HCV inhibitors

1. A compound of Formula (I):

wherein

E is —COCONR 5 R 6 , where R 5 and R 6 are each independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclylalkyl;

R 1 is alkyl, haloalkyl, cycloalkyl, or cycloalkylalkyl;

X is —O—;

R 3 is alkyl, haloalkyl, cycloalkyl, or cycloalkylalkyl;

Y is —OC(O)NH—, —NR 14 —C(O)NH—, or —NR 14 C(O)O— where each R 14 is selected from hydrogen or alkyl;

R 2 is a group of formula (b):

where:

R d1 is hydrogen, hydroxy, or alkoxy;

R d and R d2 are independently hydrogen, alkyl, halo, or alkoxy;

R d3 is hydrogen, alkyl, cycloalkyl, or cycloalkylalkyl; and

R 4 is alkyl; or

a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 wherein R d3 is hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, 1-methylpropyl, 2-methylpropyl, tert-butyl, 2,2,dimethylpropyl, 1,2-dimethylpropyl, 1,2,2-trimethylpropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl or cyclohexylmethyl.

3. The compound of claim 1 wherein R d1 is hydrogen, hydroxy, or alkoxy; R d and R d2 are independently hydrogen, alkyl, halo, or alkoxy; and R d3 is a hydrogen, alkyl or cycloalkyl.

4. The compound of claim 3 wherein R d1 is hydrogen, hydroxy, methoxy, ethoxy, n-propoxy, or iso-propoxy; R d and R d2 are independently, fluoro, chloro, methyl, ethyl, methoxy, or ethoxy.

5. The compound of claim 3 wherein R d1 is hydrogen, hydroxy, methoxy, or ethoxy; R d and R d2 are independently, hydrogen, fluoro, chloro or methyl.

6. The compound of claim 5 wherein R d1 is methoxy or ethoxy; and R d , R d2 and R d3 are each hydrogen.

7. The compound of claim 1 wherein X is —O—; R 1 is alkyl or cycloalkylalkyl; and R 3 is 1-methylethyl, 1-methylpropyl, tert-butyl, cyclopropyl, or cyclohexyl.

8. The compound of claim 7 wherein X is —O—; R 1 is cyclobutylmethyl, ethyl, or n-propyl; and R 3 is tert-butyl or cyclohexyl.

9. The compound of claim 1 wherein E is —COCONHR 6 where R 6 is hydrogen, alkyl, cycloalkyl, aralkyl, or heteroaralkyl.

10. The compound of claim 1 wherein E is —COCONHR 6 where R 6 is cyclopropyl.

11. The compound of claim 1 wherein Y is —NHC(O)NH— and R 4 is alkyl.

12. The compound of claim 1 wherein Y is —OC(O)NH— and R 4 is alkyl.

13. The compound of claim 1 , wherein the compound has the following structure:

or a pharmaceutically acceptable salt thereof.

14. The compound of claim 1 , wherein the compound has the following structure:

or a pharmaceutically acceptable salt thereof.

15. The compound of claim 1 , wherein the compound has the following structure:

or a pharmaceutically acceptable salt thereof.

16. The compound of claim 1 , wherein the compound has the following structure:

or a pharmaceutically acceptable salt thereof.

17. The compound of claim 1 , wherein the compound has the following structure:

or a pharmaceutically acceptable salt thereof.

18. The compound of claim 1 , wherein the compound has the following structure:

or a pharmaceutically acceptable salt thereof.

19. The compound of claim 1 , wherein the compound has the following structure:

or a pharmaceutically acceptable salt thereof.

20. The compound of claim 1 , wherein the compound has the following structure:

or a pharmaceutically acceptable salt thereof.

21. The compound of claim 1 , wherein the compound is selected from the group consisting of:

1-[2S-(3-tert-Butyl-ureido)-3,3-dimethyl-butyryl]-4R-(6-methoxy-isoquinolin-yloxy)-pyrrolidine-2S-carboxylic acid (1S-cyclopropylaminooxalyl-butyl)-amide;

1-[2S-(3-tert-Butyl-ureido)-3,3-dimethyl-butyryl]-4R-(6-methoxy-isoquinolin-1-yloxy)-pyrrolidine-2S-carboxylic acid (2-cyclopropylcarbamoyl-1S-cyclopropylmethyl-2-oxo-ethyl)-amide;

1-[2S-(3-tert-Butyl-ureido)-3,3-dimethyl-butyryl]-4R-(6-ethoxy-isoquinolin-yloxy)-pyrrolidine-2-carboxylic acid (2-cyclopropylcarbamoyl-1S-cyclopropylmethyl-2S-oxo-ethyl)-amide;

1-[2S-(3-tert-Butyl-ureido)-3,3-dimethyl-butyryl]-4R-(6-ethoxy-isoquinolin-1-yloxy)-pyrrolidine-2S-carboxylic acid (1S-cyclopropylaminooxalyl-butyl)-amide; and

1-[2S-(3-tert-Butyl-ureido)-3,3-dimethyl-butyryl]-4R-(6-methoxy-isoquinolin-1-yloxy)-pyrrolidine-2S-carboxylic acid (1S-cyclopropylaminooxalyl-pentyl)-amide.

22. A pharmaceutical composition comprising a compound of any one of the claims 1 - 9 , 10 - 17 , and 18 - 21 and one or more pharmaceutically acceptable excipients.

23. A method of treating hepatitis C infections in a patient comprising administering to the patient a pharmaceutical composition comprising a compound of any one of the claims 1 - 9 , 10 - 17 , and 18 - 21 and one or more pharmaceutically acceptable excipients.

24. The compound of any one of claims 1 - 9 , 10 - 17 , and 18 - 21 ; or a pharmaceutically acceptable sulfate or sulfonate salt thereof.

25. The pharmaceutical composition of claim 22 , further comprising a second antiviral agent.

26. The pharmaceutical composition of claim 25 , wherein said second antiviral agent is Ribavirin or a polymerase inhibitor.

27. A method of treating HCV infections in a patient comprising administering to said patient a compound of any of claims 1 - 9 , 10 - 17 , and 18 - 21 or a pharmaceutical composition comprising a compound of claim 1 and a second antiviral agent selected from the group consisting of interferon, pegylated or unpegylated congeners of interferon, Ribavirin, a HCV polymerase inhibitor and a toll receptor agonist.

28. A compound of Formula (I):

wherein

E is —COCONHR 6 where R 6 is cyclopropyl;

R 1 is cyclobutylmethyl, ethyl, or n-propyl;

X is —O—;

R 3 is tert-butyl;

Y is —NHC(O)NH—;

R 2 is heteroaryl optionally substituted with one or two substituents independently selected from alkoxy and haloalkyl; and

R 4 is alkyl; or

a pharmaceutically acceptable salt thereof.