Inhibitors of diacylglycerol acyltransferase

1. A compound of formula (I):

wherein:

X is C, O or N;

Y is C or N;

Z is C or N;

W is C or S, wherein if W is S, then R2 is absent;

R1 is unsubstituted heteroaryl, unsubstituted aryl, or aryl substituted with —OCF3;

R2 is H, lower alkyl or haloloweralkyl;

R3 is phenyl, pyridine or pyrimidine; and

R4 is -piperidine-trifluoromethylphenyl,

-piperazine-1-yl-benzoic acid lower alkyl ester,

-piperazine-pyrimidine,

-piperazine-lower alkoxy phenyl,

-piperazine-trifluoromethylphenyl,

-hydroxy-piperidine-lower alkoxy phenyl,

-piperazine-phenyl,

-hydroxy-piperidine-phenyl,

-piperidine-phenyl,

-hydroxy piperidine-trifluoromethylphenyl,

-piperidine-trifluoromethylphenyl,

-piperazine-halo phenyl,

-piperazine-benzoic acid,

-piperidine-lower alkyl oxadiazole,

-piperidine-cycloloweralkyloxadiazole,

-pyrrolidine-lower alkyl oxadiazole,

-piperidine-pyridinecarboxylic acid,

—O-pyrrolidine-benzoic acid,

—O-pyrrolidine-benzoic acid lower alkyl ester,

-pyrrolidine-benzoic acid lower alkyl ester,

-pyrrolidine-benzoic acid,

-piperidine-benzoic acid, or

-piperidine-benzoic acid lower alkyl ester;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein X is O and Z is N.

3. The compound according to claim 1 , wherein X is N and Y is N.

4. The compound according to claim 1 , wherein W is C.

5. The compound according to claim 1 , wherein W is C, X is O, Y is C and Z is N.

6. The compound according to claim 1 , wherein R1 is phenyl, trifluoromethoxy-phenyl or pyridine.

7. The compound according to claim 1 , wherein R2 is methyl, ethyl, trifluoromethyl or hydrogen.

8. The compound according to claim 1 , wherein R3 is pyridine or phenyl.

9. The compound according to claim 1 , wherein said compound is:

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [4-(3-trifluoromethyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-amide

4-(4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl}-piperazin-1-yl)-benzoic acid ethyl ester,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [6-(4-pyrimidin-2-yl-piperazin-1-yl)-pyridin-3-yl]-amide,

4-(4-{5-[(1-pyridin-2-yl-3-trifluoromethyl-1H-pyrazole-4-carbonyl)-amino]-pyridin-2-yl}-piperazin-1-yl)-benzoic acid ethyl ester,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {6-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-pyridin-3-yl}-amide,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {6-[4-(4-methoxy-phenyl)-piperazin-1-yl]-pyridin-3-yl}-amide,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {6-[4-(2-trifluoromethyl-phenyl)-piperazin-1-yl]-pyridin-3-yl}-amide,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {6-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-pyridin-3-yl}-amide,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {6-[4-(2-methoxy-phenyl)-piperazin-1-yl]-pyridin-3-yl}-amide,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {6-[4-(3-methoxy-phenyl)-piperazin-1-yl]-pyridin-3-yl}-amide,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [4-hydroxy-4-(3-trifluoromethyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-amide,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [6-(4-phenyl-piperazin-1-yl)-pyridin-3-yl]-amide,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (4-phenyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl)-amide,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (4-hydroxy-4-phenyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl)-amide,

1-pyridin-2-yl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid [4-(3-trifluoromethyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-amide,

1-pyridin-2-yl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid {6-[4-(4-[4-(fluoro-phenyl)-piperazin-1-yl]-pyridin-3-yl}-amide,

4-(4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl}-piperazin-1-yl)-benzoic acid,

3-(4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl}-piperazin-1-yl)-benzoic acid,

2-(4-5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl}-piperazin-1-yl)-benzoic acid,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-phenyl}-amide,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [2-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-pyrimidin-5-yl]-amide;

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-amide,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [4-(3-methyl-[1,2,4]oxadiazol-5-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-amide,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [4-(3-cyclopropyl-[1,2,4]oxadiazol-5-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-amide,

2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {6-[3-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-pyrrolidin-1-yl]-pyridin-3-yl}-amide,

2-(2-trifluoromethoxy-phenyl)-5-trifluoromethyl-oxazole-4-carboxylic acid [4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-amide,

4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carboxylic acid,

4-{4-[(4-phenyl-thiophene-2-carbonyl)-amino]-phenyl}-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carboxylic acid,

4-{4-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-phenyl}-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carboxylic acid,

4-((S)-3-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenoxy}-pyrrolidin-1-yl)-benzoic acid,

4-(4-{4-[(2-phenyl-5 trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidin-1-yl)-benzoic acid,

3-(4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidin-1-yl)-benzoic acid, or

4-(4-{4-[(5-ethyl-2-phenyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidin-1-yl)-benzoic acid.

10. The compound of claim 1 wherein said compound is of the formula:

wherein R 10 is heteroaryl, phenyl, or phenyl substituted with —OCF 3 ; or its pharmaceutically acceptable salts.

11. The compound of claim 10 wherein R4 is piperidine-trifluoromethylphenyl, hydroxy-piperidine-lower alkoxy phenyl, hydroxy-piperidine-phenyl, piperidine-trifluoromethylphenyl, piperidine-lower alkyl oxadiazole, piperidine-pyridinecarboxylic acid, piperidine-cyclopropyloxadiazole, piperidine-benzoic acid, piperidine-benzoic acid lower alkyl ester, piperidine-phenyl, or hydroxy piperidine-trifluoromethylphenyl.

12. The compound of claim 11 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [4-(3-trifluoromethyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-amide or its pharmaceutically acceptable salts.

13. The compound of claim 11 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [4-hydroxy-4-(3-trifluoromethyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-amide or its pharmaceutically acceptable salts.

14. The compound of claim 11 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (4-phenyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl)-amide or its pharmaceutically acceptable salts.

15. The compound of claim 11 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (4-hydroxy-4-phenyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl)-amide or its pharmaceutically acceptable salts.

16. The compound of claim 10 wherein R4 is piperidine-lower alkyl oxadiazole or piperidine-cycloloweralkyloxadiazole.

17. The compound of claim 16 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-amide or its pharmaceutically acceptable salts.

18. The compound of claim 16 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [4-(3-methyl-[1,2,4]oxadiazol-5-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-amide or its pharmaceutically acceptable salts.

19. The compound of claim 16 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [4-(3-cyclopropyl-[1,2,4]oxadiazol-5-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-amide or its pharmaceutically acceptable salts.

20. The compound of claim 16 wherein said compound is 2-(2-trifluoromethoxy-phenyl)-5-trifluoromethyl-oxazole-4-carboxylic acid [4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-amide or its pharmaceutically acceptable salts.

21. The compound of claim 10 wherein R4 is piperazine-1-yl-benzoic acid lower alkyl ester, -piperazine-phenyl, piperazine-halo phenyl, piperazine-benzoic acid, piperazine-pyrimidine, piperazine-lower alkoxy phenyl or piperazine-trifluoromethylphenyl.

22. The compound of claim 21 wherein said compound is 4-(4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl}-piperazin-1-yl)-benzoic acid ethyl ester or its pharmaceutically acceptable salts.

23. The compound of claim 21 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [6-(4-pyrimidin-2-yl-piperazin-1-yl)-pyridin-3-yl]amide or its pharmaceutically acceptable salts.

24. The compound of claim 21 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {6-[4-(3-methoxy-phenyl)-piperazin-1-yl]-pyridin-3-yl}-amide or its pharmaceutically acceptable salts.

25. The compound of claim 21 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {6-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-pyridin-3yl}-amide or its pharmaceutically acceptable salts.

26. The compound of claim 21 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {6-[4-(4-methoxy-phenyl)-piperazin-1-yl]-pyridin-3-yl}-amide or its pharmaceutically acceptable salts.

27. The compound of claim 21 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {6-[4-(2-trifluoromethyl-phenyl)-piperazin-1-yl]-pyridin-3-yl}-amide or its pharmaceutically acceptable salts.

28. The compound of claim 21 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {6-{4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-pyridin-3-yl}-amide or its pharmaceutically acceptable salts.

29. The compound of claim 21 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {6-[4-(2-methoxy-phenyl)-piperazin-1-yl]-kpyridin-3-yl}-amide or its pharmaceutically acceptable salts.

30. The compound of claim 21 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [6-(4-phenyl-piperazin-1-yl)-pyridin-3-yl]-amide or its pharmaceutically acceptable salts.

31. The compound of claim 21 wherein said compound is 4-(4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl)-piperazin-1-yl)-benzoic acid or its pharmaceutically acceptable salts.

32. The compound of claim 21 wherein said compound is 3-(4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl}-piperazin-1-yl)-benzoic acid or its pharmaceutically acceptable salts.

33. The compound of claim 21 wherein said compound is 2-(4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino}-pyridin-2-yl}-piperazin-1-yl)-benzoic acid or its pharmaceutically acceptable salts.

34. The compound of claim 10 wherein R4 is pyrrolidine-lower alkyl oxadiazole, or O-pyrrolidine-benzoic acid or O-pyrrolidine-benzoic acid lower alkyl ester.

35. The compound of claim 34 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {6-[3-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-pyrrolidin-1-yl]-pyridin-3-yl}-amide or its pharmaceutically acceptable salts.

36. The compound of claim 1 wherein said compound is

wherein R 10 is heteroaryl, phenyl, or phenyl substituted with —OCF 3 ; or its pharmaceutically acceptable salts.

37. The compound of claim 36 wherein R4 is piperidine-trifluoromethylphenyl, hydroxy-piperidine-lower alkoxy phenyl, hydroxy-piperidine-phenyl, piperidine-trifluoromethylphenyl, piperidine-lower alkyl oxadiazole, piperidine-pyridinecarboxylic acid, piperidine-cycloloweralkyloxadiazole, piperidine-benzoic acid, piperidine-benzoic acid lower alkyl ester, piperidine-phenyl, or hydroxy piperidine-trifluoromethylphenyl.

38. The compound of claim 36 wherein said compound is 4-{4-{(5-methyl-2-phenyl-oxazole-4-carbonyl)-aminol-phenyl}-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carboxylic acid or its pharmaceutically acceptable salts.

39. The compound of claim 37 wherein said compound is 4-(4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidin-1-yl)-benzoic acid or its pharmaceutically acceptable salts.

40. The compound of claim 37 wherein said compound is 3-(4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidin-1-yl)-benzoic acid or its pharmaceutically acceptable salts.

41. The compound of claim 37 wherein said compound is 4-(4-{4-[(5-ethyl-2-phenyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidin-1-yl)-benzoic acid or its pharmaceutically acceptable salts.

42. The compound of claim 36 wherein R4 is pyrrolidine-lower alkyl oxadiazole, O-pyrrolidine-benzoic acid or O-pyrrolidine-benzoic acid lower alkyl ester.

43. The compound of claim 42 wherein said compound is 4-(3-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenoxy}-pyrrolidin-1-yl)-benzoic acid or its pharmaceutically acceptable salts.

44. The compound of claim 36 wherein R4 is piperidine-lower alkyl oxadiazole or piperidine-cycloloweralkyloxadiazole.

45. The compound of claim 44 wherein said compound is 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid {4-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-phenyl}-amide or its pharmaceutically acceptable salts.

46. The compound of claim 1 wherein said compound is of the formula:

wherein R 10 is heteroaryl, phenyl or phenyl substituted with —OCF 3 ; or its pharmaceutically acceptable salts.

47. The compound of claim 46 wherein R 10 is a heteroaryl contains a 5 or 6 membered ring with from 1 to 2 heteroatoms selected from the group consisting of N, O and S.

48. The compound of claim 47 wherein R4 is piperazine-1-yl-benzoic acid lower alkyl ester, -piperazine-phenyl, piperazine-halophenyl, piperazine-benzoic acid, piperazine-pyrimidine, piperazine-lower alkoxy phenyl, or piperazine-trifluoromethylphenyl.

49. The compound of claim 47 wherein said compound is 4-(4-{5-[(1-pyridin-2-yl-3-trifluoromethyl-1H-pyrazole-4-carbonyl)-amino]-pyridin-2-yl}-piperazin-1-yl)-benzoic acid ethyl ester or its pharmaceutically acceptable salts.

50. The compound of claim 47 wherein said compound is 1-pyridin-2-yl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid {6-[4-(4-fluoro-phenyl)-piperazin-1-yl]-pyridin-3-yl}-amide or its pharmaceutically acceptable salts.

51. The compound of claim 46 wherein R4 is piperidine-trifluoromethylphenyl, hydroxy-piperidine-lower alkoxy phenyl, hydroxy-piperidine-phenyl, piperidine-trifluoromethylphenyl, piperidine-lower alkyl oxadiazole, piperidine-lower alkyl oxadiazole, piperidine-pyridinecarboxylic acid, piperidine-cyclopropyloxadiazole, piperidine-benzoic acid, piperidine-phenyl, or hydroxy piperidine-trifluoromethylphenyl.

52. The compound of claim 47 wherein said compound is 1-pyridin-2-yl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid [4-(3-trifluoromethyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-amide or its pharmaceutically acceptable salts.

53. The compound of claim 1 wherein said compound is of the formula:

wherein R 10 is heteroaryl, phenyl or phenyl substituted with an —OCF 3 ; or its pharmaceutically acceptable salts.

54. The compound of claim 53 wherein R4 is piperidine-trifluoromethylphenyl, hydroxy-piperidine-lower alkoxy phenyl, hydroxy-piperidine-phenyl, piperidine-trifluoromethylphenyl, piperidine-lower alkyl oxadiazole, piperidine-pyridinecarboxylic acid, piperidine-cycloloweralkyloxadiazole, piperidine-benzoic acid, piperidine-phenyl, piperidine-benzoic acid lower alkyl ester or hydroxy piperidine-trifluoromethylphenyl.

55. The compound of claim 53 wherein said compound is 4-{4-[(4-phenyl-thiophene-2-carbonyl)-amino]-phenyl}-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carboxylic acid or its pharmaceutically acceptable salts.