Claims
- 1. A compound of formula (I),
- 2. A compound according to claim 1, wherein R2 is a phenyl group optionally substituted with one or more groups selected from halogen or —(CH2)e—OR3.
- 3. A compound according to claim 1 or claim 2, wherein ring A is selected from piperidindiyl, piperazindiyl, azetidindiyl or pyrrolidindiyl.
- 4. A compound according to claim 3, wherein ring A is piperidindiyl.
- 5. A compound according to any of the preceding claims, wherein Z is O.
- 6. A compound according to any of the preceding claims, wherein het1 is selected from optionally substituted pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, triazolyl, tetrazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, piperidinyl, piperazinyl, azetidinyl, morpholinyl, 2-oxa-5-aza-bicyclo[2.2.1.]heptanyl or pyrrolidinyl.
- 7. A compound according to any claim 6, wherein het1 is selected from pyridinyl or pyrimidinyl, optionally by R3.
- 8. A compound according to any of the preceding claims, wherein het2 is selected from substituted or unsubstituted pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, triazolyl, tetrazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, piperidinyl, piperazinyl, N-methyl piperazinyl, azetidinyl, morpholinyl, 2-oxa-5-aza-bicyclo[2.2.1]heptanyl or pyrrolidinyl.
- 9. A compound according to claim 8, wherein het2 is selected from imidazolyl, piperidinyl, piperazinyl, N-methyl piperazinyl, azetidinyl, morpholinyl, 2-oxa-5-aza-bicyclo[2.2.1]heptanyl or pyrrolidinyl.
- 10. A compound according to any of the preceding claims, wherein a is 1 and b is 0.
- 11. A compound according to claim 1, which is selected from
(S)-4-[5-Butyl-4-(1-phenyl-ethyl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl; 2-[4-(4-Benzyl-5-isobutyl-4H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-pyrimidine; (S)-4-[5-Methyl-4-(1-phenyl-ethyl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl; 4-[4-Benzyl-5-butyl-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl; 2-[4-(4-Benzyl-5-isopropyl-4H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-pyrimidine; 2-[4-(4-Benzyl-5-cyclopropyl-4H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-pyrimidine; (S)-2-{4-[5-Methyl-4-(1-phenyl-propyl)-4H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-pyrimidine; 2-[4-(4-Benzyl-5-propyl-4H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-pyrimidine; 2-{4-[4-Benzyl-5-(2-chloro-phenoxymethyl)-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-pyrimidine; 2-[4-(4-Benzyl-5-butyl-4H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-pyrimidine; (S)-2-{4-[5-Methyl-4-(1-phenyl-ethyl)-4H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-pyrimidine; 2-{4-[4-Benzyl-5-(4-fluoro-phenoxymethyl)-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl}-pyrimidine; 2-{4-[5-Methyl-4-(3-methyl-benzyl)-4H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-pyrimidine; (S)-2-{4-[5-Methyl-4-(1-phenyl-ethyl)-4H-[1,2,4]triazol-3-ylmethyl]-piperidin-1-yl}-pyrimidine; 2-{4-[4-(3-Fluoro-benzyl)-5-methyl-4H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-pyrimidine; 4-(4-Benzyl-5-morpholin-4-ylmethyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-1,2′]bipyridinyl; 4-(4-Benzyl-5-benzyloxymethyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl; 4-(4-Benzyl-5-methyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl; (R)-2-[3-Methyl-5-(1-pyrimidin-2-yl-piperidin-4-yl)-[1,2,4]triazol-4-yl]-2-phenylethanol; 2-[4-(4-Benzyl-5-methyl-4H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-4-methyl-pyrimidine; 2-[4-(4-Benzyl-5-methyl-4H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-pyrimidine; 4-(4-Benzyl-5-methyl-4H-[1,2,4]triazol-3-yl)-1-phenyl-piperidine; 2-[4-(4-Benzyl-5-methyl-4H-[1,2,4]triazol-3-yl)-piperidin-1-yl]-pyrazine; 4-(4-Benzyl-5-piperidin-1-ylmethyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl; (S)-4-[4-(1-Phenyl-ethyl)-5-piperidin-1-ylmethyl-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl; 4-[4-Benzyl-5-(4-methoxy-piperidin-1-ylmethyl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl; (S)-4-[5-(4-Methoxy-piperidin-1-ylmethyl)-4-(1-phenyl-ethyl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl; 4-[4-Benzyl-5-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-4H-[1,2,4]triazol-3-ylmethyl]-piperazine-1-carboxylic acid benzyl ester; 4-[4-Benzyl-5-(2-morpholin-4-yl-ethoxymethyl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl. 4-[4-Benzyl-5-{(3R)-3-methoxy-pyrrolidin-1-ylmethyl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-[4-Benzyl-5-{(3S)-3-methoxy-pyrrolidin-1-ylmethyl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 1-[4-Benzyl-5-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-4H-[1,2,4]triazol-3-ylmethyl]-pyrrolidin-3-ol 4-(4-Benzyl-5-pyrrolidin-1-ylmethyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-[4-Benzyl-5-(2-oxa-5-aza-bicyclo[2.2.1]hept-5-ylmethyl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-[4-Benzyl-5-(4-methoxy-piperidin-1-ylmethyl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-[4-(4-Fluoro-benzyl)-5-methyl-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-[4-(3-Methoxy-benzyl)-5-methyl-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-[5-Methyl-4-(3-methyl-benzyl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-[4-(3-Chloro-benzyl)-5-methyl-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl N-Benzyl-2-[4-benzyl-5-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-4H-[1,2,4]triazol-3-yl]-acetamide 2-[4-Benzyl-5-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-4H-[1,2,4]triazol-3-ylmethoxy]-ethylamine [4-Benzyl-5-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-4H-[1,2,4]triazol-3-ylmethyl]-ethyl-amine [4-Benzyl-5-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-4H-[1,2,4]triazol-3-ylmethyl]-(2-methoxy-ethyl)-amine [4-Benzyl-5-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-4H-[1,2,4]triazol-3-ylmethyl]-(3-methoxy-propyl)-amine 1-{4-[4-Benzyl-5-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-4H-[1,2,4]triazol-3-ylmethyl]-piperazin-1-yl}-ethanone 4-[4-Benzyl-5-(4-methanesulfonyl-piperazin-1-ylmethyl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl N-[4-Benzyl-5-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-4H-[1,2,4]triazol-3-ylmethyl]-methanesulfonamide [4-Benzyl-5-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-4H-[1,2,4]triazol-3-ylmethyl]-(2-methoxy-ethyl)-methyl-amine [4-Benzyl-5-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-4H-[1,2,4]triazol-3-ylmethyl]-(3-methoxy-propyl)-methyl-amine 4-(4-Benzyl-5-morpholin-4-ylmethyl-4H-[1,2,4]triazol-3-yl)-3′-methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-(4-Benzyl-5-morpholin-4-ylmethyl-4H-[1,2,4]triazol-3-yl)-3′-trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-(4-Benzyl-5-morpholin-4-ylmethyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-3′-carbonitrile 4-(4-Benzyl-5-morpholin-4-ylmethyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-3′-carboxylic acid amide (S)-4-[4-(1-Phenyl-ethyl)-5-(4-pyridin-2-yl-piperazin-1-ylmethyl)-4H-[1,2,4]triazol-3-ylmethyl]-morpholine trihydrochloride (S)-4-[4-(1-Phenyl-ethyl)-5-(4-pyrimidin-2-yl-piperazin-1-ylmethyl)-4H-[1,2,4]triazol-3-ylmethyl]-morpholine trihydrochloride 1-[4-Benzyl-5-(1-pyrimidin-2-yl-piperidin-4-yl)-4H-[1,2,4]triazol-3-ylmethyl]-piperidin-3-ol (R)-2-[4-Benzyl-5-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-4H-[1,2,4]triazol-3-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (R)-4-[4-Benzyl-5-(tetrahydro-furan-3-yloxymethyl)-4H-[1,2,4]triazol-3-yl] 3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl (S)-4-[4-Benzyl-5-(tetrahydro-furan-3-yloxymethyl)-4H-[1,2,4]triazol-3-yl] 3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl {[4-Benzyl-5-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-4H-[1,2,4]triazol-3-ylmethyl]-methyl-amino}-acetic acid tert-butyl ester 4-[4-Benzyl-5-(tetrahydro-pyran-4-ylmethyl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-[4-Benzyl-5-(tetrahydro-furan-2-yl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-(4-Benzyl-5-ethoxymethyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-[4-Benzyl-5-(2-methoxy-ethoxymethyl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl [4-Benzyl-5-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-4H-[1,2,4]triazol-3-ylmethoxy]-acetic acid tert-butyl ester N-Benzyl-2-[4-benzyl-5-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-4H-[1,2,4]triazol-3-ylmethoxy]-acetamide 4-(4-Benzyl-5-methylsulfanylmethyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-(4-Benzyl-5-pyrazol-1-ylmethyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-(4-Benzyl-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-(4-Benzyl-5-[1,2,3]triazol-1-ylmethyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-[4-Benzyl-5-(pyridin-4-yloxymethyl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl.
- 12. A compound according to claim 11, which is selected from:
4-[4-Benzyl-5-butyl-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-(4-Benzyl-5-morpholin-4-ylmethyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-(4-Benzyl-5-benzyloxymethyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-(4-Benzyl-5-piperidin-1-ylmethyl-4H-[1,2,4]triazol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl (S)-4-[4-(1-Phenyl-ethyl)-5-piperidin-1-ylmethyl-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl 4-[4-Benzyl-5-(4-methoxy-piperidin-1-ylmethyl)-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl
- 13. The use of a compound according to formula (I) as a medicament.
- 14. A method of treatment of aggression, Alzheimer's disease, anorexia nervosa, anxiety disorder, asthma, atherosclerosis, cardiac failure, cardiovascular disease, cataract, central nervous system disease, cerebrovascular ischemia, cirrhosis, cognitive disorder, Cushing's disease, depression, diabetes mellitus, dysmenorrhoea, edema, emesis, endometriosis, gastrointestinal disease, glaucoma, gynaecological disease, heart disease, hypertension, hyponatremia, intrauterine growth retardation, ischemia, ischemic heart disease, lung tumor, micturition disorder, mittleschmerz, motion sickness, neoplasm, nephrotoxicity, non-insulin dependent diabetes, obesity, obsessive/compulsive disorder, ocular hypertension, premature ejaculation, premature labor, pulmonary disease, Raynaud's disease, renal disease, renal failure, male and female sexual dysfunction, sleep disorder, spinal cord injury, thrombosis, urogenital tract infection, urolithiasis, comprising administering a therapeutically effective amount of a compound of formula (I) to a patient suffering from such a disorder.
- 15. A method according to claim 14 wherein the disorder is dysmenorrhoea.
- 16. The use of a compound of formula (I) in the manufacture of a medicament for the treatment of aggression, Alzheimer's disease, anorexia nervosa, anxiety disorder, asthma, atherosclerosis, cardiac failure, cardiovascular disease, cataract, central nervous system disease, cerebrovascular ischemia, cirrhosis, cognitive disorder, Cushing's disease, depression, diabetes mellitus, dysmenorrhoea, edema, emesis, endometriosis, gastrointestinal disease, glaucoma, gynaecological disease, heart disease, hypertension, hyponatremia, intrauterine growth retardation, ischemia, ischemic heart disease, lung tumor, micturition disorder, mittleschmerz, motion sickness, neoplasm, nephrotoxicity, non-insulin dependent diabetes, obesity, obsessive/compulsive disorder, ocular hypertension, premature ejaculation, premature labor, pulmonary disease, Raynaud's disease, renal disease, renal failure, male and female sexual dysfunction, sleep disorder, spinal cord injury, thrombosis, urogenital tract infection, urolithiasis.
- 17. Use according to claim 16 for the treatment of dysmenorrhoea.
- 18. A pharmaceutical formulation including a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, together with a pharmaceutically acceptable excipients, diluent or carrier;
- 19. An intermediate of formula (II):
- 20. Use of a V1a antagonist in combination with an oral contraceptive for the treatment of dysmenorrhoea.
- 21. Use according to claim 20 wherein the V1a antagonist comprises a compound according to any of claims 1 to 12.
Priority Claims (1)
Number |
Date |
Country |
Kind |
0224919.1 |
Oct 2002 |
GB |
|
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of U.S. Provisional Application No. 60/428,632 filed Nov. 22, 2002 and U.K. Application No. 0224919.1 filed 25 Oct. 2002.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60428632 |
Nov 2002 |
US |