Compounds for the treatment of HIV

Patent metadata

Field	Value
Publication number	US-10370358-B2
Application number	US-201815902883-A
Country	US
Kind code	B2
Filing date	Feb 22, 2018
Priority date	Jul 6, 2011
Publication date	Aug 6, 2019
Grant date	Aug 6, 2019

Abstract

The invention provides compounds of formula (I): or a salt thereof as described herein. The invention also provides 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.

First claim

What is claimed is:

1. A method for treating an HIV infection in a human, comprising administering a compound of formula I:

or a pharmaceutically acceptable salt thereof, to the human, wherein:
A is pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein any pyridinyl, pyrimidinyl, pyrazinyl, or pyridazinyl of A is substituted with one Z 1 group and optionally substituted with 1, 2, or 3 Z 2 groups;
B is absent; or B is —O − and the nitrogen to which the —O − group is attached is N + ;
W is —CR 3a R 3b —;
R 1 is a bicyclic-heteroaryl, tricyclic-heteroaryl, bicyclic-heterocycle or tricyclic-heterocycle, wherein any bicyclic-heteroaryl, tricyclic-heteroaryl, bicyclic-heterocycle or tricyclic-heterocycle of R 1 is optionally substituted with 1, 2, 3, 4, or 5 Z 3 groups;
R 2 is a 6-membered aryl, 5-membered heteroaryl or 6-membered heteroaryl, wherein any 6-membered aryl, 5-membered heteroaryl or 6-membered heteroaryl of R 2 is optionally substituted with 1, 2, or 3 Z 4 groups;
each R 3a and R 3b is independently selected from H, (C 1 -C 6 )alkyl, (C 1 -C 3 )haloalkyl, (C 1 -C 6 )heteroalkyl, heterocyclyl(C 1 -C 6 )alkyl-;
each Z 1 is independently selected from (C 2 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 3 -C 7 )carbocycle, (C 6 -C 20 )aryl, heteroaryl, heterocycle and —OR n1 , wherein any (C 3 -C 7 )carbocycle, (C 6 -C 20 )aryl, heteroaryl and heterocycle of Z 1 is optionally substituted with 1, 2, 3, 4, or 5 Z 1a or Z 1b groups and wherein any (C 2 -C 8 )alkyl, (C 2 -C 8 )alkenyl and (C 2 -C 8 )alkynyl of Z 1 is optionally substituted with 1, 2, 3, 4, or 5 Z 1a groups;
each Z 1a is independently selected from (C 3 -C 7 )carbocycle, (C 6 -C 20 )aryl, heteroaryl, heterocycle, halogen, —CN, —OR n2 , —OC(O)R p2 , —OC(O)NR q2 R r2 , —SR n2 , —S(O)R p2 , —S(O) 2 OH, —S(O) 2 R p2 , —S(O) 2 NR q2 R r2 , —NR q2 R r2 , —NR n2 COR p2 , —NR n2 CO 2 R p2 , —NR n2 CONR q2 R r2 , —NR n2 S(O) 2 R p2 , —NR n2 S(O) 2 OR p2 , —NR p2 S(O) 2 NR q2 R r2 , NO 2 , —C(O)R n2 , —C(O)OR n2 , —C(O)NR q2 R r2 and —S(O) 2 NR n2 COR p2 , wherein any (C 3 -C 7 )carbocycle, (C 6 -C 20 )aryl, heteroaryl and heterocycle of Z 1a is optionally substituted with 1, 2, 3, 4, or 5 Z 1c or Z 1d groups;
each Z 1b is independently selected from (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl and (C 2 -C 8 )alkynyl, wherein any (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl and (C 2 -C 8 )alkynyl of Z 1b is optionally substituted with 1, 2, 3, 4, or 5 Z 1c groups;
each Z 1c is independently selected from (C 3 -C 7 )carbocycle, (C 6 -C 20 )aryl, heteroaryl, heterocycle,

halogen, —CN, —OR n3 , —OC(O)R p3 , C(O)NR q3 R r3 , —SR n3 , —S(O)R p3 , —S(O) 2 OH, —S(O) 2 R p3 , —S(O) 2 NR q3 R r3 , —NR q3 R r3 , —NR n3 COR p3 , —NR n3 CO 2 R p3 , —NR n3 ONR q3 R r3 , —NR n3 S(O) 2 R p3 , —NR n3 S(O) 2 OR p3 , —NR n3 S(O 2 NR q3 R r3 , NO 2 , —C(O)R n3 , —C(O)OR n3 , —C(O)NR q3 R r3 , (C 6 -C 20 )haloaryl, haloheteroaryl, haloheterocycle and (C 1 -C 8 )heteroalkyl;
each Z 1d is independently selected from (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl and (C 1 -C 8 )haloalkyl;
each R n1 is independently selected from (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 3 -C 7 )carbocycle, heterocycle, heteroaryl and (C 6 -C 20 )aryl, wherein any (C 3 -C 7 )carbocycle, (C 6 -C 20 )aryl, heteroaryl and heterocycle of R n1 is optionally substituted with 1, 2, 3, 4, or 5 Z 1a or Z 1b groups, and wherein any (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl and (C 2 -C 8 )alkynyl of R n1 is optionally substituted with 1, 2, 3, 4, or 5 Z 1a groups;
each R n2 is independently selected from H, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 3 -C 7 )carbocycle, heterocycle, heteroaryl and (C 6 -C 20 )aryl, wherein any (C 3 -C 7 )carbocycle, (C 6 -C 20 )aryl, heteroaryl and heterocycle of R n2 is optionally substituted with 1, 2, 3, 4, or 5 Z 1c or Z 1a groups, and wherein any (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl and (C 2 -C 8 )alkynyl of R n2 is optionally substituted with 1, 2, 3, 4, or 5 Z 1c groups;
each R p2 is independently selected from (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 3 -C 7 )carbocycle, heterocycle, heteroaryl and (C 6 -C 20 )aryl, wherein any (C 3 -C 7 )carbocycle, (C 6 -C 20 )aryl, heteroaryl and heterocycle of R p2 is optionally substituted with 1, 2, 3, 4, or 5 Z 1c or Z 1a groups, and wherein any (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl and (C 2 -C 8 )alkynyl of R p2 is optionally substituted with 1, 2, 3, 4, or 5 Z 1c groups;
R q2 and R r2 are each independently selected from H, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 3 -C 7 )carbocycle, heterocycle, heteroaryl and (C 6 -C 20 )aryl, wherein any (C 3 -C 7 )carbocycle, (C 6 -C 20 )aryl, heteroaryl and heterocycle of R q2 or R r2 is optionally substituted with 1, 2, 3, 4, or 5 Z 1c or Z 1d groups, and wherein any (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl and (C 2 -C 8 )alkynyl of R q2 or R r2 is optionally substituted with 1, 2, 3, 4, or 5 Z 1c groups, or R q2 and R r2 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;
each R n3 is independently selected from H, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 3 -C 7 )carbocycle, heterocycle, heteroaryl, (C 6 -C 20 )aryl, (C 6 -C 20 )haloaryl, haloheteroaryl, haloheterocycle, (C 1 -C 8 )haloalkyl and (C 1 -C 8 )heteroalkyl;
each R p3 is independently selected from (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 3 -C 7 )carbocycle, heterocycle, heteroaryl, (C 6 -C 20 )aryl, (C 6 -C 20 )haloaryl, haloheteroaryl, haloheterocycle, (C 1 -C 8 )haloalkyl and (C 1 -C 8 )heteroalkyl;
R q3 and R r3 are each independently selected from H, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 3 -C 7 )carbocycle, heterocycle, heteroaryl, (C 6 -C 20 )aryl, haloaryl, haloheteroaryl, haloheterocycle, (C 1 -C 8 )haloalkyl and (C 1 -C 8 )heteroalkyl, or R q3 and R r3 together with the nitrogen to which they are attached form a 5, 6 or 7-membered heterocycle;
each Z 2 is independently selected from (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )carbocycle, halogen, CN, OH and —O(C 1 -C 6 )alkyl;
each Z 3 is independently selected from (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 3 -C 7 )carbocycle, (C 6 -C 20 )aryl, halogen, —CN, —OR n4 , —S(O)R p4 , —NR n4 CO 2 R p4 , —NR n4 S(O) 2 R p4 , —C(O)R n4 , —C(O)OR n4 , —C(O)NR q4 R r4 and —B(OR q4 )(OR r4 ) wherein any (C 3 -C 7 )carbocycle and (C 6 -C 20 )aryl of Z 3 is optionally substituted with 1, 2, 3, 4, or 5 Z 3a or Z 3b groups, and wherein any (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl and (C 2 -C 8 )alkynyl of Z 3 is optionally substituted with 1, 2, 3, 4, or 5 Z 3a groups;
each Z 3a is independently selected from (C 3 -C 7 )carbocycle, (C 6 -C 20 )aryl, heteroaryl, heterocycle, halogen, —CN, —OR n5 , —OC(O)R p5 , —OC(O)NR q5 R r5 , —SR n5 , —S(O)R p5 , —S(O) 2 OH, —S(O) 2 R p5 , —S(O) 2 NR q5 R r5 , —NR q5 R r5 , —NR n5 COR p5 , —NR n5 CO 2 R p5 , —NR n5 CONR q5 R r5 , —NR n5 S(O) 2 R p5 , —NR n5 S(O) 2 OR p5 , —NR n5 S(O) 2 NR q5 R r5 , NO 2 , —C(O)R n5 , —C(O)OR n5 , and —C(O)NR q5 R r5 , wherein any (C 3 -C 7 )carbocycle, (C 6 -C 20 )aryl, heteroaryl and heterocycle of Z 1a is optionally substituted with 1, 2, 3, 4, or 5 Z 3c or Z 3d groups;
each Z 3b is independently selected from (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl and (C 2 -C 8 )alkynyl, wherein any (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl and (C 2 -C 8 )alkynyl of Z 3b is optionally substituted with 1, 2, 3, 4, or 5 Z 3c groups;
each Z 3c is independently selected from (C 3 -C 7 )carbocycle, (C 6 -C

Assignees

• Gilead Sciences Inc

Inventors

• Bondy Steven S
• Cannizzaro Carina E
• Chou Chien-Hung
• Halcomb Randall L
• Hu Yunfeng Eric
• Link John O
• Liu Qi
• Schroeder Scott D
• Tse Winston C
• Zhang Jennifer R

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/18

  for HIV · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61K31/4709

  Non-condensed quinolines and containing further heterocyclic rings · CPC title

• C07D401/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title