Claims
- 1. An HIV protease inhibitor represented by a formula:
- 2. The compound according to claim 1, wherein
X is 31Y is O, NH, or S; z is O, NH, or S; and wherein any ring carbon is optionally substituted by R2, R3, R5, or R6.
- 3. The compound according to claim 1, wherein
X is 32wherein G is C, O, NR2, or S; n is an integer between 1-2; and wherein any ring carbon is optionally substituted by R2, R3, R5, or R6.
- 4. The compound according to claim 1, wherein
X is 33wherein J is independently CH2, or O, and wherein any ring carbon is optionally substituted by R2, R3, R5, or R6.
- 5. The compound according to claim 1, wherein:
X is 34wherein any ring carbon is optionally substituted by R2, R3, R5, or R6.
- 6. The compound according to claim 1, wherein
X is 35wherein each L is independently H, lower alkyl, oxo, or L forms a carbocyclic or heterocyclic ring with M; each M is independently H, OH, chloro, fluoro, or M forms a carbocyclic or heterocyclic ring with Q, provided that if one M is OH, the other M is not OH; Q is H, OH, amino, lower alkyl, alkylamino, alkoxy, halo, or forms a 3-7-membered carbocyclic or heterocyclic ring together with T.; each F is independently H, OH, lower alkyl, halo, or spirocylopropyl, provided that if one R is OH, the other R is not OH; T is H or F, or T forms a carbocyclic or heterocyclic ring together with F.
- 7. The HIV protease inhibitor according to claim 1, wherein
X is tetrahydrofurodihydrofuranyl, tetrahydrofurotetrahydrofuranyl, tetrahydropyranotetrahydrofuranyl or tetrahydropyranodihydrofuranyl; A is OCONH; B is 36 wherein D is selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, or aralkyl optionally substituted with one or more groups selected from alkyl , halo, nitro, cyano, CF3, C3-C7 cycloalkyl, C5-C7 cycloalkenyl, R6, OR2, SR2, NHR2, OR3, SR3, NHR3, OR6, SR6, or NHR6; and A′ is N(D′)E′, wherein D′ is alkyl, alkenyl, alkynyl aryl, cycloalkyl, or aralkyl optionally substituted by alkyl, halo, or CF3, and E′ is —SO2—.
- 8. The HIV protease inhibitor according to claim 1, wherein:
X is tetrahydrofurotetrahydrofuranyl; A is OCONH; B is 37 wherein D is benzyl; and A′ is N(D′)E′, wherein D′ is isobutyl and E′ is —SO2—;
- 9. The HIV protease inhibitor according to claim 1, wherein
X is 38wherein A2, B2, and C′ are each independently O, NR2, or S; D2 is CH or N; and n is an integer between 1 and 2.
- 10. The HIV protease inhibitor according to claim 1, wherein:
X is 39wherein A3 is H, F or alkoxy; B3 is F, alkoxy, lower alkyl, or A3 and B3 can form a 3-7 membered heterocyclic ring; Z′ is O, NR2, or S; and n is an integer between 1-3.
- 11. The HIV protease inhibitor of claim 1, wherein X′ is selected from
- 12. The HIV protease inhibitor of claim 1, wherein X′ is selected from
- 13. The HIV protease inhibitor of claim 1, wherein X′ is selected from
- 14. The HIV protease inhibitor of claim 1, wherein X′ is selected from
- 15. The HIV protease inhibitor of claim 1, wherein X′ is selected from
- 16. A compound according to claim 1, bound in a complex with wild type or drug resistant mutant forms of HIV-1 protease.
- 17. A pharmaceutical composition comprising an effective amount of an inhibitor according to claim 1 and a pharmaceutically acceptable additive, excipient, or diluent.
- 18. A pharmaceutical composition comprising an effective amount inhibitor according to claim 1 and another antiretroviral agent.
- 19. A pharmaceutical composition comprising an effective amount of an inhibitor according to claim 1 and a second HIV inhibitor.
- 20. A pharmaceutical composition comprising an inhibitor according to claim 1 and an additional HIV protease inhibitor.
- 21. A pharmaceutical composition comprising an effective amount of an inhibitor according to claim 1 and an HIV reverse transcriptase inhibitor.
- 22. A method of treating a patient suffering from HIV infection, comprising administering to said patient a composition according to claim 1.
- 23. A method of treatment according to claim 22 wherein said patient is suffering from a multi-drug resistant HIV infection.
- 24. An HIV protease inhibitor having the formula I:
- 25. A compound according to claim 24, bound in a complex with wild type or drug resistant mutant forms of HIV-1 protease.
- 26. A pharmaceutical composition comprising an effective amount of an inhibitor according to claim 24 and a pharmaceutically acceptable additive, excipient, or diluent.
- 27. A pharmaceutical composition comprising an effective amount inhibitor according to claim 24 and another antiretroviral agent.
- 28. A pharmaceutical composition comprising an effective amount of an inhibitor according to claim 24 and a second HIV inhibitor.
- 29. A pharmaceutical composition comprising an inhibitor according to claim 24 and an additional HIV protease inhibitor.
- 30. A pharmaceutical composition comprising an effective amount of an inhibitor according to claim 24 and an HIV reverse transcriptase inhibitor.
- 31. A method of treating a patient suffering from HIV infection, comprising administering to said patient a composition according to claim 24.
- 32. A method of treatment according to claim 31 wherein said patient is suffering from a multi-drug resistant HIV infection.
Parent Case Info
[0001] This application claims priority under 35 USC §119 to application serial Nos. 60/344,788, filed Jan. 7, 2002, and 60/383,575, filed May 29, 2002, the specifications of which are incorporated herein by reference in their entirety.
[0002] The present invention relates to retroviral protease inhibitors and, more particularly, relates to novel compounds, compositions and methods for inhibiting retroviral proteases. This invention, in particular, relates to resistance-repellent HIV protease inhibitors, compositions, and uses thereof for treating HIV infections, particularly infections caused by one or more species of drug resistant HIV strains.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60344788 |
Jan 2002 |
US |
|
60383575 |
May 2002 |
US |