Nucleoside phosphoramidates

• US 8,716,262 B2
• Filed: 12/23/2009
• Issued: 05/06/2014
• Est. Priority Date: 12/23/2008
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Pharmasset LLC (Gilead Sciences Inc.)
• Inventors: Sofia, Michael Joseph, Du, Jinfa, Wang, Peiyuan, Nagarathnam, Dhanapalan
• Primary Examiner(s): McIntosh, III, Traviss C
• Application Number:
  US12/645,765
• Publication Number:
  US 20110015146A1
• Time in Patent Office: 1,595 Days
• Field of Search: None
• US Class Current: 514/48
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 for HIV
• 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 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A nucleoside compound having activity against hepatitis C virus is disclosed.

Claims

1. A compound represented by formula I, or its stereoisomers, salts, or pharmaceutically acceptable salts thereof:

2. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to claim 1.

3. A method of treatment of a subject infected with a virus selected from the group consisting of hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, polio virus, hepatitis A virus, bovine viral diarrhea virus or Japanese encephalitis virus which comprises administering to the subject a therapeutically effective amount of the compound according to claim 1.

4. The method of treatment according to claim 3 wherein the subject is infected with hepatitis C virus.

5. A method of treatment in a subject in need thereof, which comprises contacting at least one hepatitis C virus infected cell with at least one compound according to claim 1.

11. The compound of claim 1 wherein R⁸ is OMe.

12. The compound of claim 11 wherein R¹ is phenyl.

13. The compound of claim 12 wherein R⁴ is ⁱPr.

14. The compound of claim 12 wherein R⁴ is cyclopentyl.

15. The compound of claim 12 wherein R⁴ is hydrogen.

16. The compound of claim 11 wherein R¹ and R⁴ are both hydrogen.

17. The compound of claim 1 wherein R⁸ is OH.

18. The compound of claim 17 wherein R¹ is phenyl.

19. The compound of claim 18 wherein R⁴ is ⁱPr.

20. The compound of claim 18 wherein R⁴ is cyclopentyl.

21. The compound of claim 18 wherein R⁴ is hydrogen.

22. The compound of claim 17 wherein R¹ and R⁴ are both hydrogen.

25. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to claim 11.

26. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to claim 17.

28. A method of treatment of a subject infected with a virus selected from the group consisting of hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, polio virus, hepatitis A virus, bovine viral diarrhea virus or Japanese encephalitis virus which comprises administering to the subject a therapeutically effective amount of the compound according to claim 11.

29. The method of treatment according to claim 28 wherein the subject is infected with hepatitis C virus.

30. A method of treatment in a subject in need thereof, which comprises contacting at least one hepatitis C virus infected cell with at least one compound according to claim 11.

31. A method of treatment of a subject infected with a virus selected from the group consisting of hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, polio virus, hepatitis A virus, bovine viral diarrhea virus or Japanese encephalitis virus which comprises administering to the subject a therapeutically effective amount of the compound according to claim 17.

32. The method of treatment according to claim 31 wherein the subject is infected with hepatitis C virus.

33. A method of treatment in a subject in need thereof, which comprises contacting at least one hepatitis C virus infected cell with at least one compound according to claim 17.

6. A compound represented by formula I, or a stereoisomer thereof:

wherein

7. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to claim 6.

8. A method of treatment of a subject infected with a virus selected from the group consisting of hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, polio virus, hepatitis A virus, bovine viral diarrhea virus or Japanese encephalitis virus which comprises administering to the subject a therapeutically effective amount of the compound according to claim 6.

9. The method of treatment according to claim 8 wherein the subject is infected with hepatitis C virus.

10. A method of treatment in a subject in need thereof, which comprises contacting at least one hepatitis C virus infected cell with at least one compound according to claim 6.

23. A compound or its stereoisomer thereof selected from among

24. The compound of claim 23 or its stereoisomer thereof selected from among

27. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to claim 23.

34. A method of treatment of a subject infected with a virus selected from the group consisting of hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, polio virus, hepatitis A virus, bovine viral diarrhea virus or Japanese encephalitis virus which comprises administering to the subject a therapeutically effective amount of the compound according to claim 23.

35. The method of treatment according to claim 34 wherein the subject is infected with hepatitis C virus.

36. A method of treatment in a subject in need thereof, which comprises contacting at least one hepatitis C virus infected cell with at least one compound according to claim 23.