METHODS AND COMPOSITIONS FOR TREATING HEPATITIS C VIRUS

• US 20130017171A1
• Filed: 09/20/2012
• Published: 01/17/2013
• Est. Priority Date: 05/23/2000
• Status: Abandoned Application

• Current Assignee: Idenix Pharmaceuticals (Merck & Co., Inc.)
• Original Assignee: Idenix Pharmaceuticals (Merck & Co., Inc.), Universita' Degli Studi Di Bari (Repubblica Italiana)
• Inventors: Sommadossi, Jean-Pierre, LaColla, Paulo
• Application Number:
  US13/623,674
• Publication Number:
  US 20130017171A1
• Time in Patent Office: Days
• US Class Current: 424/85.4
• CPC Class Codes: A61K 31/7056 containing five-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 31/708 having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• 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: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: G03C 1/0051 Tabular grain emulsions

Abstract

A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Claims

1. A β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl-nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

2. The deoxynucleoside of claim 1, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methyl-nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

3. The deoxynucleoside of claim 1, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methylpyrimidine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

4. The deoxynucleoside of claim 1, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methylpyrimidine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

5. The deoxynucleoside of claim 3, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl uracil nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

6. The deoxynucleoside of claim 3, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methyl uracil nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

7. The deoxynucleoside of claim 3, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl cytosine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

8. The deoxynucleoside of claim 3, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methyl cytosine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

9. The deoxynucleoside of claim 1, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl-ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

10. The deoxynucleoside of claim 9, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methylpyrimidine ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

11. The deoxynucleoside of claim 10, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl uracil ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

12. The deoxynucleoside of claim 10, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl cytosine ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

13. A pharmaceutical composition comprising the deoxynucleoside of claim 1 and a pharmaceutically acceptable excipient.

14. The pharmaceutical composition of claim 13, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methyl-nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

15. The pharmaceutical composition of claim 13, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methylpyrimidine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

16. The pharmaceutical composition of claim 13, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methylpyrimidine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

17. The pharmaceutical composition of claim 15, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl uracil nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

18. The pharmaceutical composition of claim 15, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methyl uracil nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

19. The pharmaceutical composition of claim 15, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl cytosine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

20. The pharmaceutical composition of claim 15, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methyl cytosine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

21. The pharmaceutical composition of claim 13, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl-ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

22. The pharmaceutical composition of claim 21, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methylpyrimidine ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

23. The pharmaceutical composition of claim 22, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl uracil ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

24. The pharmaceutical composition of claim 22, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl cytosine ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

25. The pharmaceutical composition of claim 13, wherein the composition is formulated as a dosage unit for single dose administration.

26. The pharmaceutical composition of claim 25, wherein the dosage unit contains from about 50 to about 1000 mg of the deoxynucleoside.

27. The pharmaceutical composition of claim 25, wherein the dosage unit is a tablet or capsule.

28. A method for the treatment of a hepatitis C virus infection in a host, comprising administering to the host an antivirally effective amount of a deoxynucleoside, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-C-methyl-nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

29. The method of claim 28, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl-nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

30. The method of claim 28, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methyl-nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

31. The method of claim 28, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-C-methyl pyrimidine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

32. The method of claim 31, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methylpyrimidine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

33. The method of claim 31, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methylpyrimidine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

34. The method of claim 31, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-C-methyl uracil nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

35. The method of claim 31, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl uracil nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

36. The method of claim 35, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methyl uracil nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

37. The method of claim 31, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-C-methyl cytosine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

38. The method of claim 31, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl cytosine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

39. The method of claim 38, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methyl cytosine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

40. The method of claim 28, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl-ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

41. The method of claim 40, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methylpyrimidine ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

42. The method of claim 41, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl uracil ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

43. The method of claim 41, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl cytosine ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

44. The method of claim 28, wherein the host is a human.

45. The method of claim 28, wherein the antivirally effective amount is ranging from about 0.1 to about 100 mg/kg/day.

46. The method of claim 45, wherein the antivirally effective amount is ranging from about 1 to about 50 mg/kg/day.

47. The method of claim 45, wherein the antivirally effective amount is ranging from about 1 to about 20 mg/kg/day.

48. The method of claim 28, wherein the deoxynucleoside is administered in combination or alternation with a second anti-hepatitis C agent.

49. The method of claim 48, wherein the second agent is selected from the group consisting of an interferon, ribavirin, a protease inhibitor, a thiazolidine derivative, a polymerase inhibitor, and a helicase inhibitor.

50. The method of claim 48, wherein the second agent is an interferon.

51. The method of claim 48, wherein the second agent is ribavirin.

52. 2′

-C-Methyl-guanosine, or a pharmaceutically acceptable salt or prodrug thereof.

54. A pharmaceutical composition comprising the 2′

-C-methyl-guanosine of claim 52 and a pharmaceutically acceptable excipient.

53. 2′

-C-Methyl-guanosine monophosphate, diphosphate, or triphosphate.

55. A method for inhibiting replication of a hepatitis C virus in a host, comprising contacting the host with an antivirally effective amount of a deoxynucleoside, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-C-methyl-nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

56. The method of claim 55, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl-nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

57. The method of claim 55, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methyl-nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

58. The method of claim 55, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-C-methyl pyrimidine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

59. The method of claim 55, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methylpyrimidine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

60. The method of claim 59, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methylpyrimidine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

61. The method of claim 58, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-C-methyl uracil nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

62. The method of claim 61, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl uracil nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

63. The method of claim 61, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methyl uracil nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

64. The method of claim 58, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-C-methyl cytosine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

65. The method of claim 64, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl cytosine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

66. The method of claim 64, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-fluoro-2′

-C-methyl cytosine nucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

67. The method of claim 56, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl-ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

68. The method of claim 67, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methylpyrimidine ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

69. The method of claim 68, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl uracil ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

70. The method of claim 68, wherein the deoxynucleoside is a β

-D-2′

-deoxy-2′

-halo-2′

-C-methyl cytosine ribonucleoside, or pharmaceutically acceptable salt or a prodrug thereof.

71. The method of claim 55, wherein the host is a human cell.