4, 5-ring annulated indole derivatives for treating or preventing of HCV and related viral infections

1. A compound having the formula:

or a pharmaceutically acceptable salt or ester thereof, wherein

ring Z of formula (I), is

R 1 is —CH 2 —

R 2 is —C(O)OH, —C(O)NHSO 2 -alkyl, —C(O)NHSO 2 -aryl, —C(O)NHSO 2 -cycloalkyl, —C(O)NHSO 2 -alkylene-cycloalkyl or C(O)NHSO 2 R 11 ,

wherein an aryl or cycloalkyl group can be optionally substituted with up to 4 substituents, which are each independently selected from alkyl, alkenyl, alkynyl, aryl, —[C(R 12 ) 2 ] q -cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, —[C(R 12 ) 2 ] q -haloalkyl, —[C(R 12 ) 2 ] q -hydroxyalkyl, halo, hydroxy, —OR 9 , —CN, —[C(R 12 ) 2 ] q —C(O)R 8 , —[C(R 12 ) 2 ] q —C(O)OR 9 , —[C(R 12 ) 2 ] q —C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —OR 9 , —[C(R 12 ) 2 ] q —N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHC(O)R 8 , —[C(R 12 ) 2 ] q —NR 8 C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHSO 2 R 11 , —[C(R 12 ) 2 ] q —S(O) p R 11 , —[C(R 12 ) 2 ] q —SO 2 N(R 9 ) 2 and —SO 2 N(R 9 )C(O)N(R 9 ) 2 ;

R 3 is

which can be optionally substituted with up to 3 substituents, which are the same or different, and are selected from alkyl, aryl, heteroaryl-, halo, haloalkyl, hydroxyalkyl, hydroxy, —CN, —C(O)R 8 , —C(O)OR 9 , —C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —OR 9 , —[C(R 12 ) 2 ] q —N(R 9 ) 2 , and —NHC(O)R 8 ;

R 6 and R 7 are each, independently, H, alkyl, F, Cl,—CF 3 —OH, —O-alkyl, —OCF 3 , —NH 2 and —NHSO 2 -alkyl;

each occurrence of R 8 is independently H, alkyl, alkenyl, alkynyl, —[C(R 12 ) 2 ] q -aryl, —[C(R 12 ) 2 ] q -cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, haloalkyl or hydroxyalkyl;

each occurrence of R 9 is independently H, alkyl, alkenyl, alkynyl, —[C(R 12 ) 2 ] q -aryl, —[C(R 12 ) 2 ] q -cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, haloalkyl or hydroxyalkyl;

R 10 is heterocycloalkenyl, aryl, heteroaryl, wherein a heterocycloalkenyl, aryl or heteroaryl group can be optionally and independently substituted with up to 4 substituents, which are each independently selected from H, alkyl, alkenyl, alkynyl, aryl, —[C(R 12 ) 2 ] q -cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, —[C(R 12 ) 2 ] q -haloalkyl, —[C(R 12 ) 2 ] q -hydroxyalkyl, halo, hydroxy, —OR 9 , —CN, —[C(R 12 ) 2 ] q —C(O)R 8 , —[C(R 12 ) 2 ] q —C(O)OR 9 , —[C(R 12 ) 2 ] q —C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —OR 9 , —[C(R 12 ) 2 ] q —N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHC(O)R 8 , —[C(R 12 ) 2 ] q —NR 8 C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHSO 2 R 11 , —[C(R 12 ) 2 ] q —S(O) p R 11 , —[C(R 12 ) 2 ] q —SO 2 N(R 9 ) 2 and —SO 2 N(R 9 )C(O)N(R 9 ) 2 , cycloalkyl, heterocycloalkyl, hola, haloalkyl, —O-haloalkyl, —OH, —CN, —NH 2 , —NH-alkyl, —N(alkyl) 2 or —NHSO 2 -alkyl;

each occurrence of R 11 is independently alkyl, aryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, heteroaryl, haloalkyl, hydroxy or hydroxyalkyl, wherein a cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl group can be optionally and independently substituted with up to 4 substituents, which are each independently selected from —H, alkyl, alkenyl, alkynyl, aryl, —[C(R 12 ) 2 ] q -cycloalkyl, —[C(R 12 ) 2 ] q -cycloalkenyl, —[C(R 12 ) 2 ] q -heterocycloalkyl, —[C(R 12 ) 2 ] q -heterocycloalkenyl, —[C(R 12 ) 2 ] q -heteroaryl, —[C(R 12 ) 2 ] q -haloalkyl, —[C(R 12 ) 2 ] q -hydroxyalkyl, halo, hydroxy, —OR 9 , —CN, —[C(R 12 ) 2 ] q —C(O)R 8 , —[C(R 12 ) 2 ] q ——C(O)OR 9 , —[C(R 12 ) 2 ] q —C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —OR 9 , —[C(R 12 ) 2 ] q —N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHC(O)R 8 , —[C(R 12 ) 2 ] q —NR 8 C(O)N(R 9 ) 2 , —[C(R 12 ) 2 ] q —NHSO 2 -alkyl, —[C(R 12 ) 2 ] q —NHSO 2 -cycloalkyl, —[C(R 12 ) 2 ] q —NHSO 2 aryl, —[C(R 12 ) 2 ] q —SO 2 N(R 9 ) 2 and —SO 2 N(R 9 )C(O)N(R 9 ) 2 ;

each occurrence of R 12 is independently H, halo, —N(R 9 ) 2 , —OR 9 , alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, wherein a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl group can be optionally and independently substituted with up to 4 substituents, which are each independently selected from alkyl, halo, haloalkyl, hydroxyalkyl, hydroxy, —CN, —C(O)alkyl, —C(O)Oalkyl, —C(O)NHalkyl, —C(O)N(alkyl) 2 , —O-alkyl, —NH 2 , —NH(alkyl), —N(alkyl) 2 , —NHC(O)alkyl, —NHSO 2 alkyl, —SO 2 alkyl or —SO 2 NH-alkyl, or two R 12 groups, together with the carbon atoms to which they are attached, join to form a cycloalkyl, heterocycloalkyl or C═O group;

each occurrence of p is independently 0, 1 or 2; and

each occurrence of q is independently an integer ranging from 0 to 4.

2. The compound of claim 1 , wherein R 10 is a bicyclic heteroaryl group.

3. The compound of claim 1 , wherein R 10 is phenyl, pyridyl, benzimidazole, benzimidazolone, quinoline, quinolinone, quinoxaline, quinoxalinone, quinazoline, quinazolinone, naphthyridine, naphthyridinone, pteridine, pteridinone, each of which can be optionally substituted with up to 3 substituents, which are the same or different, and are selected from alkyl, cycloalkyl, heterocycloalkyl, halo, haloalkyl, —O-haloalkyl, —OH, —CN, —NH 2 , —NH-alkyl, —N(alkyl) 2 or —NHSO 2 -alkyl.

4. The compound of claim 1 , wherein R 2 is —C(O)OH or —C(O)NHSO 2 R 11 .

5. The compound of claim 1 wherein Z is:

6. A compound having the structure:

or a pharmaceutically acceptable salt or ester thereof.

7. A pharmaceutical composition comprising at least one compound of claim 1 or a pharmaceutically acceptable salt or ester thereof, and at least one pharmaceutically acceptable carrier.

8. The pharmaceutical composition of claim 7 , further comprising at least one additional antiviral agent, wherein the additional agent selected from: an HCV polymerase inhibitor; an interferon; a RNA replication inhibitor; an antisense agent; a therapeutic vaccine; a protease inhibitor; and an antibody therapy (monoclonal or polyclonal).

9. A method for treating HCV infection in a patient, the method comprising administering to the patient an effective amount of at least one compound of claim 1 or a pharmaceutically acceptable salt or ester thereof.

10. The method of claim 9 , further comprising administering to the patient at least one additional antiviral agent, wherein the additional agent is selected from: an HCV polymerase inhibitor; an interferon; a RNA replication inhibitor; an antisense agent; a therapeutic vaccine; a protease inhibitor;

and an antibody therapy (monoclonal or polyclonal).

11. The compound of claim 3 , wherein R 10 is phenyl or pyridyl.

12. The compound of claim 3 , wherein R 10 is quinoline, quinolinone, pteridine, pteridinone, each of which can be optionally substituted with up to 3 substituents, which are the same or different, and are selected from alkyl, cycloalkyl, heterocycloalkyl, halo, haloalkyl, —O-haloalkyl, —OH, —CN, —NH 2 , —NH-alkyl, —N(alkyl) 2 or —NHSO 2 -alkyl.

13. The compound of claim 1 , wherein R 2 is —C(O)OH, —C(O)NHSO 2 —CH3 or —C(O)NHSO 2 -cycloalkyl.

14. The compound of claim 1 , wherein R 3 is

15. The compound of claim 4 , wherein R 3 is

16. The compound of claim 4 , wherein Z is

17. The compound of claim 1 , wherein R 10 is

each of which can be optionally substituted with up to 3 substituents, which are the same or different, and are selected from alkyl, cycloalkyl, heterocycloalkyl, halo, haloalkyl, —O-haloalkyl, —OH, —CN, —NH 2 , —NH-alkyl, —N(alkyl) 2 or —NHSO 2 -alkyl.

18. The compound of claim 17 , wherein and R 2 is —C(O)OH or —C(O)NHSO 2 R 11 .

19. The compound of claim 6 having the structure

or a pharmaceutically acceptable salt or ester thereof.