HCV NS3 protease inhibitors

1. A compound of Formula II:

or a pharmaceutically acceptable salt thereof, wherein

each Z is independently either N or C—R 4 ;

A is a selected from the group consisting of

a) C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 8 cycloalkyl, C 6 -C 8 bridged cycloalkyl, or C 6 -C 8 bridged cycloalkenyl,

b) substituted C 1 -C 8 alkyl, substituted C 2 -C 8 alkenyl, substituted C 2 -C 8 alkynyl, substituted C 3 -C 8 cycloalkyl, substituted C 6 -C 8 bridged cycloalkyl, or substituted C 6 -C 8 bridged cycloalkenyl, each of which is substituted with 0, 1, 2, 3 or 4 independently selected R A , and 0 or 1 R B , provided that at least one R A substituent other than H, or an R B substituent is present;

c) C 1 -C 8 haloalkyl, C 3 -C 8 halocycloalkyl, or C 1 -C 8 haloalkyl substituted with R B ,

d) Aryl, and

e) Het;

J is selected from the group consisting of a direct bond,

R J is selected from the group consisting of hydrogen and C 1 -C 6 alkyl;

L is NH;

G is selected from the group consisting of

 wherein

R G is selected from the group consisting of C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl-C 1 -C 5 alkyl, or C 3 -C 6 cycloalkyl-C 1 -C 5 alkyl substituted with C 1 -C 6 alkoxy;

each R 1 is selected from the group consisting of hydrogen, C 1 -C 9 alkyl, C 1 -C 6 alkyl-R B , C 1 -C 9 hydroxylalkyl, C 3 -C 8 cycloalky, C 1 -C 4 haloalkyl, Aryl, and Het;

R 2 is selected from the group consisting of C 1 -C 9 alkyl, C 2 -C 9 alkenyl, C 2 -C 9 alkynyl, C 3 -C 8 cycloalkyl, Het, and Aryl;

R 3 is selected from the group consisting of C 1 -C 9 alkyl, C 2 -C 9 alkenyl, and C 2 -C 9 alkynyl;

T is selected from the group consisting of O, (CH 2 ) q2 , NH, SO 2 and S, wherein q 2 is 1 or 2;

Q is —(CR A 2 ) 2 or —O—CH 2 —;

each R 4 is independently selected from the group consisting of: hydrogen, halogen, OH, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 —alkyl-R B , C 1 -C 6 haloalkyl-R B , C 1 -C 6 alkoxy-R B , C 1 -C 6 haloalkoxy —R B , C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl-C 1 -C 9 alkyl, C 1 -C 6 hydroxyalkyl, O—C 1 -C 6 hydroxyalkyl, O—C 1 -C 6 alkyl-R B , CN, O—(C 1 -C 5 alkyl)-O—(C 1 -C 3 alkyl), O—(C 1 -C 5 alkyl)-O—(C 1 -C 3 alkyl)-R B , —(C 0 -C 3 alkyl)-O—(C 0 -C 3 alkyl)-(C 3 -C 8 cycloalkyl), —(C 0 -C 3 alkyl)-S—(C 0 -C 3 alkyl)-(C 3 -C 8 cycloalkyl), —(C 0 -C 3 alkyl)-S(O) 2 —(C 0 -C 3 alkyl)-(C 3 -C 8 cycloalkyl), Het, Aryl, and

 wherein X 1 is either CH 2 , NH, O, or S; X 2 is either CH or N; and X 3 is either NH, CH 2 , O, or S;

provided that two R 4 groups can join together to form methylene dioxy;

each Aryl is independently phenyl optionally substituted with 1 or 2 R C substituents;

each Het is independently either (a) 4-, 5- or 6-membered saturated or unsaturated monocyclic ring with 1 or 2 heteroatom ring atoms independently selected from the group consisting of N, O and S; or (b) 8-, 9- or 10-membered saturated or unsaturated bicyclic ring with 1, 2, or 3 heteroatom ring atoms independently selected from the group consisting of N, O and S, provided that said Het is optionally substituted with 1 or 2 R C substituents;

each R A is independently selected from the group consisting of: H, F, Cl, Br, I, OH, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkyl(NH 2 ), C 6 -C 8 bridged cycloalkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 haloalkoxy, C 3 -C 8 halocycloalkyl, SH, S(C 1 -C 6 alkyl), NH 2 , NH(C 1 -C 6 alkyl), N(C 1 -C 6 alkyl) 2 , C(O)(C 1 -C 6 alkyl), C(O)(C 3 -C 8 cycloalkyl), CONH 2 , SO 2 NH 2 , NO 2 , CN, CF 3 , CHF 2 , CH 2 F, OCHF 2 , OCF 3 , OCH 2 F, SO 2 (C 1 -C 6 alkyl), S(O)(C 1 -C 6 alkyl), —(C 1 -C 6 alkyl)S(O)(C 1 -C 6 alkyl), SO 2 (C 3 -C 6 cycloalkyl), —(C 1 -C 6 alkyl)S(O) 2 (C 1 -C 6 alkyl), —(C 1 -C 6 alkyl)N(C 1 -C 6 alkyl)SO 2 (C 1 -C 6 alkyl), N(C 1 -C 6 alkyl)SO 2 (C 1 -C 6 alkyl), SO 2 N(C 1 -C 6 alkyl) 2 , —(C 1 -C 6 alkyl)SO 2 N(C 1 -C 6 alkyl) 2 , NHCOO(C 1 -C 6 alkyl), NHCO(C 1 -C 6 alkyl), NHCONH(C 1 -C 6 alkyl), CO 2 (C 1 -C 6 alkyl), C(O)N(C 1 -C 6 alkyl) 2 , —(C 0 -C 5 alkyl)-(C 3 -C 8 cycloalkyl), —(C 0 -C 5 alkyl)-O—(C 0 -C 5 alkyl)-(C 3 -C 8 cycloalkyl), —(C 0 -C 5 alkyl)-S—(C 0 -C 5 alkyl)-(C 3 -C 8 cycloalkyl),

—(C 0 -C 5 alkyl)-S(O) 2 —(C 0 -C 5 alkyl)-(C 3 -C 8 cycloalkyl), Aryl, and Het; provided that two R A groups present on adjacent carbon atoms can together with the adjacent carbon atoms form a C 3 -C 6 cycloalkyl;

each R B is independently either Het or Aryl;

each R C is independently either halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 3 -C 6 cycloalkyl or C 1 -C 6 haloalkyl;

alternatively, with respect to A and R 1 , A is either C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, or C 3 -C 8 cycloalkyl, each of which is substituted with R A1 , and R A1 in combination with R 1 forms a C 3 -C 8 alkylene, a C 3 -C 8 alkenylene, or a C 3 -C 8 alkynylene;

alternatively, with respect to A and R 2 , A is either C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, or C 3 -C 8 cycloalkyl, each of which is substituted with R A1 , and R A1 in combination with R 2 form a C 3 -C 8 alkylene, a C 3 -C 8 alkenylene, or a C 3 -C 8 alkynylene;

alternatively, with respect to R 2 and R 3 , R 2 and R 3 form a C 3 -C 8 alkylene, C 3 -C 8 alkenylene, or C 3 -C 8 alkynylene.

2. The compound according to claim 1 , wherein Q is selected from the group consisting of —(CH 2 ) 2 —,

3. The compound according to claim 1 , wherein G is

4. The compound according to claim 1 , wherein R 1 is hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 4 haloalkyl, Aryl, or Het.

5. The compound according to claim 1 , wherein said compound of Formula II is a compound of Formula IIa:

or a pharmaceutically acceptable salt thereof,

wherein

each Z is independently either N or C—R 4 ;

A is a selected from the group consisting of:

a) C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 6 -C 8 bridged cycloalkyl, or C 6 -C 8 bridged cycloalkenyl,

b) substituted C 1 -C 8 alkyl, substituted C 2 -C 8 alkenyl, substituted C 2 -C 8 alkynyl, substituted C 3 -C 8 cycloalkyl, substituted C 6 -C 8 bridged cycloalkyl, or substituted C 6 -C 8 bridged cycloalkenyl, each of which is substituted with 0, 1, 2, 3 or 4 R A , and 0 or 1 R B , provided that at least one R A or R B substituent is present,

c) C 1 -C 8 haloalkyl, C 3 -C 8 halocycloalkyl, or C 1 -C 8 haloalkyl substituted with R B ,

d) Aryl, and

e) Het;

Q is selected from the group consisting of —(CH 2 ) 2 —,

T is selected from the group consisting of O, —(CH 2 ) q2 —, NH, SO 2 and S, wherein q 2 is 1 or 2;

G is

R 1 is hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 4 haloalkyl, C 1 -C 6 alkyl-R B , Aryl, or Het;

R 2 is selected from the group consisting of C 1 -C 9 alkyl, C 2 -C 9 alkenyl, C 2 -C 9 alkynyl, C 3 -C 8 cycloalkyl, Het, and Aryl;

R 3 is selected from the group consisting of C 1 -C 9 alkyl, C 2 -C 9 alkenyl, and C 2 -C 9 alkynyl;

each R 4 is independently selected from the group consisting of: hydrogen, halogen, OH, C 1 -C 6 alkyl, C 1 -C 4 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkyl-R B , C 1 -C 6 haloalkyl-R B , C 1 -C 6 alkoxy-R B , C 1 -C 6 haloalkoxy —R B , C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl-C 1 -C 9 alkyl, C 1 -C 6 hydroxyalkyl, O—C 1 -C 6 hydroxyalkyl, O—C 1 -C 6 alkyl-R B , CN, O—(C 1 -C 5 alkyl)-O—(C 1 -C 3 alkyl), O—(C 1 -C 5 alkyl)-O—(C 1 -C 3 alkyl)-R B , —(C 0 -C 3 alkyl)-O—(C 0 -C 3 alkyl)-(C 3 -C 8 cycloalkyl), —(C 0 -C 3 alkyl)-S—(C 0 -C 3 alkyl)-(C 3 -C 8 cycloalkyl), —(C 0 -C 3 alkyl)-S(O) 2 —(C 0 -C 3 alkyl)-(C 3 -C 8 cycloalkyl), Het, Aryl, and

 wherein X 1 is either CH 2 , NH, O, or S; X 2 is either CH or N; and X 3 is either NH, CH 2 , O, or S;

provided that two R 4 groups can join together form methylene dioxy;

each R A is independently selected from the group consisting of: F, Cl, Br, I, OH, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkyl(NH 2 ), C 6 -C 8 bridged cycloalkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 haloalkoxy, C 3 -C 8 halocycloalkyl, SH, S(C 1 -C 6 alkyl), NH 2 , NH(C 1 -C 6 alkyl), N(C 1 -C 6 alkyl) 2 , C(O)(C 1 -C 6 alkyl), C(O)(C 3 -C 8 cycloalkyl), CONH 2 , SO 2 NH 2 , NO 2 , CN, CF 3 , CHF 2 , CH 2 F, OCHF 2 , OCF 3 , OCH 2 F, SO 2 (C 1 -C 6 alkyl), S(O)(C 1 -C 6 alkyl), —(C 1 -C 6 alkyl)S(O)(C 1 -C 6 alkyl), SO 2 (C 3 -C 6 cycloalkyl), —(C 1 -C 6 alkyl)S(O) 2 (C 1 -C 6 alkyl), —(C 1 -C 6 alkyl)N(C 1 -C 6 alkyl)SO 2 (C 1 -C 6 alkyl), N(C 1 -C 6 alkyl)SO 2 (C 1 -C 6 alkyl), SO 2 N(C 1 -C 6 alkyl) 2 , —(C 1 -C 6 alkyl)SO 2 N(C 1 -C 6 alkyl) 2 , NHCOO(C 1 -C 6 alkyl), NHCO(C 1 -C 6 alkyl), NHCONH(C 1 -C 6 alkyl), CO 2 (C 1 -C 6 alkyl), C(O)N(C 1 -C 6 alkyl) 2 , —(C 0 -C 5 alkyl)-(C 3 -C 8 cycloalkyl), —(C 0 -C 5 alkyl)-O—(C 0 -C 5 alkyl)-(C 3 -C 8 cycloalkyl), —(C 0 -C 5 alkyl)-S—(C 0 -C 5 alkyl)-(C 3 -C 8 cycloalkyl), —(C 0 -C 5 alkyl)-S(O) 2 —(C 0 -C 5 alkyl)-(C 3 -C 8 cycloalkyl), Aryl, and

Het; provided that two R A groups present on adjacent carbon atoms can together with the adjacent carbon atoms form a C 3 -C 6 cycloalkyl;

each R B is independently either phenyl or a 5- or 6-membered saturated or unsaturated monocyclic ring with 1, or 2 heteroatom ring atoms independently selected from the group consisting of N, O and S, R B may be substituted with 1 or 2 independently selected R C ;

each R C is independently either halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 3 -C 6 cycloalkyl or, C 1 -C 6 haloalkyl;

each Aryl is independently phenyl optionally substituted with 1 or 2 independently selected R C ;

each Het is independently a 4-, 5- or 6-membered saturated or unsaturated monocyclic rings with 1 or 2 heteroatom ring atoms independently selected from the group consisting of N, O and S; provided that said Het is optionally substituted with 1 or 2 independently selected R C substituents;

R X if present, is a C 3 -C 8 alkylene, C 3 -C 8 alkenylene, or C 3 -C 8 alkynylene, formed between A and R 1 ,

R Y if present, is a C 3 -C 8 alkylene, C 3 -C 8 alkenylene, C 3 -C 8 alkynylene, formed between A and R 2 ,

R Z if present, is a C 3 -C 8 alkylene, C 3 -C 8 alkenylene, or C 3 -C 8 alkynylene, formed between R 2 and R 3 ,

provided that either (a) R X is present, R Y is not present and R Z is not present; (b) R Y is present, R X is not present and R Z is not present; (c) R Z is present, R X is not presen and R Y is not present; or (d) R X and R Z are present, and R Y is not present.

6. The compound according to claim 5 , wherein T is O.

7. The compound according to claim 5 , wherein A is a selected from the group consisting of

a) C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, or C 6 -C 8 bridged cycloalkyl,

b) substituted C 1 -C 6 alkyl, substituted C 3 -C 8 cycloalkyl, or substituted C 6 -C 8 bridged cycloalkyl, each of which contains 0 or 1 R A and 0 or 1 R B , provided that at least one R A substituent other than H, or an R B substituent is present;

c) Aryl; and

d) Het.

8. The compound according to claim 5 , wherein R 1 is CF 3 , CH 2 CF 3 , CHF 2 , CH 3 , or cyclopropyl.

9. The compound according to claim 5 , wherein each R 4 is independently selected from the group consisting of: hydrogen, F, Cl, OH, C 1 -C 6 alkyl, C 1 -C 2 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 6 alkyl-R B , C 3 -C 8 cycloalkyl, Het, Aryl and

wherein X 1 is either CH 2 , NH, O, or S; X 2 is either CH or N; and X 3 is either NH, CH 2 , O, or S.

10. The compound according to claim 9 , wherein each R 4 is independently selected from the group consisting of H, F, Cl, OH, C 1 -C 5 alkyl, CF 3 , CH 2 —CF 3 , and CF 2 —CH 3 .

11. The compound according to claim 5 , wherein said compound of Formula IIa is a compound of Formula IIb:

or a pharmaceutically acceptable salt thereof, wherein

each Z is independently either N or C—R 4 ;

A is a selected from the group consisting of

a) C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, or C 6 -C 8 bridged cycloalkyl,

b) substituted C 1 -C 6 alkyl, substituted C 3 -C 8 cycloalkyl, or substituted C 6 -C 8 bridged cycloalkyl, each of which contains 0 or 1 R A and 0 or 1 R B , provided that at least one R A or R B substituent is present;

c) Aryl; and

d) Het;

Q is selected from the group consisting of selected from —(CH 2 ) 2 —,

G is

R 1 is either hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 4 haloalkyl, Aryl, or Het;

each R 4 is independently selected from the group consisting of:

hydrogen, F, Cl, OH, C 1 -C 6 alkyl, C 1 -C 2 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 6 alkyl-R B , C 3 -C 8 cycloalkyl, Het, Aryl and

 wherein X 1 is either CH 2 , NH, O, or S; X 2 is either CH or N; and X 3 is either NH, CH 2 , O, or S;

each Aryl is independently phenyl optionally substituted with 1 or 2 independently selected R C ;

each Het is independently a 4-, 5- or 6-membered saturated or unsaturated monocyclic ring with 1 or 2 heteroatom ring atoms independently selected from the group consisting of N, O and S; provided that said Het is optionally substituted with 1 or 2 independently selected R C ;

each R A is independently selected from the group consisting of: F, Cl, OH, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 3 -C 8 halocycloalkyl, and C 1 -C 6 haloalkoxy;

each R B is independently either phenyl or 5- or 6-membered saturated or unsaturated monocyclic ring with 1, or 2 heteroatom ring atoms independently selected from the group consisting of N, O and S, R B may be substituted with 1 or 2 independently selected R C ; and

each R C is independently either halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 3 -C 6 cycloalkyl or C 1 -C 6 haloalkyl.

12. The compound according to claim 11 , wherein R 1 is CF 3 , CH 2 CF 3 , CHF 2 , CH 3 , or cyclopropyl.

13. The compound according to claim 11 , wherein each R 4 is independently selected from the group consisting of CF 3 , CH 2 —CF 3 , and CF 2 —CH 3 .

14. The compound according to claim 5 wherein

is selected from the group consisting of:

wherein each Z is independently either N or C—R 4 ,

each R 4 is independently selected from the group consisting of:

hydrogen, F, Cl, OH, C 1 -C 6 alkyl, C 1 -C 2 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 6 alkyl-R B , C 3 -C 8 cycloalkyl, Het, Aryl, and

 wherein X 1 is either CH 2 , NH, O, or S; X 2 is either CH or N; and X 3 is either NH, CH 2 , O, or S;

each Aryl is independently phenyl optionally substituted with 1 or 2 independently selected R C ;

each Het is independently a 4-, 5- or 6-membered saturated or unsaturated monocyclic ring with 1 or 2 heteroatom ring atoms independently selected from the group consisting of N, O and S; provided that said Het is optionally substituted with 1 or 2 independently selected R C ;

each R A is independently selected from the group consisting of F, Cl, OH, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 3 -C 8 halocycloalkyl, and C 1 -C 6 haloalkoxy;

each R B is independently either phenyl or a 5- or 6-membered saturated or unsaturated monocyclic ring with 1, or 2 heteroatom ring atoms independently selected from the group consisting of N, O and S, wherein R B may be substituted with 1 or 2 independently selected R C ; and

each R C is independently either halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 3 -C 6 cycloalkyl or C 1 -C 6 haloalkyl.

15. A compound which is selected from the group consisting of:

and pharmaceutically acceptable salts thereof.

16. The compound according to claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

17. A pharmaceutical composition comprising an effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.

18. The pharmaceutical composition according to claim 17 , further comprising a second therapeutic agent selected from the group consisting of HCV antiviral agents, immunomodulators, and anti-infective agents.

19. The pharmaceutical composition according to claim 18 , further comprising a second therapeutic agent selected from the group consisting of HCV protease inhibitors, inhibitors of HCV NS4A, inhibitors of HCV NS4B, inhibitors of HCV NS5A and inhibitors of HCV NS5B.

20. A method for treating HCV in patient comprising the step of administering to said patient a therapeutically effective amount of the compound of claim 1 .

21. A compound which is a pharmaceutically acceptable salt of

22. A compound which is

23. The compound according to claim 21 , which is the sodium or potassium salt of

24. A pharmaceutical composition comprising an effective amount of the compound of claim 21 and a pharmaceutically acceptable carrier.

25. A pharmaceutical composition comprising an effective amount of the compound of claim 22 and a pharmaceutically acceptable carrier.

26. A method for treating HCV in patient comprising the step of administering to said patient a therapeutically effective amount of the compound of claim 21 .

27. A method for treating HCV in patient comprising the step of administering to said patient a therapeutically effective amount of the compound of claim 22 .