxoI-5-ylmethylsulfanyI)-5-[4-(2,5-dimethyl-pyrrol-1-yl)-phenyl]-4- ethyl-4H-[1,2,4]triazole;
3-(3,4-Dichloro-benzylsulfanyl)-5-[4-(2,5-dimethyl-pyrrol-1-yl)-phenyI]-4-ethyl-4H- [1 ,2,4]triazole; 3-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-5-(4-trifluoromethoxy-benzylsulfanyl)-4H-
[1 ,2,4]triazole;
3-(3,5-Dimethoxy-benzylsulfanyl)-5-[4-(2,5-dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-4/--
[1 ,2,4]triazole; 3-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4H-
[1 ,2,4]triazole;
3-Benzylsulfanyl-5-[4-(2,5-dimethyl-pyrrol-1-yI)-phenyl]-4-ethyl-4H-[1,2,4]triazole;
3-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-5-(4-methanesulfonyl-benzylsulfanyl)-4H-
[1 ,2,4]triazole; 3-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-5-(3-nitro-benzylsuIfanyl)-4H-[1,2,4]triazole;
4-{5-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl}-benzoic acid methyl etser;
3-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-5-(4-nitro-benzylsulfanyl)-4 .-[1,2,4]triazole;
3-(4-Benzyloxy-benzylsulfanyl)-5-[4-(2,5-dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-4H- [1,2,4]triazole;
N-(4-{5-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenylj-4-ethyl-4/-/-[1,2,4]triazol-3-ylsulfanylmethyl}- phenyl)-acetamide;
3-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-5-(4-methoxy-benzylsulfanyl)-4 --[1,2,4]triazole;
3-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H- [1,2,4]triazole;
3-[4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-4-ethyl-5-(2-nitro-benzylsulfanyl)-4/--[1 ,2,4]triazole;
3-(2,4-Dichloro-benzylsulfanyl)-5-[4-(2,5-dimethyI-pyrrol-1-yl)-phenyl]-4-ethyl-4H-
[1 ,2,4]triazole;
3-Benzo[b]thiophen-2-yl-5-(2-chloro-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazole; 4-(5-Benzo[b]thiophen-2-yl-4-ethyl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile;
3-Benzo[b]thiophen-2-yl-5-(6-chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-4/--
[1 ,2,4]triazole;
3-Benzo[bjthiophen-2-yl-5-(4-bromo-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazole;
4-[4-(5-Benzo[b]thiophen-2-yl-4-ethyl-4 .-[1,2,4]triazol-3-ylsulfanylmethyl)-phenyl]- [1,2,3]thiadiazole;
3-Benzo[bjthiophen-2-yl-4-ethyl-5-(3-nitro-benzylsulfanyl)-4 .-[1,2,4]triazole;
4-(5-Benzo[b]thiophen-2-yI-4-ethyl-4/-/-[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzoic acid methyl etser;
3-Benzo[b]thiophen-2-yl-4-ethyl-5-(4-nitro-benzylsulfanyl)-4H-[1,2,4]triazole; 3-Benzo[b]thiophen-2-yl-5-(4-benzyloxy-benzyIsulfanyl)-4-ethyl-4H-[1,2,4]triazole;
3-Benzo[b]thiophen-2-yl-4-ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-[1,2,4]triazole; N-[4-(5-Benzo[b]thiophen-2-yl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-phenyl]-acetamide;
3-Benzo[b]thiophen-2-yl-4-ethyl-5-(4-methoxy-benzylsulfanyl)-4H-[1,2,4]triazole;
3-Benzo[b]thiophen-2-yl-4-ethyl-5-(2-nitro-benzylsulfanyl)-4H-[1,2,4]triazole;
3-(2-Chloro-benzylsulfanyl)-4-ethyl-5-(1-phenyl-5-trifluoromethyl-1H-pyrazol-4-yl)-4H- [1,2,4]triazole;
3-(6-Chloro-benzo[1,3jdioxol-5-ylmethylsulfanyl)-4-ethyl-5-(1-phenyl-5-trifluoromethyl-1H- pyrazol-4-yl)-4r/-[1,2,4]triazole;
4-{4-[4-Ethyl-5-(1 -phenyl-5-trifluoromethyl-1 tf-pyrazol-4-yl)-4H-[1 ,2,4] triazol-3- ylsulfanylmethyl]-phenyl}-[1,2,3]thiadiazole; 4-Ethyl-3-(1-phenyl-5-trifluoromethyl-1ry-pyrazol-4-yl)-5-(4-trifluoromethoxy-benzylsulfanyl)-
4H-[1,2,4]triazole;
3-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-5-(1-phenyl-5-trifluoromethyl-1ry-pyrazol-4-yl)-4/--
[1 ,2,4]triazole;
3-Benzylsulfanyl-4-ethyl-5-(1 -phenyl-5-trifluoromethyl-1 H-pyrazol-4-yl)-4H-[1 ,2,4]triazole; 4-Ethyl-3-(4-methanesulfonyl-benzylsulfanyl)-5-(1-phenyl-5-trifluoromethyl-1H-pyrazol-4-yl)-
4H-[1,2,4]triazole;
4-Ethyl-3-(3-nitro-benzylsulfanyl)-5-(1-phenyl-5-trifluoromethyl-1H-pyrazol-4-yl)-4H-
[1 ,2,4]triazole;
4-[4-Ethyl-5-(1-phenyl-5-trifluoromethyl-1H-pyrazol-4-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethylj- benzoic acid methyl etser;
3-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-5-(1-phenyl-5-trifluoromethyl-1H-pyrazol-4-yl)-4ry-
[1 ,2,4]triazole;
3-(4-Benzyloxy-benzylsulfanyl)-4-ethyl-5-(1-phenyl-5-trifluoromethyl-1/- -pyrazol-4-yl)-4 --
[1 ,2,4]triazole; 4-Ethyl-3-(4-methyl-benzylsulfanyl)-5-(1 -phenyl-5-trifluoromethyl-1 H-pyrazoi-4-yl)-4H-
[1 ,2,4]triazole;
N-{4-[4-Ethyl-5-(1 -phenyl-5-trifluoromethyl-1 H-pyrazol-4-yl)-4r.-[1 ,2,4jtriazol-3- ylsulfanylmethyl]-phenyl}-acetamide;
4-Ethyl-3-(5-methyl-2-nitro-benzylsulfanyl)-5-(1-phenyl-5-trifluoromethyl-1H-pyrazol-4-yl)-4H- [1 ,2,4]triazole;
4-Ethyl-3-(2-nitro-benzylsulfanyl)-5-(1-phenyl-5-trifluoromethyl-1 --pyrazol-4-yl)-4H-
[1 ,2,4]triazole;
3-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-5-(1-phenyl-5-trifluoromethyl-1ry-pyrazol-4-yI)-4H-
[1 ,2,4]triazole; 3-(2-Chloro-benzylsulfanyI)-5-(3-chloro-4-methyl-thiophen-2-yl)-4-ethyl-4f.-[1,2,4]triazole; 4-[5-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-4 -/-[1 ,2,4]triazol-3-ylsulfanylmethylj- benzonitrile;
3-(3-Chloro-4-methyl-thiophen-2-yl)-5-(3,4-dichloro-benzylsulfanyl)-4-ethyl-4 .-[1,2,4]triazole;
4-{4-[5-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}- [1,2,3]thiadiazole;
3-(3-Chloro-4-methyl-thiophen-2-yl)-5-cyclohexylmethylsulfanyl-4-ethyl-4H-[1,2,4]triazoIe;
3-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-5-(4-trifluoromethoxy-benzylsulfanyl)-4H-
[1 ,2,4]triazole;
3-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4 -- [1,2,4]triazole;
3-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-5-(3-nitro-benzylsulfanyl)-4 --[1 ,2,4]triazole;
4-[5-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-4 -/-[1,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser;
3-(3-Chloro-4-methyl-thiophen-2-yl)-5-(2,6-dichloro-benzylsulfanyl)-4-ethyl-4 .-[1,2,4]triazole; 3-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-5-(4-methyl-benzylsulfanyl)-4H-[1,2,4]triazole;
3-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-
[1 ,2,4]triazole;
3-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-
[1 ,2,4]triazole; 3-(3-Chloro-4-methyl-thiophen-2-yl)-4-ethyl-5-(2-nitro-benzylsuIfanyl)-4H-[1,2,4]triazole;
4-(4-Ethyl-5-pyridin-2-yl-4 -/-[1,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile;
2-[5-(6-Chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-4/-/-[1,2,4]triazol-3-yl]-pyridine
2-[5-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-4r -[1,2,4]triazol-3-yl]-pyridine;
2-[5-(4-Bromo-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-pyridine; 2-[4-Ethyl-5-(4-[1 ,2,3]thiadiazol-4-yl-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-pyridine;
2-[5-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-pyridine;
2-[4-Ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine;
2-[4-Ethyl-5-(4-methanesulfonyI-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-pyridine;
2-[4-Ethyl-5-(3-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine; 4-(4-Ethyl-5-pyridin-2-yl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzoic acid methyl etser;
2-[4-Ethyl-5-(4-nitro-benzylsulfanyl)-4/L/-[1,2,4]triazol-3-yl]-pyridine;
2-[5-(4-Benzyloxy-benzylsulfanyl)-4-ethyl-4 -/-[1,2,4]triazol-3-yl]-pyridine;
2-[4-Ethyl-5-(4-methyl-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-pyridine;
2-[4-Ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine; 2-[4-Ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine;
2-[4-EthyI-5-(2-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine; 3-[5-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-4 --[1,2,4]triazol-3-yl]-2-methylsulfanyl-pyridine;
3-[4-Ethyl-5-(4-[1,2,3]thiadiazol-4-yl-benzylsulfanyl)-4r -[1,2,4]triazol-3-yl]-2-methylsulfanyl- pyridine;
3-(5-Cyclohexylmethylsulfanyl-4-ethyl-4ry-[1,2,4]triazol-3-yl)-2-methylsulfanyl-pyridine; 3-[4-Ethyl-5-(4-trifluoromethoxy-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-2-methylsulfanyl- pyridine;
3-[5-(3,5-Dimethoxy-benzyIsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-2-methylsulfanyl-pyridine;
3-[4-Ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4ry-[1,2,4]triazol-3-yl]-2-methylsulfanyl-pyridine;
3-(5-Benzylsulfanyl-4-ethyl-4H-[1 ,2,4]triazol-3-yl)-2-methylsulfanyl-pyridine; 3-[4-Ethyl-5-(4-methanesulfonyl-benzylsulfanyl)-4/-/-[1 ,2,4]triazol-3-yl]-2-methylsulfanyl- pyridine;
4-[4-Ethyl-5-(2-methylsulfanyl-pyridin-3-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser;
3-[5-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-4/-/-[1,2,4]triazol-3-yl]-2-methylsulfanyl-pyridine; 3-[5-(4-Benzyloxy-benzylsulfanyl)-4-ethyl-4 -/-[1,2,4]triazol-3-yl]-2-methylsulfanyl-pyridine;
3-[4-Ethyl-5-(4-methyl-benzylsulfanyl)-4ry-[1,2,4]triazol-3-yl]-2-methylsulfanyl-pyridine;
3-[4-Ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-2-methylsulfanyl- pyridine;
N-{4-[4-Ethyl-5-(2-methylsulfanyl-pyridin-3-yl)-4/.-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}- acetamide;
3-[4-Ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-2-methylsulfanyl-pyridine;
3-[4-Ethyl-5-(2-nitro-benzylsulfanyl)-4 -/-[1,2,4]triazol-3-yl]-2-methylsulfanyl-pyridine;
3-(2-Chloro-benzylsulfanyl)-4-ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazole;
4-[4-Ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile; 3-(6-Chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-5-(5-methyl-thiophen-2-yl)-4H-
[1,2,4]triazole;
3-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1 ,2,4]triazole;
4-{4.[4-Methyl-5-(5-methyl-thiophen-2-yl)-4ry-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyI}-
[1,2,3jthiadiazole; 3-Cyclohexylmethylsulfanyl-4-ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazole;
4-Ethyl-3-(5-methyl-thiophen-2-yl)-5-(4-trifluoromethoxy-benzylsulfanyl)-4H-[1,2,4]triazole;
3-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazole;
4-EthyI-3-(5-methyl-thiophen-2-yl)-5-(4-trifluoromethyl-benzylsuIfanyl)-4H-[1,2,4]triazole;
3-Benzylsulfanyl-4-ethyl-5-(5-methyl-thiophen-2-yl)-4 .-[1,2,4]triazole; 4-Ethyl-3-(4-methanesulfonyl-benzylsulfanyl)-5-(5-methyl-thiophen-2-yl)-4rV-[1,2,4]triazole;
4-Ethyl-3-(5-methyl-thiophen-2-yl)-5-(3-nitro-benzylsulfanyl)-4/-/-[1,2,4jtriazole; 4-[4-Ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethylj-benzoic acid methyl etser;
4-Ethyl-3-(5-methyl-thiophen-2-yl)-5-(4-nitro-benzylsulfanyl)-4H-[1,2,4]triazole;
3-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazole; 4-Ethyl-3-(4-methyl-benzylsulfanyl)-5-(5-methyl-thiophen-2-yl)-4/-.-[1 ,2,4]triazole;
N-{4-[4-Ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazol-3-ylsuIfanylmethyl]-phenyl}- acetamide;
4-Ethyl-3-(4-methoxy-benzylsulfanyl)-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazole;
4-Ethyl-3-(5-methyl-thiophen-2-yl)-5-(2-nitro-benzylsulfanyl)-4 --[1,2,4]triazole; 3-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-5-(5-methyl-thiophen-2-yl)-4H-[1,2,4]triazole;
4-[5-(5-Chloro-thiophen-2-yl)-4-ethyl-4/--[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
3-(5-Chloro-thiophen-2-yl)-5-(3,4-dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazole;
3-(4-Bromo-benzylsulfanyl)-5-(5-chloro-thiophen-2-yl)-4-ethyl-4ry-[1,2,4]triazole;
4-{4-[5-(5-Chloro-thiophen-2-yl)-4-ethyl-4 -/-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}- [1,2,3]thiadiazole;
3-(5-Chloro-thiophen-2-yl)-5-cyclohexylmethylsulfanyl-4-ethyl-4 --[1,2,4]triazole;
3-(5-Chloro-thiophen-2-yl)-4-ethyl-5-(4-trifluoromethoxy-benzylsulfanyl)-4H-[1,2,4]triazole;
3-(5-Chloro-thiophen-2-yl)-5-(3,5-dimethoxy-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazole;
3-(5-Chloro-thiophen-2-yl)-4-ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1,2,4]triazole; 3-(5-Chloro-thiophen-2-yl)-4-ethyl-5-(3-nitro-benzylsulfanyl)-4ry-[1,2,4]triazole;
4-[5-(5-Chloro-thiophen-2-yl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser;
3-(5-Chloro-thiophen-2-yl)-5-(2,6-dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazole;
3-(5-Chloro-thiophen-2-yl)-4-ethyl-5-(4-methyl-benzylsulfanyl)-4H-[1,2,4jtriazole; 3-(5-Chloro-thiophen-2-yl)-4-ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-[1,2,4]triazole;
N-{4-[5-(5-Chloro-thiophen-2-yl)-4-ethyl-4 .-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}- acetamide;
3-(5-Chloro-thiophen-2-yl)-4-ethyl-5-(4-methoxy-benzylsulfanyl)-4H-[1,2,4]triazole;
3-(5-Chloro-thiophen-2-yl)-4-ethyl-5-(5-methyl-2-nitro-benzylsuIfanyl)-4H-[1,2,4]triazole; 3-(5-Chloro-thiophen-2-yl)-4-ethyl-5-(2-nitro-benzylsulfanyl)-4H-[1,2,4]triazole;
3-(5-Chloro-thiophen-2-yl)-5-(2,4-dichloro-benzylsulfanyl)-4-ethyl-4 .-[1,2,4]triazole;
4-[4-Ethyl-5-(1H-indol-3-yImethyl)-4ry-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
3-[5-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-ylmethyl]-1r/-indole;
3-[5-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-4 .-[1,2,4]triazol-3-ylmethyl]-1H-indole; 3-[4-Ethyl-5-(4-methanesulfonyl-benzylsulfanyl)-4/-/-[1 ,2,4]triazol-3-ylmethyl]-1 /- -indole;
3-[4-Ethyl-5-(3-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-ylmethyl]-1H-indole; 3-[4-Ethyl-5-(4-nitro-benzylsulfanyl)-4/-/-[1 ,2,4]triazol-3-ylmethylj-1H-indole;
3-[5-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-4r.-[1,2,4]triazol-3-ylmethyl]-1H-indole;
3-[5-(4-Benzyloxy-benzylsulfanyl)-4-ethyl-4W-[1,2,4]triazol-3-ylmethyl]-1 /--indole;
3-[4-Ethyl-5-(3-trifluoromethoxy-benzylsulfanyI)-4H-[1,2,4]triazol-3-ylmethyl]-1H-indole; N-{4-[4-Ethyl-5-(1A.-indol-3-ylmethyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-acetamide;
3-[4-Ethyl-5-(4-methoxy-benzylsulfanyl)-4H-[1,2,4]triazol-3-ylmethyl]-1H-indole;
3-[4-Ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-ylmethyl]-1H-indole;
3-[4-Ethyl-5-(2-nitro-benzylsulfanyI)-4H-[1,2,4]triazol-3-ylmethyI]-1/-/-indole;
3-[5-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-ylmethyl]-1H-indole; 2-[5-(6-Chloro-benzo[1,3]dioxol-5-ylmethylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-phenol;
2-[4-Ethyl-5-(4-[1,2,3]thiadiazol-4-yl-benzylsulfanyl)-4/-/-[1,2,4]triazol-3-yl]-phenol;
2-(5-Cyclohexylmethylsulfanyl-4-ethyl-4H-[1,2,4]triazol-3-yl)-phenol;
2-[5-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-4/- -[1,2,4]triazol-3-yl]-phenol;
2-[4-Ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol; 2-(5-Benzylsulfanyl-4-ethyl-4H-[1 ,2,4]triazol-3-yl)-phenol;
2-[4-Ethyl-5-(4-methanesulfonyl-benzylsuIfanyl)-4H-[1 ,2,4]triazol-3-yl]-phenol;
2-[4-Ethyl-5-(3-nitro-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-phenol;
4-[4-Ethyl-5-(2-hydroxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-benzoic acid methyl etser;
2-[4-Ethyl-5-(4-nitro-benzylsulfanyl)-4/.-[1,2,4]triazol-3-yl]-phenol; 2-[5-(2,6-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-phenol;
2-[4-Ethyl-5-(4-methyl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol;
2-[4-Ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-phenol;
N-{4-[4-Ethyl-5-(2-hydroxy-phenyl)-4/-/-[1,2,4]triazol-3-ylsulfanylmethyl]-phenyl}-acetamide;
2-[4-Ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4/-/-[1,2,4]triazol-3-yl]-phenol; 2-[4-Ethyl-5-(2-nitro-benzylsulfanyl)-4/-/-[1,2,4]triazol-3-yl]-phenol;
2-[5-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazoI-3-yl]-phenol;
5-[5-(3,4-Dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-4-methyl-[1,2,3]thiadiazole;
5-[5-(4-Bromo-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-4-methyl-[1,2,3]thiadiazole;
5-(5-CycIohexylmethylsulfanyl-4-ethyl-4H-[1,2,4]triazol-3-yl)-4-methyl-[1,2,3]thiadiazole; 5-[5-(3,5-Dimethoxy-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-4-methyl-[1,2,3]thiadiazole;
5-(5-Benzylsulfanyl-4-ethyl-4H-[1,2,4]triazol-3-yl)-4-methyl-[1 ,2,3]thiadiazole;
5-[4-Ethyl-5-(3-nitro-benzylsuIfanyl)-4H-[1,2,4jtriazol-3-yl]-4-methyl-[1,2,3]thiadiazole;
4-[4-Ethyl-5-(4-methyl-[1,2,3]thiadiazol-5-yl)-4/- -[1,2,4]triazol-3-ylsuIfanylmethylj-benzoic acid methyl etser; 5-[4-Ethyl-5-(4-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-4-methyl-[1,2,3]thiadiazole;
5-[5-(4-Benzyloxy-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazol-3-yl]-4-methyl-[1,2,3]thiadiazole; 5-[4-Ethyl-5-(4-methyl-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-4-methyl-[1,2,3]thiadiazole;
5-[4-Ethyl-5-(3-trifluoromethoxy-benzylsulfanyl)-4ry-[1,2,4]triazol-3-yI]-4-methyl-
[1 ,2,3]thiadiazole;
5-[4-Ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1,2,4]triazol-3-yl]-4-methyl- [1 ,2,3]thiadiazole;
5-[5-(2,4-Dichloro-benzylsulfanyl)-4-ethyl-4 -[1,2,4]triazol-3-yl]-4-methyl-[1,2,3]thiadiazole;
4-(5-Benzyl-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile;
3-Benzyl-5-(3,4-dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazole;
4-[4-(5-Benzyl-4-ethyl-4r -[1,2,4]triazol-3-ylsulfanylmethyl)-phenyl]-[1,2,3]thiadiazole; 3-Benzyl-5-(3,5-dimethoxy-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazole;
3-Benzyl-4-ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1 ,2,4]triazole;
3-Benzyl-5-benzylsulfanyl-4-ethyl-4H-[1,2,4]triazole;
3-Benzyl-5-(2,6-dichloro-benzylsulfanyl)-4-ethyl-4rV-[1,2,4]triazole;
3-Benzyl-4-ethyl-5-(4-methyl-benzylsulfanyl)-4H-[1 ,2,4jtriazole; 3-Benzyl-4-ethyl-5-(4-methoxy-benzylsulfanyl)-4H-[1 ,2,4]triazole;
3-Benzyl-4-ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1,2,4jtriazole;
3-Benzyl-4-ethyl-5-(2-nitro-benzylsulfanyl)-4H-[1,2,4]triazole;
3-Benzyl-5-(2,4-dichloro-benzylsulfanyl)-4-ethyl-4A7-[1,2,4]triazole;
3-(2-Bromo-phenyl)-5-(2-chloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazole; 4-[5-(2-Bromo-phenyl)-4-ethyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
3-(2-Bromo-phenyl)-5-(6-chloro-benzo[1 ,3]dioxol-5-ylmethylsuIfanyl)-4-ethyl-4 -/-[1,2,4]triazole;
3-(2-Bromo-phenyl)-5-(3,4-dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazole;
3-(2-Bromo-phenyl)-5-cyclohexylmethylsuIfanyl-4-ethyl-4H-[1,2,4]triazole;
3-(2-Bromo-phenyl)-4-ethyl-5-(4-trifluoromethoxy-benzylsulfanyl)-4/-/-[1,2,4]triazole; 3-(2-Bromo-phenyl)-5-(3,5-dimethoxy-benzylsulfanyl)-4-ethyl-4H-[1 ,2,4]triazole;
3-(2-Bromo-phenyl)-4-ethyl-5-(4-trifluoromethyl-benzylsulfanyl)-4H-[1,2,4]triazole;
3-(2-Bromo-phenyl)-4-ethyl-5-(3-nitro-benzylsulfanyl)-4H-[1,2,4]triazole;
3-(4-Benzyloxy-benzylsuIfanyl)-5-(2-bromo-phenyl)-4-ethyl-4 -/-[1,2,4]triazole;
3-(2-Bromo-phenyl)-4-ethyl-5-(4-methoxy-benzylsulfanyl)-4H-[1,2,4]triazole; 3-(2-Bromo-phenyl)-4-ethyl-5-(5-methyl-2-nitro-benzylsulfanyl)-4H-[1,2,4]triazole;
3-(2-Bromo-phenyl)-5-(2,4-dichloro-benzylsulfanyl)-4-ethyl-4H-[1,2,4]triazole;
2-[4-(3-Methoxy-propyl)-5-(1-methyl-piperidin-2-yl)-4H-[1,2,4]triazol-3-ylsuIfanylmethyIj- benzonitrile;
2-[4-(3-Methoxy-propyl)-5-(1-methyl-piperidin-2-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]- pyridine;
2-[5-(2-Methoxy-ethylsulfanyl)-4-(3-methoxy-propyl)-4H-[1,2,4]triazol-3-yl]-1-methyl-piperidine; 2-[4-(2-Methoxy-ethyl)-5-(1-methyl-piperidin-2-yl)-4/-/-[1,2,4]triazol-3-ylsulfanylmethyl]- benzonitrile;
2-[4-(2-Methoxy-ethyl)-5-(1-methyl-piperidin-2-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-pyridine;
2-[4-(2-Methoxy-ethyl)-5-(2-methoxy-ethylsulfanyl)-4H-[1,2,4jtriazol-3-yl]-1-methyl-piperidine; 2-[4-Cyclopropyl-5-(1-methyl-piperidin-2-yl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
2-[4-Cyclopropyl-5-(1-methyl-piperidin-2-yl)-4ry-[1,2,4jtriazol-3-ylsulfanylmethyl]-pyridine;
2-[4-Cyclopropyl-5-(2-methoxy-ethylsulfanyl)-4ry-[1,2,4]triazol-3-yl]-1-methyl-piperidine;
2-[5-(1-Methyl-piperidin-2-yl)-4-(2-piperidin-1-yl-ethyl)-4H-[1,2,4]triazol-3-ylsulfanylmethylj- benzonitrile; 2-[5-(1-Methyl-piperidin-2-yl)-4-(2-piperidin-1-yl-ethyl)-4 .-[1,2,4]triazol-3-ylsulfanylmethyl]- pyridine;
2-[4-Cyclopropylmethyl-5-(1-methyl-piperidin-2-yl)-4/-/-[1,2,4]triazol-3-ylsulfanylmethyl]- benzonitrile;
2-[4-Cyclopropylmethyl-5-(1-methyl-piperidin-2-yI)-4ry-[1,2,4]triazol-3-ylsulfanylmethylj- pyridine;
2-[4-Cyclopropylmethyl-5-(2-methoxy-ethylsulfanyl)-4H-[1,2,4]triazol-3-ylj-1-methyl-piperidine;
2-[5-(2-Hydroxy-phenyl)-4-(3-methoxy-propyl)-4H-[1,2,4]triazol-3-ylsuIfanylmethylj- benzonitrile;
2-[4-(3-Methoxy-propyl)-5-(pyridin-2-ylmethylsulfanyl)-4 V-[1,2,4]triazol-3-yl]-phenol; 2-[5-(2-Methoxy-ethylsulfanyl)-4-(3-methoxy-propyl)-4H-[1,2,4]triazol-3-yl]-phenol;
2-[5-(2-Hydroxy-phenyl)-4-(2-methoxy-ethyl)-4/-/-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
2-[4-(2-Methoxy-ethyl)-5-(pyridin-2-ylmethylsulfanyl)-4ry-[1,2,4]triazol-3-yl]-phenol;
2-[4-(2-Methoxy-ethyl)-5-(2-methoxy-ethylsulfanyl)-4r.-[1,2,4]triazol-3-yl]-phenoI;
2-[4-Cyclopropyl-5-(2-hydroxy-phenyl)-4/-/-[1,2,4jtriazol-3-ylsulfanylmethyl]-benzonitrile; 2-[4-Cyclopropyl-5-(pyridin-2-ylmethylsulfanyl)-4 .-[1,2,4]triazol-3-yI]-phenol;
2-[4-Cyclopropyl-5-(2-methoxy-ethylsulfanyl)-4H-[1,2,4]triazol-3-yl]-phenol;
2-[5-(2-Hydroxy-phenyl)-4-(2-piperidin-1-yl-ethyl)-4/-/-[1,2,4]triazol-3-ylsulfanylmethyl]- benzonitrile;
2-[4-(2-Piperidin-1-yl-ethyl)-5-(pyridin-2-ylmethylsulfanyl)-4H-[1 ,2,4]triazol-3-yl]-phenol; 2-[5-(2-Methoxy-ethylsulfanyl)-4-(2-piperidin-1 -yl-ethyl)-4/-/-[1 ,2,4]triazol-3-yl]-phenol;
2-[4-Cyclopropylmethyl-5-(2-hydroxy-phenyl)-4r -[1 ,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
2-[4-Cyclopropylmethyl-5-(pyridin-2-ylmethylsulfanyl)-4 -/-[1 ,2,4]triazol-3-yl]-phenol;
2-[4-Cyclopropylmethyl-5-(2-methoxy-ethylsulfanyl)-4H-[1,2,4]triazoI-3-yl]-phenol;
2-[5-(2-Methoxy-phenyl)-4-(3-methoxy-propyI)-4H-[1,2,4]triazoI-3-ylsulfanylmethylj- benzonitrile;
2-[5-(2-Methoxy-phenyI)-4-(3-methoxy-propyl)-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-pyridine; 3-(2-Methoxy-ethylsulfanyl)-5-(2-methoxy-phenyl)-4-(3-methoxy-propyl)-4ry-[1 ,2,4]triazole;
2-[4-(2-Methoxy-ethyl)-5-(2-methoxy-phenyl)-4/-/-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
2-[4-(2-Methoxy-ethyl)-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-pyridine;
4-(2-Methoxy-ethyl)-3-(2-methoxy-ethylsulfanyl)-5-(2-methoxy-phenyl)-4/-/-[1 ,2,4]triazole; 2-[4-Cyclopropyl-5-(2-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsuIfanylmethyl]-benzonitrile;
2-[4-Cyclopropyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-pyridine;
4-Cyclopropyl-3-(2-methoxy-ethylsulfanyl)-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazole;
2-[5-(2-Methoxy-phenyl)-4-(2-piperidin-1-yl-ethyl)-4 .-[1 ,2,4jtriazol-3-ylsulfanylmethylj- benzonitrile; 2-[5-(2-Methoxy-phenyl)-4-(2-piperidin-1-yl-ethyl)-4H-[1 ,2,4]triazol-3-ylsulfanylmethyI]-pyridine;
1-{2-[3-(2-Methoxy-ethylsulfanyl)-5-(2-methoxy-phenyl)-[1 ,2,4jtriazol-4-yl]-ethyl}-piperidine;
2-[4-Cyclopropylmethyl-5-(2-methoxy-phenyl)-4AV-[1 ,2,4]triazol-3-ylsulfanylmethylj- benzonitrile;
2-[4-Cyclopropylmethyl-5-(2-methoxy-phenyl)-4H-[1 ,2,4]triazol-3-ylsulfanyImethyl]-pyridine; 4-Cyclopropylmethyl-3-(2-methoxy-ethylsulfanyl)-5-(2-methoxy-phenyl)-4r -[1 ,2,4]triazole;
2-[4-(3-Methoxy-propyl)-5-thiophen-2-yl-4ry-[1 ,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
2-[4-(3-Methoxy-propyl)-5-thiophen-2-yl-4ry-[1 ,2,4]triazol-3-ylsulfanylmethyl]-pyridine;
3-(2-Methoxy-ethylsulfanyl)-4-(3-methoxy-propyl)-5-thiophen-2-yl-4/-/-[1 ,2,4]triazole;
2-[4-(2-Methoxy-ethyl)-5-thiophen-2-yl-4H-[1,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile; 2-[4-(2-Methoxy-ethyl)-5-thiophen-2-yl-4/-/-[1 ,2,4]triazol-3-ylsulfanylmethyl]-pyridine;
4-(2-Methoxy-ethyl)-3-(2-methoxy-ethylsulfanyl)-5-thiophen-2-yl-4H-[1 ,2,4]triazole;
2-(4-Cyclopropyl-5-thiophen-2-yl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile;
2-(4-Cyclopropyl-5-thiophenr2-yl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-pyridine;
4-Cyclopropyl-3-(2-methoxy-ethylsulfanyl)-5-thiophen-2-yl-4H-[1 ,2,4]triazole; 2-[4-(2-Piperidin-1-yl-ethyl)-5-thiophen-2-yl-4 .-[1 ,2,4]triazol-3-ylsulfanylmethyl]-benzonitrile;
2-[4-(2-Piperidin-1-yl-ethyl)-5-thiophen-2-yl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl]-pyridine;
1-{2-[3-(2-Methoxy-ethylsulfanyl)-5-thiophen-2-yl-[1 ,2,4]triazol-4-yl]-ethyl}-piperidine;
2-(4-Cyclopropylmethyl-5-thiophen-2-yl-4H-[1 ,2,4]triazol-3-ylsulfanylmethyl)-benzonitrile;
2-(4-Cyclopropylmethyl-5-thiophen-2-yl-4/-/-[1 ,2,4]triazol-3-ylsulfanylmethyl)-pyridine; 4-Cyclopropylmethyl-3-(2-methoxy-ethylsulfanyl)-5-thiophen-2-yl-4H-[1 ,2,4]triazole; or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric forms.
38. A pharmaceutical composition which comprises the combination according of any of the claims 1-37 and a pharmaceutically acceptable carrier.
39. A pharmaceutical composition made by combining an 11β-HSD1 inhibitor, an antihypertensive agent and a pharmaceutically acceptable carrier.
40. A process for making a pharmaceutical composition comprising combining an 11 ?-HSD1 inhibitor, an antihypertensive agent and a pharmaceutically acceptable carrier.
41. The use of the combination according to any of the claims 1-37, for the preparation of a pharmaceutical composition for treating or preventing diseases or disorders involving the metabolic syndrome, insulin resistance, dyslipidemia, obesity or hypertension.
42. A method of treating or preventing diseases or disorders involving the metabolic syndrome comprising administering to a patient in need of such treatment a therapeutically effective amount of the combination of claim 1.
43. A method of treating or preventing diseases or disorders involving the metabolic syndrome, insulin resistance, dyslipidemia, obesity or hypertension comprising administering to a patient in need of such treatment a therapeutically effective amount of the pharmaceutical composition of claim 39.
44. The combination according to claim 1 wherein the antihypertensive agent is selected from the group consisting of: β-blockers, /?2-receptor blockers, ACE (angiotensin converting enzyme) inhibitors, calcium channel blockers, α-blockers, diuretics, loop-diuretics, potassium sparing diuretics, endothelin ET-A antagonists, endothelin antagonists, renin inhibitors, vasopressin V1 antagonists, vasopressin V2 antagonists, B-type natriuretic peptide agonists, angiotensin II antagonists, 5- HT2 agonists, adenosine A1 antagonists, thromboxane A2 antagonists, endopeptidase inhibitors, nitric oxide agonists, dopamine D1 antagonists, dopamine D2 agonists, n-3 fatty acids, prostacyclin agonists, PGE1 agonists, Na+/K+ ATPase modulators, Potassium channel activators, and vaccines.
45. The combination according to claim 44 wherein the antihypertensive agent is selected from the group consisting of: alprenolol, atenolol, timolol, pindolol, propranolol, metoprolol, bisoprololfumerate, esmolol, acebutelol, acebutolol, betaxolol, celiprolol, nebivolol, tertatolol, oxprenolol, amusolalul, carvedilol, labetalol, S-atenolol, OPC-1085, quinapril, lisinopril, enalapril, captopril, benazepril, perindopril, trandolapril, fosinopril, ramipril, cilazapril, delapril, imidapril, moexipril, spirapril, temocapril, zofenopril, S-5590, fasidotril, Hoechst-Marion Roussel: 100240 (EP 00481522), omapatrilat, gemopatrilat and GW-660511 , nifedipine, felodipine, nicardipine, isradipine, nimodipine, diltiazem, amlodipine, nitrendipine, verapamil, lacidipine, lercanidipine, aranidipine, cilnidipine, clevidipine, azelnidipine, barnidipine, efonodipine, iasidipine, iemildipine, iercanidipine, manidipine, nilvadipine, pranidipine, furnidipine, doxazosin, urapidil, prazosin, terazosin, bunazosin and OPC-28326, bendroflumetazide, chlorothalidone, hydrochlorothiazide and clopamide, bumetanide, furosemide, torasemide, amiloride, spironolactone, ABT-546, ambrisetan, atrasentan, SB-234551 , CM 034, S-0139, YM-598, bosentan, J-104133, aliskiren, OPC-21268, tolvaptan, SR-121463, OPC-31260, Nesiritide, irbesartan, candesartancilexetil, losartan, valsartan, telmisartan, eprosartan, candesartan, CL- 329167, eprosartan, iosartan, olmesartan, pratosartan, TA-606, YM-358, fenoldopam, ketanserin, naftopidil, N-0861 , FK-352, KT2-962, ecadotril, LP-805, MYD-37, nolomirole, omacor, treprostinil, beraprost, ecraprost, PST-2238, KR-30450, PMD-3117, Indapamides, CGRP-unigene, guanylate cyclase stimulators, hydralazines, methyldopa, docarpamine, moxonidine, CoAprovel, and MondoBiotech-811.
46. The combination according to any of the claims 2-5 wherein the antihypertensive agent is selected from the group consisting of: β-blockers, ?2-receptor blockers, ACE (angiotensin converting enzyme) inhibitors, calcium channel blockers, α-blockers, diuretics, loop-diuretics, potassium sparing diuretics, endothelin ET-A antagonists, endothelin antagonists, renin inhibitors, vasopressin V1 antagonists, vasopressin V2 antagonists, B-type natriuretic peptide agonists, angiotensin II antagonists, 5- HT2 agonists, adenosine A1 antagonists, thromboxane A2 antagonists, endopeptidase inhibitors, nitric oxide agonists, dopamine D1 antagonists, dopamine D2 agonists, n-3 fatty acids, prostacydin agonists, PGE1 agonists, Na+/K+ ATPase modulators, Potassium channel activators, and vaccines.
47. The combination according to claim 46 wherein the antihypertensive agent is selected from the group consisting of: alprenolol, atenolol, timolol, pindolol, propranolol, metoprolol, bisoprololfumerate, esmolol, acebutelol, acebutolol, betaxolol, celiprolol, nebivolol, tertatolol, oxprenolol, amusolalul, carvedilol, labetalol, S-atenolol, OPC-1085, quinapril, lisinopril, enalapril, captopril, benazepril, perindopril, trandolapril, fosinopril, ramipril, cilazapril, delapril, imidapril, moexipril, spirapril, temocapril, zofenopril, S-5590, fasidotril, Hoechst-Marion Roussel: 100240 (EP 00481522), omapatrilat, gemopatrilat and GW-660511 , nifedipine, felodipine, nicardipine, isradipine, nimodipine, diltiazem, amlodipine, nitrendipine, verapamil, lacidipine, lercanidipine, aranidipine, cilnidipine, clevidipine, azelnidipine, barnidipine, efonodipine, iasidipine, iemildipine, iercanidipine, manidipine, nilvadipine, pranidipine, furnidipine, doxazosin, urapidil, prazosin, terazosin, bunazosin and OPC-28326, bendroflumetazide, chlorothalidone, hydrochlorothiazide and clopamide, bumetanide, furosemide, torasemide, amiloride, spironolactone, ABT-546, ambrisetan, atrasentan, SB-234551 , CM 034, S-0139, YM-598, bosentan, J-104133, aliskiren, OPC-21268, tolvaptan, SR- 21463, OPC-31260, Nesiritide, irbesartan, candesartancilexetil, losartan, valsartan, telmisartan, eprosartan, candesartan, CL- 329167, eprosartan, iosartan, olmesartan, pratosartan, TA-606, YM-358, fenoldopam, ketanserin, naftopidil, N-0861, FK-352, KT2-962, ecadotril, LP-805, MYD-37, nolomirole, omacor, treprostinil, beraprost, ecraprost, PST-2238, KR-30450, PMD-3117, Indapamides, CGRP-unigene, guanylate cyclase stimulators, hydralazines, methyldopa, docarpamine, moxonidine, CoAprovel, and MondoBiotech-811.
48. The combination according to any of the claims 6-26 wherein the antihypertensive agent is selected from the group consisting of: β-blockers, ?2-receptor blockers, ACE (angiotensin converting enzyme) inhibitors, calcium channel blockers, α-blockers, diuretics, loop-diuretics, potassium sparing diuretics, endothelin ET-A antagonists, endothelin antagonists, renin inhibitors, vasopressin V1 antagonists, vasopressin V2 antagonists, B-type natriuretic peptide agonists, angiotensin II antagonists, 5- HT2 agonists, adenosine A1 antagonists, thromboxane A2 antagonists, endopeptidase inhibitors, nitric oxide agonists, dopamine D1 antagonists, dopamine D2 agonists, n-3 fatty acids, prostacydin agonists, PGE1 agonists, Na+/K+ ATPase modulators, Potassium channel activators, and vaccines.
49. The combination according to claim 48 wherein the antihypertensive agent is selected from the group consisting of: alprenolol, atenolol, timolol, pindolol, propranolol, metoprolol, bisoprololfumerate, esmolol, acebutelol, acebutolol, betaxolol, celiprolol, nebivolol, tertatolol, oxprenolol, amusolalul, carvedilol, labetalol, S-atenolol, OPC-1085, quinapril, lisinopril, enalapril, captopril, benazepril, perindopril, trandolapril, fosinopril, ramipril, cilazapril, delapril, imidapril, moexipril, spirapril, temocapril, zofenopril, S-5590, fasidotril, Hoechst-Marion Roussel: 100240 (EP 00481522), omapatrilat, gemopatrilat and GW-660511 , nifedipine, felodipine, nicardipine, isradipine, nimodipine, diltiazem, amlodipine, nitrendipine, verapamil, lacidipine, lercanidipine, aranidipine, cilnidipine, clevidipine, azelnidipine, barnidipine, efonodipine, iasidipine, iemildipine, iercanidipine, manidipine, nilvadipine, pranidipine, furnidipine, doxazosin, urapidil, prazosin, terazosin, bunazosin and OPC-28326, bendroflumetazide, chlorothalidone, hydrochlorothiazide and clopamide, bumetanide, furosemide, torasemide, amiloride, spironolactone, ABT-546, ambrisetan, atrasentan, SB-234551, CM 034, S-0139, YM-598, bosentan, J-104133, aliskiren, OPC-21268, tolvaptan, SR-121463, OPC-31260, Nesiritide, irbesartan, candesartancilexetil, losartan, valsartan, telmisartan, eprosartan, candesartan, CL- 329167, eprosartan, iosartan, olmesartan, pratosartan, TA-606, YM-358, fenoldopam, ketanserin, naftopidil, N-0861, FK-352, KT2-962, ecadotril, LP-805, MYD-37, nolomirole, omacor, treprostinil, beraprost, ecraprost, PST-2238, KR-30450, PMD-3117, Indapamides, CGRP-unigene, guanylate cyclase stimulators, hydralazines, methyldopa, docarpamine, moxonidine, CoAprovel, and MondoBiotech-811.
50. The combination according to claim 27-31 wherein the antihypertensive agent is selected from the group consisting of: β-blockers, ?2-receptor blockers, ACE (angiotensin converting enzyme) inhibitors, calcium channel blockers, α-blockers, diuretics, loop-diuretics, potassium sparing diuretics, endothelin ET-A antagonists, endothelin antagonists, renin inhibitors, vasopressin V1 antagonists, vasopressin V2 antagonists, B-type natriuretic peptide agonists, angiotensin II antagonists, 5- HT2 agonists, adenosine A1 antagonists, thromboxane A2 antagonists, endopeptidase inhibitors, nitric oxide agonists, dopamine D1 antagonists, dopamine D2 agonists, n-3 fatty acids, prostacydin agonists, PGE1 agonists, Na+/K+ ATPase modulators, Potassium channel activators, and vaccines.
51. The combination according to claim 50 wherein the antihypertensive agent is selected from the group consisting of: alprenolol, atenolol, timolol, pindolol, propranolol, metoprolol, bisoprololfumerate, esmolol, acebutelol, acebutolol, betaxolol, celiprolol, nebivolol, tertatolol, oxprenolol, amusolalul, carvedilol, labetalol, S-atenolol, OPC-1085, quinapril, lisinopril, enalapril, captopril, benazepril, perindopril, trandolapril, fosinopril, ramipril, cilazapril, delapril, imidapril, moexipril, spirapril, temocapril, zofenopril, S-5590, fasidotril, Hoechst-Marion Roussel: 100240 (EP 00481522), omapatrilat, gemopatrilat and GW-660511, nifedipine, felodipine, nicardipine, isradipine, nimodipine, diltiazem, amlodipine, nitrendipine, verapamil, lacidipine, lercanidipine, aranidipine, cilnidipine, clevidipine, azelnidipine, barnidipine, efonodipine, iasidipine, iemildipine, iercanidipine, manidipine, nilvadipine, pranidipine, furnidipine, doxazosin, urapidil, prazosin, terazosin, bunazosin and OPC-28326, bendroflumetazide, chlorothalidone, hydrochlorothiazide and clopamide, bumetanide, furosemide, torasemide, amiloride, spironolactone, ABT-546, ambrisetan, atrasentan, SB-234551 , CI-1034, S-0139, YM-598, bosentan, J-104133, aliskiren, OPC-21268, tolvaptan, SR-121463, OPC-31260, Nesiritide, irbesartan, candesartancilexetil, losartan, valsartan, telmisartan, eprosartan, candesartan, CL- 329167, eprosartan, iosartan, olmesartan, pratosartan, TA-606, YM-358, fenoldopam, ketanserin, naftopidil, N-0861 , FK-352, KT2-962, ecadotril, LP-805, MYD-37, nolomirole, omacor, treprostinil, beraprost, ecraprost, PST-2238, KR-30450, PMD-3117, Indapamides, CGRP-unigene, guanylate cyclase stimulators, hydralazines, methyldopa, docarpamine, moxonidine, CoAprovel, and MondoBiotech-811.
52. The combination according to claim 32 or 33 wherein the antihypertensive agent is selected from the group consisting of: β-blockers, ?2-receptor blockers, ACE (angiotensin converting enzyme) inhibitors, calcium channel blockers, α-blockers, diuretics, loop-diuretics, potassium sparing diuretics, endothelin ET-A antagonists, endothelin antagonists, renin inhibitors, vasopressin V1 antagonists, vasopressin V2 antagonists, B-type natriuretic peptide agonists, angiotensin II antagonists, 5- HT2 agonists, adenosine A1 antagonists, thromboxane A2 antagonists, endopeptidase inhibitors, nitric oxide agonists, dopamine D1 antagonists, dopamine D2 agonists, n-3 fatty acids, prostacydin agonists, PGE1 agonists, Na+/K+ ATPase modulators, Potassium channel activators, and vaccines.
53. The combination according to claim 52 wherein the antihypertensive agent is selected from the group consisting of: alprenolol, atenolol, timolol, pindolol, propranolol, metoprolol, bisoprololfumerate, esmolol, acebutelol, acebutolol, betaxolol, celiprolol, nebivolol, tertatolol, oxprenolol, amusolalul, carvedilol, labetalol, S-atenolol, OPC-1085, quinapril, lisinopril, enalapril, captopril, benazepril, perindopril, trandolapril, fosinopril, ramipril, cilazapril, delapril, imidapril, moexipril, spirapril, temocapril, zofenopril, S-5590, fasidotril, Hoechst-Marion Roussel: 100240 (EP 00481522), omapatrilat, gemopatrilat and GW-660511 , nifedipine, felodipine, nicardipine, isradipine, nimodipine, diltiazem, amlodipine, nitrendipine, verapamil, lacidipine, lercanidipine, aranidipine, cilnidipine, clevidipine, azelnidipine, barnidipine, efonodipine, iasidipine, iemildipine, iercanidipine, manidipine, nilvadipine, pranidipine, furnidipine, doxazosin, urapidil, prazosin, terazosin, bunazosin and OPC-28326, bendroflumetazide, chlorothalidone, hydrochlorothiazide and clopamide, bumetanide, furosemide, torasemide, amiloride, spironolactone, ABT-546, ambrisetan, atrasentan, SB-234551 , CI-1034, S-0139, YM-598, bosentan, J-104133, aliskiren, OPC-21268, tolvaptan, SR-121463, OPC-31260, Nesiritide, irbesartan, candesartancilexetil, losartan, valsartan, telmisartan, eprosartan, candesartan, CL- 329167, eprosartan, iosartan, olmesartan, pratosartan, TA-606, YM-358, fenoldopam, ketanserin, naftopidil, N-0861 , FK-352, KT2-962, ecadotril, LP-805, MYD-37, nolomirole, omacor, treprostinil, beraprost, ecraprost, PST-2238, KR-30450, PMD-3117, Indapamides, CGRP-unigene, guanylate cyclase stimulators, hydralazines, methyldopa, docarpamine, moxonidine, CoAprovel, and MondoBiotech-811.
54. The combination according to any of the claims 34-37 wherein the antihypertensive agent is selected from the group consisting of: β-blockers, j-2-receptor blockers, ACE (angiotensin converting enzyme) inhibitors, calcium channel blockers, α-blockers, diuretics, loop-diuretics, potassium sparing diuretics, endothelin ET-A antagonists, endothelin antagonists, renin inhibitors, vasopressin V1 antagonists, vasopressin V2 antagonists, B-type natriuretic peptide agonists, angiotensin II antagonists, 5- HT2 agonists, adenosine A1 antagonists, thromboxane A2 antagonists, endopeptidase inhibitors, nitric oxide agonists, dopamine D1 antagonists, dopamine D2 agonists, n-3 fatty acids, prostacydin agonists, PGE1 agonists, Na+/K+ ATPase modulators, Potassium channel activators, and vaccines.
55. The combination according to claim 54 wherein the antihypertensive agent is selected from the group consisting of: alprenolol, atenolol, timolol, pindolol, propranolol, metoprolol, bisoprololfumerate, esmolol, acebutelol, acebutolol, betaxolol, celiprolol, nebivolol, tertatolol, oxprenolol, amusolalul, carvedilol, labetalol, S-atenolol, OPC-1085, quinapril, lisinopril, enalapril, captopril, benazepril, perindopril, trandolapril, fosinopril, ramipril, cilazapril, delapril, imidapril, moexipril, spirapril, temocapril, zofenopril, S-5590, fasidotril, Hoechst-Marion Roussel: 100240 (EP 00481522), omapatrilat, gemopatrilat and GW-660511, nifedipine, felodipine, nicardipine, isradipine, nimodipine, diltiazem, amlodipine, nitrendipine, verapamil, lacidipine, lercanidipine, aranidipine, cilnidipine, clevidipine, azelnidipine, barnidipine, efonodipine, iasidipine, iemildipine, iercanidipine, manidipine, nilvadipine, pranidipine, furnidipine, doxazosin, urapidil, prazosin, terazosin, bunazosin and OPC-28326, bendroflumetazide, chlorothalidone, hydrochlorothiazide and clopamide, bumetanide, furosemide, torasemide, amiloride, spironolactone, ABT-546, ambrisetan, atrasentan, SB-234551, CM 034, S-0139, YM-598, bosentan, J-104133, aliskiren, OPC-21268, tolvaptan, SR-121463, OPC-31260, Nesiritide, irbesartan, candesartancilexetil, losartan, valsartan, telmisartan, eprosartan, candesartan, CL- 329167, eprosartan, iosartan, olmesartan, pratosartan, TA-606, YM-358, fenoldopam, ketanserin, naftopidil, N-0861, FK-352, KT2-962, ecadotril, LP-805, MYD-37, nolomirole, omacor, treprostinil, beraprost, ecraprost, PST-2238, KR-30450, PMD-3117, Indapamides, CGRP-unigene, guanylate cyclase stimulators, hydralazines, methyldopa, docarpamine, moxonidine, CoAprovel, and MondoBiotech-811.
56. A kit comprising an amount of an 11 ?-HSD1 inhibitor and a pharmaceutically acceptable carrier, vehicle, or diluent in a first unit dosage form; an amount of antihypertensive agent and a pharmaceutically acceptable carrier, vehicle, or diluent in a second unit dosage form; and a container.
57. The use of the combination according to any of the claims 1-37, for the preparation of a pharmaceutical composition for treating or preventing diseases or disorders involving the metabolic syndrome, insulin resistance, dyslipidemia, obesity or hypertension, said use comprising administering to a patient in need of said treatment (i) a first amount of an 1 λβ HSD1 inhibitor and (ii) a second amount of an antihypertensive agent, wherein said first and second amounts together are effective for said treatment.
58. A method for treating or preventing diseases or disorders involving the metabolic syndrome, insulin resistance, dyslipidemia, obesity or hypertension, said method comprising administering to a patient in need of said treatment (i) a first amount of an 1 λβ HSD1 inhibitor and (ii) a second amount of an antihypertensive agent, wherein said first and second amounts together are effective for said treatment.
PCT/DK2004/000254 2003-04-11 2004-04-06 Combination of an 11beta-hydroxysteroid dehydrogenase type 1 inhibitor and an antihypertensive agent WO2004089416A2 (en)

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US11/254,125 US7501405B2 (en) 2003-04-11 2005-10-11 Combination therapy using an 11β-hydroxysteroid dehydrogenase type 1 inhibitor and an antihypertensive agent for the treatment of metabolic syndrome and related diseases and disorders
US12/363,056 US20090137574A1 (en) 2003-04-11 2009-01-30 Combination Therapy Using an 11Beta-Hydroxysteroid Dehydrogenase Type 1 Inhibitor and an Antihypertensive Agent for the Treatment of Metabolic Syndrome and Related Diseases and Disorders

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US46736303P 2003-05-02 2003-05-02
US46743703P 2003-05-02 2003-05-02
US46745303P 2003-05-02 2003-05-02
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US46728403P 2003-05-02 2003-05-02
US60/467,284 2003-05-02
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US60/467,362 2003-05-02
US60/467,437 2003-05-02
US60/467,800 2003-05-02
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US47442103P 2003-05-30 2003-05-30
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US48609403P 2003-07-10 2003-07-10
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