SUBSTITUTED TARAXASTANES USEFUL FOR TREATING VIRAL INFECTIONS

Abstract

Substituted taraxastanes useful for treating viral infections, are provided herein. Thus, in a first aspect, the invention provides compounds of Formula I

Description

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. ¹H NMR Spectra for compound 11 in CDCl₃ and DMSO.

FIG. 2. IR Spectra for compound 11, 4 accumulations, resolution 4 cm⁻¹.

FIG. 3. ¹H NMR Spectra for compound 12 in CDCl₃ and DMSO.

FIG. 4. IR Spectra for compound 12, 4 accumulations, resolution 4 cm⁻¹.

Claims

1. A compound having the formula

2. A compound or salt of claim 1 having the formula

3. A compound or salt of claim 1 wherein X is —O—.

4. A compound or salt of claim 3 wherein R1 is an optionally substituted C2-C20carboxyalkanoyl wherein within the alkanoyl a single methylene is optionally replaced by —O—.

5. A compound or salt of claim 3, wherein R1 is a C4-C16 carboxyalkanoyl group that is geminally substituted at the 3′ carbon atom.

6. A compound or salt of claim 3, wherein R1 has the formula —(C═O)CH2CR′R″(CH2)nCOOH where n is an integer of from 0 to 12;R′ and R″ are each independently C1-C4alkyl, orR′ is hydrogen and R″ is C1-C4alkyl, orR′ and R″ are taken together to from 3- to 7-membered cycloalkyl ring or a 3- to 7-membered heterocycloalkyl ring having 1 or 2 heteroatoms independently chosen from N, O, and S.

7. A compound or salt of claim 6, wherein n is an integer of from 0 to 4.

8. A compound or salt of claim 6, wherein R′ and R″ are both methyl and n is 0 or 1.

9. A compound or salt of claim 3, wherein R1 has the formula —(C═O)CH2O(CH2)nCOOH where n is an integer of from 0 to 12.

10. A compound or salt of claim 1 wherein R1—X— is one of

11. A compound or salt of claim 3, wherein R1 is

12. A compound or salt of claim 1 wherein R2 is a group of the formula (i)

13. A compound or salt of claim 1, wherein R2 is —(C═O)NHR3.

14. A compound or salt of claim 13 wherein R3 is an optionally substituted C2-C20alkyl wherein within the alkyl a single methylene is optionally replaced by —(C═O)NR5—.

15. A compound or salt of claim 13, wherein R3 is terminally substituted with —COOH, —(C═O)OCH3, or —CONH2.

16. A compound or salt of claim 1, wherein R2 is

17. A pharmaceutical composition, comprising a compound or salt of claim 1, in combination with at least one pharmaceutically acceptable carrier.

18. The pharmaceutical composition of claim 17 additionally comprising one or more other active agents; wherein the active agent is an anti-viral agent, an immunostimulatory agent, or a combination of the foregoing.

19. The pharmaceutical composition of claim 18, wherein the anti-viral agent is zidovudine, lamivudine, zalcitabine, stavudine, didanosine, tenofovir, abacavir, nevirapine; delavirdine, emtricitabine, efavirenz, saquinavir, ritonavir, indinavir, nelfinavir, lopinavir, amprenavir, atazanavir, enfuvirtide, hydroxyurea, interleukin-2, amantadine, alpha-interferon, beta-interferon, gamma-interferon, rifampin, ribavirin, foscarnet, elvucitabine, phosphonoacetic acid, acyclovir, gancyclovir, or a combination of one or more of the foregoing.

20. The pharmaceutical composition of claim 17, wherein the composition is formulated as an injectable fluid, an aerosol, a cream, an oral liquid, a tablet, a gel, a pill, a capsule, a syrup, or a transdermal patch.

21. A method for inhibiting viral replication in cells, the method comprising contacting cells infected with a virus with a compound or salt of claim 1, in an amount sufficient to detectably inhibit viral replication in vitro, and thereby inhibiting viral replication in the cells.

22-25. (canceled)

26. A method of treating a patient infected with a retrovirus or susceptible to infection by a retrovirus comprising providing a therapeutically effective amount of a compound or salt of claim 1 to the patient.

27. The method of claim 26, wherein the patient is a human patient.

28. The method of claim 26 or 27 wherein the retrovirus is HIV.

29. The method of claim 28 wherein the retrovirus is HIV-1.

30. A method of reducing mortality of HIV-1 infection comprising providing a therapeutically effective amount of a compound of claim 1 to a human patient infected with HIV-1.