2',4'-SUBSTITUTED NUCLEOSIDES AS ANTIVIRAL AGENTS

• US 20140235563A1
• Filed: 04/30/2014
• Published: 08/21/2014
• Est. Priority Date: 11/20/2007
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Pharmasset LLC (Gilead Sciences Inc.), Gilead Sciences Inc.
• Inventors: Sofia, Michael Joseph, Du, Jinfa
• Granted Patent: US 9,296,777 B2
• Time in Patent Office: Days
• US Class Current: 514/46
• CPC Class Codes: A61K 31/7064 containing condensed or non-condensed pyrimidines
• 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: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/073 with 2-deoxyribosyl as the saccharide radical
• CPC Class Codes: C07H 19/14 Pyrrolo-pyrimidine radicals
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 19/173 with 2-deoxyribosyl as the saccharide radical

Abstract

Embodiments of the invention are to compounds, methods, and compositions for use in the treatment of viral infections. More specifically embodiments of the invention are 2′,4′-substituted nucleoside compounds useful for the treatment of viral infections, such as HIV, HCV, and HBV infections.

Claims

1-11. -11. (canceled)

12. A compound of the following formula:

13. The compound of claim 12, wherein R² is F;

R is H; and

R³ is OH.

14. The compound of claim 13, wherein R⁴ is H, a lower alkyl, CH₂F, N₃, halogen, alkenyl, alkynyl, or Br-vinyl.

15. The compound of claim 14, wherein R⁴ is N₃.

16. The compound of claim 14, wherein R⁴ is a lower alkyl.

17. The compound of claim 16, wherein R⁴ is an ethyl.

18. The compound of claim 14, wherein R⁵ and R⁶, are independently H, OH, NH₂, or alkyl of C₁-C₆.

19. The compound of claim 18, wherein R⁵ is NH₂, and R⁶ is H.

20. The compound of claim 15, wherein the compound is:

21. A method of treating a Hepatitis B virus (HBV) infection, Hepatitis C virus (HCV) infection and/or human immunodeficiency virus (HIV) infection, comprising administering to a subject in need thereof an effective amount of a compound according to claim 12.

22. The method of claim 21, wherein R² is F;

R is H; and

R³ is OH.

23. The method of claim 22, wherein R⁴ is H, a lower alkyl, CH₂F, N₃, halogen, alkenyl, alkynyl, or Br-vinyl.

24. The method of claim 23, wherein R⁴ is N₃.

25. The method of claim 23, wherein R⁴ is a lower alkyl.

26. The method of claim 25, wherein R⁴ is an ethyl.

27. The method of claim 23, wherein R⁵ and R⁶, are independently H, OH, NH₂, or alkyl of C₁-C₆.

28. The method of claim 27, wherein R⁵ is NH₂, and R⁶ is H.

29. The method of claim 24, wherein the compound is:

30. The method of claim 21, wherein the method is for treating Hepatitis B virus (HBV) infection or human immunodeficiency virus (HIV) infection.

31. The method of claim 21, further comprising administering one or more antiviral agents, antibacterial agents, antiproliferative agents, or a combination thereof.

32. The method of claim 21, wherein the compound is administered orally.

33. The method of claim 32, wherein between about 0.1 g and about 10 g of the compound is administered daily in a monotherapy or a combination therapy.

34. A compound of the following formula:

35. The compound of claim 34, wherein the compound is selected from the group consisting of:

36. A method of treating a Hepatitis B virus (HBV) infection, Hepatitis C virus (HCV) infection and/or human immunodeficiency virus (HIV) infection, comprising administering to a subject in need thereof an effective amount of a compound according to claim 34.

37. The method of claim 36, wherein the compound is selected from the group consisting of:

38. The method of claim 36, further comprising administering one or more antiviral agents, antibacterial agents, antiproliferative agents, or a combination thereof.

39. The method of claim 36, wherein the compound is administered orally.