Inhibitors of hepatitis C virus polymerase

1. A compound according to Formula I:

or a pharmaceutically acceptable salt thereof,

wherein:

X is —NR 1 — and Y is —CH 2 —;

R 1 is —C 5-6 hydroxyalkyl, —S(O) 2 —C 0-4 alkyl-R O , —C 0-4 alkyl-R O , —C 0-3 alkyl-C(O)—C 0-4 alkyl-R O , or —C 0-3 alkyl-C(O)O—C 0-4 alkyl-R O ;

wherein:

R M and R N are independently hydrogen or —C 1-4 alkyl; and

R O is (a) a 5- to 7-membered cycloalkyl group, substituted with a —C 1-3 alkyl, aryl, —O-aryl, or —NR M R N moiety, (b) a 7-membered cycloalkyl group [optionally substituted with a hydroxyl], or (c) a 6- to 10-membered monocyclic or bicyclic aryl, substituted with one to three moieties independently selected from —C 1-4 alkyl, halogen, —NR M R N , —C 1-4 haloalkyl, —C 1-4 alkoxy, —C 1-4 hydroxyalkyl, cyano, —O-aryl, and aryl, provided that at least one such substitution is —C 1-4 alkoxy, —C 1-4 hydroxyalkyl, cyano, or —O-aryl;

R 2 is —C 1-5 alkyl optionally substituted with 1-5 halogens, —C 1-5 alkoxy, —C 5-7 cycloalkyl-C 0-3 alkyl in which the alkyl is optionally substituted with 1-3 halogens, —C 1-4 alkyl-C 3-5 cycloalkyl, or phenyl optionally substituted with 1 or 2 halogens or —C 1-3 alkyl groups optionally substituted with 1-3 halogens;

R 3 is —R A —R B ;

wherein R A is a phenyl moiety optionally substituted with one or two Z, in which each Z is independently halogen, —C 1-3 alkyl, —C 1-3 haloalkyl, —C 1-3 alkoxy, or cyano; and

wherein R B is —N(R U )C(O)—R Q ;

wherein R Q is thiazolyl, optionally substituted with one or two R Z , in which each R Z is independently —C 1-3 alkyl, —C 1-3 alkoxy, or —NR M R N ; and

R U is hydrogen or —C 1-4 alkyl;

provided that, when R A is phenyl, then R B appears at the para or meta position relative to the thiophene moiety; and

R 4 is hydrogen, —C 1-4 alkyl, —C 1-4 alkyl-OC(O)O—C 1-4 alkyl, —C 1-4 alkyl-OC(O)—C 1-4 alkyl, —C 1-4 alkyl-OC(O)O—C 3-6 cycloalkyl, —C 0-3 alkyl-C 5-6 aryl, or —C 1-4 alkyl-NR V R W ; and

R V and R W are independently hydrogen or —C 1-4 alkyl.

2. A compound according to claim 1 , wherein R A is phenyl.

3. A compound according to claim 2 , wherein R B appears at the para position relative to the thiophene moiety.

4. A compound according to claim 3 , wherein R B is —NHC(O)—R Q .

5. A compound according to claim 1 , wherein R 2 is —C 5-6 cycloalkyl-C 1-3 alkyl.

6. A compound according to claim 1 , wherein R 4 is hydrogen.

7. A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

5-(3-methyl-4-(thiazole-4-carboxamido)phenyl)-3-(1-methyl-5-(4-methylcyclohexyl)-1,2,3,6-tetrahydropyridin-4-yl) thiophene-2-carboxylic acid;

5-(3-methoxy-4-(thiazole-4-carboxamido)phenyl)-3-(1-methyl-5-(4-methylcyclohexyl)-1,2,3,6-tetrahydropyridin-4-yl)thiophene-2-carboxylic acid;

5-(3-cyano-4-(thiazole-4-carboxamido)phenyl)-3-(1-methyl-5-(4-methylcyclohexyl)-1,2,3,6-tetrahydropyridin-4-yl)thiophene-2-carboxylic acid;

5-(3-ethyl-4-(thiazole-4-carboxamido)phenyl)-3-(1-methyl-5-(4-methylcyclohexyl)-1,2,3,6-tetrahydropyridin-4-yl)thiophene-2-carboxylic acid;

3-(1-methyl-5-(4-methylcyclohexyl)-1,2,3,6-tetrahydropyridin-4-yl)-5-(4-(thiazole-4-carboxamido)-3-(trifluoromethyl)phenyl)thiophene-2-carboxylic acid;

3-(1-methyl-4-(4-methylcyclohexyl)-1,2,5,6-tetrahydropyridin-3-yl)-5-(3-methyl-4-(thiazole-4-carboxamido)phenyl)thiophene-2-carboxylic acid;

3-(1-(2-hydroxyethyl)-4-(4-methylcyclohexyl)-1,2,5,6-tetrahydropyridin-3-yl)-5-(3-methyl-4-(thiazole-4-carboxamido)phenyl)thiophene-2-carboxylic acid;

3-(4-(4,4-difluorocyclohexyl)-1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-5-(4-(thiazole-4-carboxamido)phenyl)thiophene-2-carboxylic acid;

3-(5-(2,4-dichlorophenyl)-1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5-(4-(thiazole-4-carboxamido)phenyl)thiophene-2-carboxylic acid; and

3-(1-methyl-5-(p-tolyl)-1,2,3,6-tetrahydropyridin-4-yl)-5-(4-(thiazole-4-carboxamido)phenyl)thiophene-2-carboxylic acid.

8. A composition comprising a compound according to claims 1 and least one pharmaceutically acceptable carrier or excipient.

9. A composition comprising a compound according to claim 7 and at least one pharmaceutically acceptable carrier or excipient.

10. A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

5-(3-chloro-4-(thiazole-4-carboxamido)phenyl)-3-(1-methyl-5-(4-methylcyclohexyl)-1,2,3,6-tetrahydropyridin-4-yl)thiophene-2-carboxylic acid;

3-(1-(2-hydroxyethyl)-4-(4-methylcyclohexyl)-1,2,5,6-tetrahydropyridin-3-yl)-5-(4-(thiazole-4-carboxamido)phenyl)thiophene-2-carboxylic acid;

3-(1-(2,3-dihydroxypropyl)-4-(4-methylcyclohexyl)-1,2,5,6-tetrahydropyridin-3-yl)-5-(4-(thiazole-4-carboxamido)phenyl)thiophene-2-carboxylic acid;

5-(3-fluoro-4-(thiazole-4-carboxamido)phenyl)-3-(1-methyl-4-(4-methylcyclohexyl)-1,2,5,6-tetrahydropyridin-3-yl)thiophene-2-carboxylic acid;

3 -(5-cyclohexyl- 1-methyl- 1,2,3 ,6-tetrahydro-pyridin-4-yl)-5- {4- [(thiazole-4-carbonyl)-amino]-phenyl }-thiophene-2-carboxylic acid; and

3 -(4-cyclohexyl- 1-methyl- 1,2,5 ,6-tetrahydro-pyridin-3 -yl)-5-{4-[(thiazole-4-carbonyl)-amino]-phenyl }-thiophene-2-carboxylic acid.