Compounds for the treatment of HIV

Patent metadata

Field	Value
Publication number	US-11034668-B2
Application number	US-201916419578-A
Country	US
Kind code	B2
Filing date	May 22, 2019
Priority date	Jul 6, 2011
Publication date	Jun 15, 2021
Grant date	Jun 15, 2021

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 compound of formula Ik:

wherein:
each Z 2a is H;
W is —CR 3a R 3b — or absent;
R 1 is heterocycle, optionally substituted with one or more Z 3 groups;
R 2 is phenyl, optionally substituted with one or more Z 4 groups;
R 3a and R 3b together with the carbon to which they are attached form a (C 3 -C 6 )carbocycle;
each Z 1 is independently aryl wherein any aryl is optionally substituted with one or more Z 1a groups;
each Z 1a is independently selected from halogen, —and —C(O)NR q2 R r2 ;
R q2 and R r2 are each H
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, aryl, halogen, —CN, —OR n4 , —S(O) 2 R p4 , —NR q4 R r4 , —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 aryl of Z 3 is optionally substituted with one or more 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 one or more Z 3a groups;
each Z 3a is independently selected from aryl, halogen, and —OR n5 ;
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 one or more Z 3c groups;
each Z 3c is independently selected from (C 3 -C 7 )carbocycle, aryl, heteroaryl, heterocycle, halogen, —CN, —OR n6 , —OC(O)R p6 , —OC(O)NR q6 R r6 , —SR n6 , —S(O)R p6 , —S(O) 2 OH, —S(O) 2 R p6 , —S(O) 2 NR q6 R r6 , —NR q6 R r6 , —NR n6 COR p6 , —NR q6 CO 2 R p6 , —NR n6 CONR q6 R r6 , —NR n6 S(O) 2 R p6 , —NR n6 S(O) 2 OR p6 , —NR n6 S(O) 2 NR q6 R r6 , NO 2 , —C(O)R n6 , —C(O)OR n6 , —C(O)NR q6 R r6 , haloaryl, haloheteroaryl, haloheterocycle and (C 1 -C 8 )heteroalkyl;
each R n4 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 aryl, wherein any (C 3 -C 7 )carbocycle, aryl, heteroaryl and heterocycle of R n4 is optionally substituted with one or more 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 R n4 is optionally substituted with one or more Z 3a groups;
each R p4 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 aryl, wherein any (C 3 -C 7 )carbocycle, aryl, heteroaryl, or heterocycle of R p4 is optionally substituted with one or more Z 3a or Z 3b groups, and wherein any (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl or (C 2 -C 8 )alkynyl of R p4 is optionally substituted with one or more Z 3a groups;
R q4 and R r4 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 aryl, wherein any (C 3 -C 7 )carbocycle, aryl, heteroaryl and heterocycle of R q4 or R r4 is optionally substituted with one or more 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 R q4 or R r4 is optionally substituted with one or more Z 3a groups, or R q4 and R r4 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 one or more Z 3a or Z 3b groups;
each R n5 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 aryl, wherein any (C 3 -C 7 )carbocycle, aryl, heteroaryl and heterocycle of R n5 is optionally substituted with one or more Z 3c or Z 3d groups, and wherein any (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl and (C 2 -C 8 )alkynyl of R n5 is optionally substituted with one or more Z 3c groups;
each R n6 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, aryl, haloaryl, haloheteroaryl, haloheterocycle, (C 1 -C 8 )haloalkyl and (C 1 -C 8 )heteroalkyl;
each R p6 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, aryl, haloaryl, haloheteroaryl, haloheterocycle, (C 1 -C 8 )haloalkyl and (C 1 -C 8 )heteroalkyl;
R q6 and R r6 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, aryl, haloaryl, haloheteroaryl, haloheterocycle, (C 1 -C 8 )haloalkyl and (C 1 -C 8 )heteroalkyl, or R q6 and R r6 together with the nitrogen to which they are attached form a 5, 6 or 7-membered heterocycle;
each Z 4 is independently halogen;
or a salt thereof.

2. The compound of claim 1 , wherein W is absent.

3. The compound of claim 1 , wherein each Z 3a is independently fluoro or —C(O)NH 2 .

4. The compound of claim 1 , wherein the

moiety is:

5. The compound of claim 1 , wherein R 2 is 3,5-halophenyl.

6. The compound of claim 1 , wherein each Z 4 is fluoro.

7. The compound of claim 1 , wherein R 2 is

8. The compound of claim 1 , wherein R 1 is pyrrolidinyl.

9. The compound of claim 1 , wherein R 1 is morpholinyl.

10. The compound of claim 1 , wherein each Z 3 is independently selected from (C 1 -C 8 )alkyl, aryl, —OR n4 , —C(O)R n4 , —C(O)OR n4 , and —C(O)NR q4 R r4 wherein any aryl of Z 3 is optionally substituted with one or more Z 3a or Z 3b groups, and wherein any (C 1 -C 8 )alkyl of Z 3 is optionally substituted with one or more Z 3a groups.

11. The compound of claim 1 , wherein each Z 3 is independently selected from hydroxy, benzyloxy, benzyl, cyclopentanecarbonyl, phenylcarbonyl, phenoxy, phenyl, ethoxycarbonyl, and tert-butoxycarbonyl.

12. The compound of claim 1 , wherein R 1 is selected from:

13. The compound of claim 1 selected from:

and salts thereof.

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

15. A method for treating a Retroviridae virus infection in a mammal comprising administering a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to the mammal.

16. The

Assignees

• Gilead Sciences Inc

Inventors

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

Classifications

• C07D491/04

  Ortho-condensed systems · CPC title

• C07D495/04

  Ortho-condensed systems · CPC title

• A61K31/4709

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

• A61K31/444

  containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone · CPC title

• C07D403/14

  containing three or more hetero rings · CPC title