Claims for Patent: 9,951,043

Summary for Patent: 9,951,043

Title:	Therapeutic compounds
Abstract:	Compounds of formula (I) or salts thereof are disclosed. Also disclosed are pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for treating a Retroviridae viral infection including an infection caused by the HIV virus.
Inventor(s):	Gediminas Brizgys, Eda Canales, Chien-Hung Chou, Michael Graupe, Randall L. Halcomb, Yunfeng Eric Hu, Scott E. Lazerwith, John O. Link, Qi Liu, Yafan Lu, Roland D. SAITO, Scott D. Schroeder, John R. SOMOZA, Winston C. Tse, Jennifer R. Zhang
Assignee:	Gilead Sciences Inc
Application Number:	US14/771,779
Patent Claims:	1. A compound of formula Hie: wherein A1 is OH, C—Z3, or nitrogen; A2 is CH or nitrogen; R1 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 R1 is optionally substituted with 1, 2, 3, 4 or 5 Z4 groups, wherein the Z4 groups are the same or different; each R3a and R3b is independently H or (C1-C3)alkyl; Z1 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 Z1 is optionally substituted with 1, 2, 3, 4 or 5 Z1a or Z1b, wherein the Z1a and Z1b groups are the same or different; each Z1a is independently (C3-C7)carbocycle, 5-12 membered heteroaryl, 3-12 membered heterocycle, halogen, —CN, —ORn1, —OC(O)Rp1, —OC(O)NRq1Rr1, —SRn1, —S(O)Rp1, —S(O)2OH, —S(O)2Rp1, —S(O)2NRq1Rr1, —NRq1Rr1, —NRn1CORp1, —NRn1CO2Rp1, —NRn1CONRq1Rr1, —NRn1S(O)2Rp1, —NRn1S(O)2ORp1, —NRn1S(O)2NRq1Rr1, —C(O)Rn1, —C(O)ORn1, —C(O)Nrq1Rr1 and —S(O)2NRn1CORp1, wherein any (C3-C7)carbocycle, 5-12 membered heteroaryl and 3-12 membered heterocycle of Z1a is optionally substituted with 1, 2, 3, 4 or 5 Z1c or Z1d groups, wherein the Z1c and Z1d groups are the same or different; each Z1b is independently (C1-C8)alkyl optionally substituted with 1, 2, 3, 4 or 5 halogen, which are the same or different; each Z1c is independently halogen, —CN, —OH, —NH2, —C(O)Nq2Rr2, or (C1-C8)heteroalkyl; each Z1d is independently (C1-C8)alkyl or (C1-C8)haloalkyl; each Rn1 is independently H, (C1-C8)alkyl, (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl, wherein any (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl of Rn1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c or Z1d groups, wherein the Z1c and Z1d groups are the same or different, and wherein any (C1-C8)alkyl of Rn1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c groups, wherein the Z1c groups are the same or different; each Rp1 is independently (C1-C8)alkyl, (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl, wherein any (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl of Rp1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c or Z1d groups, wherein the Z1c and Z1d groups are the same or different, and wherein any (C1-C8)alkyl of Rp1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c groups, wherein the Z1c groups are the same or different; each Rq1 and Rr1 is independently H, (C1-C8)alkyl, (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl, wherein any (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl of Rq1 or Rr1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c or Z1d groups, wherein the Z1c and Z1d groups are the same or different, and wherein any (C1-C8)alkyl of Rq1 or Rr1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c groups, wherein the Z1c groups are the same or different, or Rq1 and Rr1 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 Z1c or Z1d groups, wherein the Z1c and Z1d groups are the same or different; each Rq2 and Rr2 is independently H, (C1-C8)alkyl, (C3-C7)carbocycle, or Rq2 and Rr2 together with the nitrogen to which they are attached form a 5, 6, or 7-membered heterocycle; Z2 is (C2-C8)alkenyl, (C2-C8)alkynyl, 6-12 membered aryl, 5-12 membered C-linked-heteroaryl, 3-12 membered C-linked-heterocycle, —C(O)Rn3, or —C(O)NRq3Rr3, wherein any 6-12 membered aryl, 5-12 membered C-linked-heteroaryl, or 3-12 membered C-linked-heterocycle of Z2 is optionally substituted with 1, 2, 3, 4 or 5 Z2b or Z2c groups, wherein the Z2b and Z2c groups are the same or different, and wherein any (C2-C8)alkenyl or (C2-C8)alkynyl of Z2 is optionally substituted with 1, 2, 3, 4, or 5 Z2c groups, wherein the Z2c groups are the same or different; each Rn3 is independently H or (C1-C4)alkyl; each Rq3 and Rr3 is independently H or (C1-C4)alkyl; each Z2b is independently oxo, (C1-C4)alkyl, (C1-C4)heteroalkyl or (C1-C4)haloalkyl; each Z2c is independently oxo, halogen, —CN, —ORn4, —OC(O)Rp4, —OC(O)NRq4Rr4, —SRn4, —S(O)Rp4, —S(O)2OH, —S(O)2Rp4, —S(O)2NRq4Rr4, —NRq4Rr4, —NRn4CORp4, —NRn4CO2Rp4, —NRn4CONRq4Rn4, —NRn4S(O)2Rp4, —NRn4S(O)2ORp4, —NRn4S(O)2NRq4Rr4, —NO2, —C(O)Rn4, —C(O)ORn4, or —C(O)NRq4Rr4; each Rn4 is independently H, (C1-C4)alkyl, (C1-C4)haloalkyl, or (C1-C4)heteroalkyl, each Rp4 is independently (C1-C8)alkyl, (C1-C4)haloalkyl, or (C1-C4)heteroalkyl; each Rq4 and Rr4 is independently H, (C1-C4)alkyl, (C1-C4)haloalkyl, or (C1-C4)heteroalkyl; each Z3 is independently a (C1-C4)heteroalkyl, each Z4 is independently oxo, (C1-C8)alkyl, (C3-C7)carbocycle, halogen, —CN, —ORn5, —NRq5Rr5, —NRn5CORp5, —NRn5CO2Rp5, —C(O)Rn5, —C(O)ORn5, or —C(O)NRq5Rr5, wherein any (C3-C7)carbocycle or (C1-C8)alkyl of Z4 is optionally substituted with 1, 2, 3, 4 or 5 Z4a groups, wherein the Z4a groups are the same or different; each Z4a is independently halogen, —CN, or —ORn6; each Rn5, Rp5, Rq5, Rr5, and Rn6 is independently H or (C1-C4)alkyl; each Z5 is independently halogen, which may be same or different; and n 0, 1, 2, or 3; or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R1 is wherein C together with the two carbon atoms to which it is attached forms a 3-7 membered monocyclic-carbocycle or 5-9 membered bicyclic-carbocycle, wherein any 3-7 membered monocyclic-carbocycle or 5-9 membered bicyclic-carbocycle of C is optionally substituted with 1, 2, 3, or 4 Z4 groups, wherein the Z4 groups are the same or different. 3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is 4. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Z1 is wherein each Z1w is independently Z1a, Z1b, or H. 5. The compound of claim 4, or a pharmaceutically acceptable salt thereof, wherein: each Z1a is independently halogen, —CN, —ORn1, —NRn1S(O)2Rp1, —NRn1S(O)2NRq1Rr1, —NRq1Rr1, —NRn1CORp1, —NRn1CONRq1Rr1, or —NRn1CO2Rp1; each Z1b is independently (C1-C8alkyl), wherein the (C1-C8alkyl) is optionally substituted with 1, 2, or 3 halogen, which are the same or different; and at least one of Z1w is Z1a or Z1b. 6. The compound of claim 5, or a pharmaceutically acceptable salt thereof, wherein each Z1a is independently halogen, —NRn1S(O)2Rp1, or —NRn1S(O)2NRq1Rr1. 7. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the moiety is wherein Z5a is H or halogen. 8. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein A1 is CH or C—Z3; and A2 is CH. 9. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R3a and R3b are each H. 10. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R3a is methyl and R3b is H. 11. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Z2 is (C2-C8)alkynyl, optionally substituted with 1, 2, or 3 Z2c groups. 12. The compound of claim 11, or a pharmaceutically acceptable salt thereof, wherein each Z2c is independently halogen, —ORn4, NRq4Rr4, —NRn4CO2Rp4, —C(O)ORn4, or —C(O)NRq4Rr4. 13. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 optionally substituted with 1, 2, 3, 4, or 5 Z4 groups is 14. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Z1 is phenyl, 5-6 membered monocyclic-heteroaryl, 8-10 membered bicyclic-heteroaryl, 8-10 membered bicyclic-heterocycle, or 9-12 membered tricyclics heterocycle, wherein any phenyl, 5-6 membered monocyclic-heteroaryl, 8-10 membered bicyclic-heteroaryl, 8-10 membered bicyclic-heterocycle, or 9-12 membered tricyclic-heterocycle of Z1 is optionally substituted with 1, 2, 3, 4, or 5 Z1a or Z1b groups. 15. A compound or a pharmaceutically acceptable salt thereof, which is 16. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 17. 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 or combinations thereof. 18. 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. 19. A method for treating an HIV infection in a patient in need thereof 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 site inhibitor or combinations thereof. 20. A compound of formula IIIe: wherein A1 is CH; A2 is CH; R1 has the following formula: wherein C together with the two carbon atoms to which it is attached forms a 3-7 membered monocyclic-carbocycle or 5-9 membered bicyclic-carbocycle, wherein any 3-7 membered monocyclic-carbocycle or 5-9 membered bicyclic-carbocycle of C is optionally substituted with 1, 2, 3, or 4 Z4 groups, wherein the Z4 groups are the same or different; R3a and R3b are each H; Z1 is wherein each Z1w is independently Z1a, Z1b, or H each Z1a is independently (C3-C7)carbocycle, 5-12 membered heteroaryl, 3-12 membered heterocycle, halogen, —CN, —ORn1, —OC(O)Rp1, —OC(O)NRq1Rr1, —SRn1, —S(O)Rp1, —S(O)2OH, —S(O)2Rp1, —S(O)2NRq1Rr1, —NRq1Rp1, —NRn1CORp1, —NRn1CO2Rp1, —NRn1CONRq1Rr1, —NRn1S(O)2Rp1, —NRn1S(O)2ORp1, —NRn1S(O)2NRq1Rr1, —C(O)Rn1, —C(O)ORn1, —C(O)NRq1Rr1 and —S(O)2NRn1CORp1, wherein any (C3-C7)carbocycle, 5-12 membered heteroaryl and 3-12 membered heterocycle of Z1a is optionally substituted with 1, 2, 3, 4 or 5 Z1c or Z1d groups, wherein the Z1c and Z1d groups are the same or different; each Z1b is independently (C1-C8)alkyl optionally substituted with 1, 2, 3, 4 or 5 halogen, which are the same or different; each Z1c is independently halogen —CN, —OH, —NH2, —C(O)NRq2Rr2, or (C1-C8)heteroalkyl; each Z1d is independently (C1-C8)alkyl or (C1-C8)haloalkyl; each Rn1 is independently H, (C1-C8)alkyl, (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl, wherein any (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl of Rn1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c or Z1d groups, wherein the Z1c and Z1d groups are the same or different, and wherein any (C1-C8)alkyl of Rn1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c groups, wherein the Z1c groups are the same or different; each Rp1 is independently (C1-C8)alkyl, (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl, wherein any (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl of RP1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c or Z1d groups, wherein the Z1c and Z1d groups are the same or different, and wherein any (C1-C8)alkyl of Rp1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c groups, wherein the Z1c groups are the same or different; each Rq1 and Rr1 is independently H, (C1-C8)alkyl, (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl, wherein any (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl of Rq1 or Rr1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c or Z1d groups, wherein the Z1c and Z1d groups are the same or different, and wherein any (C1-C8)alkyl of Rq1 or Rr1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c groups, wherein the Z1c groups are the same or different, or Rq1 and Rr1 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 Z1c or Z1d groups, wherein the Z1c and Z1d groups are the same or different; each Rq2 and Rr2 is independently H, (C1-C8)alkyl, (C3-C7)carbocycle, or Rq2 and Rr2 together with the nitrogen to which they are attached form a 5, 6, or 7-membered heterocycle; Z2 is (C2-C8)alkynyl, optionally substituted with 1, 2, 3, 4, or 5 Z2c groups, wherein the Z2c groups are the same or different; each Z2c is independently oxo, halogen, —CN, —ORn4, —OC(O)Rp4, —OC(O)NRq4Rr4, —SRn4, —S(O)Rp4, —S(O)2OH, —S(O)2Rp4, —S(O)2NRq4Rr4, —NRq4Rr4, —NRn4CORp4, —NRn4CO2Rp4, —NRn4CONRq4Rr4, —NRn4S(O)2Rp4, —NRn4S(O)2ORp4, —NRn4S(O)2NRq4Rr4, —NO2, —C(O)Rn4, —C(O)ORn4, or —C(O)NRq4Rr4; each Rn4 is independently H, (C1-C4)alkyl, (C1-C4)haloalkyl, or (C1-C4)heteroalkyl; each Rp4 is independently (C1-C8)alkyl, (C1-C4)haloalkyl, or (C1-C4)heteroalkyl; each Rq4 and Rr4 is independently H, (C1-C4)alkyl, (C1-C4)haloalkyl, or (C1-C4)heteroalkyl; each Z4 is independently oxo, (C1-C8)alkyl, (C3-C7)carbocycle, halogen, —CN, —ORn5, —NRq5Rr5, —NRn5CORp5, —NRn5CO2Rp5, —C(O)Rn5, —C(O)ORn5, or —C(O)NRq5Rr5, wherein any (C3-C7)carbocycle or (C1-C8)alkyl of Z4 is optionally substituted with 1, 2, 3, 4 or 5 Z4a groups, wherein the Z4a groups are the same or different; each Z4a is independently halogen, —CN, or —ORn6; each Rn5, Rp5, Rq5, Rr5, and Rn6 is independently H or (C1-C4)alkyl; each Z5 is independently halogen, which may be same or different; and n is 0, 1, 2, or 3; or a pharmaceutically acceptable salt thereof. 21. The compound of claim 20, or a pharmaceutically acceptable salt thereof, wherein the moiety is wherein Z5a is H or halogen. 22. The compound of claim 20, or a pharmaceutically acceptable salt thereof, wherein Z2 is of the formula: 23. The compound of claim 20, or a pharmaceutically acceptable salt thereof, wherein: each Z1a is independently halogen, —CN, —ORn1, —NRn1S(O)2Rp1, —NRn1S(O)2NRq1Rr1, —NRq1Rr1, —NRn1CORp1, —NRn1CONRq1Rr1, or —NRn1CO2Rp1; each Z1b is independently (C1-C8alkyl), wherein the (C1-C8alkyl) is optionally substituted with 1, 2, or 3 halogen, which are the same or different; and at least one of Z1w is Z1a or Z1b. 24. The compound of claim 20, or a pharmaceutically acceptable salt thereof, wherein R1 is 25. The compound of claim 20, or a pharmaceutically acceptable salt thereof, wherein R1 optionally substituted with 1, 2, 3, or 4 Z4 groups is 26. A pharmaceutical composition comprising a compound of claim 20, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 27. A pharmaceutical composition comprising a compound of claim 20, 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 or combinations thereof. 28. A method for treating a HIV infection in a patient in need thereof comprising administering a therapeutically effective amount of a compound of claim 20, or a pharmaceutically acceptable salt thereof, to the patient. 29. A method for treating an HIV infection in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound of claim 20, 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 site inhibitor or combinations thereof. 30. A compound of formula IIIe: wherein A1 is CH; A2 is CH; R1 is: R3a and R3b are each R Z1 is wherein each Z1w is independently Z1a, Z1b, or H; each Z1a is independently halogen, —CN, —ORn1, —NRn1S(O)2Rp1, —NRn1S(O)2NRq1Rr1, —NRq1Rr1, —NRn1CORp1, —NRn1CONRq1Rr1, or —NRn1CO2Rp1; each Z1b is independently (C1-C8alkyl), wherein the (C1-C8alkyl) is optionally substituted with 1, 2, or 3 halogen, which are the same or different; and at least one of Z1w is Z1a or Z1b; each Z1c is independently halogen, —CN, —OH, —NH2, —C(O) NRq2Rr2, or (C1-C8) heteroalkyl; each Z1d is independently (C1-C8) alkyl or (C1-C8)haloalkyl; each Rn1 is independently H, (C1-C8) alkyl, (C3-C7) carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl, wherein any (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl of Rn1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c or Z1d groups, wherein the Z1c and Z1d groups are the same or different, and wherein any (C1-C8)alkyl of Rn1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c groups, wherein the Z1c groups are the same or different; each Rp1 is independently (C1-C8)alkyl, (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl, wherein any (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl of Rp1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c or Z1d groups, wherein the Z1c and Z1d groups are the same or different, and wherein any (C1-C8)alkyl of Rp1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c groups, wherein the Z1c groups are the same or different; each Rq1 and Rr1 is independently H, (C1-C8)alkyl, (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl, wherein any (C3-C7)carbocycle, 3-7 membered heterocycle, or 5-6 membered monocyclic-heteroaryl of Rq1 or Rr1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c or Z1d groups, wherein the Z1c and Z1d groups are the same or different, and wherein any (C1-C8)alkyl of Rq1 or Rr1 is optionally substituted with 1, 2, 3, 4 or 5 Z1c groups, wherein the Z1c groups are the same or different, or Rq1 and Rr1 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 Z1c or Z1d groups, wherein the Z1c and Z1d groups are the same or different; each Rq2 and Rr2 is independently H, (C1-C8)alkyl, (C3-C7)carbocycle, or Rq2 and Rr2 together with the nitrogen to which they are attached form a 5, 6, or 7-membered heterocycle; Z2 is of the formula: Z2c is oxo, halogen, —CN, —ORn4, —OC(O)Rp4, —OC(O)NRq4Rr4, —SRn4, —S(O)Rp4, —S(O)2OH, —S(O)2Rp4, —S(O)2NRq4Rr4, —NRq4Rr4, —NRn4CORp4, —NRn4CO2Rp4, —NRn4CONRq4Rr4, —NRn4S(O)2Rp4, —NRn4S(O)2ORp4, —NRn4S(O)2NRq4Rr4, —NO2, —C(O)Rn4, —C(O)ORn4, or —C(O)NRq4Rr4; each Rn4 is independently H, (C1-C4)alkyl, (C1-C4)haloalkyl, or (C1-C4)heteroalkyl; each Rp4 is independently (C1-C8)alkyl, (C1-C4)haloalkyl, or (C1-C4)heteroalkyl; each Rq4 and Rr4 is independently H, (C1-C4)alkyl, (C1-C4)haloalkyl, or (C1-C4)heteroalkyl; and the moiety is wherein Z5a is H or halogen; or a pharmaceutically acceptable salt thereof. 31. A pharmaceutical composition comprising a compound of claim 30, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 32. A pharmaceutical composition comprising a compound of claim 30, 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. 33. A method for treating a HIV infection in a patient in need thereof comprising administering a therapeutically effective amount of a compound of claim 30, or a pharmaceutically acceptable salt thereof, to the patient. 34. A method for treating an HIV infection in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound of claim 30, 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 site inhibitor and combinations thereof.