Pyridin-4-yl derivatives

1. A compound of the Formula (I),

wherein

A represents

wherein the asterisks indicate the bond that is linked to the pyridine group of Formula (I);

R 1 represents 3-pentyl, 3-methyl-but-1-yl, cyclopentyl, or cyclohexyl;

R 2 represents methoxy;

R 3 represents 2,3-dihydroxypropoxy, —OCH 2 —CH(OH)—CH 2 —NHCO—CH 2 OH, —OCH 2 —CH(OH)—CH 2 N(CH 3 )—CO—CH 2 OH, —NHSO 2 CH 3 , or —NHSO 2 CH 2 CH 3 ; and

R 4 represents ethyl or chloro;

or salts thereof.

2. A compound according to claim 1 , wherein the stereocenter of the R 3 groups 2,3-dihydroxypropoxy, —OCH 2 —CH(OH)—CH 2 —NHCO—CH 2 OH, and —OCH 2 —CH(OH)—CH 2 N(CH 3 )—CO—CH 2 OH is in the S-configuration, or salts thereof.

3. A compound according to claim 1 , wherein the stereocenter of the R 3 groups 2,3-dihydroxypropoxy, —OCH 2 —CH(OH)—CH 2 —NHCO—CH 2 OH, and —OCH 2 —CH(OH)—CH 2 N(CH 3 )—CO—CH 2 OH is in the R-configuration, or salts thereof.

4. A compound according to claim 1 , wherein A represents

wherein the asterisk indicates the bond that is linked to the pyridine group of Formula (I), or salts thereof.

5. A compound according to claim 1 , wherein A represents

wherein the asterisk indicates the bond that is linked to the pyridine group of Formula (I), or salts thereof.

6. A compound according to claim 1 , wherein A represents

or salts thereof.

7. A compound according to claim 1 , wherein R 1 represents 3-pentyl, or salts thereof.

8. A compound according to claim 1 , wherein R 1 represents 3-methyl-but-1-yl, or salts thereof.

9. A compound according to claim 1 , wherein R 1 represents cyclopentyl, or salts thereof.

10. A compound according to claim 1 , wherein R 1 represents cyclohexyl, or salts thereof.

11. A compound according to claim 1 , wherein R 3 represents 2,3-dihydroxypropoxy, or salts thereof.

12. A compound according to claim 1 , wherein R 3 represents —OCH 2 —CH(OH)—CH 2 —NHCO—CH 2 OH, or salts thereof.

13. A compound according to claim 1 , wherein R 3 represents —OCH 2 —CH(OH)—CH 2 N(CH 3 )—CO—CH 2 OH, or salts thereof.

14. A compound according to claim 1 , wherein R 3 represents —NHSO 2 CH 3 , or salts thereof.

15. A compound according to claim 1 , wherein R 3 represents —NHSO 2 CH 2 CH 3 , or salts thereof.

16. A compound according to claim 1 , wherein R 4 represents ethyl, or salts thereof.

17. A compound according to claim 1 , wherein R 4 represents chloro, or salts thereof.

18. A compound according to claim 1 selected from the group consisting of:

(S)-3-(2-Ethyl-4-{5-[2-(1-ethyl-propyl)-6-methoxy-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenoxy)-propane-1,2-diol;

(S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol;

(R)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol;

(S)-3-{4-[5-(2-cyclohexyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol;

ethanesulfonic acid {2-chloro-4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-amide;

N—[(S)-3-(2-ethyl-4-{5-[2-(1-ethyl-propyl)-6-methoxy-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenoxy)-2-hydroxy-propyl]-2-hydroxy-acetamide;

N—((S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

N—((S)-3-{4-[5-(2-cyclohexyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

N—((S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-N-methyl-acetamide;

N-(2-chloro-4-{5-[2-(1-ethyl-propyl)-6-methoxy-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenyl)-methanesulfonamide;

N-{2-chloro-4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-methanesulfonamide;

(S)-3-{2-chloro-4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-propane-1,2-diol;

N—((S)-3-{2-chloro-4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

(S)-3-(2-ethyl-4-{5-[2-methoxy-6-(3-methyl-butyl)-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenoxy)-propane-1,2-diol;

N—[(S)-3-(2-ethyl-4-{5-[2-methoxy-6-(3-methyl-butyl)-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenoxy)-2-hydroxy-propyl]-2-hydroxy-acetamide;

N-{2-chloro-4-[5-(2-cyclohexyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-methanesulfonamide;

N-(2-ethyl-4-{5-[2-(1-ethyl-propyl)-6-methoxy-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenyl)-methanesulfonamide;

N-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenyl}-methanesulfonamide;

N-{4-[5-(2-cyclohexyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenyl}-methanesulfonamide;

(S)-3-{4-[3-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol;

(R)-3-{4-[3-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol;

N—((S)-3-{4-[3-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

N—((R)-3-{4-[3-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

(S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol;

(R)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol;

N—((S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide; and

N—((R)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

or salts of these compounds.

19. A compound according to claim 1 selected from the group consisting of:

(S)-3-{2-chloro-4-[5-(2-cyclohexyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-propane-1,2-diol; and

N-(2-ethyl-4-(5-(2-isopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)methanesulfonamide;

or salts of these compounds.

20. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

21. A method for the treatment of diseases or disorders associated with an activated immune system comprising administering the compound of claim 1 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof.

22. The method of claim 21 , wherein the diseases or disorders is selected from the group consisting of rejection of transplanted organs such as kidney, liver, heart, lung, pancreas, cornea, and skin; graft-versus-host diseases brought about by stem cell transplantation; autoimmune syndromes including rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, psoriasis, psoriatic arthritis, thyroiditis such as Hashimoto's thyroiditis, uveo-retinitis; atopic diseases such as rhinitis, conjunctivitis, dermatitis; asthma; type I diabetes; post-infectious autoimmune diseases including rheumatic fever and post-infectious glomerulonephritis.

23. The compound according to claim 1 which is (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol or a salt thereof.

24. The compound according to claim 1 which is N-((2S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-N-methyl-acetamide or a salt thereof.

25. The compound according to claim 1 which is N-{2-chloro-4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-methanesulfonamide or a salt thereof.

26. The compound according to claim 1 which is N-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenyl}-methanesulfonamide or a salt thereof.

27. The pharmaceutical composition according to claim 20 , wherein the compound according to claim 1 is (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol or a pharmaceutically acceptable salt thereof.

28. The pharmaceutical composition according to claim 20 , wherein the compound according to claim 1 is N-((2S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-N-methyl-acetamide or a pharmaceutically acceptable salt thereof.

29. The pharmaceutical composition according to claim 20 , wherein the compound according to claim 1 is N-{2-chloro-4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-methanesulfonamide or a pharmaceutically acceptable salt thereof.

30. The pharmaceutical composition according to claim 20 , wherein the compound according to claim 1 is N-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenyl}-methanesulfonamide or a pharmaceutically acceptable salt thereof.

31. The method according to claim 22 , wherein the compound according to claim 1 is (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol or a pharmaceutically acceptable salt thereof.

32. The method according to claim 22 , wherein the compound according to claim 1 is N-((2S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-N-methyl-acetamide or a pharmaceutically acceptable salt thereof.

33. The method according to claim 22 , wherein the compound according to claim 1 is N-{2-chloro-4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-methanesulfonamide or a pharmaceutically acceptable salt thereof.

34. The method according to claim 22 , wherein the compound according to claim 1 is N-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenyl}-methanesulfonamide or a pharmaceutically acceptable salt thereof.

35. A method for the prevention of graft-versus-host diseases brought about by stem cell transplantation or rejection of transplanted organs selected from the group consisting of kidney, liver, heart, lung, pancreas, cornea, and skin, comprising administering the compound of claim 1 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof.

36. A method for decreasing the number of circulating lymphocytes in a patient in need thereof comprising administering to said patient the compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

37. The method according to claim 36 , wherein said patient is suffering from a disease or disorder associated with an activated immune system.

38. The method according to claim 37 , wherein the compound according to claim 1 is (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol or a pharmaceutically acceptable salt thereof.

39. The method according to claim 37 , wherein the compound according to claim 1 is N-((2S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-N-methyl-acetamide or a pharmaceutically acceptable salt thereof.

40. The method according to claim 37 , wherein the compound according to claim 1 is N-{2-chloro-4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-methanesulfonamide or a pharmaceutically acceptable salt thereof.

41. The method according to claim 37 , wherein the compound according to claim 1 is N-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenyl}-methanesulfonamide or a pharmaceutically acceptable salt thereof.

42. The method according to claim 21 , wherein the compound according to claim 1 is

(S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol or a pharmaceutically acceptable salt thereof.

43. The method according to claim 21 , wherein the compound according to claim 1 is N-((2S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-N-methyl-acetamide or a pharmaceutically acceptable salt thereof.

44. The method according to claim 21 , wherein the compound according to claim 1 is N-{2-chloro-4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-methanesulfonamide or a pharmaceutically acceptable salt thereof.

45. The method according to claim 21 , wherein the compound according to claim 1 is N-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenyl}-methanesulfonamide or a pharmaceutically acceptable salt thereof.