Thiazole derivatives and use thereof

1. A method of treating an individual having a disease or disorder comprising the administration of a pharmaceutically effective amount of a compound of Formula I to an individual having a disease or disorder selected from multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosis, inflammatory bowel disease, lung inflammation, thrombosis, brain inflammation chronic obstructive pulmonary disease, anaphylactic shock, fibrosis, pancreatitis, psoriasis, allergic diseases, atherosclerosis, heart hypertrophy, cardiac myocyte dysfunction, elevated blood pressure, vasoconstriction, asthma, multi-organ failure, stroke or ischemic conditions, ischemia-reperfusion, platelet aggregation/activation, skeletal muscle atrophy/hypertrophy, leukocyte recruitment in cancer tissue, metastasis, melanoma, Karposi's sarcoma, acute and chronic bacterial and viral infections, sepsis, graft rejection, glomerulo sclerosis, glomerulo nephritis, progressive renal fibrosis, Alzheimer's disease, Huntington's disease, CNS trauma, endothelial or epithelial injuries in the lung or general lung airways inflammation, wherein said compound of Formula (I) is

wherein:

R 1 is selected from H, acyl, or a substituted acyl;

R 2 is a C 1 -C 6 -alkyl, or substituted C 1 -C 6 -alkyl;

R 3 is selected from the following thienyl groups, defined as T1 and T2:

wherein:

R 4 is selected from:

a sulfonyl group SO 2 —R, wherein R is selected from heteroaryl or heterocycloalkyl; and

R 5 and R 6 are independently selected from H, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl groups; a substituted C 1 -C 6 -alkyl, substituted C 2 -C 6 -alkenyl, substituted C 2 -C 6 -alkynyl groups or halogen;

and isomers, enantiomers, diastereomers, racemates or pharmaceutically acceptable salts thereof.

2. The method according to claim 1 , wherein R 1 is acetyl.

3. The method according to claim 1 , wherein R 2 is methyl.

4. The method according to claim 1 , wherein R 3 is the thienyl group T1.

5. The method according to claim 1 , wherein R 3 is the thienyl group T2.

6. The method according to claim 1 , wherein R 4 is SO 2 —R and R is heteroaryl.

7. The method according to claim 1 , wherein R 4 is SO 2 —R and R is heterocycloalkyl.

8. The method according to claim 1 , wherein R 5 and R 6 are H.

9. The method according to claim 1 , said thiazole compound being selected from the following compounds:

N-(4-methyl-5-{5[(prop-2-yn-1-ylamino)sulfonyl]-2-thienyl}-1,3-thiazol-2-yl)acetamide;

N-(5-{5-[(4-acetylpiperazin-1-yl)sulfonyl]-2-thienyl}-4-methyl-1,3-thiazol-2-yl)acetamide;

N-{5-[5-({[2-(dimethylamino)ethyl]amino}sulfonyl)-2-thienyl]-4-methyl-1,3-thiazol-2-yl}acetamide;

N-[4-methyl-5-(5-{[(1-methylpiperidin-4-yl)amino]sulfonyl}-2-thienyl)-1,3-thiazol-2-yl]acetamide;

N-[5-(5-{[[2-(dimethylamino)ethyl](methyl)amino]sulfonyl}-2-thienyl)-4-methyl-1,3-thiazol-2-yl]acetamide;

5-(2-amino-4-methyl-1,3-thiazol-5-yl)-N-(2-morpholin-4-ylethyl)thiophene-2-sulfonamide;

methyl5-{[4-methyl-5-(5-{[(2-morpholin-4-ylethyl)amino]sulfonyl}-2-thienyl)-1,3-thiazol-2-yl]amino}-5-oxopentanoate;

N-(4-methyl-5-{5-[(4-methylpiperazin-1-yl)sulfonyl]-2-thienyl}-1,3-thiazol-2-yl)acetamide;

N-[4-methyl-5-(5-{[(2-morpholin-4-ylethyl)amino]sulfonyl}-2-thienyl)-1,3-thiazol-2-yl]acetamide;

N-{5-[5-({[3-(dimethylamino)propyl]amino}sulfonyl)-2-thienyl]-4-methyl-1,3-thiazol-2-yl}acetamide;

N-{4-methyl-5-[5-(piperazin-1-ylsulfonyl)-2-thienyl]-1,3-thiazol-2-yl}acetamide;

N˜2˜-({5-[2-(acetylamino)-4-methyl-1,3-thiazol-5-yl]-2-thienyl}sulfonyl)-N˜1˜-methylglycinamide;

N-{5-[5-({[2-(acetylamino)ethyl]amino}sulfonyl)-2-thienyl]-4-methyl-1,3-thiazol-2-yl}acetamide;

N-{5-[5-({[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]amino}sulfonyl)-2-thienyl]-4-methyl-1,3-thiazol-2-yl}acetamide;

methylN-({5-[2-(acetylamino)-4-methyl-1,3-thiazol-5-yl]-2thienyl}sulfonyl)serinate;

N-({5-[2-(acetylamino)-4-methyl-1,3-thiazol-5-yl]-2-thienyl}sulfonyl)serine;

N-[5-(5-{[(2,3-dihydroxypropyl)amino]sulfonyl}-2-thienyl)-4-methyl-1,3-thiazol-2-yl]acetamide;

N-(5-{5-[(dimethylamino)sulfonyl]-2-thienyl}-4-methyl-1,3-thiazol-2-yl)acetamide;

N-{4-methyl-5-[5-({methyl[2-(methylamino)ethyl]amino}sulfonyl)-2-thienyl]-1,3-thiazol-2-yl}acetamide;

N-[5-(5-{[[2-(diethylamino)ethyl](methyl)amino]sulfonyl}-2-thienyl)-4-methyl-1,3-thiazol-2-yl]acetamide;

N-[5-(5-{[(2-methoxyethyl)(methyl)amino]sulfonyl}-2-thienyl)-4-methyl-1,3-thiazol-2-yl]acetamide;

N-[5-(5-{[[2-(dimethylamino)ethyl](ethyl)amino]sulfonyl}-2-thienyl)-4-methyl-1,3-thiazol-2-yl]acetamide;

N-{5-[5-({[2-(dimethylamino)ethyl]amino}sulfonyl)-3-thienyl]-4-methyl-1,3-thiazol-2-yl}acetamide;

N-[4-methyl-5-(5-{[(2-morpholin-4-ylethyl)amino]sulfonyl}-3-thienyl)-1,3-thiazol-2-yl]acetamide;

N-[4-methyl-5-(5-{[(2-piperidin-1-ylethyl)amino]sulfonyl}-3-thienyl)-1,3-thiazol-2-yl]acetamide;

N-{4-methyl-5-[5-(piperazin-1-ylsulfonyl)-3-thienyl]-1,3-thiazol-2-yl}acetamide;

N-{5-[5-({[3-(dimethylamino)propyl]amino}sulfonyl)-3-thienyl]-4-methyl-1,3-thiazol-2-yl}acetamide;

N-[4-methyl-5-(5-{[(1-methylpiperidin-4-yl)amino]sulfonyl}-3-thienyl)-1,3-thiazol-2-yl]acetamide;

N-(4-methyl-5-{5-[(4-methylpiperazin-1-yl)sulfonyl]-3-thienyl}-1,3-thiazol-2-yl)acetamide;

tert-butyl[1-({4-[2-(acetylamino)-4-methyl-1,3-thiazol-5-yl]-2 thienyl}sulfonyl)piperidin-4-yl]methylcarbamate;

N-(5-{5-[(3-hydroxypyrrolidin-1-yl)sulfonyl]-3-thienyl}-4-methyl-1,3-thiazol-2-yl)acetamide;

N-[5-(5-{[(3-hydroxypropyl)amino]sulfonyl}-3-thienyl)-4-methyl-1,3-thiazol-2-yl]acetamide;

N-[5-(5-{[(cis-4-hydroxycyclohexyl)amino]sulfonyl}-3-thienyl)-4-methyl-1,3-thiazol-2-yl]acetamide;

N-(5-{5-[(4-methoxypiperidin-1-yl)sulfonyl]-3-thienyl}-4-methyl-1,3-thiazol-2-yl)acetamide;

N-[4-methyl-5-(5-{[4-(methylamino)piperidin-1-yl]sulfonyl}-3-thienyl)-1,3-thiazol-2-yl]acetamide;

N-[5-(5-{[[2-(dimethylamino)ethyl](methyl)amino]sulfonyl}-3-thienyl)-4-methyl-1,3-thiazol-2-yl]acetamide;

N-[5-(5-{[(1S,5S,7S)-7-(hydroxymethyl)-6,8-dioxa-3-azabicyclo[3.2.1]oct-3-yl]sulfonyl}-3-thienyl)-4-methyl-1,3-thiazol-2-yl]acetamide;

N-[5-(5-{[(2-hydroxyethyl)amino]sulfonyl}-3-thienyl)-4-methyl-1,3-thiazol-2-yl]acetamide;

N-(5-{5-[(4-hydroxypiperidin-1-yl)sulfonyl]-3-thienyl}-4-methyl-1,3-thiazol-2-yl)acetamide;

N-[5-(5-{[(2,3-dihydroxypropyl)amino]sulfonyl}-3-thienyl)-4-methyl-1,3-thiazol-2-yl]acetamide;

N-(4-methyl-5-{5-[(1H-tetrazol-5-ylamino)sulfonyl]-3-thienyl}-1,3-thiazol-2-yl)acetamide;

N-{4-methyl-5-[5-(pyrrolidin-1-ylsulfonyl)-3-thienyl]-1,3-thiazol-2-yl}acetamide;

4-methyl-5-{5-[(4-methylpiperazin-1-yl)sulfonyl]-3-thienyl}-1,3-thiazol-2-amine;

methyl 5-[(4-methyl-5-{5-[(4-methylpiperazin-1-yl)sulfonyl]-3-thienyl}-1,3-thiazol-2-yl)amino]-5-oxopentanoate;

1-{[4-(2-amino-4-methyl-1,3-thiazol-5-yl)-2-thienyl]sulfonyl}piperidin-4-ol;

N-{4-methyl-5-[5-(morpholin-4-ylsulfonyl)-3-thienyl]-1,3-thiazol-2-yl}acetamide;

N-(5-{2-chloro-5-[(4-methylpiperazin-1-yl)sulfonyl]-3-thienyl}-4-methyl-1,3-thiazol-2-yl)acetamide;

N-(5-{5-[(3-hydroxypiperidin-1-yl)sulfonyl]-3-thienyl}-4-methyl-1,3-thiazol-2-yl)acetamide; or

N-(5-{5-[(allylamino)sulfonyl]-3-thienyl}-4-methyl-1,3-thiazol-2-yl)acetamide.

10. The method according to claim 1 , wherein said individual has CNS trauma.

11. The method according to claim 1 , wherein said individual has Alzheimer's disease or Huntington's disease.

12. The method according to claim 1 , wherein said individual has atherosclerosis, heart hypertrophy, cardiac myocyte dysfunction, elevated blood pressure or vasoconstriction.

13. The method according to claim 1 , wherein said individual has chronic obstructive pulmonary disease.

14. The method according to claim 1 , wherein said individual has anaphylactic shock.

15. The method according to claim 1 , wherein said individual has fibrosis.

16. The method according to claim 1 , wherein said individual has leukocyte recruitment in cancer tissue.

17. The method according to claim 1 , wherein said individual has a melanoma.

18. The method according to claim 1 , wherein said individual has an acute or chronic bacterial or viral infection.

19. The method according to claim 1 , wherein said individual has an allergic disease.

20. The method according to claim 1 , wherein said individual has asthma.

21. The method according to claim 1 , wherein said individual has pancreatitis.

22. The method according to claim 1 , wherein said individual has multi-organ failure.

23. The method according to claim 1 , wherein said individual has a stroke.

24. The method according to claim 1 , wherein said individual has platelet aggregation.

25. The method according to claim 1 , wherein said individual has metastasis.

26. The method according to claim 1 , wherein said individual has pulmonary disease.

27. The method according to claim 1 , wherein said individual has glomerulo nephritis or glomerulo sclerosis.

28. The method according to claim 1 , wherein said individual has sepsis.

29. The method according to claim 1 , wherein said individual has a graft rejection.

30. The method according to claim 1 , wherein said individual has general lung airways inflammation.

31. The method according to claim 1 , wherein said individual has multiple sclerosis.

32. The method according to claim 1 , wherein said individual has psoriasis.

33. The method according to claim 1 , wherein said individual has rheumatoid arthritis.

34. The method according to claim 1 , wherein said individual has systemic lupus erythematosis.

35. The method according to claim 1 , wherein said individual has inflammatory bowel disease.

36. The method according to claim 1 , wherein said individual has lung inflammation.

37. The method according to claim 1 , wherein said individual has thrombosis.

38. The method according to claim 1 , wherein said individual has brain inflammation.