Inhibitors of hepatitis C virus NS3 protease

1. A compound, or enantiomers, stereoisomers, rotamers, tautomers, diastereomers and racemates of said compound, or a pharmaceutically acceptable salt, solvate or ester of said compound, said compound having the general structure shown in Formula I:

wherein:

R 1 is H, OR 8 , NR 9 R 10 , or CHR 9 R 10 , wherein R 8 , R 9 and R 10 can be the same or different, each being independently selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, aryl-, heteroaryl-, cycloalkyl-, heterocyclyl-, arylalkyl-, and heteroarylalkyl; or R 10 is R 14 wherein R 14 is H, alkyl, aryl, heteroaryl, cycloalkyl, alkyl-aryl, alkyl-heteroaryl, aryl-alkyl, alkenyl, alkynyl or heteroaryl-alkyl;

A and M can be the same or different, each being independently selected from R, OR, NHR, NRR′, SR, SO 2 R, and halo; or A and M are connected to each other such that the moiety:

shown above in Formula I forms either a three, four, six, seven or eight-membered cycloalkyl, a four to eight-membered heterocyclyl, a six to ten-membered aryl, or a five to ten-membered heteroaryl;

E is C(H) or C(R);

L is C(H) or C(R),

R, R′, R 2 , and R 3 can be the same or different, each being independently selected from the group consisting of H, alkyl-, alkenyl-, alkynyl-, cycloalkyl-, heterocyclyl-, aryl-, heteroaryl-, (cycloalkyl)alkyl-, (heterocyclyl)alkyl-, aryl-alkyl-, and heteroaryl-alkyl-; or alternately R and R′ in NRR′ are connected to each other such that NRR′ forms a four to eight-membered heterocyclyl;

and Y is selected from the following moieties:

wherein G is NH; and R 15 , R 16 , R 17 and R 18 can be the same or different, each being independently selected from the group consisting of H, alkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, or alternately, R 15 and R 16 are connected to each other to form a four to eight-membered cycloalkyl, heteroaryl or heterocyclyl structure, and likewise, independently R 17 and R 18 are connected to each other to form a three to eight-membered cycloalkyl or heterocyclyl;

wherein each of said alkyl, aryl, heteroaryl, cycloalkyl or heterocyclyl can be unsubstituted or optionally independently substituted with one or more moieties selected from the group consisting of: hydroxy, alkoxy, aryloxy, thio, alkylthio, arylthio, amino, amido, alkylamino, arylamino, alkylsulfonyl, arylsulfonyl, sulfonamido, alkyl, aryl, heteroaryl, alkylsulfonamido, arylsulfonamido, keto, carboxy, carbalkoxy, carboxamido, alkoxycarbonylamino, alkoxycarbonyloxy, alkylureido, arylureido, halo, cyano, and nitro.

2. The compound of claim 1 , wherein R 1 is NR 9 R 10 , and R 9 is H, R 10 is H, or R 14 wherein R 14 is H, alkyl, aryl, heteroaryl, cycloalkyl, alkyl-aryl, alkyl-heteroaryl, aryl-alkyl, alkenyl, alkynyl or heteroaryl-alkyl.

3. The compound of claim 2 , wherein R 14 is selected from the group consisting of:

4. The compound of claim 1 , wherein R 2 is selected from the group consisting of the following moieties:

5. The compound of claim 1 , wherein R 3 is selected from the group consisting of:

wherein R 31 is OH or O-alkyl; and

R 32 is H, C(O)CH 3 , C(O)OtBu or C(O)N(H)tBu.

6. The compound of claim 1 , wherein R 3 is selected from the group consisting of the following moieties:

7. The compound of claim 1 , wherein Y is selected from the following moieties:

wherein G is NH; and R 15 , R 16 , R 17 and R 18 are as defined in claim 1 .

8. The compound of claim 7 , wherein Y is selected from the group consisting of:

wherein Y 31 is selected from the group consisting of:

Y 32 is selected from the group consisiting of:

and Y 12 is selected from the group consisting of H, CO 2 H, CO 2 Me, OMe, F, Cl, Br, NH 2 , N(H)S(O 2 )CH 3 , N(H)C(O)CH 3 , NO 2 , NMe 2 , S(O 2 )NH 2 , CF 3 , Me, OH, OCF 3 , and C(O)NH 2 and Y 33 is selected from the group consisting of:

9. The compound of claim 1 , wherein the moiety:

is selected from the following structures:

10. The compound of claim 9 , wherein the moiety:

is selected from the following structures:

11. The compound of claim 10 , wherein the moiety:

is selected from the following structures:

12. The compound of claim 1 , R 1 is NHR 14 where R 14 is selected from the group consisting of:

R 2 is selected from the group consisting of the following moieties:

R 3 is selected from the group consisting of the following moieties:

Y is selected from the group consisting of:

wherein Y 31 is selected from the group consisting of:

Y 32 is selected from the group consisting of:

and Y 12 is selected from the group consisting of H, CO 2 H, CO 2 Me, OMe, F, Cl, Br, NH 2 , N(H)S(O 2 )Ch 3 , N(H)C(O)CH 3 , NO 2 , NMe 2 , S(O 2 )NH 2 , CF 3 , Me, OH, OCF 3 , and C(O)NH 2 and Y 33 is selected from the group consisting of:

and the moiety:

13. A pharmaceutical composition comprising as an active ingredient at least one compound of claim 1 .

14. The pharmaceutical composition of claim 13 for use in treating disorders associated with HCV.

15. The pharmaceutical composition of claim 14 additionally comprising at least one pharmaceutically acceptable carrier.

16. The pharmaceutical composition of claim 15 , additionally containing at least one antiviral agent.

17. The pharmaceutical composition of claim 16 , additionally containing at least one interferon.

18. The pharmaceutical composition of claim 17 , wherein said at least one antiviral agent is ribavirin and said at least one interferon is α-interferon or pegylated interferon.

19. A method of treating an infenction by HCV, said method comprising administering to a patient in need of such treatment a pharmaceutical composition which comprises therapeutically effective amounts of at least one compound of claim 1 .

20. The method of claim 19 , wherein said administration is oral or subcutaneous.

21. A method of preparing a pharmaceutical composition for treating the disorders associated with the HCV, said method comprising bringing into intimate physical contact at least one compound of claim 1 and at least one pharmaceutically acceptable carrier.

22. A compound exhibiting HCV protease inhibitory activity, or enantiomers, stereoisomers, rotamers, tautomers, diastereomers and racemates of said compound, or a pharmaceutically acceptable salt, solvate or ester of said compound, said compound being selected from the compounds of structures listed below:

23. A pharmaceutical composition for treating an infection by HCV, said composition comprising therapeutically effective amount of one or more compounds in claim 22 and a pharmaceutically acceptable carrier.

24. The pharmaceutical composition of claim 23 , additionally containing at least one antiviral agent.

25. The pharmaceutical composition of claim 24 , additionally containing at least one interferon or PEG-interferon alpha conjugate.

26. The pharmaceutical composition of claim 25 , wherein said at least one antiviral agent is ribavirin and said at least one interferon is α-interferon or pegylated interferon.

27. A method of treatment of a hepatitis C virus infection, comprising administering an effective amount of one or more compounds of claim 22 .

28. A method of treating an infection by HCV, said method comprising administering to a patient in need of such treatment, a pharmaceutical composition which comprises therapeutically effective amounts of at least one compound, or enantiomers, stereoisomers, rotamers, tautomers, diastereomers and racemates of said compound, or a pharmaceutically acceptable salt, solvate or ester of said compound, said compound being selected from the following:

29. A compound of claim 1 in purified form.