Methods and compositions for treating hepatitis C virus

• US 7,608,597 B2
• Filed: 06/20/2003
• Issued: 10/27/2009
• Est. Priority Date: 05/23/2000
• Status: Expired due to Term

• 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
• Primary Examiner(s): McIntosh, III, Traviss C
• Application Number:
  US10/602,691
• Publication Number:
  US 20040097461A1
• Time in Patent Office: 2,321 Days
• Field of Search: 514/43, 536/26.23, 536/26.26, 536/26.7, 536/27.13, 536/27.2
• US Class Current: 514/42
• 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, comprising administering an effective amount of a purine or pyrimidine β

-D-2′

-methyl-ribofuranosyl nucleoside or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.

2. The method of claim 1, wherein the nucleoside or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof, is a pyrimidine nucleoside.

3. The method of claim 1, wherein the nucleoside or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof, is a purine nucleoside.

4. The method of claim 1, wherein the β

-D-2′

-methyl-ribofuranosyl nucleoside or a phosphate thereof, or a phannaceutically acceptable salt or ester thereof is administered in combination or alternation with a second anti-hepatitis C agent.

5. The method of claim 4, wherein the second agent is selected from the group consisting of an interferon, ribavirin, a protease inhibitor, a thaizolidine derivative, a polymerase inhibitor, and a helicase inhibitor.

6. The method of claim 5, wherein the second agent is an interferon.

7. The method of claim 5, wherein the second agent is an ribavirin.

8. The method of claim 1, wherein the β

-D-2′

-methyl-ribofuranosyl nucleoside or a phosphate thereof, or a pharmaceutically acceptable salt or ester is in the form of a dosage unit.

9. The method of claim 8, wherein the dosage unit contains 50 to 1000 mg.

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

11. The method of claim 1, wherein the β

D-2′

-methyl-ribofuranosyl nucleoside or phosphate thereof, or a pharmaceutically acceptable salt or ester thereof, is in substantially pure form.

12. The method of claim 11, wherein the β

D-2′

-methyl-ribofuranosyl nucleoside or phosphate thereof, or a pharmaceutically acceptable salt or ester thereof is at least 90% by weight of the β

-D-isomer.

13. The method of claim 11, wherein the β

D-2′

-methyl-ribofuranosyl nucleoside or phosphate thereof, or a pharmaceutically acceptable salt or ester thereof is at least 95% by weight of the β

D-isomer.

14. The method of claim 1, wherein the β

D-2′

-methyl-ribofuranosyl nucleoside is administered.

15. The method of claim 1, wherein the β

D-2′

-methyl-ribofuranosyl nucleoside is administered in the form of a pharmaceutically acceptable salt.

16. The method of claim 1, wherein the β

D-2′

-methyl-ribofuranosyl nucleoside is administered in the form of a pharmaceutically acceptable ester.

17. The method of claim 14, wherein the nucleoside is a pyrimidine nucleoside.

18. The method of claim 15, wherein the nucleoside is a pyrimidine nucleoside.

19. The method of claim 16, wherein the nucleoside is a pyrimidine nucleoside.

20. The method of claim 14, wherein the nucleoside is a purine nucleoside.

21. The method of claim 15, wherein the nucleoside is a purine nucleoside.

22. The method of claim 16, wherein the nucleoside is a purine nucleoside.

23. The method of claim 1, wherein a phosphate, or a pharmaceutically acceptable salt thereof, of the β

-D-2′

-methyl-ribofuranosyl nucleoside is administered.

24. The method of claim 2, wherein the pyrimidine nucleoside or phosphate thereof, or a pharmaceutically acceptable salt or ester thereof, is a cytidine nucleoside.

25. The method of claim 3, wherein the purine nucleoside or phosphate thereof, or a pharmaceutically acceptable salt or ester thereof, is a guanosine nucleoside.

26. The method of claim 24, wherein a phosphate, or a pharmaceutically acceptable salt thereof, of the cytidine nucleoside is administered.

27. The method of claim 25, wherein a phosphate, or a pharmaceutically acceptable salt thereof, of the guanosine nucleoside is administered.

28. The method of claim 1, wherein the nucleoside or phosphate thereof, or a pharmaceutically acceptable salt or ester thereof, is administered to a host.

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

30. A method for the treatment of a hepatitis C virus infection in a host, comprising contacting a hepatitis C virus in the host with a compound of claim 1 or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.

31. A method for the treatment of a hepatitis C virus infection in a host, comprising contacting a cell in the host infected with a hepatitis C virus with a compound of claim 1 or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.

32. A method for the treatment of a hepatitis C virus infection in a host, comprising contacting a hepatitis C virus in the host with a compound of claim 24 or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.

33. A method for the treatment of a hepatitis C virus infection in a host, comprising contacting a cell in the host infected with a hepatitis C virus with a compound of claim 25 or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.