2′-spiro-nucleosides and derivatives thereof useful for treating hepatitis C virus and dengue virus infections

• US 9,394,331 B2
• Filed: 07/15/2014
• Issued: 07/19/2016
• Est. Priority Date: 11/30/2010
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Pharmasset LLC (Gilead Sciences Inc.)
• Inventors: Du, Jinfa, Sofia, Michael Joseph
• Primary Examiner(s): LEWIS, PATRICK T
• Application Number:
  US14/332,255
• Publication Number:
  US 20150018300A1
• Time in Patent Office: 735 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/7052 having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
• CPC Class Codes: A61K 31/706 containing six-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 31/7064 containing condensed or non-condensed pyrimidines
• 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 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/22 for herpes viruses
• 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: C07H 19/207 the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine adenine dinucleotide or nicotinamide-adenine dinucleotide
• CPC Class Codes: C07H 23/00 Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12 esters with inorganic acids C07H11/00; metal salts, see parent compounds
• 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

Disclosed herein are 2′-spiro-nucleosides and derivatives thereof useful for treating a subject infected by hepatitis C virus or dengue virus.

Claims

1. A method of treating a hepatitis C virus infection in a subject in need thereof, comprising administering to the subject an effective amount of the compound:

2. The method of claim 1, wherein the hepatitis C virus is of genotype 1b.

3. The method of claim 1, wherein the compound is administered by suppository administration.

4. The method of claim 1, wherein the compound is administered orally.

5. The method of claim 4, wherein the compound is administered in the form of a tablet, capsule, solution, emulsion, syrup or a suspension.

6. The method of claim 4, wherein the compound is administered at a daily dosage of from about 0.01 gm to about 1 gm.

7. The method of claim 1, wherein the method further comprises administering an effective amount of another antiviral agent.

8. The method of claim 7, wherein the another antiviral agent is a NS3 protease inhibitor, NS4 inhibitor, NS5A inhibitor or NS5B inhibitor.

9. The method of claim 8, wherein the another antiviral agent is a NS3 protease inhibitor.

10. The method of claim 7, wherein the compound and the another antiviral agent are formulated in same dosage form or separate dosage forms.

11. The method of claim 7, wherein the administering of the compound and the another antiviral agent is concurrent or alternative.

12. A method of treating a hepatitis C virus infection in a subject in need thereof, comprising administering to the subject an effective amount of the compound:

13. The method of claim 12, wherein the hepatitis C virus is of genotype 1b.

14. The method of claim 12, wherein the compound is administered by suppository administration.

15. The method of claim 12, wherein the compound is administered orally.

16. The method of claim 15, wherein the compound is administered in the form of a tablet, capsule, solution, emulsion, syrup or a suspension.

17. The method of claim 15, wherein the compound is administered at a daily dosage of from about 0.01 gm to about 1 gm.

18. The method of claim 12, wherein the method further comprises administering an effective amount of another antiviral agent.

19. The method of claim 18, wherein the another antiviral agent is a NS3 protease inhibitor, NS4 inhibitor, NS5A inhibitor or NS5B inhibitor.

20. The method of claim 19, wherein the another antiviral agent is a NS3 protease inhibitor.

21. The method of claim 18, wherein the compound and the another antiviral agent are formulated in same dosage form or separate dosage forms.

22. The method of claim 18, wherein the administering of the compound and the another antiviral agent is concurrent or alternative.

23. A method of treating a dengue virus infection in a subject in need thereof, comprising administering to the subject an effective amount of the compound:

24. The method of claim 23, wherein the compound is administered by suppository administration.

25. The method of claim 23, wherein the compound is administered orally.

26. The method of claim 25, wherein the compound is administered in the form of a tablet, capsule, solution, emulsion, syrup or a suspension.

27. The method of claim 25, wherein the compound is administered at a daily dosage of from about 0.01 gm to about 1 gm.

28. The method of claim 23, wherein the method further comprises administering an effective amount of another antiviral agent.

29. The method of claim 28, wherein the compound and the another antiviral agent are formulated in same dosage form or separate dosage forms.

30. The method of claim 28, wherein the administering of the compound and the another antiviral agent is concurrent or alternative.

31. A method of treating a dengue virus infection in a subject in need thereof, comprising administering to the subject an effective amount of the compound:

32. The method of claim 31, wherein the compound is administered by suppository administration.

33. The method of claim 31, wherein the compound is administered orally.

34. The method of claim 33, wherein the compound is administered in the form of a tablet, capsule, solution, emulsion, syrup or a suspension.

35. The method of claim 33, wherein the compound is administered at a daily dosage of from about 0.01 gm to about 1 gm.

36. The method of claim 31, wherein the method further comprises administering an effective amount of another antiviral agent.

37. The method of claim 36, wherein the compound and the another antiviral agent are formulated in same dosage form or separate dosage forms.

38. The method of claim 36, wherein the administering of the compound and the another antiviral agent is concurrent or alternative.

39. A compound of formula:

40. A compound of formula: