HCV NS3 protease inhibitors

1. A compound of formula (I):

or a pharmaceutically acceptable salt, or hydrate thereof,

wherein:

is selected from the group of rings consisting of:

heterocyclic ring systems, wherein the points of attachment to variables Y and X are independently selected from a first pair of atoms comprising a first carbon ring atom and second carbon ring atom, and a second pair of atoms comprising a carbon ring atom and a nitrogen ring atom, and the heterocyclic ring system is selected from the group consisting of:

a) an 8-, 9- or 10-membered saturated or unsaturated bicyclic ring with 1, 2, or 3 heteroatom ring atoms selected from the group consisting of N, O or S, and

b) an 11- to 15-membered saturated or unsaturated tricyclic ring with 1, 2, 3, or 4 heteroatom ring atoms selected from the group consisting of N, O or S,

wherein said heterocyclic ring system is unsubstituted, mono-substituted with R 5 , or disubstituted with groups independently selected from R 5 ;

R 1 is CO 2 R 10 or CONR 10 SO 2 R 6 ;

R 5 is H, OR 10 , or aryl; wherein aryl is phenyl;

R 6 is C 3 -C 6 cycloalkyl;

Z is C 3-9 alkylene which is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from —C 1-6 alkyl, where 2 of the substituents optionally form a spiro or fused ring contain the substituent atoms and shared atom or atoms;

X is

is —O or —C(O)O—,

Y is selected from the group consisting of:

1) —C 1-7 alkylene-Y 1 —, and

2) —C 2-7 alkenylene-Y 1 —,

wherein Y 1 is —OC(O)—, —NR 17 C(O)—, or —C(O)—, each alkylene, and alkenylene is unsubstituted or substituted with C 1-6 alkyl, any two adjacent carbon atoms in Y optionally form a C 3-6 membered ring containing 0 to 3 heteroatoms selected from the group consisting of N, O and S, and each alkylene, and alkenylene chain optionally includes an oxygen atom in place of a methylene moiety;

each R 10 is independently H or C 1-6 alkyl; and

R 17 is C 1-6 alkyl or a C 1-6 alkylene moiety that, together with another carbon atom in Y, forms a heterocyclic ring containing one nitrogen and 2-7 carbon atoms.

2. The compound of claim 1 , wherein Y is —C 1-7 alkylene-Y 1 — or —C 2-7 alkenylene-Y 1 —, wherein Y 1 is —OC(O)— or —C(O)—, and each alkylene, and alkenylene is unsubstituted or substituted with C 1-2 alkyl.

3. The compound of claim 2 , wherein Y is selected from the group consisting of —CH═CHCH 2 C(CH 3 ) 2 CH 2 OC(O)—, —CH═CHCH 2 CH(CH 3 )CH 2 OC(O)—, —CH═CH(CH 2 ) 4 OC(O)—, —(CH 2 ) 3 C(CH 3 ) 2 CH 2 OC(O)—, —(CH 2 ) 3 CH(CH 3 )CH 2 OC(O)—, —(CH 2 ) 6-8 OC(O)—, —CH═CH(CH 2 ) 2 C(CH 3 ) 2 CH 2 OC(O)—, —CH═CH(CH 2 ) 2 CH(CH 3 )CH 2 OC(O)—, —CH═CH(CH 2 ) 5 C(O)—(CH 2 ) 4 C(CH 3 ) 2 CH 2 OC(O)—, —(CH 2 ) 4 CH(CH 3 )CH 2 OC(O)—, —(CH 2 ) 7 C(O)—, —CH═CH(CH 2 ) 3 OC(O)—, —CH═CH(CH 2 ) 5 OC(O)—, —CH═CH(CH 2 ) 3 CH(CH 3 )CH 2 OC(O)—, —CH═CH(CH 2 ) 3 C(CH 3 ) 2 CH 2 OC(O)—, —CH═CH(CH 2 ) 6 C(O)—, —(CH 2 ) 5 C(CH 3 ) 2 CH 2 OC(O)—, and —(CH 2 ) 5 CH(CH 3 )CH 2 OC(O)—.

4. The compound of claim 1 , wherein Z is —(CH 2 ) 3 —.

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

wherein p and q are independently 1 or 2, and D is N or CH.

6. The compound of claim 5 , wherein R 5 is selected from the group consisting of H, —OC 1-6 alkyl and phenyl, and p and q are 1.

7. The compound of claim 6 , selected from the group consisting of A is selected from the group consisting of:

8. A compound of claim 1 , or a

pharmaceutically acceptable salt, or hydrate thereof, selected from the group consisting of:

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

10. The pharmaceutical composition of claim 9 , further comprising a second therapeutic agent selected from the group consisting of a HCV antiviral agent, an immunomodulator, and an anti-infective agent.

11. The pharmaceutical composition of claim 10 , wherein the HCV antiviral agent is an antiviral selected from the group consisting of a HCV protease inhibitor and a HCV NS5B polymerase inhibitor.

12. A method of inhibiting HCV NS3 protease in a subject in need thereof, said method comprising administering to the subject an effective amount of a compound of formula (I):

or a pharmaceutically acceptable salt, or hydrate thereof,

wherein:

is selected from the group of rings consisting of:

heterocyclic ring systems, wherein the points of attachment to variables Y and X are independently selected from a first pair of atoms comprising a first carbon ring atom and second carbon ring atom, and a second pair of atoms comprising a carbon ring atom and a nitrogen ring atom, and the heterocyclic ring system is selected from the group consisting of:

a) an 8-, 9- or 10-membered saturated or unsaturated bicyclic ring with 1, 2, or 3 heteroatom ring atoms selected from the group consisting of N, O or S, and

b) an 11- to 15-membered saturated or unsaturated tricyclic ring with 1, 2, 3, or 4 heteroatom ring atoms selected from the group consisting of N, O or S,

wherein said heterocyclic ring system is unsubstituted, mono-substituted with R 5 , or disubstituted with groups independently selected from R 5 ;

R 1 is CO 2 R 10 or CONR 10 SO 2 R 6 ;

R 5 is H, OR 10 , or aryl wherein aryl is phenyl;

R 6 is C 3 -C 6 cycloalkyl;

Z is C 3-9 alkylene which is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from —C 1-6 alkyl, where 2 of the substituents optionally form a spiro or fused ring contain the substituent atoms and shared atom or atoms;

X is

O or —C(O)O—;

Y is selected from the group consisting of:

1) —C 1-7 alkylene-Y 1 —, and

2) —C 2-7 alkenylene-Y 1 —,

wherein Y 1 is —OC(O)—, —NR 17 C(O)—, or —C(O), each alkylene, and alkenylene is unsubstituted or substituted with C 1-6 alkyl, any two adjacent carbon atoms in Y optionally form a C 3-6 membered ring containing 0 to 3 heteroatoms selected from the group consisting of N, O and S, and each alkylene, and alkenylene chain optionally includes an oxygen atom in place of a methylene moiety;

R 10 is independently H or C 1 -C 6 alkyl; and

R 17 is C 1-6 alkyl or a C 1-6 alkylene moiety that, together with another carbon atom in Y, forms a heterocyclic ring containing one nitrogen and 2-7 carbon atoms.

13. A method of treating infection by HCV in a subject in need thereof, said method comprising administering to the subject an effective amount of a compound of formula (I):

or a pharmaceutically acceptable salt, or hydrate or prodrug-thereof,

wherein:

is selected from the group of rings consisting of:

a heterocyclic ring systems, wherein the points of attachment to variables Y and X are independently selected from a first pair of atoms comprising a first carbon ring atom and second carbon ring atom, and a second pair of atoms comprising a carbon ring atom and a nitrogen ring atom, and the heterocyclic ring system is selected from the group consisting of:

a) an 8-, 9- or 10-membered saturated or unsaturated bicyclic ring with 1, 2, or 3 heteroatom ring atoms selected from the group consisting of N, O or S, and

b) an 11- to 15-membered saturated or unsaturated tricyclic ring with 1, 2, 3, or 4 heteroatom ring atoms selected from the group consisting of N, O or S,

wherein said heterocyclic ring system is unsubstituted, mono-substituted with R 5 , or disubstituted with groups independently selected from R 5 ;

R 1 is CO 2 R 10 or CONR 10 SO 2 R 6 ;

R 5 is H, or aryl; wherein aryl is phenyl;

R 6 is C 3 -C 6 cycloalkyl;

Z is C 3-9 alkylene which is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from —C 1-6 alkyl, where 2 of the substituents optionally form a spiro or fused ring contain the substituent atoms and shared atom or atoms;

X is

—O or —C(O)O—;

Y is selected from the group consisting of:

1) alkylene-Y 1 —, and

2) alkenylene-Y 1 —,

wherein Y 1 is —OC(O)—, —NR 17 C(O)—, or —C(O), each alkylene, and alkenylene is unsubstituted or substituted with C 1-6 alkyl, any two adjacent carbon atoms in Y optionally form a C 3-6 membered ring containing 0 to 3 heteroatoms selected from the group consisting of N, O and S, and each alkylene, and alkenylene and chain optionally includes an oxygen atom in place of a

each R 10 is independently H or C 1 -C 6 alkyl; and

R 17 is C 1-6 alkyl or a C 1-6 alkylene moiety that, together with another carbon atom in Y, forms a heterocyclic ring containing one nitrogen and 2-7 carbon atoms.