Nucleoside analog inhibitors of reverse transcriptase

• US 20040235869A1
• Filed: 05/19/2004
• Published: 11/25/2004
• Est. Priority Date: 05/20/2003
• Status: Active Grant

• Current Assignee: Board of Trustees of The University of Illinois
• Original Assignee: Board of Trustees of The University of Illinois
• Inventors: Liu, Xianjun, Huang, Raven H.
• Granted Patent: US 7,550,442 B2
• Time in Patent Office: Days
• US Class Current: 514/263.38
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 473/00 Heterocyclic compounds containing purine ring systems
• CPC Class Codes: C07D 473/18 one oxygen and one nitrogen atom, e.g. guanine
• CPC Class Codes: C07D 473/34 attached in position 6, e.g. adenine

Abstract

Compounds of formula (XXIII), or pharmaceutically acceptable salts or esters thereof, are inhibitors of reverse transcriptase:

R₄ is a nucleoside with Q substituting a 3′ hydroxyl group, and Q is a moiety of formulas (XXIV)-(XXXII):

Claims

1. A compound of formula (XXIII), or pharmaceutically acceptable salts or esters thereof:

2. The compound of claim 1, wherein R₄ is a natural nucleoside with Q substituting a 3′

hydroxyl group.

3. The compound of claim 1, wherein R₄ is a universal nucleoside with Q substituting a 3′

hydroxyl group.

4. The compound of claim 1, selected from the group consisting of compounds of formulas (II) and (XIII)-(XXII):

5. The compound of claim 1, selected from the group consisting of compounds of formulas (V)-(XII):

6. The compound of claim 1, wherein the compound is in unit dosage form.

7. The compound of claim 2, wherein the compound is in unit dosage form.

8. The compound of claim 3, wherein the compound is in unit dosage form.

9. The compound of claim 4, wherein the compound is in unit dosage form.

10. A method of treating a subject infected with a retrovirus, comprising administering to the subject the compound of claim 1.

11. A method of treating a subject infected with a retrovirus, comprising administering to the subject the compound of claim 2.

12. A method of treating a subject infected with a retrovirus, comprising administering to the subject the compound of claim 3.

13. A method of treating a subject infected with a retrovirus, comprising administering to the subject the compound of claim 4.

14. The method of claim 10, wherein the retrovirus is a human immunodeficiency virus.

15. The method of claim 11, wherein the retrovirus is a human immunodeficiency virus.

16. The method of claim 12, wherein the retrovirus is a human immunodeficiency virus.

17. The method of claim 13, wherein the retrovirus is a human immunodeficiency virus.

18. The method of claim 14, wherein the subject has acquired immune deficiency syndrome.

19. The method of claim 15, wherein the subject has acquired immune deficiency syndrome.

20. The method of claim 16, wherein the subject has acquired immune deficiency syndrome.

21. The method of claim 17, wherein the subject has acquired immune deficiency syndrome.

22. A method of inhibiting reverse transcriptase, comprising providing a triphosphate of the compound of claim 1 as a substrate for the reverse transcriptase.

23. The method of claim 22, wherein the reverse transcriptase is human immunodeficiency virus reverse transcriptase.