Novel bicyclic sulfonamide derivatives which are L-CPT1 inhibitors

Abstract

The invention is concerned with novel heterobicyclic derivatives of formula (I)

Description

Claims

1. A compound of formula (I):

2. The compound according to claim 1, wherein R11, R12, R13, R14, R15, R16, R17 and R18 independently from each other are hydrogen, halogen, hydroxy, lower alkyl, lower-alkoxy, fluoro-lower-alkyl, fluoro-lower-alkoxy, hydroxy-lower-alkyl, aryl or cyano.

3. The compound according to claim 1, wherein V is —C(R7)— and R7 is as defined in claim 1.

4. The compound according to claim 1, wherein W is a single bond.

5. The compound according to claim 1, wherein X is O, S, SO2 or N(R10) and R10 is as defined in claim 1.

6. The compound according to claim 1, wherein Y is —C(R11R12)— or —C(R11R12)C(R13R14)—, and R11, R12, R13 and R14 are as defined in claim 1.

7. The compound according to claim 1, wherein R1, R2, R3, R4 and R5 independently from each other are hydrogen, halogen, lower-alkyl, fluoro-lower-alkyl, lower-alkoxy, fluoro-lower-alkoxy or NH2—C(O).

8. The compound according to claim 1, wherein R1, R2, R3, R4 and R5 independently from each other are hydrogen, halogen or lower-alkoxy.

9. The compound according to claim 1, wherein R1 is lower-alkoxy.

10. The compound according to claim 1, wherein R1 is methoxy.

11. The compound according to claim 1, wherein R2, R3 and R5 are hydrogen.

12. The compound according to claim 1, wherein R4 is halogen.

13. The compound according to claim 1, wherein R4 is chloro.

14. The compound according to claim 1, wherein R6 is an aryl or heteroaryl group, which aryl or heteroaryl group is optionally substituted by 1 to 4 substituents selected from the group consisting of halogen, cyano, lower-alkyl, carboxy-lower-alkyl, lower-alkoxy, COOH, 1H-tetrazol-5-yl and 5-oxo-4H-[1,2,4]oxadiazol-3-yl.

15. The compound according to claim 1, wherein R6 is a phenyl, pyridinyl, pyrazolyl or thiazolyl group, which group is optionally substituted by 1 to 2 substituents selected from the group consisting of halogen, cyano, lower-alkyl, carboxy-lower-alkyl, lower-alkoxy, COOH, 1H-tetrazol-5-yl and 5-oxo-4H-[1,2,4]oxadiazol-3-yl.

16. The compound according to claim 1, wherein R6 is a phenyl, pyridinyl or thiazolyl group, which group is optionally substituted by 1 to 2 substituents selected from the group consisting of halogen, carboxy-lower-alkyl and COOH.

17. The compound according to claim 1, wherein R6 is 4-carboxy-phenyl, 3-fluoro-4-carboxy-phenyl, 3-chloro-4-carboxy-phenyl, 2-carboxy-pyridin-5-yl, 4-carboxy-methyl-phenyl, 4-carboxy-methyl-thiazol-2-yl or 2-carboxy-methyl-thiazol-4-yl.

18. The compound according to claim 1, wherein R7 is hydrogen, halogen, lower-alkyl, lower-alkoxy or fluoro-lower-alkoxy.

19. The compound according to claim 1, wherein R7 is hydrogen or halogen.

20. The compound according to claim 1, wherein R7 is hydrogen or fluoro.

21. The compound according to claim 1 wherein R8 and R9 are hydrogen.

22. The compound according to claim 1, wherein R10 is hydrogen.

23. The compound according to claim 1, wherein R11, R12, R13, R14, R15, R16, R17 and R18 independently from each other are hydrogen or phenyl.

24. The compound according to claim 1, wherein R11, R12, R13, R14, R15, R16, R17 and R18 are hydrogen.

25. The compound according to claim 1, wherein R11, R12, R13, R14, R15, R16, R17 and R18 are hydrogen, COOH or C(O)O-lower-alkyl.

26. The compound according to claim 1, selected from the group consisting of

27. The compound according to claim 1, selected from the group consisting of

28. The compound according to claim 1, selected from the group consisting of

29. The compound according to claim 1, selected from the group consisting of

30. A process for the manufacture of compounds of formula (I) as defined in claim 1, comprising the step of: a) reacting a compound of formula (XIV)

31. A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier and/or adjuvant.

32. A method for the therapeutic and/or prophylactic treatment of diseases which are modulated by L-CPT1 inhibitors, comprising the step of administering a therapeutically effective amount of a compound according to claim 1 to a human being or animal in need thereof.

33. The method according to claim 32, wherein said diseases are hyperglycemia, glucose tolerance disorders, diabetes and associated pathologies, non insulin dependent diabetes mellitus, obesity, hypertension, insulin resistance syndrome, metabolic syndrome, hyperlipidemia, hypercholesterolemia, fatty liver disease, atherosclerosis, congestive heart failure or renal failure,