发明名称 THERAPEUTIC COMPOUNDS
摘要 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.
申请公布号 US2016083368(A1) 申请公布日期 2016.03.24
申请号 US201514836774 申请日期 2015.08.26
申请人 Gilead Sciences, Inc. 发明人 Brizgys Gediminas;Canales Eda;Halcomb Randall L.;Hu Yunfeng Eric;Kato Darryl;Link John O.;Liu Qi;Saito Rpland D.;Tse Winston C.;Zhang Jennifer R.
分类号 C07D401/14;A61K45/06;A61K31/4439;C07D471/04;A61K31/444;C07D493/04;A61K31/4709;C07D403/14;C07D405/14;C07D413/14;A61K31/5377;A61K31/496;A61K31/506;C07D519/00 主分类号 C07D401/14
代理机构 代理人
主权项 1. A compound of formula I: wherein A1 is C—Z3 or nitrogen; A2 is C—Z3 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 oxo, (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)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 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 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 heteroaryl, 3-12 membered heterocycle, wherein any (C2-C8)alkenyl, (C2-C8)alkynyl, 6-12 membered aryl, 5-12 membered heteroaryl, or 3-12 membered heterocycle of Z2 is substituted with 1 or 2 Z2b groups and optionally 1, 2, or 3 Z2c groups, wherein the Z2b and 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 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 Z2b is optionally substituted with 1, 2, 3, 4, or 5 Z2d groups; 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, —C(O)NRq4Rr4, or (C1-C4) alkyl optionally substituted with 1, 2, or 3 halogen or —ORn4; each Z2d 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, —C(O)NRq4Rr4, or (C1-C4) alkyl optionally substituted with 1, 2, or 3 halogen or —ORn4; each Rn4 is independently H, (C1-C4)alkyl optionally substituted with 1, 2, or 3 —OH groups, (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 H or —NRq4Rr4; 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.
地址 Foster City CA US