Claims
- 1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound of formula I wherein A together with the double bond of formula I is thiophene, R1 is optionally substituted C1-6-alkyl or optionally substituted aryl, R2 is optionally substituted C1-6-alkyl, optionally substituted aralkyl, or —COR3, wherein R3 is optionally substituted C1-6-alkyl, optionally substituted aralkyl, or optionally substituted aryl, R4 and R5 independently are hydrogen, halogen, perhalomethyl, optionally substituted C1-6-alkyl, hydroxy, optionally substituted C1-6-alkoxy, nitro, cyano, amino, optionally substituted mono- or optionally substituted di-C1-6-alkylamino, acylamino, C1-6-alkoxycarbonyl, carboxy or carbamoyl, n is 0, and m is 1, or a pharmaceutically acceptable salt thereof, or an optical isomer or mixture of optical isomers thereof, or a tautomeric form thereof.
- 2. The pharmaceutical composition of claim 1, wherein each one of R1, R2, and R3 is substituted with one or more substituents.
- 3. The pharmaceutical composition of claim 1, wherein R1 is optionally substituted phenyl.
- 4. The pharmaceutical composition of claim 1, wherein the substituents of R1 are independently halogen, perhalomethyl, perhalomethoxy, or C1-6-alkoxy.
- 5. The pharmaceutical composition of claim 4, wherein the substituents of R1 are independently chloro, trifluoromethyl, methoxy, and trifluoromethoxy.
- 6. The pharmaceutical composition of claim 5, wherein R1 is phenyl, 4-chlorophenyl, 4-trifluoromethylphenyl, or 4-trifluoromethoxyphenyl.
- 7. The pharmaceutical composition of claim 1, wherein R1 is 2,3-dihydrobenzofuran or 4-methoxyphenyl.
- 8. The pharmaceutical composition of claim 1, wherein R2 is —COR3 or (CH2)q-aryl, and q is 0, 1, 2, 3, 4, 5, or 6.
- 9. The pharmaceutical composition of claim 8, wherein R2 is —COR3.
- 10. The pharmaceutical composition of claim 9, wherein R3 is phenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-trifluoromethylphenyl, 4-(2-dimethylaminoethoxy)phenyl, or 4-(2-morpholin-4-ylethoxy)phenyl.
- 11. The pharmaceutical composition of claim 9, wherein R3 is 4-methylphenyl, 3,4-dimethoxyphenyl, 4-ethoxyphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, dimethylaminophenyl, 4-(2-carboxyethenyl)phenyl, 4-(2-dimethylaminoethoxy)phenyl, 4-(2-morpholin-4-ylethoxy)phenyl, 1 H-indol-5-yl, 3-chloro-4-methoxyphenyl, or 1 H-benzimidazol-5-yl.
- 12. The pharmaceutical composition of claim 1, wherein R4 and R5 independently are hydrogen, halogen, perhalomethyl, C1-6-alkyl, hydroxy, C1-6-alkoxy, nitro, cyano, amino, mono- or di-C1-6-alkylamino, acylamino, C1-6-alkoxycarbonyl, carboxy or carbamoyl.
- 13. The pharmaceutical composition of claim 12, wherein R4 and R5 independently are hydrogen, chloro, or methoxy.
- 14. The pharmaceutical composition of claim 1, whereinR1 is phenyl, phenyl substituted with one or more halogen, perhalomethyl, perhalomethoxy, C1-6-alkoxy, or 2,3-dihydrobenzofuran; and R2 is —COR3 wherein R3 is phenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-trifluoromethylphenyl, 4-(2-dimethylaminoethoxy)phenyl, 4-(2-morpholin-4-ylethoxy)phenyl, 4-methylphenyl, 3,4-dimethoxyphenyl, 4-ethoxyphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, dimethylaminophenyl, 4-(2-carboxyethenyl)phenyl, 4-(2-dimethylaminoethoxy)phenyl, 4-(2-morpholin-4-ylethoxy)phenyl, 1 H-indol-5-yl, 3-chloro-4-methoxyphenyl, or 1 H-benzimidazol-5-yl.
- 15. The pharmaceutical composition of claim 14, wherein R4 and R5 independently are hydrogen, halogen, perhalomethyl, C1-6-alkyl, hydroxy, C1-6-alkoxy, nitro, cyano, amino, mono- or di-C1-6-alkylamino, acylamino, C1-6-alkoxycarbonyl, carboxy or carbamoyl.
- 16. The pharmaceutical composition of claim 1, wherein the compound is of formula Ia: wherein R7 is hydrogen, halogen, methoxy, perhalomethoxy, perhalomethyl, diloweralkylamino, or nitro, and R6 and R8 independently are hydrogen, hydroxy, halogen, methyl, tert-butyl, phenyl, dimethylamino, methoxy, ethoxy, 2-dimethylaminoethoxy, 2-carboxyethenyl, 2-morpholin-4-ylethoxy, perhalomethyl, perhalomethoxy, carboxy, cyano, methylthio, methylsulfonyl, acetamido, nitro, acetyl, acetoxy, or hydroxymethyl.
- 17. The pharmaceutical composition of claim 1, wherein the compound is of formula (Ia): wherein R7 is halogen, perhalomethyl, or perhalomethoxy, and R6 and R8 independently are hydrogen, methoxy, ethoxy, hydroxy, fluoro, chloro, bromo, iodo, methyl, trifluoromethyl, dimethylamino, 2-carboxyethenyl, 2-dimethylaminoethoxy, or 2-morpholin-4-ylethoxy.
- 18. The pharmaceutical composition of claim 17, wherein R7 is chloro, methoxy, trifluoromethyl or trifluoromethoxy.
- 19. The pharmaceutical composition of claim 18, wherein R6 and R8 independently are hydrogen, methoxy, chloro, trifluoromethyl, 2-dimethylaminoethoxy, or 2-morpholin-4-ylethoxy.
- 20. The pharmaceutical composition of claim 17, wherein R6 and R8 independently are hydrogen, methoxy, chloro, trifluoromethyl, 2-dimethylaminoethoxy, or 2-morpholin-4-ylethoxy.
- 21. The pharmaceutical composition of claim 1, wherein the compound is of formula (Ib): wherein R6 is hydroxy, halogen, methyl, dimethylamino, methoxy, ethoxy, perhalomethyl, perhalomethoxy, cyano, methylthio, acetyl, acetoxy, or hydroxymethyl, and R7 is hydrogen, halogen, methoxy, perhalomethoxy, perhalomethyl, diloweralkylamino, or nitro.
- 22. The pharmaceutical composition of claim 1, wherein the compound is of formula (Ic): wherein R7 is hydrogen, halogen, methoxy, perhalomethoxy, perhalomethyl, diloweralkylamino, or nitro, and R9 is 4-pyridyl, 5-hydroxypyrazin-2-yl, 5-chloro-6-hydroxypyridin-3-yl, 2-chloropyridin-3-yl, benzofuran-2-yl, benzothiophen-2-yl, 7-methoxybenzofuran-2-yl, indolyl, benzimidazol, thienyl, or chlorothiophenyl.
- 23. The pharmaceutical composition of claim 22, wherein R9 is benzothiophen-2-yl, 1 H-indol-5-yl, 1 H-benzimidazol-5-yl, or 5-chlorothiophen-2-yl.
- 24. The pharmaceutical composition of claim 1, wherein the compound is of formula (Ic): wherein R7 is hydrogen, halogen, methoxy, perhalomethoxy, perhalomethyl, diloweralkylamino, or nitro, and R9 is indolyl or benzimidazol.
- 25. The pharmaceutical composition of claim 1, wherein the compound is of formula (Id): wherein R7 is hydrogen, halogen, methoxy, perhalomethoxy, perhalomethyl, diloweralkylamino, or nitro, and R10 is 2-(4-methoxyphenyl)-ethenyl, 2-(3-methoxyphenyl)-ethenyl, 2-(4-chlorophenyl)-ethenyl, 2-(4-fluorophenyl)-ethenyl, 2-(4-trifluoromethylphenyl)-ethenyl, 2-(4-methoxyphenyl)-ethyl, 2-(4-chlorophenyl)-ethyl, 4-chlorobenzyl, 4-methoxybenzyl, 2-(2-furyl)-ethenyl, 2-(4,5-dimethyl-2-furyl)-ethenyl, 2-(5-methyl-2-furyl)-ethenyl, 2-(3-furyl)-ethenyl, 2-(2-thienyl)-ethenyl, or 2-(3-thienyl)-ethenyl.
- 26. The pharmaceutical composition of claim 25, wherein R10 is 2-(4-methoxyphenyl)-ethenyl, 2-(2-furyl)-ethenyl, 2-(5-methyl-2-furyl)-ethenyl, 2-(3-furyl)-ethenyl, or 2-(3 -thienyl)-ethenyl.
- 27. The pharmaceutical composition of claim 1, wherein the compound is of formula (Id): whereinR7 is hydrogen, halogen, methoxy, perhalomethoxy, perhalomethyl, diloweralkylamino, or nitro, and R10 is 4-methoxyphenyl-2-ethenyl.
- 28. The pharmaceutical composition of claim 1, wherein the compound is of formula (Ie): wherein R6 and R8 independently are hydrogen, hydroxy, halogen, methyl, tert-butyl, phenyl, dimethylamino, methoxy, ethoxy, 2-dimethylaminoethoxy, 2-carboxyethenyl, 2-morpholin-4-ylethoxy, perhalomethyl, perhalomethoxy, carboxy, cyano, methylthio, methylsulfonyl, acetamido, nitro, acetyl, acetoxy, or hydroxymethyl, and R11 is pyridyl.
- 29. The pharmaceutical composition of claim 1, wherein the compound is of formula (If): wherein R10 is 2-(4-methoxyphenyl)-ethenyl, 2-(3-methoxyphenyl)-ethenyl, 2-(4-chlorophenyl)-ethenyl, 2-(4-fluorophenyl)-ethenyl, 2-(4-trifluoromethylphenyl)-ethenyl, 2-(4-methoxyphenyl)-ethyl, 2-(4-chlorophenyl)-ethyl, 4-chlorobenzyl, 4-methoxybenzyl, 2-(2-furyl)-ethenyl, 2-(4,5-dimethyl-2-furyl)-ethenyl, 2-(5-methyl-2-furyl)-ethenyl, 2-(3-furyl)-ethenyl, 2-(2-thienyl)-ethenyl, or 2-(3-thienyl)-ethenyl, and R11 is pyridyl.
- 30. The pharmaceutical composition of claim 29, wherein R11 is 4-pyridyl.
- 31. A pharmaceutical composition of claim 1, wherein the compound is of formula (Ig): wherein R6 and R8 independently are hydrogen, hydroxy, halogen, methyl, tert-butyl, phenyl, dimethylamino, methoxy, ethoxy, 2-dimethylaminoethoxy, 2-carboxyethenyl, 2-morpholin-4-ylethoxy, perhalomethyl, perhalomethoxy, carboxy, cyano, methylthio, methylsufonyl, acetamido, nitro, acetyl, acetoxy, or hydroxymethyl, and R12 is aryl or aralkyl.
- 32. A pharmaceutical composition of claim 31, wherein R12 is 4-trifluoromethoxyphenyl or benzyl.
- 33. A pharmaceutical composition of claim 1, wherein the compound is of formula (Ih): wherein R12 is 4-trifluoromethoxyphenyl or benzyl, and R13 is 2-(4-methoxyphenyl)-ethenyl, 2-(3-methoxyphenyl)-ethenyl, 2-(4-chlorophenyl)-ethenyl, 2-(4-fluorophenyl)-ethenyl, 2-(4-trifluoromethylphenyl)-ethenyl, 2-(4-methoxyphenyl)-ethyl, 2-(4-chlorophenyl)-ethyl, 4-chlorobenzyl, 4-methoxybenzyl, 2-(2-furyl)-ethenyl, 2-(4,5-dimethyl-2-furyl)-ethenyl, 2-(5-methyl-2-furyl)-ethenyl, 2-(3-furyl)-ethenyl, 2-(2-thienyl)-ethenyl, or 2-(3-thienyl)-ethenyl.
- 34. The pharmaceutical composition of claim 1, wherein the compound is:[4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-]pyridin-5-yl]-(4-methoxyphenyl)-methanone; (4-Chlorophenyl)-[4-(4-chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-methanone; (4-Chlorophenyl)-[4-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-thineo[3,2-c]pyridin-5-yl]-methanone; (2-Chlorophenyl)-[4-(4-methoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-methanone; (4-Chlorophenyl)-[4-(methoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-methanone; [4-(4-Methoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-trifluoromethylphenyl)-methanone; (2-Chloropyridin-3-yl)-[4-(4-methoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-methanone; [4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(2-thienyl)-methanone; [4-(4-Methoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(2-thienyl)-methanone; (4-Chlorophenyl)-(4-propyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl)-methanone; or a pharmaceutically acceptable salt thereof, or an optical isomer or mixture of optical isomers thereof, or a tautomeric form thereof.
- 35. The pharmaceutical composition of claim 1, wherein the compound is:[4-(4-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; [4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-phenyl-methanone; (−)-[4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; (4-Chlorophenyl)-[4-(4-chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-methanone; [4-(5-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5yl]-(4-methoxyphenyl)-methanone; [4-(4-Trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; [4-(4- Trifluoromethoxyphenyl)-4,5,6,7- tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; (4-Methoxyphenyl)-[4-(4-methoxyphenyl)-4,5,6,7- tetrahydro-thieno[3,2-c]pyridin-5-yl]methanone; (5-Chlorothiophen-2-yl)-[4-(4-dimethylaminophenyl)4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl)-methanone; (4-Chlorophenyl)-[4-(4-dimethylaminophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl)-methanone; (4-Methoxyphenyl)-[4-phenyl-4,5 ,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl)-methanone; [4-(4-Dimethylaminophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; (5-Chlorothiophen-2-yl)-(4-phenyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl)-methanone; or a pharmaceutically acceptable salt thereof, or an optical isomer or mixture of optical isomers thereof, or a tautomeric form thereof.
- 36. The pharmaceutical composition of claim 1, wherein the compound is:(+)-[4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; (−)-[4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; (+)-[4-(4-Methoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-trifluoromethylphenyl)-methanone; (−)-[4-(4-Methoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-trifluoromethylphenyl)-methanone; [4-(4-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; (+)-[4-(4-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3 ,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; (−)-[4-(4-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; [4-(4-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(3-methoxyphenyl)-methanone; (+)-[4-(4-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(3-methoxyphenyl)-methanone; (−)-[4-(4-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(3-methoxyphenyl)-methanone; [4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-phenyl-methanone; (+)-[4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-phenyl-methanone; (−)-[4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5 -yl]-phenyl-methanone; (4-(2-Dimethylaminoethoxy)phenyl)-[4-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno [3,2-c]pyridin-5-yl]-methanone; (+)-(4-(2-Dimethylaminoethoxy)phenyl)-[4-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno [3,2-c]pyridin-5-yl]-methanone; (−)-(4-(2-Dimethylaminoethoxy)phenyl)-[4-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno [3,2-c]pyridin-5-yl]-methanone; [4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-(2-[2-morpholin-4-ylethoxy)phenyl]-methanone; (+)-[4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-(2-[2-morpholin-4-ylethoxy) phenyl]-methanone; (−)-[4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-(2-[2-morpholin-4-ylethoxy) phenyl]-methanone; [4-(4-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-dimethylaminophenyl)-methanone; 3-{4-[4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine-5-carbonyl ]phenyl}acrylic acid; (4-Chlorophenyl)-[4-(4-chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-methanone; [4-(4-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; [4-(4-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; [4-(2-Dimethylaminoethoxy)-phenyl]-[4-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno [3,2-c]pyridin-5-yl]-methanone; [4-(2-Dimethylaminoethoxy)-phenyl]-[4-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno [3 ,2-c]pyridin-5-yl]-methanone; [4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3 ,2-c]pyridin-5-yl]-[4-(2-morpholin-4-ylethoxy) phenyl]-methanone; [4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-[4-(2-morpholin-4-ylethoxy) phenyl]-methanone; [4-(4-Trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; [4-(4-Trifluoromethoxyphenyl)4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; [4-(4-Trifluoromethoxyphenyl)4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; [4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-( 1 H-indol-5-yl)-methanone; (1 H-Indol-5-yl)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-methanone; [4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-fluorophenyl)-methanone; [4-(4-Trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-fluorophenyl)-methanone; 4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-[4-(2-dimethylaminoethoxy) phenyl]-methanone; [4-(2-Dimethylaminoethoxy)phenyl]-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno [3,2-c]pyridin-5-yl]-methanone; [4-(3,4-Dimethoxyphenyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-6-yl]-[4-(2-dimethylaminoethoxy)-phenyl ]-methanone; (3,4-Dimethoxyphenyl)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno [3,2-c]pyridin-5-yl]methanone; (3-Chloro-4-methoxyphenyl)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c ]pyridin-5-yl]methanone; (4-Ethoxyphenyl)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]methanone; (4-Methylpheny2)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]methanone; 3-(4-Methoxyphenyl)-1-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno [3,2-c]pyridin-5-yl]propenone; (1 H-Benzimidazol-5-yl)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]methanone; or a pharmaceutically acceptable salt thereof, or an optical isomer or mixture of optical isomers thereof, or a tautomeric form thereof.
- 37. The pharmaceutical composition of claim 1, wherein the compound is:(+)-[4-(4-Methoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-trifluoromethylphenyl)-methanone; [4-(4-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-dimethylaminophenyl)-methanone; [4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(1 H-indol-5-yl)-methanone; (1 H-Indol-5-yl)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-methanone; [4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3 ,2-c]pyridin-5-yl]-(4-fluorophenyl)-methanone; [4-(4-Trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-fluorophenyl)-methanone; (3,4-Dimethoxyphenyl)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno [3,2-c]pyridin-5-yl]methanone; (3-Chloro-4-methoxyphenyl)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]methanone; (4-Ethoxyphenyl)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl ]methanone; (4-Methylphenyl)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl ]methanone; 3-(4-Methoxyphenyl)-1-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno [3,2-c]pyridin-5-yl]propenone; (1 H-Benzimidazol-5-yl)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c ]pyridin-5-yl]methanone; (4-Methoxyphenyl)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]- methanone; [4-(4-Trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; [4-(4-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methylsulfanylphenyl)-methanone; 4-[4-(4-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine-5-carbonyl]benzoic acid methyl ester; (4-Hydroxymethylphenyl)-[4-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c ]pyridin-5-yl]methanone; (4-Acetoxyphenyl)-[4-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl ]methanone; (4-Cyanophenyl)-[4-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl ]methanone; 1-{4-[4-(4-Trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3 ,2-c]pyridine-5-carbonyl ]phenyl }ethanone; 3-(5-Methylfuran-2-yl)-1-[4-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c ]pyridin-5-yl]propenone; 3-Furan-3-yl-1-[4-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl ]propenone; 3-Thiophen-3-yl-1-[4-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl ]propenone; (4-Methylsulfanylphenyl)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c ]pyridin-5-yl]methanone; (4-Dimethylaminophenyl)-[4-(4-trifluoromethoxypheny2)-4,5,6,7-tetrahydro-thieno[3,2-c ]pyridin-5-yl]methanone; (4-Hydroxymethylphenyl)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno(3,2-c ]pyridin-5-yl]methanone; 3-Furan-3-yl-1-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl ]propenone; [4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3 ,2-c]pyridin-5-yl]-(4-hydroxyphenyl) methanone; (4-Hydroxymethylphenyl)-(4-phenyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl) methanone; [4-(4-Dimethylaminophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl)-(4-hydroxymethylphenyl)-methanone; (4-Chlorophenyl)-(4-phenyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl)methanone; [4-(4-Dimethylaminophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-methoxyphenyl)-methanone; (4-Dimethylaminophenyl)-(4-phenyl-4,5,6,7-tetrahydro-thieno[3 ,2-c]pyridin-5-yl)-methanone; (4-Dimethylaminophenyl)-[4-(4-dimethylaminophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c ]pyridin-5-yl]-methanone; 3-Furan-3 -yl- 1 -(4-phenyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl)-propenone; [4-(4-Chlorophenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]-(4-hydroxyphenyl)-methanone; (1 -Benzoimidazol-5-yl)-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c ]pyridin-5-yl]methanone, more polar enantiomer; 3-(4-Fluorophenyl)-1-[4-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl]propenone; or a pharmaceutically acceptable salt thereof, or an optical isomer or mixture of optical isomers thereof, or a tautomeric form thereof.
- 38. The pharmaceutical composition of claim 1 in the form of an oral dosage unit or a parenteral dosage unit.
- 39. The pharmaceutical composition of claim 38 wherein the compound is present in an amount in a range from about 0.05 to 1000 mg.
- 40. A method of treating or preventing a disease of the endocrine system, comprising administering to a subject in need thereof an effective amount of a compound of formula I wherein A together with the double bond of formula I is thiophene, R1 is optionally substituted C1-6-alkyl or optionally substituted aryl, R2 is optionally substituted C1-6-alkyl, optionally substituted aralkyl, or —COR3, wherein R3 is optionally substituted C1-6-alkyl, optionally substituted aralkyl, or optionally substituted aryl, R4 and R5 independently are hydrogen, halogen, perhalomethyl, optionally substituted C1-6-alkyl, hydroxy, optionally substituted C1-6-alkoxy, nitro, cyano, amino, optionally substituted mono- or optionally substituted di-C1-6-alkylamino, acylamino, C1-6-alkoxycarbonyl, carboxy or carbamoyl, n is 0, and m is 1, or a pharmaceutically acceptable salt thereof, or an optical isomer or mixture of optical isomers thereof, or a tautomeric form thereof.
- 41. The method of claim 40, wherein the disease is diabetes.
- 42. The method of claim 41, wherein the disease is NIDDM.
- 43. The method of claim 40, wherein the disease is hyperglycemia or hypoglycemia.
- 44. The method of claim 40, whereinR1 is phenyl, phenyl substituted with one or more halogen, perhalomethyl, perhalomethoxy, C1-6-alkoxy, or 2,3-dihydrobenzofuran; and R2 is —COR3 wherein R3 is phenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-trifluoromethylphenyl, 4-(2-dimethylaminoethoxy)phenyl, 4-(2-morpholin-4-ylethoxy)phenyl, 4-methylphenyl, 3,4-dimethoxyphenyl, 4-ethoxyphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, dimethylaminophenyl, 4-(2-carboxyethenyl)phenyl, 4-(2-dimethylaminoethoxy)phenyl, 4-(2-morpholin-4-ylethoxy)phenyl, 1 H-indol-5-yl, 3-chloro-4-methoxyphenyl, or 1 H-benzimidazol-5-yl.
- 45. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound of formula I wherein A together with the double bond of formula I is benzene, R1 is optionally substituted C1-6-alkyl or optionally substituted aryl, R2 is optionally substituted C1-6-alkyl, optionally substituted aralkyl, or —COR3, wherein R3 is optionally substituted C1-6-alkyl, optionally substituted aralkyl, or optionally substituted aryl, R4 and R5 independently are hydrogen, halogen, perhalomethyl, optionally substituted C-6-alkyl, hydroxy, optionally substituted C1-6-alkoxy, nitro, cyano, amino, optionally substituted mono- or optionally substituted di-C1-6-alkylamino, acylamino, C1-6-alkoxycarbonyl, carboxy or carbamoyl, is 0, and m is 1, or a pharmaceutically acceptable salt thereof, or an optical isomer or mixture of optical isomers thereof, or a tautomeric form thereof, wherein the compound is selected from the group consisting of: [7-Chloro-1-(2,3-dihydrobenzofuran-7-yl)-8-methoxy-1,2,4,5-tetrahydrobenzo[d]azepin-3-yl]-[4-(2-dimethylaminoethoxy)-phenyl ]-methanone; (1-Benzyl-1,2,3,4-tetrahydro-isoquinolin-2-yl)-(4-methoxyphenyl)methanone; (1-Benzyl-1,2,3,4-tetrahydro-isoquinolin-2-yl)-(4-chlorophenyl)methanone; (1 H-Benzoimidazol-5-yl)-(1-benzyl-1,2,3,4-tetrahydro-isoquinolin-2-yl)methanone; 1-(1-Benzyl-1,2,3,4-tetrahydro-isoquinolin-2-yl)-3-furan-3 -ylpropenone; 1-(1-Benzyl-1,2,3,4-tetrahydro-isoquinolin-2-yl)-3-(4-methoxyphenyl)propenone; 1-(1-Benzyl-1,2,3,4-tetrahydro-isoquinolin-2-yl)-3-(4-methoxyphenyl)propan-1-one; 1-(1-Benzyl-1,2,3,4-tetrahydro-isoquinolin-2-yl)-2-(4-methoxyphenyl)ethanone; (5-Chlorothiophen-2-yl)-[1-(4-trifluoromethoxyphenyl)- 1,2,3 ,4-tetrahydroisoquinolin-2-yl]-methanone; (4-Chlorophenyl)-[1-(4-trifluoromethoxyphenyl)-1,2,3,4-tetrahydroisoquinolin-2-yl]-methanone; (4-Methoxyphenyl)-[1-(4-trifluoromethoxyphenyl)-1,2,3,4-tetrahydroisoquinolin-2-yl]-methanone; 3-(4-Methoxyphenyl)-1-[1-(4-trifluoromethoxyphenyl)- 1,2,3,4-tetrahydroisoquinolin-2-yl]propenone; and 3-Furan-3-yl-1-[1-(4-trifluoromethoxyphenyl)-1,2,3,4-tetrahydroisoquinolin-2-yl]propenone.
Priority Claims (2)
Number |
Date |
Country |
Kind |
0249/97 |
Mar 1997 |
DK |
|
1365/97 |
Nov 1997 |
DK |
|
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims priority of U.S. provisional application Ser. Nos. 60/041,641 and 60/067,809 filed on Mar. 27, 1997 and Dec. 8, 1997, respectively, and of Danish application nos. 0249/97 and 1365/97 filed Mar. 7, 1997 and Nov. 27, 1997, respectively, the contents of which are fully incorporated herein by reference.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4681888 |
Esanu |
Jul 1987 |
|
Foreign Referenced Citations (4)
Number |
Date |
Country |
0 088 250 |
Sep 1983 |
EP |
0 157 324 |
Oct 1985 |
EP |
WO 8705295 |
Sep 1987 |
WO |
WO 9634870 |
Nov 1996 |
WO |
Non-Patent Literature Citations (2)
Entry |
Chemical Abstracts 77:5364, Saito et al, 1972. |
Chemical Abstracts 77:96746, Paul et al, 1972. |
Provisional Applications (2)
|
Number |
Date |
Country |
|
60/041641 |
Mar 1997 |
US |
|
60/067809 |
Dec 1997 |
US |