Therapeutic compounds
The invention provides compounds having Formula (I): or a pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions comprising the same, processes for their preparation, and methods of treating and preventing HIV infection by their administration.
1. A compound of formula I:
wherein
A is 3-6 membered carbocycle;
n is 0, 1, or 2;
m is 0, 1, or 2;
R 1 is 5-12 membered heteroaryl or 5-12 membered heterocycle, wherein any 5-12 membered heteroaryl or 5-12 membered heterocycle of R 1 is unsubstituted or substituted with 1, 2, 3, 4 or 5 Z 1 groups, wherein the Z 1 groups are the same or different;
each Z 1 is independently (C 1 -C 6 )alkyl; (C 3 -C 7 )carbocycle; halogen, or —CN, wherein any (C 1 -C 6 )alkyl or (C 3 -C 7 )carbocycle of Z 1 is unsubstituted or substituted with 1, 2, 3, 4 or 5 Z 1a groups, wherein the Z 1a groups are the same or different;
each Z 1a is independently halogen; (C 3 -C 7 )carbocycle; —OH, or —CN;
R 2 is hydrogen, halogen, —OH, or —CN;
R 3 is (C 1 -C 6 )alkyl or 3-5 membered heterocycle, wherein the (C 1 -C 6 )alkyl is unsubstituted or substituted with 1, 2, or 3 halogen atoms;
R 4 is
R 5 is hydrogen or halogen; and
R 6 is (C 1 -C 3 )alkyl;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, which is a compound of formula Ia:
wherein:
n is 0, 1, or 2;
m is 0 or 1;
R 1 is 5-9 membered heteroaryl or 5-9 membered heterocycle, wherein any 5-9 membered heteroaryl or 5-9 membered heterocycle of R 1 is unsubstituted or substituted with 1, 2, 3, 4 or 5 Z 1 groups, wherein the Z 1 groups are the same or different;
each Z 1 is independently (C 1 -C 6 )alkyl, (C 3 -C 7 )carbocycle, or halogen, wherein any (C 1 -C 6 )alkyl or (C 3 -C 7 )carbocycle of Z 1 is unsubstituted or substituted with 1, 2, 3, 4 or 5 Z 1a groups, wherein the Z 1a groups are the same or different;
each Z a is independently halogen or (C 3 -C 7 )carbocycle;
R 2 is hydrogen or iodide;
R 3 is (C 1 -C 2 )alkyl or 3-5 membered heterocycle, wherein the (C 1 -C 2 )alkyl is unsubstituted or substituted with 2 or 3 halogen atoms;
R 5 is hydrogen, chorine, or fluorine; and
R 6 is (C 1 -C 3 )alkyl.
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
n is 0, 1, or 2;
m is 0 or 1;
R 1 is 5-9 membered heteroaryl that is unsubstituted or substituted with 1, 2, 3, 4 or 5 Z 1 groups, wherein the Z 1 groups are the same or different;
each Z 1 is independently (C 1 -C 6 )alkyl, (C 3 -C 7 )carbocycle, or halogen, wherein any (C 1 -C 6 )alkyl or (C 3 -C 7 )carbocycle of Z 1 is unsubstituted or substituted with 1, 2, 3, 4 or 5 Z 1a groups, wherein the Z 1a groups are the same or different;
each Z 1a is independently halogen or (C 3 -C 7 )carbocycle;
R 2 is hydrogen or iodide;
R 3 is (C 1 -C 2 )alkyl or 3-5 membered heterocycle, wherein the (C 1 -C 2 )alkyl is unsubstituted or substituted with 2 or 3 fluorine atoms;
R 5 is hydrogen, chorine, or fluorine; and
R 6 is methyl.
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
n is 0, 1, or 2;
m is 0 or 1;
R 1 is 5-9 membered heteroaryl that is unsubstituted or substituted with 1, 2, 3, 4 or 5 Z 1 groups, wherein the Z 1 groups are the same or different;
each Z 1 is independently (C 1 -C 6 )alkyl, (C 3 -C 7 )carbocycle, or halogen, wherein any (C 1 -C 6 )alkyl or (C 3 -C 7 )carbocycle of Z 1 is unsubstituted or substituted with 1, 3, 4 or 5 Z 1a groups, wherein the Z 1a groups are the same or different;
each Z 1a is independently halogen or (C 3 -C 7 )carbocycle;
R 2 is hydrogen;
R 3 is (C 1 -C 2 )alkyl or 4-membered heterocycle, wherein the (C 1 -C 2 )alkyl is unsubstituted or substituted with 2 or 3 fluorine atoms;
R 5 is hydrogen, chorine, or fluorine; and
R 6 methyl.
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 1.
6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 0.
7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is
8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is
9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is
10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is
11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is
12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is
13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is
14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, which is a compound of formula Ib:
15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, which is a compound of formula Ic:
16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z 1 is (C 1 -C 6 )alkyl substituted with 2 or 3 halogen atoms, a cyclopropyl group, or halogen.
17. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z 1 is —CHF 2 , —CF 3 , or halogen.
18. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is hydrogen or iodide.
19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is (C 1 -C 3 )alkyl or a 4-membered heterocycle, wherein the (C 1 -C 3 )alkyl is unsubstituted or substituted with 1, 2, or 3 halogen atoms.
20. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is methyl, —CH 2 CHF 2 , —CH 2 CF 3 , or
21. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is hydrogen, chloride, or fluoride.
22. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 1 and R 6 is (C 1 -C 3 )alkyl.
23. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 1 and R 6 is methyl.
24. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, which is
25. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
26. A method for treating a HIV infection in a patient in need thereof comprising administering a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to the patient.