Methods and compositions for treating flaviviruses and pestiviruses

• US 7,105,493 B2
• Filed: 06/20/2003
• Issued: 09/12/2006
• Est. Priority Date: 05/26/2000
• 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): Wilson, James O.
• Assistant Examiner(s): McIntosh, III, Traviss C.
• Application Number:
  US10/602,694
• Publication Number:
  US 20040102414A1
• Time in Patent Office: 1,180 Days
• Field of Search: 514/42, 514/43, 514/44, 514/45, 514/46, 514/49, 514/50
• US Class Current: 514/42
• CPC Class Codes: A61K 31/7052 having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
• CPC Class Codes: A61K 31/7056 containing five-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 31/7072 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 38/21 Interferons [IFN]
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 19/10 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 19/23 Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22
• 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 method and composition for treating a host infected with flavivirus or pestivirus comprising administering an effective flavivirus or pestivirus 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 flavivirus or pestivirus infection in a host, comprising administering to said host an anti-virally effective amount of a β

-D-2′

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

2. The method of claim 1, wherein the nucleoside is a pyrimidine nucleoside.

3. The method of claim 1, wherein the nucleoside is a purine nucleoside.

4. The method of claim 1 wherein the β

-D-2′

-methyl-ribofuranosyl nucleoside is administered in combination or alternation with a second anti-flavivirus or anti-pestivirus agent.

5. The method of claim 4, wherein the second anti-flavivirus or anti-pestivirus agent is selected from the group consisting of interferon, ribavirin, a protease inhibitor, a thiazolidine derivative, a polymerase inhibitor, and a helicase inhibitor.

6. The method of claim 5, wherein the second anti-flavivirus or anti-pestivirus agent is interferon.

7. The method of claim 5, wherein the second anti-flavivirus or anti-pestivirus agent is ribavirin.

8. The method of claim 1, wherein the compound is in the form of a dosage unit.

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

-D-2′

methyl-ribofuranosyl nucleoside.

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

11. The method of claim 1, wherein the host is a human.

12. The method of claim 1, wherein the β

-D-2′

-methyl-ribofuranosyl nucleoside is in substantially pure form.

13. The method of claim 12, wherein the β

-D-2′

-methyl-ribofuranosyl nucleoside is at least 90% by weight of the β

-D-isomer.

14. The method of claim 12, wherein the β

-D-2′

-methyl-ribofuranosyl nucleoside is at least 95% by weight of the β

-D-isomer.

15. The method of claim 1, wherein the flavivirus or pestivirus is a Dengue virus.

16. The method of claim 1, wherein the flavivirus or pestivirus is a West Nile virus.

17. The method of claim 1, wherein the flavivirus or pestivirus is a yellow fever virus.

18. The method of claim 1, wherein the flavivirus or pestivirus is a bovine viral diarrhea virus (BVDV).