Compounds useful in HIV therapy
The invention relates to compounds of Formula (I), salts thereof, combinations, pharmaceutical compositions thereof, as well as therapeutic methods of treatment and prevention.
1. A compound represented by the Formula (I):
or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
R, R′, R″ and R′″ are each independently selected from H and CH 3 ;
X 1 and X 2 are each independently selected from the group consisting of O and S; and
L is a linker represented by the formula:
wherein:
Ar 12 and Ar 13 are each independently selected from (C 6 -C 14 )aryl;
Alk 3 is selected from:
and t and u are each independently selected from 1 to 12.
2. The compound according to claim 1 , wherein t and u are independently selected from 1 to 6.
3. The compound according to claim 2 , wherein t and u are independently selected from 1 to 4.
4. The compound according to claim 1 , wherein Alk 3 is:
5. The compound according to claim 4 , wherein Alk 3 is:
6. The compound according to claim 1 , wherein Ar 12 and Ar 13 are each Independently C 6-9 aryl.
7. The compound according to claim 6 , wherein Ar 12 and Ar 13 are each C 9 aryl.
8. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable excipient.
9. The composition according to claim 8 , wherein said composition is adapted for parenteral administration.
10. A method of depleting latent HIV infected cells comprising administering to a subject a compound of claim 1 or a pharmaceutically acceptable salt or stereoisomer thereof.
11. A method of treating an HIV infection in a subject comprising administering to the subject a compound of claim 1 or a pharmaceutically acceptable salt or stereoisomer thereof.
12. A compound represented by the Formula (I):
or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
R, R′, R″ and R′″ are each independently selected from H and CH 3 ;
X 1 and X 2 are each independently selected from the group consisting of O and S; and
L is a linker represented by the formula:
wherein:
Ar 12 and Ar 13 are each independently selected from (C 6 -C 9 )aryl;
Alk 3 is selected from:
and t and u are each independently selected from 1 to 6.
13. The compound according to claim 12 , wherein Alk 3 is:
14. The compound according to claim 12 , wherein Ar 12 and Ar 13 are each C 9 aryl.
15. A pharmaceutical composition comprising a compound according to claim 12 , or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable excipient.
16. The composition according to claim 15 , wherein said composition is adapted for parenteral administration.
17. A method of depleting latent HIV infected cells comprising administering to a subject a compound of claim 12 or a pharmaceutically acceptable salt or stereoisomer thereof.
18. A method of treating an HIV infection in a subject comprising administering to the subject a compound of claim 12 or a pharmaceutically acceptable salt or stereoisomer thereof.
19. A combination comprising a compound according to claim 1 , a pharmaceutically acceptable salt or stereoisomer thereof and one or more pharmaceutical agents active against HIV.
20. A method of treating an HIV infection in a subject comprising administering to the subject a combination of claim 19 .
21. A method of depleting latent HIV infected cells comprising administering to a subject a combination of claim 19 .
22. A combination comprising a compound having the structure:
or a pharmaceutically acceptable salt thereof and one or more pharmaceutical agents active against HIV.
23. A method of treating an HIV infection in a subject comprising administering to the subject a combination of claim 22 .
24. A method of depleting latent HIV infected cells comprising administering to a subject a combination of claim 22 .