Compounds and methods for the treatment or prevention of
Compounds represented by formula: wherein X, Y and Z are as defined herein, pharmaceutically acceptable salts thereof, and related compounds, are suitable for use in treating or preventing a Flaviviridae viral infection in a host.
1. A compound selected from:
3-[(4-METHYL-CYCLOHEXANECARBONYL)-(4-OXO-CYCLOHEXYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID;
3-[(4-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID;
3-[(4-HYDROXYIMINO-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID;
3-[(4-METHOXYIMINO-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID;
3-[(4-METHOXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID;
5-(4-FLUORO-PHENYL)-3-[(4-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID;
5-(3-FLUORO-PHENYL)-3-[(4-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID;
5-(4-CHLORO-PHENYL)-3-[(4-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID;
3-[(4-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-(4-METHOXY-PHENYL)-THIOPHENE-2-CARBOXYLIC ACID;
5-(4-CYANO-PHENYL)-3-[(4-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID;
3-[(4-CARBOXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID;
5-(3,4-DIFLUORO-PHENYL)-3-[(4-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID;
5-(4-ACETYL-PHENYL)-3-[(4-HYDROXY-CYCLOHEXYL)-(4METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID;
3-[(4-HYDROXY-4-METHYL-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID;
3-[(3-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID;
and
pharmaceutically acceptable salts thereof.
2. A compound according to claim 1 , wherein said compound is 3-[(4-METHYL-CYCLOHEXANECARBONYL)-(4-OXO-CYCLOHEXYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
3. A compound according to claim 1 , wherein said compound is 3-[(4-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
4. A compound according to claim 1 , wherein said compound is 3-[(4-HYDROXYIMINO-CYCLOHEXYL)-(4-METHYL-CYCLOHXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
5. A compound according to claim 1 , wherein said compound is 3-[(4-METHOXYIMINO-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
6. A compound according to claim 1 , wherein said compound is 3-[(4-METHOXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
7. A compound according to claim 1 , wherein said compound is 5-(4-FLUORO-PHENYL)-3-[(4-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
8. A compound according to claim 1 , wherein said compound is 5-(3-FLUORO-PHENYL)-3-[(4-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
9. A compound according to claim 1 , wherein said compound is 5-(4-CHLORO-PHENYL)-3-[(4-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
10. A compound according to claim 1 , wherein said compound is 3-[(4-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-(4-METHOXY-PHENYL)-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
11. A compound according to claim 1 , wherein said compound is 5-(4-CYANO-PHENYL)-3-[(4-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
12. A compound according to claim 1 , wherein said compound is 3-[(4-CARBOXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
13. A compound according to claim 1 , wherein said compound is 5-(3,4-DIFLUORO-PHENYL)-3-[(4-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
14. A compound according to claim 1 , wherein said compound is 5-(4-ACETYL-PHENYL)-3-[(4-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
15. A compound according to claim 1 , wherein said compound is 3-[(4-HYDROXY-4-METHYL-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
16. A compound according to claim 1 , wherein said compound is 3-[(3-HYDROXY-CYCLOHEXYL)-(4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
17. A compound according to claim 1 , wherein said compound has a monosubstituted-cyclohexyl group attached to the amino and the mono-substituent group of the cyclohexyl group attached to the amino is in the trans position relative to the amino.
18. A compound according to claim 17 , wherein said compound has a 3-substituted-cyclohexyl group or 4-substituted-cyclohexyl group attached to the amino.
19. A compound according to claim 18 , wherein said compound has a 4-hydroxy-cyclohexyl group attached to the amino.
20. A compound according to claim 1 , wherein said compound has a monosubstituted-cyclohexyl group attached to the amino and the mono-substituent group of the cyclohexyl group attached to the amino is in the cis position relative to the amino.
21. A compound according to claim 20 , wherein said compound has a 3-substituted-cyclohexyl group or 4-substituted-cyclohexyl group attached to the amino.
22. A compound according to claim 21 , wherein said compound has a 4-hydroxy-cyclohexyl group attached to the amino.
23. A compound according to claim 17 , wherein said compound has a monosubstituted-cyclohexyl group attached to the carbonyl and the mono-substituent of the cyclohexyl group attached to the carbonyl is in the trans position relative to the carbonyl.
24. A compound according to claim 18 , wherein said compound has a monosubstituted-cyclohexyl group attached to the carbonyl and the mono-substituent of the cyclohexyl group attached to the carbonyl is in the trans position relative to the carbonyl.
25. A compound according to claim 19 , wherein said compound has a monosubstituted-cyclohexyl group attached to the carbonyl and the mono-substituent of the cyclohexyl group attached to the carbonyl is in the trans position relative to the carbonyl.
26. A compound according to claim 23 , wherein said compound has a 4-hydroxy-cyclohexyl group attached to the carbonyl.
27. A compound according to claim 24 , wherein said compound has a 4-hydroxy-cyclohexyl group attached to the carbonyl.
28. A compound according to claim 25 , wherein said compound has a 4-hydroxy-cyclohexyl group attached to the carbonyl.
29. A compound according to claim 18 , wherein said compound is selected from compounds of the following formulas and pharmaceutically acceptable salts thereof:
30. A compound according to claim 29 , wherein said compound is selected from compounds of the following formulas and pharmaceutically acceptable salts thereof:
31. A compound according to claim 3 , wherein said compound is 3-[trans-4-HYDROXY-CYCLOHEXYL)-(trans -4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
32. A compound according to claim 3 , wherein said compound is 3-[(cis-4-HYDROXY-CYCLOHEXYL)-(trans-4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-5-PHENYL-THIOPHENE-2-CARBOXYLIC ACID, or a pharmaceutically acceptable salt thereof.
33. A compound according to any one of claims any one of claims 1 , 29 , 31 and 32 , wherein said compound is a sodium salt.
34. A pharmaceutical composition comprising at least one compound according to any one of claims 1 , 29 , 31 and 32 and at least one pharmaceutically acceptable carrier or excipient.
35. A composition according to claim 34 , wherein said compound is a sodium salt.
36. A method for treating a HCV infection in a host comprising administering to the host a therapeutically effective amount of at least one compound according to any one of claims 1 , 29 , 31 and 32 .
37. A method according to claim 36 , wherein said pharmaceutically acceptable salt is a sodium salt.
38. A method according to claim 36 , wherein said HCV of genotype 1b.
39. A method for inhibiting or reducing the activity of HCV polymerase in a host comprising administering to said host a therapeutically effective amount of at least one compound according to any one of claims 1 , 29 , 31 and 32 .
40. A method according to claim 39 , wherein said compound is a sodium salt.