Compounds, their preparation and use

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof:

wherein X 1 is hydrogen, halogen, hydroxy, cyano, or amino; or

X 1 is C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aralkyl, heteroaralkyl, arylC 2-6 -alkynyl, heteroarylC 2-6 -alkynyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio, C 3-6 -cycloalkylthio, C 1-6 -alkylcarbonyl, arylcarbonyl, C 1-6 -alkylsulfonyl, C 1-6 -alkylsulfonyloxy, arylsulfonyl, arylsulfonyloxy, C 1-6 -alkylamido, arylamido, C 1-6 -alkylaminocarbonyl, C 1-6 -alkylamino, C 1-6 -dialkylamino or C 3-6 -cycloalkylamino each of which is optionally substituted with one or more halogens; or

X 1 is aryl or heteroaryl each of which is optionally substituted with one or more substituents, where said substituents independently are:

halogen, hydroxy, cyano, amino or carboxy; or

C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aralkyl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio, C 3-6 -cycloalkylthio, C 1-6 -alkylcarbonyl, arylcarbonyl, C 1-6 -alkylsulfonyl, C 1-6 -alkylsulfonyloxy, arylsulfonyl, arylsulfonyloxy, C 1-6 -alkylamido, arylamido, C 1-6 -alkylaminocarbonyl, C 1-6 -alkylamino, C 1-6 -dialkylamino or C 3-6 -cycloalkylamino each of which is optionally substituted with one or more halogens;

X 2 is hydrogen, halogen, hydroxy, cyano, or amino; or

X 2 is C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aralkyl, heteroaralkyl, arylC 2-6 -alkynyl, heteroarylC 2-6 -alkynyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio, C 3-6 -cycloalkylthio, C 1-6 -alkylcarbonyl, arylcarbonyl, C 1-6 -alkylsulfonyl, C 1-6 -alkylsulfonyloxy, arylsulfonyl, arylsulfonyloxy, C 1-6 -alkylamido, arylamido, C 1-6 -alkylaminocarbonyl, C 1-6 -alkylamino, C 1-6 -dialkylamino or C 3-6 -cycloalkylamino each of which is optionally substituted with one or more halogens; or

X 2 is aryl or heteroaryl each of which is optionally substituted with one or more substituents, where said substituents independently are:

halogen, hydroxy, cyano, amino or carboxy; or

C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aralkyl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio, C 3-6 -cycloalkylthio, C 1-6 -alkylcarbonyl, arylcarbonyl, C 1-6 -alkylsulfonyl, C 1-6 -alkylsulfonyloxy, arylsulfonyl, arylsulfonyloxy, C 1-6 -alkylamido, arylamido, C 1-6 -alkylaminocarbonyl, C 1-6 -alkylamino, C 1-6 -dialkylamino or C 3-6 -cycloalkylamino each of which is optionally substituted with one or more halogens;

Ar is arylene which is optionally substituted with one or more substituents, where said substituents independently are:

halogen, hydroxy or cyano; or

C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio or C 3-6 -cycloalkylthio each of which is optionally substituted with one or more halogens; or

two of the substituents when placed in adjacent positions together with the atoms to which they are attached my form a five to eight member ring;

Y 1 is O or S;

Y 2 is O or S;

Z 1 is —(CH 2 ) n — wherein n is 0, 1, 2 or 3;

Z 2 is —(CH 2 ) m — wherein m is 1, 2 or 3;

R 1 is hydrogen, halogen or R 1 is

C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aralkyl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio or C 3-6 -cycloalkylthio each of which is optionally substituted with one or more halogens; and

R 2 is hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 4-6 -alkenynyl or aryl.

2. The compound according to claim 1 , wherein X 1 is halogen or cyano.

3. The compound according to claim 1 , wherein X 1 is C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aralkyl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio, C 3-6 -cycloalkylthio, C 1-6 -alkylcarbonyl, arylcarbonyl, C 1-6 -alkylsulfonyl, C 1-6 -alkylsulfonyloxy, arylsulfonyl, arylsulfonyloxy, C 1-6 -alkylamido, arylamido, C 1-6 -alkylaminocarbonyl, C 1-6 -alkylamino, C 1-6 -dialkylamino or C 3-6 -cycloalkylamino each of which is optionally substituted with one or more halogens.

4. The compound according to claim 3 , wherein X 1 is C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aralkyl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio, C 3-6 -cycloalkylthio, arylcarbonyl, C 1-6 -alkylsulfonyl, C 1-6 -alkylsulfonyloxy, arylsulfonyl, arylsulfonyloxy each of which is optionally substituted with one or more halogens.

5. The compound according to claim 4 , wherein X 1 is C 1-6 -alkyl, aralkyl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, each of which is optionally substituted with one or more halogens.

6. The compound according to claim 5 , wherein X 1 is C 1-6 -alkyl or C 1-6 -alkoxy, each of which is optionally substituted with one or more halogens.

7. The compound according to claim 1 , wherein X 1 is aryl optionally substituted with one or more substituents, where said substituents independently are:

halogen; or

C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -alkylsulfonyl or C 1-6 -alkylsulfonyloxy each of which is optionally substituted with one or more halogens.

8. The compound according to claim 7 , wherein X 1 is aryl optionally substituted with one or more substituents, where said substituents independently are:

halogen; or

C 1-6 -alkyl optionally substituted with one or more halogens.

9. The compound according to claim 8 , wherein X 1 is aryl optionally substituted with one or more halogens.

10. The compound according to any one of the claim 9 , wherein X 1 is phenyl optionally substituted with one or more substituents, where said substituents independently are:

halogen; or

C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -alkylsulfonyl or C 1-6 -alkylsulfonyloxy each of which is optionally substituted with one or more halogens.

11. The compound according to claim 10 , wherein X 1 is phenyl optionally substituted with one or more substituents, where said substituents independently are:

halogen; or

C 1-6 -alkyl optionally substituted with one or more halogens.

12. The compound according to claim 11 , wherein X 1 is phenyl optionally substituted with one or more halogens.

13. The compound according to claim 1 , wherein X 1 is heteroaryl optionally substituted with one or more substituents, where said substituents independently are:

halogen; or

C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -alkylsulfonyl or C 1-6 -alkylsulfonyloxy each of which is optionally substituted with one or more halogens.

14. The compound according to claim 13 , wherein X 1 is heteroaryl optionally substituted with one or more substituents, where said substituents independently are:

halogen; or

C 1-6 -alkyl optionally substituted with one or more halogens.

15. The compound according to claim 14 , wherein X 1 is heteroaryl optionally substituted with one or more halogens.

16. The compound according to any one of the claim 15 , wherein X 1 is furyl or thienyl optionally substituted with one or more halogens.

17. The compound according to claim 16 , wherein X 2 is halogen or cyano.

18. The compound according to claim 16 , wherein X 2 is C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aralkyl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio, C 3-6 -cycloalkylthio, C 1-6 -alkylcarbonyl, arylcarbonyl, C 1-6 -alkylsulfonyl, C 1-6 -alkylsulfonyloxy, arylsulfonyl, arylsulfonyloxy, C 1-6 -alkylamido, arylamido, C 1-6 -alkylaminocarbonyl, C 1-6 -alkylamino, C 1-6 -dialkylamino or C 3-6 -cycloalkylamino each of which is optionally substituted with one or more halogens.

19. The compound according to claim 18 , wherein X 2 is C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aralkyl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio, C 3-6 -cycloalkylthio, arylcarbonyl, C 1-6 -alkylsulfonyl, C 1-6 -alkylsulfonyloxy, arylsulfonyl, arylsulfonyloxy each of which is optionally substituted with one or more halogens.

20. The compound according to claim 19 , wherein X 2 is C 1-6 -alkyl, aralkyl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, each of which is optionally substituted with one or more halogens.

21. The compound according to claim 20 , wherein X 2 is C 1-6 -alkyl or C 1-6 -alkoxy, each of which is optionally substituted with one or more halogens.

22. The compound according to claim 16 wherein X 2 is aryl optionally substituted with one or more substituents, where said substituents independently are:

halogen; or

C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -alkylsulfonyl or C 1-6 -alkylsulfonyloxy each of which is optionally substituted with one or more halogens.

23. The compound according to claim 22 , wherein X 2 is aryl optionally substituted with one or more substituents, where said substituents independently are:

halogen; or

C 1-6 -alkyl optionally substituted with one or more halogens.

24. The compound according to claim 23 , wherein X 2 is aryl optionally substituted with one or more halogens.

25. The compound according to claim 24 , wherein X 2 is phenyl optionally substituted with one or more substituents, where said substituents independently are:

halogen; or

C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -alkylsulfonyl or C 1-6 -alkylsulfonyloxy each of which is optionally substituted with one or more halogens.

26. The compound according to claim 25 , wherein X 2 is phenyl optionally substituted with one or more substituents where said substituents independently are:

halogen; or

C 1-6 -alkyl optionally substituted with one or more halogens.

27. The compound according to claim 26 , wherein X 2 is phenyl optionally substituted with one or more halogens.

28. The compound according to claim 16 , wherein X 2 is heteroaryl optionally substituted with one or more substituents where said substituents independently are:

halogen; or

C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -alkylsulfonyl or C 1-6 -alkylsulfonyloxy each of which is optionally substituted with one or more halogens.

29. The compound according to claim 28 , wherein X 2 is heteroaryl optionally substituted with one or more substituents where said substituents independently are:

halogen; or

C 1-6 -alkyl optionally substituted with one or more halogens.

30. The compound according to claim 29 , wherein X 2 is heteroaryl optionally substituted with one or more halogens.

31. The compound according to claim 30 , wherein X 2 is furyl or thienyl optionally substituted with one or more halogens.

32. The compound according to claim 31 , wherein Ar is phenylene which is optionally substituted with one or more substituents, where said substituents independently are:

halogen, hydroxy or cyano; or

C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio or C 3-6 -cycloalkylthio each of which is optionally substituted with one or more halogens; or

two of the substituents when placed in adjacent positions together with the atoms to which they are attached my form a five to eight member ring.

33. The compound according to claim 32 , wherein Ar is phenylene which is optionally substituted with one or more substituents, where said substituents independently are:

halogen; or

C 1-6 -alkyl, C 1-6 -alkoxy, aryloxy or aralkoxy each of which is optionally substituted with one or more halogens; or

two of the substituents when placed in adjacent positions together with the atoms to which they are attached form a five membered ring.

34. The compound according to claim 33 , wherein Ar is phenylene which is optionally substituted with methyl.

35. The compound according to claim 34 , wherein Ar is phenylene.

36. The compound according to claim 35 , wherein Y 1 is S.

37. The compound according to claim 36 , wherein Y 2 is O.

38. The compound according to claim 37 , wherein n is 1 or 2.

39. The compound according to claim 38 , wherein m is 1.

40. The compound according to claim 39 , wherein R 1 is hydrogen or R 1 is C 1-6 -alkyl, aralkyl, C 1-6 -alkoxy, aryloxy, aralkoxy each of which is optionally substituted with one or more halogens.

41. The compound according to claim 40 , wherein R 1 is hydrogen or R 1 is C 1-6 -alkyl, C 1-6 -alkoxy each of which is optionally substituted with one or more halogens.

42. The compound according to claim 41 , wherein R 1 is hydrogen.

43. The compound according to claim 42 , wherein R 2 is hydrogen.

44. The compound according to claim 1 , where the compound is a compound selected from the group consisting of:

{4-[2-(2-Bromo-10,11-dihydro-dibenzo[a,d]cyclohepten-5-ylidene)-ethylsulfanyl]-2-methyl-phenoxy}-acetic acid; and

{4-[2-(2-Phenyl-10,11-dihydro-dibenzo[a,d]cyclohepten-5-ylidene)-ethylsulfanyl]-2-methyl-phenoxy}-acetic acid;

or a pharmaceutically acceptable salt thereof.

45. The compound according to claim 1 , which is a PPARδ agonist.

46. The compound according to claim 45 , which is a selective PPARδ agonist.

47. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier or excipient.

48. The pharmaceutical composition according to claim 47 in unit dosage form, comprising from 0.05 mg to 1000 mg, or from 0.1 to 500 mg, or from 0.5 mg to 200 mg of the compound.

49. A method of treating a disease, disorder, or condition comprising administering to a subject a compound according to claim 1 , where the disease, disorder, or condition is selected from the group consisting of type 1 diabetes, type 2 diabetes, dyslipidemia, syndrome X, metabolic syndrome, impaired glucose tolerance, insulin resistance, hypertrigyceridaemia, obesity, cardiovascular diseases, atherosclerosis, and hypercholesteremia.