Thiazoles and methods of their use
View Patent ↗This invention concerns novel thiazole compounds. Methods of using these compounds for the treatment, prevention and management of various diseases or disorders, as well as pharmaceutical compositions of these compounds, are also disclosed.
1. A compound of formula (1):
or a pharmaceutically acceptable salt, stereoisomer or solvate thereof, wherein:
R 1 , R 2 , R 3 , R 4 and R 5 are each independently H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted heterocycle; optionally substituted arylalkyl, optionally substituted heterocycloalkylalkyl, or optionally substituted heteroarylalkyl; or
R 1 and R 2 , and R 4 and R 5 , with the nitrogen atom to which they are attached, independently form an optionally substituted heterocycle.
2. The compound of claim 1 , wherein R 3 is alkyl.
3. The compound of claim 1 , wherein R 1 and R 2 , with the nitrogen atom to which they are attached form an optionally substituted heterocycle.
4. The compound of claim 3 , wherein the heterocycle formed by R 1 and R 2 is optionally substituted piperidine.
5. The compound of claim 3 , wherein the heterocycle formed by R 1 and R 2 is optionally substituted morpholine.
6. The compound of claim 3 , wherein the heterocycle formed by R 1 and R 2 is optionally substituted piperazine.
7. The compound of claim 1 , wherein R 4 is H and R 5 is alkyl or cycloalkyl.
8. The compound of claim 1 , wherein R 4 is H and R 5 is optionally substituted aminocarbonyl.
9. The compound of claim 1 , wherein R 4 and R 5 , with the nitrogen to which they are attached, form an optionally substituted heterocycle.
10. The compound of claim 9 , wherein the heterocycle formed by R 4 and R 5 is optionally substituted pyrrolidine.
11. The compound of claim 1 , which is stereomerically pure.
12. The compound of claim 1 , which is:
(S)-(4-(ethylamino)-2-((4-methylpiperidin-1-yl)methyl)thiazol-5-yl)(2-(methoxymethyl)pyrrolidin-1-yl)methanone;
4-(ethylamino)-2-((4-methylpiperidin-1-yl)methyl)-N-(pentan-3-yl)thiazole-5-carboxamide;
N-cyclopropyl-4-(methylamino)-2-(piperidin-1-ylmethyl)thiazole-5-carboxamide;
N-cyclopentyl-4-(methylamino)-2-(piperidin-1-ylmethyl)thiazole-5-carboxamide;
N-(2-(dimethylamino)-2-oxoethyl)-4-(2-methoxyethylamino)-2-(morpholinomethyl)thiazole-5-carboxamide;
N-sec-butyl-2-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-4-(ethylamino)thiazole-5-carboxamide;
2-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-4-(ethylamino)-N-(1-methoxypropan-2-yl)thiazole-5-carboxamide;
2-((4-benzylpiperazin-1-yl)methyl)-N-(1-methoxypropan-2-yl)-4-(propylamino)thiazole -5-carboxamide;
N-cyclopropyl-4-(hexylamino)-2-(piperidin-1-ylmethyl)thiazole-5-carboxamide; or
4-(hexylamino)-N-(pentan-3-yl)-2-(piperidin-1-ylmethyl)thiazole-5-carboxamide.
13. A pharmaceutical composition comprising a compound of formula (1):
or a pharmaceutically acceptable salt, stereoisomer or solvate thereof, wherein:
R 1 and R 2 , and R 4 and R 5 , with the nitrogen atom to which they are attached, independently form an optionally substituted heterocycle.
14. The pharmaceutical composition of claim 13 , which further comprises a pharmaceutically acceptable carrier or excipient.
15. The pharmaceutical composition of claim 14 , which is a single dosage form.
16. The dosage form of claim 15 , which is suitable for oral, parenteral or transdermal administration.