›5--Caboxamido or 5--fluoro!--›2', 3'--unsaturated or 3'--modified!--pyrimidine nucleosides

• US 5,905,070 A
• Filed: 12/30/1997
• Issued: 05/18/1999
• Est. Priority Date: 01/27/1995
• Status: Expired due to Fees

• Current Assignee: Emory University
• Original Assignee: Emory University
• Inventors: Schinazi, Raymond F., Liotta, Dennis C.
• Primary Examiner(s): Knode, Marian C.
• Assistant Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US09/001,084
• Time in Patent Office: 504 Days
• Field of Search: 514/2, 514/45, 514/49, 514/50, 514/269, 514/274, 536/28.5, 536/28.52, 536/28.53, 536/28.55, 536/28.2, 536/26.8, 536/26.23, 536/26.26, 544/370, 544/317
• US Class Current: 514/49
• 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 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 37/04 Immunostimulants
• CPC Class Codes: C07H 19/06 Pyrimidine radicals

Abstract

A method and composition for the treatment of HIV and HBV infections in humans and other host animals is disclosed that includes the administration of an effective amount of a 5-carboxamido or 5-fluoro!-2'"'"',3'"'"'-dideoxy-2'"'"',3'"'"'-didehydro-pyrimidine nucleoside or a 5-carboxamido or 5-fluoro!-3'"'"'-modified-pyrimidine nucleoside, or a mixture or a pharmaceutically acceptable derivative thereof, including a 5'"'"' or N⁴ alkylated or acylated derivative, or a pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier.

Claims

1. A composition comprising an effective HIV or HBV treatment amount of a β

-D-nucleoside of the formula;

##STR3## wherein R is hydrogen acyl, monophosphate, diphosphate, or triphosphate;

in combination or alternation with a second compound selected from the group consisting of 2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, 2-hydroxymethyl-5-(cytosin-1-yl)-1,3-oxathiolane, 9-(4-hydroxymethyl)-2-cyclopenten-1-yl)-guanine (carbovir), 9-((2-hydroxyethoxy)methyl)-guanine (acyclovir), interferon, 3'"'"'-deoxy-3'"'"'-azidothymidine (AZT), 2'"'"',3'"'"'-dideoxyinosine (DDI), 2'"'"',3'"'"'-dideoxycytidine (DDC), (-)-2'"'"'-fluoro-5-methyl-β

-L-arabinofuranosyluridine (L-(-)-FMAU), and 2'"'"',3'"'"'-didehydro-2'"'"',3'"'"'-dideoxythymidine (D4T).

2. The composition of claim 1, wherein R is hydrogen.

3. The composition of claim 1, wherein R is monophosphate.

4. The composition of claim 1, wherein R is selected from the group consisting of diphosphate and triphosphate.

5. The composition of claim 1, wherein R is diphosphate.

6. The composition of claim 1, wherein the second compound is 2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane.

7. The composition of claim 1, wherein the second compound is 2-hydroxymethyl-5-(cytosin-1-yl)-1,3-oxathiolane.

8. The composition of claim 1, wherein the second compound is carbovir.

9. The composition of claim 1, wherein the second compound is acyclovir.

10. The composition of claim 1, wherein the second compound is interferon.

11. The composition of claim 1, wherein the second compound is AZT.

12. The composition of claim 1, wherein the second compound is DDI.

13. The composition of claim 1, wherein the second compound is DDC.

14. The composition of claim 1, wherein the second compound is L-(-)-FMAU.

15. The composition of claim 1, wherein the second compound is D4T.

16. The composition of claim 1, wherein the combination is effective against HIV.

17. The composition of claim 1, where the alternation is effective against HIV.

18. The composition of claim 1, wherein the combination is effective against HBV.

19. The composition of claim 1, wherein the alternation is effective against HBV.