Therapeutic compounds

1. A compound of formula I:

wherein

A 1 is C—Z 3 or nitrogen;

A 2 is C—Z 3 or nitrogen;

R 1 is 6-12 membered aryl, 5-12 membered heteroaryl, or 3-12 membered heterocycle, wherein any 6-12 membered aryl, 5-12 membered heteroaryl, or 3-12 membered heterocycle of R 1 is optionally substituted with 1, 2, 3, 4 or 5 Z 4 groups, wherein the Z 4 groups are the same or different;

each R 3a and R 3b is independently H or (C 1 -C 3 )alkyl;

Z 1 is 6-12 membered aryl, 5-14 membered heteroaryl, or 3-14 membered heterocycle, wherein any 6-12 membered aryl, 5-14 membered heteroaryl, or 3-14 membered heterocycle of Z 1 is optionally substituted with 1, 2, 3, 4 or 5 Z 1a or Z 1b , wherein the Z 1a and Z 1b groups are the same or different;

each Z 1a is independently oxo, (C 3 -C 7 )carbocycle, 5-12 membered heteroaryl, 3-12 membered heterocycle, halogen, —CN, —OR n1 , —OC(O)R p1 , —OC(O)NR q1 R r1 , —SR n1 , —S(O)R p1 , —S(O) 2 OH, —S(O) 2 R p1 , —S(O) 2 NR q1 R r1 , —NR q1 R r1 , —NR n1 COR p1 , —NR n1 CO 2 R p1 , —NR n1 CONR q1 R r1 , —NR n1 S(O) 2 R p1 , —NR n1 S(O) 2 OR p1 , —NR n1 S(O) 2 NR q1 R r1 , —C(O)R n1 , —C(O)OR n1 , —C(O)NR q1 R r1 and —S(O) 2 NR n1 COR p1 , wherein any (C 3 -C 7 )carbocycle, 5-12 membered heteroaryl and 3-12 membered heterocycle of Z 1a is optionally substituted with 1, 2, 3, 4 or 5 Z 1c or Z 1d groups, wherein the Z 1c and Z 1d groups are the same or different;

each Z 1b is independently (C 1 -C 8 )alkyl optionally substituted with 1, 2, 3, 4 or 5 halogen, which are the same or different;

each Z 1c is independently halogen, —CN, —OH, —NH 2 , —C(O)NR q2 R r2 , or (C 1 -C 8 )heteroalkyl;

each Z 1d is independently (C 1 -C 8 )alkyl or (C 1 -C 8 )haloalkyl;

each R n1 is independently H, (C 1 -C 8 )alkyl, (C 3 -C 7 )carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl, wherein any (C 3 -C 7 )carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl of R n1 is optionally substituted with 1, 2, 3, 4 or 5 Z 1c or Z 1d groups, wherein the Z 1c and Z 1d groups are the same or different, and wherein any (C 1 -C 8 )alkyl of R n1 is optionally substituted with 1, 2, 3, 4 or 5 Z 1c groups, wherein the Z 1c groups are the same or different;

each R p1 is independently (C 1 -C 8 )alkyl, (C 3 -C 7 )carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl, wherein any (C 3 -C 7 )carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl of R p1 is optionally substituted with 1, 2, 3, 4 or 5 Z 1c or Z 1d groups, wherein the Z 1c and Z 1d groups are the same or different, and wherein any (C 1 -C 8 )alkyl of R p1 is optionally substituted with 1, 2, 3, 4 or 5 Z 1c groups, wherein the Z 1c groups are the same or different;

each R q1 and R r1 is independently H, (C 1 -C 8 )alkyl, (C 3 -C 7 )carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl, wherein any (C 3 -C 7 )carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl of R q1 or R r1 is optionally substituted with 1, 2, 3, 4 or 5 Z 1c or Z 1d groups, wherein the Z 1c and Z 1d groups are the same or different, and wherein any (C 1 -C 8 )alkyl of R q1 or R r1 is optionally substituted with 1, 2, 3, 4 or 5 Z 1c groups, wherein the Z 1c groups are the same or different, or R q1 and R r1 together with the nitrogen to which they are attached form a 5, 6 or 7-membered heterocycle, wherein the 5, 6 or 7-membered heterocycle is optionally substituted with 1, 2, 3, 4 or 5 Z 1c or Z 1d groups, wherein the Z 1c and Z 1d groups are the same or different;

each R q2 and R r2 is independently H, (C 1 -C 8 )alkyl, (C 3 -C 7 )carbocycle, or R q2 and R r2 together with the nitrogen to which they are attached form a 5, 6, or 7-membered heterocycle;

Z 2 is (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, 6-12 membered aryl, 5-12 membered heteroaryl, 3-12 membered heterocycle, wherein any (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, 6-12 membered aryl, 5-12 membered heteroaryl, or 3-12 membered heterocycle of Z 2 is substituted with 1 or 2 Z 2b groups and optionally 1, 2, or 3 Z 2c groups, wherein the Z 2b and Z 2c groups are the same or different;

each R n3 is independently H or (C 1 -C 4 )alkyl;

each R q3 and R r3 is independently H or (C 1 -C 4 )alkyl;

each Z 2b is independently 6-12 membered aryl, 5-12 membered heteroaryl, 3-9 membered carbocycle, 3-12 membered heterocycle, or amino substituted with 3-12 membered heterocycle, 5-12 membered heteroaryl, 3-9 membered carbocycle, or 3-12 membered heterocycle, wherein any 6-12 membered aryl, 5-12 membered heteroaryl, 3-9 membered carbocycle, or 3-12 membered heterocycle of Z 2b is optionally substituted with 1, 2, 3, 4, or 5 Z 2d groups;

each Z 2c is independently oxo, halogen, —CN, —OR n4 , —OC(O)R p4 , —OC(O)NR q4 R r4 , —SR n4 , —S(O)R p4 , —S(O) 2 OH, —S(O) 2 R p4 , —S(O) 2 NR q4 R r4 , —NR q4 R r4 , —NR n4 COR p4 , —NR n4 CO 2 R p4 , —NR n4 CONR q4 R r4 , —NR n4 S(O) 2 R p4 , —NR n4 S(O) 2 OR p4 , —NR n4 S(O) 2 NR q4 R r4 , —NO 2 , —C(O)R n4 , —C(O)OR n4 , —C(O)NR q4 R r4 , or (C 1 -C 4 ) alkyl optionally substituted with 1, 2, or 3 halogen or —OR n4 ;

each Z 2d is independently oxo, halogen, —CN, —OR n4 , —OC(O)R p4 , —OC(O)NR q4 R r4 , —SR n4 , —S(O)R p4 , —S(O) 2 OH, —S(O) 2 R p4 , —S(O) 2 NR q4 R r4 , —NR q4 R r4 , —NR n4 COR p4 , —NR n4 CO 2 R p4 , —NR n4 CONR q4 R r4 , —NR n4 S(O) 2 R p4 , —NR n4 S(O) 2 OR p4 , —NR n4 S(O) 2 NR q4 R r4 , —NO 2 , —C(O)R n4 , —C(O)OR n4 , —C(O)NR q4 R r4 , or (C 1 -C 4 ) alkyl optionally substituted with 1, 2, or 3 halogen or —OR n4 ;

each R n4 is independently H, (C 1 -C 4 )alkyl optionally substituted with 1, 2, or 3 —OH groups, (C 1 -C 4 )haloalkyl, or (C 1 -C 4 )heteroalkyl;

each R p4 is independently (C 1 -C 8 )alkyl, (C 1 -C 4 )haloalkyl, or (C 1 -C 4 )heteroalkyl;

each R q4 and R r4 is independently H, (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, or (C 1 -C 4 )heteroalkyl;

each Z 3 is independently H or —NR q4 R r4 ;

each Z 4 is independently oxo, (C 1 -C 8 )alkyl, (C 3 -C 7 )carbocycle, halogen, —CN, —OR n5 , —NR q5 R r5 , —NR n5 COR p5 , —NR n5 CO 2 R p5 , —C(O)R n5 , —C(O)OR n5 , or —C(O)NR q5 R r5 , wherein any (C 3 -C 7 )carbocycle or (C 1 -C 8 )alkyl of Z 4 is optionally substituted with 1, 2, 3, 4 or 5 Z 4a groups, wherein the Z 4a groups are the same or different;

each Z 4a is independently halogen, —CN, or —OR n6 ;

each R n5 , R p5 , R q5 , R r5 , and R n6 is independently H or (C 1 -C 4 )alkyl;

each Z 5 is independently halogen, which may be same or different; and

n is 0, 1, 2, or 3;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the moiety

wherein Z 5a is H or halogen.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3a and R 3b are each H.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, which is a compound of formula II

wherein Z 3 is H or —NH 2 and Z 5a is H or halogen.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z 2 is (C 2 -C 8 )alkynyl or 5-6 membered C-linked-monocyclic-heteroaryl, wherein any (C 2 -C 8 )alkynyl or 5-6 membered C-linked-monocyclic-heteroaryl of Z 2 is substituted with 1 or 2 Z 2b groups and optionally substituted with 1, 2, or 3 Z 2c groups.

6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein Z 2 is (C 2 -C 8 )alkynyl substituted with 1 or 2 Z 2b groups and optionally substituted with 1, 2, or 3 Z 2c groups.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each Z 2c is independently halogen, —OR n4 , NR q4 R r4 , —NR n4 CO 2 R p4 , —C(O)OR n4 , or —C(O)NR q4 R r4 .

8. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein each Z 2c is independently halogen or —OR n4 .

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each Z 2b is independently phenyl, 5-10 membered C-linked-heteroaryl, 3-7 membered carbocycle, 4-6 membered C-linked-heterocycle or amino substituted with 4-5 membered heterocycle, wherein any phenyl, 5-10 membered C-linked-heteroaryl, 3-7 membered carbocycle, 4-6 membered C-linked-heterocycle, or 4-5 membered heterocycle of Z 2b is optionally substituted with 1, 2, 3, 4, or 5 Z 2d groups, wherein each Z 2d is independently oxo, halogen, —CN, —OR n4 , —OC(O)R p4 , —OC(O)NR q4 R r4 , —SR n4 , —S(O)R p4 , —S(O) 2 OH, —S(O) 2 R p4 , —S(O) 2 NR q4 R r4 , —NR q4 R r4 , —NR n4 COR p4 , —NR n4 CO 2 R p4 , —NR n4 CONR q4 R r4 , —NR n4 S(O) 2 R p4 , —NR n4 S(O) 2 OR p4 , —NR n4 S(O) 2 NR q4 R r4 , —NO 2 , —C(O)R n4 , —C(O)OR n4 , —C(O)NR q4 R r4 , or (C 1 -C 4 ) alkyl optionally substituted with 1, 2, or 3 halogen or —OR n4 .

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, which is a compound of formula III

wherein the Z 2b is optionally substituted with 1, 2 or 3 Z 2d groups, and Z 5a is H or halogen.

11. The compound of claim 10 , or a pharmaceutically acceptable salt thereof, wherein Z 2b is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, dihydroquinolinyl, dihydropyridinyl, oxetanyl, azetidinyl, pyrrolidinyl, tetrahydropyranyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, hexahydrofuro[2,3-b]furanyl, oxaspiro[3.3]heptanyl, oxazolidinyl, dioxanyl, dihydroimidazo[2,1-c][1,4]oxazinyl, oxotriazolyl, phenyl, pyridinyl, pyrimidinyl, pyrrolo[2,3-b]pyridinyl, imidazolyl, furanyl, or triazolyl, wherein Z 2b is optionally substituted with 1, 2 or 3 Z 2d groups.

12. The compound of claim 11 , or a pharmaceutically acceptable salt thereof, wherein Z 2b is optionally substituted with 1, 2 or 3 Z 2d groups, wherein each Z 2d group is independently halogen, —CN, OR n4 , —NR q4 R r4 , oxo, (C 1 -C 4 )alkyl optionally substituted with —OH, C(O)R n4 , where R n4 is (C 1 -C 4 )alkyl optionally substituted with 1, 2, or 3 —OH groups.

13. The compound of claim 11 , or a pharmaceutically acceptable salt thereof, wherein Z 2b is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, optionally substituted with 1, 2, or 3 Z 2d groups, wherein each Z 2d group is independently —CN, halogen or —OH.

14. The compound of claim 10 , or a pharmaceutically acceptable salt thereof, wherein Z 2b optionally substituted with 1, 2 or 3 Z 2d groups is

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, which is a compound of formula IV

wherein each Z 2c′ is independently hydrogen, (C 1 -C 4 )alkyl, or OR n4 where R n4 is hydrogen or (C 1 -C 4 ) alkyl, and where n′ is 1, 2, or 3; and Z 5a is H or halogen.

16. The compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein each Z 2c′ is independently hydrogen, methyl, or —OH.

17. The compound of claim 16 , or a pharmaceutically acceptable salt thereof, wherein Z 2b is phenyl, piperazinyl, morpholinyl, triazolyl, azetidinyl, imidazoyl, furanyl, cyclopropyl, oxazolidinyl, or amino substituted with azetidinyl, wherein each Z 2b is optionally substituted with 1, 2 or 3 Z 2d groups, wherein each Z 2d group is independently halogen, oxo, or (C 1 -C 4 )alkyl.

18. The compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein the moiety

wherein Z 2b is optionally substituted with 1, 2 or 3 Z 2d groups, is

19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is

wherein

D, together with the two carbon atoms to which it is attached, forms a 3-7 membered monocyclic-carbocycle, 6 membered aryl, 6 membered heteroaryl, or 5-9 membered bicyclic-carbocycle, wherein any 3-7 membered monocyclic-carbocycle, 6 membered aryl, 6 membered heteroaryl, or 5-9 membered bicyclic-carbocycle of D is optionally substituted with 1, 2, 3, 4 or 5 Z 4 groups, wherein the Z 4 groups are the same or different.

20. The compound of claim 19 , or a pharmaceutically acceptable salt thereof, wherein D, together with the two carbon atoms to which it is attached, forms a 5-6 membered monocyclic-carbocycle, 6 membered aryl, or 6 membered bicyclic-carbocycle, wherein any 5-6 membered monocyclic-carbocycle, 6 membered aryl, or 6 membered bicyclic-carbocycle of D is optionally substituted with 1, 2, 3, 4 or 5 Z 4 groups, wherein the Z 4 groups are the same or different.

21. The compound of claim 20 , or a pharmaceutically acceptable salt thereof, wherein D, together with the two carbon atoms to which it is attached, forms a phenyl, cyclohexyl, cyclopentyl, or bicyclohexyl group, wherein any phenyl, cyclohexyl, cyclopentyl, or bicyclohexyl group of D is optionally substituted with 1, 2, 3, 4 or 5 Z 4 groups, wherein the Z 4 groups are the same or different.

22. The compound of claim 19 , or a pharmaceutically acceptable salt thereof, wherein each Z 4 is independently (C 1 -C 6 )alkyl, —CN, or halogen, wherein any (C 1 -C 6 )alkyl of Z 4 is optionally substituted with 1, 2, 3, 4 or 5 halogen, which may be the same or different.

23. The compound of claim 22 , or a pharmaceutically acceptable salt thereof, wherein each Z 4 is independently (C 1 -C 3 )alkyl, —CN, or halogen, wherein any (C 1 -C 3 )alkyl of Z 4 is optionally substituted with 1, 2, 3, 4 or 5 halogen, which may be the same or different.

24. The compound of claim 19 , or a pharmaceutically acceptable salt thereof, wherein R 1 is

25. The compound of claim 19 , or a pharmaceutically acceptable salt thereof, wherein R 1 optionally substituted with 1, 2, 3, 4, or 5 Z 4 groups is

26. The compound of claim 19 , or a pharmaceutically acceptable salt thereof, wherein R 1 optionally substituted with 1, 2, 3, 4, or 5 Z 4 groups is

27. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z 1 is phenyl, 8-10 membered bicyclic-heteroaryl, 8-10 membered bicyclic-heterocycle, or 9-12 membered tricyclic-heterocycle, wherein any phenyl, 8-10 membered bicyclic-heteroaryl, 8-10 membered bicyclic-heterocycle, or 9-12 membered tricyclic-heterocycle of Z 1 is optionally substituted with 1, 2, 3, 4, or 5 Z 1a or Z 1b groups.

28. The compound of claim 27 , or a pharmaceutically acceptable salt thereof, wherein Z 1 is phenyl, 8-10 membered bicyclic-heteroaryl or 8-10 membered bicyclic-heterocycle, wherein any 8-10 membered bicyclic-heteroaryl or 8-10 membered bicyclic-heterocycle has 3-9 carbon atoms and 1-5 heteroatoms in the ring system, and wherein any phenyl, 8-10 membered bicyclic-heteroaryl, or 8-10 membered bicyclic-heterocycle of Z 1 is optionally substituted with 1, 2, 3, 4, or 5 Z 1a or Z 1b groups.

29. The compound of any claim 28 , or a pharmaceutically acceptable salt thereof, wherein each Z 1a is independently oxo, (C 3 -C 7 )carbocycle, halogen, —CN, —OH, —O—(C 1 -C 8 )alkyl, —NR q1 R r1 , —NR n1 COR p1 , —NR n1 CO 2 R p1 , —NR n1 CONR q1 , —NR n1 S(O) 2 R p1 , —NR n1 S(O) 2 NR q1 R r1 , or —C(O)NR q1 R r1 .

30. The compound of claim 28 , or a pharmaceutically acceptable salt thereof, wherein each Z 1b is independently methyl or difluoromethyl.

31. The compound of claim 28 , or a pharmaceutically acceptable salt thereof, wherein Z 1 is

optionally substituted with 1, 2, 3, 4 or 5 Z 1a or Z 1b .

32. The compound of claim 31 , or a pharmaceutically acceptable salt thereof, wherein each Z 1a is independently oxo, —NR q1 R r1 —, —OH, halogen, or —NR n1 S(O) 2 R p1 .

33. The compound of claim 28 , or a pharmaceutically acceptable salt thereof, wherein Z 1 optionally substituted with 1, 2, 3, 4, or 5 Z 1a or Z 1b groups is

34. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z 2 substituted with 1 or 2 Z 2b groups, and optionally 1, 2, or 3 Z 2c groups is selected from

35. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, which is

36. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, which is

37. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

38. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and an additional therapeutic agent, wherein the additional therapeutic agent is an HIV protease inhibiting compound, an HIV non-nucleoside inhibitor of reverse transcriptase, an HIV nucleoside inhibitor of reverse transcriptase, an HIV nucleotide inhibitor of reverse transcriptase, an HIV integrase inhibitor, a gp41 inhibitor, a CXCR4 inhibitor, a gp120 inhibitor, a CCR5 inhibitor, a capsid polymerization inhibitor, or a non-catalytic site HIV integrase inhibitor and combinations thereof.

39. A method for treating a HIV infection in a patient having a HIV infection comprising administering a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to the patient.

40. A method for treating an HIV infection in a patient having a HIV infection comprising administering to the patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, in combination with a therapeutically effective amount of an additional therapeutic agent, wherein the additional therapeutic agent is an HIV protease inhibiting compound, an HIV non-nucleoside inhibitor of reverse transcriptase, an HIV nucleoside inhibitor of reverse transcriptase, an HIV nucleotide inhibitor of reverse transcriptase, an HIV integrase inhibitor, a gp41 inhibitor, a CXCR4 inhibitor, a gp120 inhibitor, a CCR5 inhibitor, a capsid polymerization inhibitor, or a non-catalytic site HIV integrase inhibitor and combinations thereof.