Therapeutic compounds

摘要

Compounds of formula I:;
or pharmaceutically acceptable 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.

主权项

1. A compound of formula I: wherein: A is  wherein each Z3a is independently selected from H or Z3; R1 is a bicyclic-heteroaryl or tricyclic-heteroaryl, wherein the bicyclic-heteroaryl or tricyclic-heteroaryl has 4-9 carbon atoms and 1-5 heteroatoms selected from nitrogen, sulfur, and oxygen, and wherein the bicyclic-heteroaryl or tricyclic-heteroaryl of R1 is optionally substituted with 1, 2, 3, 4, or 5 Z4 groups; R2 is phenyl optionally substituted with 1, 2, or 3 Z5 groups; each R3a and R3b is independently selected from H, halogen, (C1-C3)alkyl, and (C1-C3)haloalkyl, or R3a is selected from H, (C1-C3)alkyl and (C1-C3)haloalkyl and R3b is selected from —OH and —CN; Z1 is phenyl, monocyclic-heteroaryl or bicyclic-heterocycle, wherein the monocyclic-heteroaryl or bicyclic-heterocycle has 4-8 carbon atoms and 1-3 heteroatoms and, wherein any phenyl, monocyclic-heteroaryl or bicyclic-heterocycle of Z1 is optionally substituted with 1, 2, 3, 4, or 5 Z1a or Z1b; each Z1a is independently selected from 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, NO2, —C(O)Rn1, —C(O)ORn1, —C(O)NRq1Rr1 and —S(O)2NRn1CORp1; each Z1b is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl, wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Z1b is optionally substituted with 1, 2, 3, 4, or 5 Z1c groups; each Z1c is independently selected from halogen, —CN, —ORn2, —OC(O)Rp2, —OC(O)NRq2Rr2, —SRn2, —S(O)Rp2, —S(O)2OH, —S(O)2Rp2, —S(O)2NRq2Rr2, —NRq2Rr2, —NRn2CORp2, —NRn2CO2Rp2, —NRn2CONRq2Rr2, —NRn2S(O)2Rp2, —NRn2S(O)2ORp2, —NRn2S(O2NRq2Rr2, NO2, —C(O)Rn2, —C(O)ORn2, and —C(O)NRq2Rr2; each Z1d is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl and (C1-C8)haloalkyl; each Rn1 is independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, and (C2-C8)alkynyl, wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Rn1 is optionally substituted with 1, 2, 3, 4, or 5 Z1c groups; each Rp1 is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl, and (C2-C8)alkynyl, wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Rp1 is optionally substituted with 1, 2, 3, 4, or 5 Z1c groups; Rq1 and Rr1 are each independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Rq1 or Rr1 is optionally substituted with 1, 2, 3, 4, or 5 Z1c groups; each Rn2 is independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C1-C8)haloalkyl and (C1-C8)heteroalkyl; each Rp2 is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C1-C8)haloalkyl and (C1-C8)heteroalkyl; Rq2 and Rr2 are each independently selected from H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C1-C8)haloalkyl and (C1-C8)heteroalkyl; Z2 is selected from —ORs3 —OC(O)Rp3, —OC(O)NRq3Rr3, —SRn3, —S(O)Rp3, —S(O)2Rp3, —S(O)2NRq3Rr3, —NRq3Rr3, —NRn3CORp3, —NRn3CO2Rp3, —NRn3S(O)2Rp3, —NRn3S(O)2ORp3 and —NRn3S(O)2NRq3Rr3; each Z2a is independently selected from 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, —NRn4CONRq2Rr4, —NRn4S(O)2Rp4, —NRn4S(O)2ORp4, —NRn4S(O)2NRq4Rr4, NO2, —C(O)Rn4, —C(O)ORn4, and —C(O)NRq4Rr4, each Z2b is independently selected from (C1-C4)alkyl, (C1-C4)heteroalkyl and (C1-C4)haloalkyl; each Z2c is independently selected from 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, —C(O)NRq4Rr4; each Rn3 is independently selected from H, (C1-C4)alkyl, (C2-C4)alkenyl, and (C2-C4)alkynyl, wherein any (C1-C4)alkyl, (C2-C4)alkenyl or (C2-C4)alkynyl of Rn3 is optionally substituted with 1, 2, 3, 4, or 5 Z2a groups; each Rp3 is independently selected from (C1-C4)alkyl, (C1-C4)haloalkyl, (C2-C4)alkenyl, and (C2-C4)alkynyl, wherein any (C1-C4)alkyl, (C2-C4)alkenyl and (C2-C4)alkynyl of Rp3 is optionally substituted with 1, 2, 3, 4, or 5 Z2a groups; Rq3 and Rr3 are each independently selected from H, (C1-C4)alkyl, and (C2-C4)alkenyl, wherein any (C1-C4)alkyl and (C2-C4)alkenyl of Rq3 or Rr3 is optionally substituted with 1, 2, 3, 4, or 5 Z2a groups, or Rq3 and Rr3 together with the nitrogen to which they are attached form a heterocycle or heteroaryl selected from triazolyl, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, homopiperidinyl, morpholinyl, piperazinyl, isoindolinyl, 2-oxa-6-azaspiro[3.3]heptanyl, and imidazolidinyl wherein the triazolyl, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, homopiperidinyl, morpholinyl, piperazinyl, isoindolinyl, 2-oxa-6-azaspiro[3.3]heptanyl, and imidazolidinyl is optionally substituted with 1, 2, 3, 4, or 5 Z2b, Z2c, or oxo groups; each Rs3 is independently selected from (C2-C4)alkenyl or (C2-C4)alkynyl, wherein any (C2-C4)alkenyl or (C2-C4)alkynyl of Rs3 is optionally substituted with 1, 2, 3, 4, or 5 Z2a groups, or Rs3 is (C1-C4)alkyl substituted with 1, 2, 3, 4, or 5 Z2a groups; each Rn4 is independently selected from H, (C1-C4)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C1-C4)haloalkyl and (C1-C4)heteroalkyl; each Rp4 is independently selected from (C1-C8)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)haloalkyl and (C1-C4)heteroalkyl; Rq4 and Rr4 are each independently selected from H, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)haloalkyl and (C1-C4)heteroalkyl; each Z3 is independently selected from halogen, (C1-C4)alkyl, —OH, —CN, (C1-C4)heteroalkyl and (C1-C4)haloalkyl; each Z4 is independently selected from (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, halogen, —CN, —ORn5, —OC(O)Rp5, —OC(O)NRq5Rr5, —SRn5, —S(O)Rp5, —S(O)2OH, —S(O)2Rp5, —S(O)2NRq5Rr5, —NRq5Rr5, —NRn5CORp5, —NRn5CO2Rp5, —NRn5CONRq5Rr5, —NRn5S(O)2Rp5, —NRn5S(O)2ORp5, —NRn5S(O)2NRq5Rr5, NO2, —C(O)Rn5, —C(O)ORn5, —C(O)NRq5Rr5 and —B(ORq5)(ORr5), wherein any (C1-C8)alkyl, (C2-C8)alkenyl and (C2-C8)alkynyl of Z4 is optionally substituted with 1, 2, 3, 4, or 5 Z4a groups; each Z4a is independently selected from halogen, —CN, —ORn6, —OC(O)Rp6, —OC(O)NRq6Rr6, —SRn6, —S(O)Rp6, —S(O)2OH, —S(O)2Rp6, —S(O)2NRq6Rr6, —NRq6Rr6, —NRn6CORp6, —NRn6CO2Rp6, —NRn6CONRq6Rr6, —NRn6S(O)2Rp6, —NRn6S(O)2ORp6, —NRn6S(O)2NRq6Rr6, NO2, —C(O)Rn6, —C(O)ORn6, and —C(O)NRq6Rr6; each Z4b is independently selected from (C1-C4)alkyl, (C2-C4)alkenyl and (C2-C4)alkynyl, wherein any (C1-C4)alkyl, (C2-C4)alkenyl and (C2-C4)alkynyl of Z4b is optionally substituted with 1, 2, 3, 4, or 5 Z4c groups; each Z4c is independently selected from halogen, —CN, —ORn7, —OC(O)Rp7, —OC(O)NRq7Rr7, —SRn7, —S(O)Rp7, —S(O)2OH, —S(O)2Rp7, —S(O)2NRq7Rr7, —NRq7Rr7, —NRn7CORp7, —NRn7CO2Rp7, —NRn7CONRq7Rr7, —NRn7S(O)2Rp7, —NRn7S(O)2ORp7, NRn7S(O)2NRq7Rr7, NO2, —C(O)Rn7, —C(O)ORn7, —C(O)NRq7Rr7 and (C1-C4)heteroalkyl; each Z4d is independently selected from (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, and (C1-C4)haloalkyl; each Rn5 is independently selected from H, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, wherein any (C1-C4)alkyl, (C2-C4)alkenyl and (C2-C4)alkynyl of Rn5 is optionally substituted with 1, 2, 3, 4, or 5 Z4a groups; each Rp5 is independently selected from (C1-C4)alkyl, (C2-C4)alkenyl, and (C2-C4)alkynyl, wherein any (C1-C4)alkyl, (C2-C4)alkenyl or (C2-C4)alkynyl of Rp5 is optionally substituted with 1, 2, 3, 4, or 5 Z4a groups; Rq5 and Rr5 are each independently selected from H, (C1-C4)alkyl, (C2-C4)alkenyl, and (C2-C4)alkynyl, wherein any (C1-C4)alkyl, (C2-C4)alkenyl and (C2-C4)alkynyl of Rq5 or Rr5 is optionally substituted with 1, 2, 3, 4, or 5 Z4a groups; each Rn6 is independently selected from H, (C1-C4)alkyl, (C2-C4)alkenyl, and (C2-C4)alkynyl, wherein any (C1-C4)alkyl, (C2-C4)alkenyl and (C2-C4)alkynyl of Rn6 is optionally substituted with 1, 2, 3, 4, or 5 Z4c groups; each Rp6 is independently selected from (C1-C4)alkyl, (C2-C4)alkenyl, and (C2-C4)alkynyl, wherein any (C1-C4)alkyl, (C2-C4)alkenyl and (C2-C4)alkynyl of Rp6 is optionally substituted with 1, 2, 3, 4, or 5 Z4c groups; Rq6 and Rr6 are each independently selected from H, (C1-C4)alkyl, (C2-C4)alkenyl, and (C2-C4)alkynyl, wherein any (C1-C4)alkyl, (C2-C4)alkenyl and (C2-C4)alkynyl of Rq6 or Rr6 is optionally substituted with 1, 2, 3, 4, or 5 Z4c groups; each Rn7 is independently selected from H, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)haloalkyl and (C1-C4)heteroalkyl; each Rp7 is independently selected from (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)haloalkyl and (C1-C4)heteroalkyl; Rq7 and Rr7 are each independently selected from H, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4) haloalkyl and (C1-C4) heteroalkyl, each Z5 is independently selected from (C1-C6)alkyl, halogen, —CN, and —ORn8, wherein any (C1-C6)alkyl of Z5 is optionally substituted with 1, 2, 3, 4, or 5 halogen; and each Rn8 is independently selected from H, (C1-C3)alkyl, and (C1-C3)haloalkyl; or a salt thereof.