Antiviral compounds and methods of administration

• US 6,686,462 B2
• Filed: 02/28/1997
• Issued: 02/03/2004
• Est. Priority Date: 02/28/1997
• Status: Expired due to Fees

• Current Assignee: Dana-Farber Cancer Institute, Regents of the University of California (University of California)
• Original Assignee: Dana-Farber Cancer Institute, Regents of the University of California (University of California)
• Inventors: Hostetler, Karl Y., Beadle, James R., Kini, Ganesh D., Rosowsky, Andre, Richman, Douglas D.
• Primary Examiner(s): Wilson, James O.
• Assistant Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US08/808,847
• Time in Patent Office: 2,531 Days
• Field of Search: 514/47, 514/48, 514/51, 536/26.5, 536/26.7, 536/26.71, 536/26.72, 536/26.74, 536/26.8
• US Class Current: 536/26.8
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids

Abstract

The invention provides lipophilic phosphonoacid/nucleoside conjugates that exhibit exceptional antiviral activity, including activity against drug-resistant HIV strains. Compounds of the invention include phosphonoacid/nucleoside conjugates where the carboxyl group and phosphonyl groups of the phosphonacid are esterified whereby the compound contains at least one lipophilic group and at least one nucleoside group.

Claims

1. A compound selected from the group consisting of:

3′

-azido-3′

-deoxy-5′

-O-(1-octadecyloxycarbonylphosphinyl)thymidine;

3′

-azido-3′

-deoxy-5′

-O-(1-eicosanyloxycarbonylphosphinyl)thymidine;

3′

-azido-3′

-deoxy-5′

-O-(1-docosanyloxycarbonylphosphinyl)thymidine; and

3′

-azido-3′

-deoxy-5′

-O-[(3β

-cholest-5-enyl)oxycarbonylphosphinyl)]thymidine.

2. A compound of claim 1 wherein the compound is 3′

-azido-3′

-deoxy-5′

-O-(1-octadecyloxycarbonylphosphinyl)thymidine.

3. A compound of claim 1 wherein the compound is 3′

-azido-3′

-deoxy-5′

-O-(1-eicosanyloxycarbonylphosphinyl)thymidine.

4. A compound of claim 1 wherein the compound is 3′

-azido-3′

-deoxy-5′

-O-(1-docosanyloxycarbonylphosphinyl)thymidine.

5. A compound of claim 1 wherein the compound is 3′

-azido-3′

-deoxy-5′

-O-[(3β

cholest-5-enyl)oxycarbonylphosphinyl)]thymidine;

6. A method of treating mammalian cells infected with an HIV virus comprising administering to the cells an effective anti-HIV amount of a compound of any one of claims 2 through 5.

7. The method of claim 6 wherein the HIV virus infecting the cells is resistant to a reverse transcriptase inhibitor.

8. A method of treating a mammal suffering from an HIV infection comprising administering to the mammal a therapeutically effective amount of a compound of any one of claims 2 through 5.

9. A pharmaceutically composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of any one of claims 2 through 5.

10. A compound of the formula IIA: