Methods and compositions for treating hepatitis C virus

• US 10,363,265 B2
• Filed: 12/28/2012
• Issued: 07/30/2019
• Est. Priority Date: 05/23/2000
• Status: Expired due to Fees

• Current Assignee: Idenix Pharmaceuticals LLC (Merck & Co., Inc.)
• Original Assignee: Idenix Pharmaceuticals LLC (Merck & Co., Inc.)
• Inventors: Sommadossi, Jean-Pierre, La Colla, Paolo
• Primary Examiner(s): McIntosh, III, Traviss C
• Application Number:
  US13/730,669
• Publication Number:
  US 20130149283A1
• Time in Patent Office: 2,405 Days
• Field of Search: None
• 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 method for the treatment of a hepatitis C virus infection in a host, comprising administering to the host an antivirally effective amount of a compound of Formula V:

2. The method of claim 1, comprising administering the compound or a pharmaceutically acceptable salt thereof in combination or alternation with a second anti-hepatitis C virus agent.

3. The method of claim 2, wherein the second anti-hepatitis C virus agent is selected from the group consisting of interferon, ribavirin, a protease inhibitor, a thiazolidine derivative, a polymerase inhibitor, and a helicase inhibitor.

4. The method of claim 2, wherein the second anti-hepatitis C virus agent is a protease inhibitor.

5. The method of claim 2, wherein the second anti-hepatitis C virus agent is ribavirin.

6. The method of claim 1, wherein the compound is in the form of a dosage unit.

7. The method of claim 6, wherein the dosage unit contains from about 50 to about 1000 mg of the compound.

8. The method of claim 6, wherein the dosage unit is a tablet or capsule.

9. The method of claim 1, wherein the host is a human.

10. The method of claim 1, wherein the compound is in substantially pure form.

11. The method of claim 1, wherein the compound is at least 90% by weight of the β

-D-isomer.

12. The method of claim 1, wherein the compound is at least 95% by weight of the β

-D-isomer.

13. The method of claim 1, wherein:

R¹ is H, monophosphate, diphosphate, triphosphate, a stabilized phosphate prodrug, lower acyl, or a pharmaceutically acceptable leaving group which, when administered in vivo, provides a compound wherein R¹ is H or phosphate.

14. The method of claim 1, wherein R¹ is monophosphate, diphosphate, triphosphate or a stabilized phosphate prodrug.

15. The method of claim 1, wherein said host is a human.

16. The method of claim 15, wherein X¹ is H, and Y is either OH or NH₂.

17. The method of claim 16, wherein Y is OH.

18. The method of claim 17, wherein R¹ is a stabilized phosphate prodrug.

19. The method of claim 17, wherein R¹ is a pharmaceutically acceptable leaving group which, when administered in vivo, provides a compound wherein R¹ is phosphate.

20. The method of claim 17, wherein R¹ is a triphosphate.

21. A method for inhibiting the replication of a hepatitis C virus in a host, comprising contacting the host with an antivirally effective amount of a compound of Formula X:

22. The method of claim 21, wherein the host is a cell.

23. The method of claim 21, wherein R⁶ is methyl.

24. The method of claim 21, wherein:

R¹ is H, monophosphate, diphosphate, triphosphate, a stabilized phosphate prodrug, lower acyl, or a pharmaceutically acceptable leaving group which, when administered in vivo, provides a compound wherein R¹ is H or phosphate.

25. The method of claim 21, wherein R¹ is monophosphate, diphosphate, triphosphate or a stabilized phosphate prodrug.

26. The method of claim 21, wherein R¹ is monophosphate, diphosphate, triphosphate, a stabilized phosphate prodrug, or a pharmaceutically acceptable leaving group which, when administered in vivo, provides a compound wherein R¹ is phosphate.

27. The method of claim 26, wherein said host is a human.

28. The method of claim 27, wherein R⁶ is methyl.

29. The method of claim 28, wherein said pyrimidine base is either uracil or cytosine.

30. The method of claim 29, wherein said pyrimidine base is uracil.

31. The method of claim 30, wherein R¹ is a stabilized phosphate prodrug.

32. The method of claim 30, wherein R¹ is a pharmaceutically acceptable leaving group which, when administered in vivo, provides a compound wherein R¹ is phosphate.

33. The method of claim 29, wherein R¹ is a triphosphate.