Methods and compositions for treating flaviviruses and pestiviruses

• US 6,812,219 B2
• Filed: 05/23/2001
• Issued: 11/02/2004
• Est. Priority Date: 05/26/2000
• Status: Expired due to Term

• Current Assignee: Idenix Pharmaceuticals LLC (Merck & Co., Inc.), Universita' Degli Studi Di Bari (Repubblica Italiana), Universita' Degli Studi Di Cagliari (Repubblica Italiana)
• Original Assignee: Idenix Pharmaceuticals (Merck & Co., Inc.)
• Inventors: Sommadossi, Jean-Pierre, LaColla, Paulo
• Primary Examiner(s): McIntosh, III, Traviss C.
• Application Number:
  US09/863,816
• Publication Number:
  US 20030060400A1
• Time in Patent Office: 1,259 Days
• Field of Search: 514/42, 514/43, 514/49, 514/50, 536/22.1, 536/28.1, 536/28.4, 536/28.5, 536/28.53
• US Class Current: 514/49
• 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 in need thereof, comprising administering to said host an antivirally effective amount of a β

-D nucleoside compound of the structure;

or a pharmaceutically acceptable salt or prodrug thereof, optionally in a pharmaceutically acceptable carrier or diluent.

10. The method of any one of claims 1, 2, 3, or 4-9, wherein the pharmaceutically acceptable carrier is suitable for oral delivery.

11. The method of any one of claims 1, 2, 3, or 4-9, wherein the pharmaceutically acceptable carrier is suitable for intravenous delivery.

12. The method of any one of claims 1, 2, 3, or 4-9, wherein the pharmaceutically acceptable carrier is suitable for parenteral delivery.

13. The method of any one of claims 1, 2, 3, or 4-9, wherein the pharmaceutically acceptable carrier is suitable for intradermal delivery.

14. The method of any one of claims 1, 2, 3, or 4-9, wherein the pharmaceutically acceptable carrier is suitable for subcutaneous delivery.

15. The method of any one of claims 1, 2, 3, or 4-9, wherein the pharmaceutically acceptable carrier is suitable for topical delivery.

16. The method of any one of claims 1, 2, 3, or 4-9, wherein the compound is in the form of a dosage unit, such that said dosage unit contains 10 to 1500 mg of the compound.

17. The method of any one of claims 1, 2, 3, or 4-9, wherein the compound is in the form of a dosage unit that is a tablet or capsule.

18. The method of claim 16, wherein the dosage unit is a tablet or capsule.

19. The method of any one of claims 1, 2, or 3 wherein the host is a human.

20. The method of any one of claims 1, 2, 3, or 4-9, wherein the pestivirus or flavivirus is bovine viral diarrhea virus (BVDV).

21. The method of any one of claims 1, 2, 3, or 4-9, wherein the pestivirus or flavivirus is a Dengue virus.

22. The method of any one of claims 1, 2, 3, or 4-9, wherein the pestivirus or flavivirus is a West Nile virus.

23. The method of any one of claims 1, 2, 3, or 4-9, wherein the pestivirus or flavivirus is a yellow fever virus.

24. The method as in any one of claims 1-3 or 4-9, wherein the compound is at least 85% by weight free of the β

-L-isomer.

25. The method as in any one of claims 1-3 or 4-9, wherein the compound is at least 90% by weight free of the β

-L-isomer.

26. The method as in any one of claims 1-3 or 4-9, wherein the compound is at least 95% by weight free of the β

-L-isomer.

2. A method for the treatment of a flavivirus or pestivirus infection in a host in need thereof, comprising administering to said host an antivirally effective amount of a β

-D nucleoside compound of the structure;

or a pharmaceutically acceptable salt or prodrug thereof, optionally in a pharmaceutically acceptable carrier or diluent.

3. A method for the treatment of a flavivirus or pestivirus infection in a host in need thereof, comprising administering to said host an antivirally effective amount of a β

-D nucleoside compound of the structure;

or a pharmaceutically acceptable salt or prodrug thereof, optionally in a pharmaceutically acceptable carrier or diluent.

4. A method for the treatment of a flavivirus or pestivirus infection in a human in need thereof, comprising administering to said human an antivirally effective amount of a β

-D nucleoside compound of the structure;

or a pharmaceutically acceptable salt or ester thereof.

5. A method for the treatment of a flavivirus or pestivirus infection in a human in need thereof, comprising administering to said human an antivirally effective amount of a β

-D nucleoside compound of the structure;

or a pharmaceutically acceptable salt or ester thereof.

6. A method for the treatment of a flavivirus or pestivirus infection in a human in need thereof, comprising administering to said human an antivirally effective amount of a β

-D nucleoside compound of the structure;

or a pharmaceutically acceptable salt or ester thereof.

7. A method for the treatment of a flavivirus or pestivirus infection in a human in need thereof, comprising administering to said human an antivirally effective amount of a β

-D nucleoside compound of the structure;

or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.

8. A method for the treatment of a flavivirus or pestivirus infection in a human in need thereof, comprising administering to said human an antivirally effective amount of a β

-D nucleoside compound of the structure;

or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier or diluent.

9. A method for the treatment of a flavivirus or pestivirus infection in a human in need thereof, comprising administering to said human an antivirally effective amount of a β

-D nucleoside compound of the structure;

or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier or diluent.

27. A method for the treatment of flavivirus or pestivirus infection in a human in need thereof, comprising administering to said human an antivirally effective amount of a β

-D nucleoside compound of the structure;

28. A method for the treatment of flavivirus or pestivirus infection in a human in need thereof, comprising administering to said human an antivirally effective amount of a β

-D nucleoside compound of the structure;

29. A method for the treatment of a flavivirus or pestivirus infection in a human in need thereof, comprising administering to said human an antivirally effective amount of a β

-D nucleoside compound of the structure;

30. A method for the treatment of a flavivirus or pestivirus infection in a host in need thereof, comprising administering to said host an antivirally effective amount of a β

-D-2′

-C-branched pyrimidine nucleoside.

32. The method of any one of claims 30-31, wherein the host is a human.

31. A method for the treatment of a flavivirus or pestivirus infection in a host in need thereof, comprising administering to said host an antivirally effective amount of a β

-D-2′

-C-branched pyrimidine ribonucleoside.