[;5-Carboxamido or 5-fluoro];-[;2′,3′-unsaturated or 3′-modified];-pyrimidine nucleosides

• US 6,391,859 B1
• Filed: 10/02/2000
• Issued: 05/21/2002
• 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): Geist, Gary
• Assistant Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US09/677,161
• Time in Patent Office: 596 Days
• Field of Search: 514/45-51
• 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: 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 method for treating a host infected with human immunodeficiency virus comprising administering an effective amount of a physiologically acceptable ester of β

-D-2′

,3′

-dideoxy-2′

,3′

-didehydro-5-fluorocytidine (D4FC) or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 further comprising administering the ester of β

-D-2′

,3′

-dideoxy-2′

,3′

-didehydro-5-fluorocytidine (D4FC) or a pharmaceutically acceptable salt thereof, in combination or alternation with one or more agents selected from the group consisting of 2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane (FTC), (−

)-cis-2′

, 3′

-dideoxy-3′

-thiacytidine (3TC), 9-(4-(hydroxymethyl)-2-cyclopenten-1-yl)guanine(carbovir), 9-((2-hydroxyethoxy)methyl)guanine(acyclovir), interferon, 9-(4-hydroxy-3-(hydroxymethyl)-butyl)guanine(penciclovir), 3′

-deoxy-3′

-azido-thymidine (AZT), 2′

,3′

-dideoxyinosine (DDI), 2′

,3′

-dideoxycytidine (DDC), (−

)-2′

-fluoro-5-methyl-β

-L-ara-uridine (L-FMAU) and 2′

, 3′

-didehydro-2′

,3′

-dideoxythymidine (D4T).

3. The method of claim 1, further comprising administering the ester of β

-D-2′

,3′

-dideoxy-2′

,3′

-didehydro-5-fluorocytidine (D4FC) or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier.

4. The method of claim 3, wherein the carrier is suitable for intravenous delivery.

5. The method of claim 3, wherein the carrier is suitable for parenteral delivery.

6. The method of claim 3, wherein the carrier is suitable for intradermal delivery.

7. The method of claim 3, wherein the carrier is suitable for subcutaneous delivery.

8. The method of claim 3, wherein the carrier is suitable for topical delivery.

9. The method of claim 1, further comprising administering the ester of β

-D-2′

,3′

-dideoxy-2′

,3′

-didehydro-5-fluorocytidine (D4FC) or a pharmaceutically acceptable salt thereof in the form of a tablet.

10. The method of claim 3, wherein the carrier is suitable for oral delivery.