Methods and compositions for treating hepatitis C virus using 4'-modified nucleosides

• US 20040006007A1
• Filed: 09/30/2002
• Published: 01/08/2004
• Est. Priority Date: 09/28/2001
• Status: Active Grant

• Current Assignee: Centre National De La Recherche Scientifique, Idenix Pharmaceuticals (Merck & Co., Inc.), Universite Montpellier II
• Original Assignee: Gilles Gosselin, Jean-Louis Imbach, Jean-Pierre Sommadossi
• Inventors: Sommadossi, Jean-Pierre, Gosselin, Gilles, Imbach, Jean-Louis
• Granted Patent: US 7,138,376 B2
• Time in Patent Office: Days
• US Class Current: 514/8
• 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: C07H 19/056 Triazole or tetrazole radicals
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07J 1/00 Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
• CPC Class Codes: C07K 9/00 Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof

Abstract

A compound, method and composition for treating a host infected with a hepatitis C viral comprising administering an effective hepatitis C treatment amount of a described 4′-disubstituted nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Claims

1. A compound of Formula I:

15. The compound as described in any of the preceding claims 1-14, wherein the said compound is in the form of a dosage unit.

16. The compound as described in claim 15, wherein the dosage unit contains 10 to 1500 mg of said compound.

17. The compound as described in claim 15 or 16, wherein said dosage unit is a tablet or capsule.

2. A compound of Formula II:

3. A compound selected from Formulas III, IV and V, or a pharmaceutically acceptable salt or prodrug thereof, is provided:

64. A compound as in claims 3, 4, 5, 6, 7, or 8, in which the purine or pyrimidine base is selected from the group comprising of

65. A compound as in claims 3, 4, 5, 6, 7, or 8, in which the purine or pyrimidine base is selected from the following group:

66. A compound as in claims 3, 4, 5, 6, 7, or 8, in which the purine or pyrimidine base is selected from the following group:

4. A compound of Formula III, IV or V, or a pharmaceutically acceptable salt or prodrug thereof, is provided:

5. A compound of Formula III, IV or V, or a pharmaceutically acceptable salt or prodrug thereof, is provided:

6. A compound of Formula III, IV or V, or a pharmaceutically acceptable salt or prodrug thereof, is provided:

7. A compound of Formula IV, or its pharmaceutically acceptable salt or prodrug, is provided:

8. A compound of Formula VI, or a pharmaceutically acceptable salt or prodrug thereof:

9. A compound of the structure:

10. A compound of the structure:

11. A compound of the structure:

12. A compound of the structure:

13. A compound of the structure:

14. A compound of the structure:

18. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of Formula I:

38. The pharmaceutical composition as described in any of the preceding claims 18-37, wherein the said compound is in the form of a dosage unit.

39. The pharmaceutical composition as described in claim 38, wherein the dosage unit contains 10 to 1500 mg of said compound.

40. The pharmaceutical composition as described in claim 38 or 39, wherein said dosage unit is a tablet or capsule.

19. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of Formula II:

20. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound selected from Formulas III, IV and V, or a pharmaceutically acceptable salt or prodrug thereof, is provided:

21. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of Formula VI, or a pharmaceutically acceptable salt or prodrug thereof:

22. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of structure:

23. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of structure:

24. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of structure:

25. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of structure:

26. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of structure:

27. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of structure:

28. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of Formula I:

29. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of Formula IV:

30. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound selected from Formulas III, IV and V, or a pharmaceutically acceptable salt or prodrug thereof, is provided:

31. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of Formula VI, or a pharmaceutically acceptable salt or prodrug thereof:

32. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of structure:

33. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of structure:

34. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of structure:

35. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of structure:

36. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of structure:

37. A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of structure:

41. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula I:

42. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula II:

43. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound selected from Formulas III, IV and V, or a pharmaceutically acceptable salt or prodrug thereof, is provided:

67. A method of treatment or prophylaxis as in claims 43, 44, 53, or 54, in which the purine or pyrimidine base is selected from the group comprising of.

68. A method of treatment or prophylaxis as in claims 43, 44, 53, or 54, in which the purine or pyrimidine base is selected from the group comprising of:

69. A method of treatment or prophylaxis as in claims 43, 44, 53, or 54, in which the purine or pyrimidine base is selected from the group comprising of:

44. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula VI, or a pharmaceutically acceptable salt or prodrug thereof:

45. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

46. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

47. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

48. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

49. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

50. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

51. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula I:

61. Method of treatment as described in any of the preceding claims 51-60, wherein the said compound is in the form of a dosage unit.

62. Method of treatment as described in claim 61, wherein the dosage unit contains 10 to 1500 mg of said compound.

63. Method of treatment as described in claim 61 or 62, wherein said dosage unit is a tablet or capsule.

52. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula II:

53. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound selected from Formulas III, IV and V:

54. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula VI, or a pharmaceutically acceptable salt or prodrug thereof:

55. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

56. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

57. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

58. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

59. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure:

60. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an antivirally effective amount of a compound of the structure: