Thiazole derivatives and use thereof

1. A thiazole derivative according to Formula (I),

wherein R 1 is selected from —C(O)R 5 , C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl, heteroaryl C 1 -C 6 -alkyl, C 3 -C 8 cycloalkyl C 1 -C 6 -alkyl or heterocycloalkyl C 1 -C 6 -alkyl;

R 2 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;

R 3 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;

R 4 is selected from —C(O)R 6 , aryl, heteroaryl, heterocycloalkyl or C 3 -C 8 cycloalkyl;

R 5 is selected from H, hydroxyl, alkoxy, amino, aryl, heteroaryl, C 3 -C 8 cycloalkyl or heterocycloalkyl;

R 6 is selected from H, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl, heteroaryl C 1 -C 6 -alkyl or amino; and

X is S;

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

2. The thiazole derivative according to claim 1 , wherein R 1 is —C(O)R 5 .

3. The thiazole derivative according to claim 1 , wherein R 1 is selected from C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl, heteroaryl C 1 -C 6 -alkyl, C 3 -C 8 cycloalkyl C 1 -C 6 -alkyl or heterocycloalkyl C 1 -C 6 -alkyl.

4. The thiazole derivative according to claim 1 , wherein R 2 is H.

5. The thiazole derivative according to claim 1 , wherein R 3 is methyl.

6. The thiazole derivative according to claim 1 , wherein R 4 is selected from aryl, heterocycloalkyl or C 3 -C 8 cycloalkyl.

7. The thiazole derivative according to claim 1 , wherein R 4 is —C(O)R 6 .

8. The thiazole derivative according to claim 1 , wherein R 5 is selected from hydroxyl or alkoxy.

9. The thiazole derivative according to claim 1 , wherein R 5 is amino.

10. The thiazole derivative according to claim 1 , wherein R 5 is selected from aryl, heteroaryl, C 3 -C 8 cycloalkyl or heterocycloalkyl.

11. The thiazole derivative according to claim 1 , wherein R 6 is selected from C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl or C 1 -C 6 -alkyl.

12. The thiazole derivative according to claim 1 , wherein R 6 is optionally substituted amino.

13. The thiazole derivative according to claim 1 , wherein X is S.

14. The thiazole derivative according to claim 1 , wherein R 1 is —C(O)R 5 , R 2 is H and R 3 is methyl.

15. The thiazole derivative according to claim 1 , wherein R 1 is selected from C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl or heteroaryl C 1 -C 6 -alkyl;

R 2 is H and R 3 is methyl.

16. The thiazole derivative according to claim 1 , said thiazole derivative being selected from the following group:

Ethyl 2′-(acetylamino)-4′-methyl-4,5′-bi-1,3-thiazole-2-carboxylate;

2′-(acetylamino)-N-allyl-4′-methyl-4,5′-bi-1,3-thiazole-2-carboxamide;

N-[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]acetamide;

2′-(acetylamino)-4′-methyl-4,5′-bi-1,3-thiazole-2-carboxylic acid;

2′-(acetylamino)-N-(2-methoxyethyl)-4′-methyl-4,5′-bi-1,3-thiazole-2-carboxamide;

2′-(acetylamino)-4′-methyl-N-(tetrahydrofuran-2-ylmethyl)-4,5′-bi-1,3-thiazole-2-carboxamide;

2′-(acetylamino)-N-[2-(dimethylamino)ethyl]-4′-methyl-4,5′-bi-1,3-thiazole-2-carboxamide;

N-[4′-methyl-2-(morpholin-4-ylcarbonyl)-4,5′-bi-1,3-thiazol-2′-yl]acetamide;

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

2′-(acetylamino)-N-[3-(dimethylamino)propyl]-4′-methyl-4,5′-bi-1,3-thiazole-2-carboxamide;

2′-(acetylamino)-N-(2-hydroxyethyl)-4′-methyl-4,5-bi-1,3-thiazole-2-carboxamide;

2′-(acetylamino)-N-(2-cyanoethyl)-4′-methyl-4,5′-bi-1,3-thiazole-2-carboxamide;

2′-(acetylamino)-4′-methyl-N-1H-tetrazol-5-yl-4,5′-bi-1,3-thiazole-2-carboxamide:

4-({[2′-(acetylamino)-4′-methyl-4,5′-bi-1,3-thiazol-2-yl]carbonyl}amino)benzoic acid;

3-({[2′-(acetylamino)-4′-methyl-4,5′-bi-1,3-thiazol-2-yl]carbonyl}amino)benzoic acid;

2′-(acetylamino)-4′-methyl-N-[3-(1H-tetrazol-5-yl)phenyl]-4,5′-bi-1,3-thiazole-2-carboxamide;

2′-(acetylamino)-N-benzyl-4′-methyl-4,5′-bi-1,3-thiazole-2-carboxamide;

2′-(acetylamino)-4′-methyl-N-propyl-4,5′-bi-1,3-thiazole-2-carboxamide;

2′-(acetylamino)-4′-methyl-N-[4-(1H-tetrazol-5-yl)phenyl]-4,5′-bi-1,3-thiazole-2-carboxamide;

3-({[2′-(acetylamino)-4′-methyl-4,5′-bi-1,3-thiazol-2-yl]carbonyl}amino)-2-hydroxy benzoic acid;

1-{[2′-(acetylamino)-4′-methyl-4,5′-bi-1,3-thiazol-2-yl]carbonyl}piperidine-3-carboxylic acid;

5-({[2′-(acetylamino)-4′-methyl-4,5′-bi-1,3-thiazol-2-yl]carbonyl}amino)-2-hydroxy benzoic acid;

N-[4′-methyl-2-(2H-tetrazol-5-ylmethyl)-4,5′-bi-1,3-thiazol-2′-yl]acetamide;

1-{[2′-(acetylamino)-4′-methyl-4,5′-bi-1,3-thiazol-2-yl]carbonyl}piperidine-4-carboxylic acid;

2′-(acetylamino)-N-[3-(5-amino-1,3,4-thiadiazol-2-yl)phenyl]-4′-methyl-4,5′-bi-1,3-thiazole-2-carboxamide;

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

N-(2-{[4-(hydroxymethyl)piperidin-1-yl]carbonyl}-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl)acetamide;

N-(2-{[4-(2-hydroxyethyl)piperidin-1-yl]carbonyl}-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl)acetamide;

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

2′-(acetylamino)-N-1H-1,2,3-benzotriazol-5-yl-4′-methyl-4,5′-bi-1,3-thiazole-2-carboxamide;

4-({[2′-(acetylamino)-4′-methyl-4,5′-bi-1,3-thiazol-2-yl]carbonyl}amino)-2-hydroxy benzoic acid;

4-({[2′-(acetylamino)-4′-methyl-4,5′-bi-1,3-thiazol-2-yl]carbonyl}amino)-2-fluoro benzoic acid;

2′-(acetylamino)-N-[3-(5-hydroxy-1,3,4-oxadiazol-2-yl)phenyl]-4′-methyl-4,5′-bi-1,3-thiazole-2-carboxamide;

2′-(acetylamino)-N-[4-(5-hydroxy-1,3,4-oxadiazol-2-yl)phenyl]-4′-methyl-4,5′-bi-1,3-thiazole-2-carboxamide;

N-[2-(hydroxymethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]acetamide;

N-(2-methoxyethyl)-N′-[4′-methyl-2-(morpholin-4-ylcarbonyl)-4,5′-bi-1,3-thiazol-2′-yl]urea;

Ethyl N-({[4′-methyl-2-(morpholin-4-ylcarbonyl)-4,5′-bi-1,3-thiazol-2′-yl]amino }carbonyl)-beta-alaninate;

N-[2-(1,4-dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]acetamide;

2′-(acetylamino)-N-(2,3-dihydroxypropyl)-4′-methyl-4,5′-bi-1,3-thiazole-2-carboxamide;

N-[4′-methyl-2-(morpholin-4-ylcarbonyl)-4,5′-bi-1,3-thiazol-2′-yl]urea;

N-{4′-methyl-2-[(3-oxopiperazin-1-yl)carbonyl]-4,5′-bi-1,3-thiazol-2′-yl}acetamide;

N-{4′-methyl-2-[(4-oxopiperidin-1-yl)carbonyl]-4,5′-bi-1,3-thiazol-2′-yl}acetamide;

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

2′-(acetylamino)-4′-methyl-N-prop-2-yn-1-yl-4,5′-bi-1,3-thiazole-2-carboxamide;

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

N˜1˜,N˜1˜-dimethyl-N˜2˜-({[4′-methyl-2-(morpholin-4-ylcarbonyl)-4,5′-bi-1,3-thiazol-2′-yl]amino}carbonyl)glycinamide;

N-({[4′-methyl-2-(morpholin-4-ylcarbonyl)-4,5′-bi-1,3-thiazol-2′-yl]amino}carbonyl)-beta-alanine;

N-{2-[(4-fluoropiperidin-1-yl)carbonyl]-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl}acetamide;

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

Ethyl N-({[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]amino}carbonyl)-beta-alaninate;

N-(2-{[(1R,5R,7R)-7-(hydroxymethyl)-6,8-dioxa-3-azabicyclo[3.2.1]oct-3-yl]carbonyl}-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl)acetamide;

Tert-butyl N-({[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]amino}carbonyl)-beta-alaninate;

[4′-methyl-2′-(pyrazin-2-ylamino)-4,5′-bi-1,3-thiazol-2-yl]acetonitrile;

Ethyl 4′-methyl-2′-(pyrazin-2-ylamino)-4,5′-bi-1,3-thiazole-2-carboxylate;

[4′-methyl-2′-(1H-pyrazol-3-ylamino)-4,5′-bi-1,3-thiazol-2-yl]acetonitrile;

N-[4′-methyl-2-(2-morpholin-4-yl-2-oxoethyl)-4,5′-bi-1,3-thiazol-2′-yl]acetamide;

2-[2′-(acetylamino)-4′-methyl-4,5′-bi-1,3-thiazol-2-yl]acetamide;

tert-butyl 4-{[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]amino}-4-oxobutanoate;

methyl 5-{[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]amino}-5-oxopentanoate;

methyl 6-{[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]amino}-6-oxohexanoate;

2′-(acetylamino)-N,N,4′-trimethyl-4,5′-bi-1,3-thiazole-2-carboxamide;

2′-(acetylamino)-4′-methyl-4,5′-bi-1,3-thiazole-2-carboxamide;

4-{[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]amino}-4-oxobutanoic acid;

5-{[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]amino}-5-oxopentanoic acid;

tert-butyl N-({[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]amino}carbonyl)glycinate;

tert-butyl 4-[({[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]amino}carbonyl)amino]butanoate;

N˜2˜-({[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]amino}carbonyl)-N˜1˜,N˜1˜-dimethylglycinamide;

tert-butyl N-({[4′-methyl-2-(morpholin-4-ylcarbonyl)-4,5′-bi-1,3-thiazol-2′-yl]amino}carbonyl)-beta-alaninate;

N-[4′-methyl-2-(morpholin-4-ylcarbonyl)-4,5′-bi-1,3-thiazol-2′-yl]-N-(2-morpholin-4-yl-2-oxoethyl)urea;

N-[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]-N-(2-morpholin-4-yl-2-oxoethyl)urea;

methyl N-({[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]amino}carbonyl)-beta-alaninate;

N˜3˜-({[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]amino}carbonyl)-N˜1˜,N˜1˜-diisopropyl-beta-alaninamide;

N˜3˜-({[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]amino}carbonyl)-N˜1˜-(2-hydroxy-1,1-dimethylethyl)-beta-alaninamide;

N˜1˜-(tert-butyl)-N˜3˜-({[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]amino}carbonyl)-beta-alaninamide;

N-[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]-N-[3-(2,2-dimethyl-1,3-thiazolidin-3-yl)-3-oxopropyl]urea;

N-[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]-N-[3-(4,4-dimethyl-1,3-oxazolidin-3-yl)-3-oxopropyl]urea;

N˜2˜-({[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]amino}carbonyl)-N˜1˜-(2,2-dimethylpropyl)glycinamide;

N-(3-azocan-1-yl-3-oxopropyl)-N-[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]urea;

N-[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]-N′-[2-(1-isopropyl-1H-imidazol-4-yl)ethyl]urea;

N-[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]-N′-[2-(1-ethyl-1H-imidazol-4-ypethyl]urea;

N-[2-(5-tert-butyl-1,2,4-oxadiazol-3-yl)ethyl]-N′-[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl]urea;

N-[2-(cyanomethyl)-4′-methyl-4,5′-bi-1,3-thiazol-2-yl]-N′[ 2 -(5-isopropyl-1,2,4-oxadiazol-3-yl)ethyl]urea; or

N-(4′-methyl-2-{[5-(1-methylpiperidin-4-yl)-1,2,4-oxadiazol-3-yl]methyl}-4,5′-bi-1,3-thiazol-2′-yl)acetamide.

17. A thiazole derivative according to Formula (Ia)

wherein R 1 is selected from —C(O)R 5 , C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl, heteroaryl C 1 -C 6 -alkyl, C 3 -C 8 cycloalkyl C 1 -C 6 -alkyl or heterocycloalkyl C 1 -C 6 -alkyl;

R 2 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;

R 3 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;

R 5 is selected from H, hydroxyl, alkoxy, amino, aryl, heteroaryl, C 3 -C 8 cycloalkyl or heterocycloalkyl;

X is S;

and isomers, enantiomers, diastereomers, racemates or pharmaceutically acceptable salts thereof, with the proviso that the compounds of formula Ia are not the following compounds:

[4,5′-bithiazole]-2-acetonitrile, 2′-amino-4′-methyl;

2′-amino-4′-methyl-(phenylhydrazono)-[4,5′-bithiazole]-2-acetonitrile;

2′-amino-[(4-chlorophenyl)hydrazono]-4′-methyl-[4,5′-bithiazole]-2-acetonitrile; or

[4,5′-bithiazole]-4′-carboxylic acid, 2′-amino-2-methyl-, ethyl ester.

18. The thiazole derivative according to claim 17 , wherein R 1 is —C(O)R 5 .

19. The thiazole derivative according to claim 17 , wherein R 1 is selected from C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl, heteroaryl C 1 -C 6 -alkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 -alkyl or heterocycloalkyl C 1 -C 6 -alkyl.

20. The thiazole derivative according to claim 17 , wherein R 2 is H.

21. The thiazole derivative according to claim 17 , wherein R 3 is methyl.

22. A method of treating autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, platelet aggregation, transplantation, erythrocyte deficiency, graft rejection or lung injuries comprising the administration of a pharmaceutically effective amount of a compound of Formula I,

wherein R 1 is selected from —C(O)R 5 , C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl, heteroaryl C 1 -C 6 -alkyl, C 3 -C 8 cycloalkyl C 1 -C 6 -alkyl or heterocycloalkyl C 1 -C 6 alkyl;

R 2 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;

R 3 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;

R 4 is selected from —C(O)R 6 , aryl, heteroaryl, heterocycloalkyl or C 3 -C 8 cycloalkyl;

R 5 is selected from H, hydroxyl, alkoxy, amino, aryl, heteroaryl, C 3 -C 8 cycloalkyl or heterocycloalkyl;

R 6 selected from H, C 1 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl, heteroaryl C 1 -C 6 -alkyl or amino; and

X is S;

and isomers, enantiomers, diastereomers, racemates or pharmaceutically acceptable salts thereof or Formula Ia,

wherein R 1 is selected from —C(O)R 5 , C 1 -C 6 -alkyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl, heteroaryl C 1 -C 6 -alkyl, C 3 -C 8 cycloalkyl C 1 -C 6 -alkyl or heterocycloalkyl C 1 -C 6 -alkyl;

R 2 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;

R 3 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;

R 5 is selected from H, hydroxyl, alkoxy, amino, aryl, heteroaryl, C 3 -C 8 cycloalkyl or heterocycloalkyl;

X is S;

and isomers, enantiomers, diastereomers, racemates or pharmaceutically acceptable salts thereof, with the proviso that the compounds of formula Ia are not the following compounds:

[4,5′-bithiazole]-2-acetonitrile, 2′-amino-4′-methyl;

2′-amino-4′-methyl-(phenylhydrazono)-[4,5′-bithiazolel]-2-acetonitrile;

2′amino-[(4-chlorophenyl)hydrazonol]-4′-methyl-[4,5′-bithiazole]-2-acetonitrile; or

[4,5′-bithiazole]-4′-carboxylic acid, 2′-amino-2-methyl-, ethyl ester to an individual in need of treatment, wherein said autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, platelet aggregation, transplantation, erythrocyte deficiency, graft rejection or lung injuries are selected from multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosis, inflammatory bowel disease, lung inflammation, thrombosis, brain inflammation, Alzheimer's disease, Huntington's disease, CNS trauma, stroke, ischemic conditions, atherosclerosis, heart hypertrophy, cardiac myocyte dysfunction, elevated blood pressure, vasoconstriction, chronic obstructive pulmonary disease, anaphylactic shock fibrosis, psoriasis, allergic diseases, asthma, stroke, ischemic conditions, ischemia-reperfusion, platelet aggregation/activation skeletal muscle atrophy/hypertrophy, acute and chronic bacterial and viral infections, sepsis, graft rejection, glomerulo sclerosis, glomerulo nephritis, progressive renal fibrosis, endothelial and epithelial injuries in the lung, or general lung airway inflammation.

23. The method according to claim 22 , wherein said autoimmune disorders or inflammatory diseases are selected from multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosis, inflammatory bowel disease, lung inflammation, thrombosis or brain inflammation.

24. The method according to claim 22 , wherein said neurodegenerative diseases are selected from Alzheimer's disease, Huntington's disease, CNS trauma, stroke or ischemic conditions.

25. The method according to claim 22 , wherein said cardiovascular diseases are selected from atherosclerosis, heart hypertrophy, cardiac myocyte dysfunction, elevated blood pressure or vasoconstriction.

26. The method according to claim 22 , wherein said autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, platelet aggregation, transplantation, erythrocyte deficiency, graft rejection or lung injuries are selected from chronic obstructive pulmonary disease, anaphylactic shock, fibrosis, psoriasis, allergic diseases, asthma, stroke or ischemic conditions, ischemia-reperfusion, platelet aggregation/activation, skeletal muscle atrophy/hypertrophy, acute and chronic bacterial and viral infections, sepsis, graft rejection, glomerulo sclerosis, glomerulo nephritis, progressive renal fibrosis, endothelial and epithelial injuries in the lung, or general lung airway inflammation.

27. A pharmaceutical composition comprising at least one thiazole derivative of Formula I,

wherein R 1 is selected from —C(O)R 5 , C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl, heteroaryl C 1 -C 6 -alkyl, C 3 -C 8 cycloalkyl C 1 -C 6 -alkyl or heterocycloalkyl C 1 -C 6 -alkyl;

R 2 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl:

R 3 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;

R 4 is selected from —C(O)R 6 , aryl, heteroaryl, heterocycloalkyl or C 3 -C 8 cycloalkyl;

R 5 is selected from H, hydroxyl, alkoxy, amino, aryl, heteroaryl, C 3 -C 8 cycloalkyl or heterocycloalkyl;

R 6 selected from H, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl, heteroaryl C 1 -C 6 -alkyl or amino; and

X is S;

and isomers, enantiomers, diastereomers, racemates or pharmaceutically acceptable salts thereof, or Formula Ia,

wherein R 1 is selected from —C(O)R 5 , C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl, heteroaryl C 1 -C 6 -alkyl, C 3 -C 8 cycloalkyl C 1 -C 6 -alkyl or heterocycloalkyl C 1 -C 6 -alkyl;

R 2 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;

R 3 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;

R 5 is selected from H, hydroxyl, alkoxy, amino, aryl, heteroaryl, C 3 -C 8 cycloalkyl or heterocycloalkyl;

X is S;

and isomers, enantiomers, diastereomers, racemates or pharmaceutically acceptable salts thereof, with the proviso that the compounds of formula Ia are not the following compounds:

[4,5′-bithiazole]-2-acetonitrile, 2′-amino-4′-methyl;

2′-amino-4′-methyl-(phenylhydrazono)-[4,5′-bithiazolel]-2-acetonitrile;

2′-[(4-chlorophenyl)hydrazono]-4′-methyl-[4,5′-bithiazole]-2-acetonitrile; or

[4,5′-bithiazole]-4′-carboxylic acid, 2′-amino-2-methyl-, ethyl ester, and a pharmaceutically acceptable carrier, diluent or excipient thereof.

28. A method of treating cancer comprising the administration of a pharmaceutically effective amount of a compound of Formula I,

wherein R 1 is selected from —C(O)R 5 , C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl, heteroaryl C 1 -C 6 -alkyl, C 3 -C 8 cycloalkyl C 1 -C 6 -alkyl or heterocycloalkyl C 1 -C 6 -alkyl;

R 2 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;

R 3 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;

R 4 is selected from —C(O)R 6 , aryl, heteroaryl, heterocycloalkyl or C 3 -C 8 cycloalkyl;

R 5 is selected from H, hydroxyl, alkoxy, amino, aryl, heteroaryl, C 3 -C 8 cycloalkyl or heterocycloalkyl;

R 6 selected from H, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl, heteroaryl C 1 -C 6 -alkyl or amino; and

X is S;

and isomers, enantiomers, diastereomers, racemates or pharmaceutically acceptable salts thereof or Formula Ia,

wherein R 1 is selected from —C(O)R 5 , C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl C 1 -C 6 -alkyl, heteroaryl C 1 -C 6 -alkyl, C 3 -C 8 cycloalkyl C 1 -C 6 -alkyl or heterocycloalkyl C 1 -C 6 -alkyl;

R 2 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;

R 3 is selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;

R 5 is selected from H, hydroxyl, alkoxy, amino, aryl, heteroaryl, C 3 -C 8 cycloalkyl or heterocycloalkyl;

X is S;

and isomers, enantiomers, diastereomers, racemates or pharmaceutically acceptable salts thereof, with the proviso that the compounds of formula la are not the following compounds:

[4,5′-bithiazole]-2-acetonitrile, 2′-amino-4′-methyl;

2′-amino-4′-methyl-(phenylhydrazono)-[4,5′-bithiazole]-2-acetonitrile;

2′-amino-[(4-chlorophenyl)hydrazono]-4′-methyl-[4,5′-bithiazole]-2-acetonitrile; or

[4,5′-bithiazole]-4′-carboxylic acid, 2′-amino-2-methyl-, ethyl ester, wherein said cancer is selected from invasion metastasis, melanoma, or Kaposi's sarcoma.