3-HETEROCYCLIC SUBSTITUTED INDOLE DERIVATIVES AND METHODS OF USE THEREOF

• US 20110165118A1
• Filed: 11/13/2008
• Published: 07/07/2011
• Est. Priority Date: 11/16/2007
• Status: Active Grant

• Current Assignee: Merck Sharp & Dohme LLC (Merck & Co., Inc.)
• Original Assignee: Schering Corporation (Merck & Co., Inc.)
• Inventors: Hong, Liwu, Duca, Jose S., Pu, Haiyan, McKittrick, Brian A., Chan, Tin-Yau, Wang, Li, Lesburg, Charles A., Vaccaro, Henry M.
• Granted Patent: US 8,765,757 B2
• Time in Patent Office: Days
• US Class Current: 424/85.4
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/14 containing three or more hetero rings
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 495/04 Ortho-condensed systems

Abstract

The present invention relates to 3-Heterocyclic Substituted Indole Derivatives, compositions comprising at least one 3-Heterocyclic Substituted Indole Derivative, and methods of using the 3-Heterocyclic Substituted Indole Derivatives for treating or preventing a viral infection or a virus-related disorder in a patient.

Claims

1. A compound having the formula:

2. The compound of claim 1, wherein R² is —

C(O)NHSO₂R¹¹ and R¹¹ is alkyl, aryl, cycloalkyl, haloalkyl, heteroaryl, heterocycloalkyl or hydroxyalkyl.

3. The compound of claim 1, wherein R² is —

C(O)NHSO₂N(R⁹)₂ and R⁹ is independently selected from H, alkyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl.

8. The compound of claim 1, wherein R³ is:

9. The compound of claim 1, wherein R¹ is —

[C(R¹²)₂]_r- and R¹⁰ is;

12. The compound of claim 1, wherein R⁴, R⁶ and R⁷ are each H, and R⁵ is H, halo or haloalkyl.

15. The compound of claim 1 having the formula:

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

38. 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 thereof.

40. The method of claim 38, 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 viral replication inhibitor, an antisense agent, a therapeutic vaccine, a viral protease inhibitor, a virion production inhibitor, an antibody therapy (monoclonal or polyclonal), and any agent useful for treating an RNA-dependent polymerase-related disorder.

4-7. -7. (canceled)

10-11. -11. (canceled)

13-14. -14. (canceled)

16-18. -18. (canceled)

19. A compound having the formula:

20. The compound of claim 19, wherein R² is —

C(O)OR⁹ or —

C(O)N(R⁹)₂.

22. The compound of claim 19, wherein R³ is:

23. The compound of claim 19, wherein R¹ is —

[C(R¹²)₂]_r- and R¹⁰ is;

26. The compound of claim 19, wherein R⁴, R⁶ and R⁷ are each H, and R⁵ is H, halo or haloalkyl.

29. The compound of claim 19 having the formula:

35. A composition comprising at least one compound of claim 19 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

39. 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 19 or a pharmaceutically acceptable salt thereof.

41. The method of claim 39, 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 viral replication inhibitor, an antisense agent, a therapeutic vaccine, a viral protease inhibitor, a virion production inhibitor, an antibody therapy (monoclonal or polyclonal), and any agent useful for treating an RNA-dependent polymerase-related disorder.

21. (canceled)

24-25. -25. (canceled)

27-28. -28. (canceled)

30-32. -32. (canceled)

33. A compound having the structure 1-285 as numbered in the above specification, or a pharmaceutically acceptable salt thereof.

36-37. -37. (canceled)