Therapeutic compounds
Compounds disclosed herein including compounds of formula I′: and salts thereof are provided. Pharmaceutical compositions comprising compounds disclosed herein, processes for preparing compounds disclosed herein, intermediates useful for preparing compounds disclosed herein and therapeutic methods for treating an HIV infection using compounds disclosed herein are also provided.
1. A compound, or a pharmaceutically acceptable salt thereof, of formula I′:
wherein:
R 4 is:
A is phenyl, 6-membered N-heteroaryl, thiazolyl, pyridinyl-2(1H)-one, tetrahydropyrimidin-2(1H)-one, imidazolidinyl-2-one, pyrrolidinyl-2-one, pyrrolidinyl, pyrazin-2(1H)-one, piperazinyl-2-one, piperazinyl, morpholinyl, or piperidinyl, wherein A is optionally substituted with 1 to 5 Z 1a groups;
B is (C 6 -C 20 )aryl, heteroaryl or heterocycle, wherein B is optionally substituted with 1 to 5 Z 1b groups; or A and B together form a bicyclic (C 9 -C 14 )aryl, bicyclic heteroaryl or bicyclic heterocycle, wherein bicyclic (C 9 -C 14 )aryl, bicyclic heteroaryl or bicyclic heterocycle is optionally substituted with 1 to 5 Z 1b groups;
each Z 1a is independently halo, (C 1 -C 3 )alkyl, (C 2 -C 3 )alkenyl, (C 2 -C 3 )alkynyl, (C 1 -C 3 )haloalkyl, (C 3 -C 7 )carbocycle, heterocycle, —O(C 1 -C 3 )alkyl, —O(C 2 -C 3 )alkenyl, —O(C 2 -C 3 )alkynyl, —NR c R d , —R a C(O)R a , —C(O)OR b or —C(O)NR c R d , wherein any (C 3 -C 7 )carbocycle and heterocycle of Z 1a is optionally substituted with 1 to 5 halogen or (C 1 -C 6 )alkyl;
each Z 1b is independently halo, CN, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )carbocycle, heteroaryl, heterocycle, (C 6 -C 20 )aryl(C 1 -C 6 )alkyl-, —OH, —O(C 1 -C 6 )alkyl, —O(C 2 -C 6 )alkenyl, —O(C 2 -C 6 )alkynyl, —NR c R d , —NR a C(O)R a , —C(O)OR b or —C(O)NR c R d , wherein any (C 3 -C 7 )carbocycle and heterocycle of Z 1b is optionally substituted with 1 to 5 halogen or (C 1 -C 6 )alkyl; and
R a , R b , R c and R d are each independently H or (C 1 -C 6 )alkyl;
wherein each heteroaryl, as a monocyclic ring or portion of a 2 to 3 ring system, has 1 to 6 carbon atoms and 1 to 4 heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, and each heterocycle, as a monocyclic ring or portion of a 2 to 3 ring system, has 1 to 6 carbon atoms and 1 to 3 heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
A is pyridinyl, pyrimidinyl or pyrazinyl, optionally substituted with 1 to 5 Z 1a groups; and
B is (C 6 -C 20 )aryl, heteroaryl or heterocycle, optionally substituted with 1 to 5 Z 1b groups.
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
A is pyridinyl, pyrimidinyl or pyrazinyl; and
B is heteroaryl or heterocycle, optionally substituted with 1 to 5 Z 1b groups.
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
A is pyridinyl, pyrimidinyl or pyrazinyl; and
B is a 4-6 membered monocyclic heterocycle optionally substituted with 1 to 5 Z 1b groups.
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
A is pyridinyl, pyrimidinyl or pyrazinyl; and
B is phenyl, pyridinyl, indazolyl, pyrazolo[4,3-b]pyridinyl, pyrimidinyl, pyrazolyl, benzo[d]imidazolyl, indazolyl, 1H-benzo[d]imidazolyl-2(3H)-one, 2H-pyrido[3,2-b][1,4]oxazinyl-3(4H)-one, 2,6-naphthyridin-1(2H)-one, 1,7-naphthyridinyl-8(7H)-one, 1H-indazolyl-3(2H)-one, quinolinyl-2(1H)-one, quinolinyl, pyrrolo[2,3-b]pyridinyl, pyrrolidinyl, piperazinyl, phenyl, imidazolyl, piperidinyl, morpholinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, pyrimidinyl-2,4(1H,3H)-dionyl, pyridinyl-2(1H)-one, 1H-pyrazolo[3,4-c]pyridinyl, indolinyl-2-one, 1H-pyrrolo[3,4-c]pyridinyl-3(2H)-one, 2,3-dihydro-1H-pyrrolo[3,2-c]pyridinyl, pyrazolyl, pyrimidinyl-2(1H)-one, azetidinyl, tetrahydro-2H-pyranyl, 3,6-dihydro-2H-pyranyl, 1,2,3,6-tetrahydropyridine, 1H-pyrazolo[3,4-b]pyridinyl, 2H-benzo[b][ 1 , 4 ]oxazinyl-3(4H)-one, 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, indolinyl, 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one, 3H -imidazo[4,5-b]pyridinyl or 1H-benzo[d][1,2,3]triazolyl, wherein B is optionally substituted with 1 to 5 Z 1b groups.
6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is pyridinyl, pyrimidinyl or pyrazinyl, and B is piperazinyl or azetidinyl, optionally substituted with 1 to 5 Z 1b groups.
7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is not substituted with Z 1a .
8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z 1b is (C 1 -C 6 )alkyl.
9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is not substituted with Z 1a ; and Z 1b is (C 1 -C 6 )alkyl.
10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A and B together form a bicyclic (C 9 -C 14 )aryl, bicyclic heteroaryl or bicyclic heterocycle, wherein bicyclic (C 9 -C 14 )aryl, bicyclic heteroaryl or bicyclic heterocycle is optionally substituted with 1 to 5 Z 1b groups.
11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each Z 1b is independently CN, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )carbcycle, heteroaryl, heterocycle, (C 6 -C 20 )aryl(C 1 -C 6 )alkyl-, —OH, —O(C 1 -C 6 )alkyl, —O(C 2 -C 6 )alkenyl, —O(C 2 -C 6 )alkynyl, —NR c R d , —NR a C(O)R a , or —C(O)NR c R d .
12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
13. A compound, or a pharmaceutically acceptable salt thereof, having the structure:
14. A compound, or a pharmaceutically acceptable salt thereof, having the structure:
15. A compound, or a pharmaceutically acceptable salt thereof, having the structure:
16. A compound, or a pharmaceutically acceptable salt thereof, having the structure:
17. A compound, or a pharmaceutically acceptable salt thereof, having the structure:
18. A compound, or a pharmaceutically acceptable salt thereof, having the structure:
19. A compound, or a pharmaceutically acceptable salt thereof, having the structure:
20. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.