MODIFIED 2' AND 3'-NUCLEOSIDE PRODRUGS FOR TREATING FLAVIVIRIDAE INFECTIONS

• US 20150017124A1
• Filed: 07/17/2014
• Published: 01/15/2015
• Est. Priority Date: 06/28/2002
• Status: Abandoned Application

• Current Assignee: Centre National De La Recherche Scientifique, Idenix Pharmaceuticals (Merck & Co., Inc.), Universita' Degli Studi Di Bari (Repubblica Italiana), Universite Montpellier II
• Original Assignee: Centre National De La Recherche Scientifique, Idenix Pharmaceuticals (Merck & Co., Inc.), Universita' Degli Studi Di Bari (Repubblica Italiana), Universite Montpellier II
• Inventors: STORER, Richard, GOSSELIN, Gilles, SOMMADOSSI, Jean-Pierre, LACOLLA, Paolo
• Application Number:
  US14/334,381
• Publication Number:
  US 20150017124A1
• Time in Patent Office: Days
• US Class Current: 424/85.7
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• 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 38/212 IFN-alpha
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C07H 19/00 Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 19/048 Pyridine radicals
• CPC Class Codes: C07H 19/056 Triazole or tetrazole radicals
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 19/22 : Pteridine radicals

Abstract

2′ and/or 3′ prodrugs of 1′, 2′, 3′ or 4′-branched nucleosides, and their pharmaceutically acceptable salts and derivatives are described. These prodrugs are useful in the prevention and treatment of Flaviviridae infections, including HCV infection, and other related conditions. Compounds and compositions of the prodrugs of the present invention are described. Methods and uses are also provided that include the administration of an effective amount of the prodrugs of the present invention, or their pharmaceutically acceptable salts or derivatives. These drugs may optionally be administered in combination or alteration with further anti-viral agents to prevent or treat Flaviviridae infections and other related conditions.

Claims

1-13. -13. (canceled)

14. A method for the treatment of a host infected with a Flaviviridae virus, comprising administering to the host an effective treatment amount of a compound of Formula (IX):

15. The method of claim 14, wherein X is O, and each Y³ is H.

16. The method of claim 14, wherein the Flaviviridae virus is hepatitis C virus.

17. The method of claim 16, wherein the second anti-viral agent is an interferon, a ribavirin, or a combination thereof.

18. The method of claim 14, wherein the second antiviral agent is ribavirin.

19. The method of claim 17, wherein the second antiviral agent is pegylated interferon alpha 2a.

20. The method of claim 19, further comprising administering ribavirin to the host.

21. The method of claim 15, wherein R¹ is monophosphate, diphosphate, triphosphate, a stabilized phosphate;

and R² is H.

22. The method of claim 21, wherein Base* is uracil.

23. The method of claim 21, wherein the second antiviral agent is an interferon, a ribavirin, or a combination thereof.

24. The method of claim 23, wherein the second antiviral agent is ribavirin.

25. The method of claim 23, further comprising administering pegylated interferon alpha 2a to the host.

26. The method of claim 14, wherein X is O, each Y³ is H;

R² is H and R¹ is monophosphate, diphosphate, triphosphate, or a stabilized phosphate.

27. The method of claim 26, wherein R¹ is monophosphate, diphosphate, or triphosphate.

28. A method for the treatment of a host infected with a Flaviviridae virus, comprising administering to the host an effective treatment amount of a compound of the formula:

29. The method of claim 28, wherein R¹ is H, monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug.

30. The method of claim 28, wherein each Y³ is H.

31. The method of claim 28, wherein Base is uracil.

34. The method of claim 28, wherein the Flaviviridae virus is hepatitis C virus.

32. A method for the treatment of a host infected with a Flaviviridae virus, comprising administering to the host an effective treatment amount of a compound of the formula:

33. The method of claim 32, wherein Base* is uracil.

35. The method of claim 32, wherein the Flaviviridae virus is hepatitis C virus.