2-quinolinyl-acetic acid derivatives as HIV antiviral compounds

Patent metadata

Field	Value
Publication number	US-9296758-B2
Application number	US-201113806048-A
Country	US
Kind code	B2
Filing date	Jul 1, 2011
Priority date	Jul 2, 2010
Publication date	Mar 29, 2016
Grant date	Mar 29, 2016

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 the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS or ARC symptoms in a mammal using compounds of formula (I).

First claim

What is claimed is:

1. The compound of of formula Ih, or a pharmaceutically acceptable salt thereof:

 wherein:
R 1 is R 1a or R 1b ;
R 4 is R 4a ;
R 5 is R 5a or R 5b ;
R 6 is R 6a or R 6b ;
R 7 is R 7a or R 7b ;
R 1a is selected from the group consisting of:
a) H, halo, (C 1 -C 6 )alkyl and (C 1 -C 6 )haloalkyl;
b) (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 7 )cycloalkyl, nitro, cyano, (C 6 -C 20 )aryl, heterocycle and heteroaryl;
c) —C(═O)—R 11 , —C(═O)—O—R 11 , —O—R 11 , —S—R 11 , —SO 2 —R 11 , —(C 1 -C 6 )alkyl-R 11 , —(C 1 -C 6 )alkyl-C(═O)—R 11 , —(C 1 -C 6 )alkyl-C(═O)—O—R 11 , —(C 1 -C 6 )alkyl-O—R 11 , —(C 1 -C 6 )alkyl-S—R 11 , —(C 1 -C 6 )alkyl-S(O)—R 11 and —(C 1 -C 6 )alkyl-SO 2 —R 11 , wherein each R 11 is independently selected from the group consisting of H, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )cycloalkyl, (C 6 -C 20 )aryl, heterocycle and heteroaryl; and
d) —N(R 9 )R 10 , —C(═O)—N(R 9 )R 10 , —O—C(═O)—N(R 9 )R 10 , —SO 2 —N(R 9 )R 10 , —(C 1 -C 6 )alkyl-N(R 9 )R 10 , —(C 1 -C 6 )alkyl-C(═O)—N(R 9 )R 10 , —(C 1 -C 6 )alkyl-O—C(═O)—N(R 9 )R 10 and —(C 1 -C 6 )alkyl-SO 2 —N(R 9 )R 10 , wherein each R 10 is independently selected from the group consisting of R 11 , —(C 1 -C 6 )alkyl-R 11 , —SO 2 —R 11 , —C(═O)—R 11 , —C(═O)OR 11 and —C(═O)N(R 9 )R 11 , each R 9 is independently selected from the group consisting of H, (C 1 -C 6 )alkyl and (C 3 -C 7 )cycloalkyl, and wherein each R 11 is independently selected from the group consisting of H, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )cycloalkyl, (C 6 -C 20 )aryl, heterocycle and heteroaryl,
and wherein any (C 6 -C 20 )aryl, heterocycle or heteroaryl of R 1a is optionally independently substituted with 1 to 3 Z 10 groups;

R 1b is selected from the group consisting of:
a) —(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl-(C 3 -C 7 )carbocycle, —(C 1 -C 6 )alkyl-S—(C 1 -C 6 )alkyl-(C 3 -C 7 )carbocycle, —(C 1 -C 6 )alkyl-S(O)—(C 1 -C 6 )alkyl-(C 3 -C 7 )carbocycle, —(C 1 -C 6 )alkyl-SO 2 —(C 1 -C 6 )alkyl-(C 3 -C 7 )carbocycle, —(C 1 -C 6 )alkyl-SO 2 —(C 1 -C 6 )alkyl-Z 13 , —C(O)—(C 1 -C 6 )alkyl-Z 13 , —O—(C 1 -C 6 )alkyl-Z 13 , —S—(C 1 -C 6 )alkyl-Z 13 , —S(O)—(C 1 -C 6 )alkyl-Z 13 , —SO 2 —(C 1 -C 6 )alkyl-Z 13 , —(C 1 -C 6 )alkyl-Z 14 , —(C 1 -C 6 )alkyl-C(O)—(C 1 -C 6 )alkyl-Z 13 , —(C 1 -C 6 )alkyl-C(O)—O—(C 1 -C 6 )alkyl-Z 13 , —(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl-Z 13 ,—(C 1 -C 6 )alkyl-S—(C 1 -C 6 )alkyl-Z 13 , —(C 2 -C 6 )alkenyl-(C 1 -C 6 )haloalkyl, —(C 2 -C 6 )alkynyl-(C 1 -C 6 )haloalkyl, —(C 3 -C 7 )halocarbocycle, —NR a SO 2 NR c R d , —NR a SO 2 O(C 3 -C 7 )carbocycle, —NR a ,SO 2 O(C 6 -C 20 )aryl, —(C 2 -C 6 )alkenyl-(C 3 -C 7 )carbocycle, —(C 2 -C 6 )alkenyl-(C 6 -C 20 )aryl, —(C 2 -C 6 )alkenyl-heteroaryl, —(C 2 -C 6 )alkenyl-heterocycle, —(C 2 -C 6 )alkynyl—(C 3 -C 7 )carbocycle, —(C 2 -C 6 )alkynyl-(C 6 -C 20 )aryl, —(C 2 -C 6 )alkynyl-heteroaryl —(C 2 -C 6 )alkynyl-heterocycle, —(C 3 -C 7 )carbocycle-Z 1 and -halo(C 1 -C 6 )alkyl-Z 3 , wherein each (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )carbocycle, (C 3 -C 7 )halocarbocycle, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 6 -C 20 )aryl, heterocycle and heteroaryl, either alone or as part of a group, is optionally independently substituted with 1 to 5 Z 1 groups;
b) spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle, wherein each spiro-bicyclic carbocycle, fused-bicyclic carbocycle and bridged-bicyclic carbocycle is optionally independently substituted with 1 to 5 Z 1 groups, wherein two Z 1 groups together with the atom or atoms to which they are attached optionally form a (C 3 -C 7 )carbocycle or heterocycle, wherein the (C 3 -C 7 )carbocycle or heterocycle is optionally independently substituted with 1 to 5 Z 1 groups;
c) (C 1 -C 6 )alkyl, wherein (C 1 -C 6 )alkyl is independently substituted with 1 to 5 Z 2 groups and optionally independently substituted with 1 to 5 Z 1 groups;
d) —X(C 1 -C 6 )alkyl, —X(C 1 -C 6 )haloalkyl, —X(C 2 -C 6 )alkenyl, —X(C 2 -C 6 )alkynyl and —X(C 3 -C 7 )carbocycle, wherein each X(C 1 -C 6 )alkyl and X(C 1 -C 6 )haloalkyl is independently substituted with 1 to 5 Z 3 groups and optionally independently substituted with 1 to 5 Z 1 groups, and wherein each X(C 2 -C 6 )alkenyl, X(C 2 -C 6 )alkynyl and X(C 3 -C 7 )carbocycle is independently substituted with 1 to 5 Z 4 groups and optionally independently substituted with 1 to 5 Z 1 groups;
e) (C 6 -C 20 )aryl, heteroaryl, heterocycle, —X(C 6 -C 20 )aryl, —Xheteroaryl and —Xheterocycle, wherein each (C 6 -C 20 )aryl, heteroaryl and heterocycle, either alone or as part of a group, is independently substituted with 1 to 5 Z 5 groups and optionally independently substituted with 1 to 5 Z 1 groups;
f) (C 1 -C 6 )haloalkyl, (C 3 -C 7 )carbocycle, (C 2 -C 6 )alkenyl, and (C 2 -C 6 )alkynyl, wherein each (C 1 -C 6 )haloalkyl, (C 3 -C 7 )carbocycle, (C 2 -C 6 )alkenyl and (C 2 -C 6 )alkynyl is independently substituted with 1 to 5 Z 6 groups and optionally independently substituted with 1 to 5 Z 1 groups; and
g) —NR e R f , —C(O)NR e R f , —OC(O)NR e R f , —SO 2 NR e R f , —(C 1 -C 6 )alkyl-NR e R f , —(C 1 -C 6 )alkylC(O)—NR e R f , —(C 1 -C 6 )alkyl-O—C(O)—NR e R f and —(C 1 -C 6 )alkyl-SO 2 NR e R f , wherein each (C 1 -C 6 )alkyl, as part of a group, is optionally independently substituted with 1 to 5 Z 1 groups,

R 4a is selected from the group consisting of:

R 5a is selected from the group consisting of:
a) halo, nitro and cyano;
b) R 11 , —C(═O)—R 11 , —C(═O)—O—R 11 , —O—R 11 , —S—R 11 , —S(O)—R 11 , —SO 2 —R 11 , —(C 1 -C 6 )alkyl-R 11 , —(C 1 -C 6 )alkyl-C(═O)—R 11 , —(C 1 -C 6 )alkyl-C(═O)—O—R 11 , —(C 1 -C 6 )alkyl-O—R 11 , —(C 1 -C 6 )alkyl-S—R 11 , —(C 1 -C 6 )alkyl-S(O)—R 11 and —(C 1 -C 6 )alkyl-SO 2 —R 11 , wherein each R 11 is independently selected from the group consisting of H, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )cycloalkyl, (C 6 -C 20 )aryl, heterocycle and heteroaryl, wherein each (C 6 -C 20 )aryl, heterocycle and heteroaryl is optionally independently substituted with 1 to 3 Z 11 groups;
c) —N(R 9 )R 10 , —C(═O)—N(R 9 )R 10 , —O—C(═O)—N(R 9 )R 10 , —SO 2 —N(R 9 )R 10 , —(C 1 -C 6 )alkyl-N(R 9 )R 10 , —(C 1 -C 6 )alkyl-C(═O)—N(R 9 )R 10 —(C 1 -C 6 )alkyl-O—C(═O)—N(R 9 )R 10 , and —(C 1 -C 6 )alkyl-SO 2 —N(R 9 )R 10 , wherein each R 10 is independently selected from the group consisting of R 11 , —(C 1 -C 6 )alkyl-R 11 , SO 2 —R 11 , —C(═O)—R 11 , —C(═O)OR 11 and —C(═O)N(R 9 )R 11 , each R 9 is independently selected from the group consisting of H, (C 1 -C 6 )alkyl and (C 3 -C 7 )cycloalkyl, and wherein each R 11 is independently selected from the group consisting of H, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )cycloalkyl, (C 6 -C 20 )aryl, heterocycle and heteroaryl;

R 5b is selected from the group consisting of:
a) —(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl-(C 3 -C 7 )carbocycle, —(C 1 -C 6 )alkyl-S—(C 1 -C 6 )alkyl-(C 3 -C 7 )carbocycle, —(C 1 -C 6 )alkylS(O)—(C 1 -C 6 )alkyl-(C 3 -C 6 )carbocycle, —(C 1 -C 6 )alkylSO 2 (C 1 -C 6 )alkyl-(C 3 -C 7 )carbocycle, —(C 2 -C 6 )alkenyl-(C 1 -C 6 )haloalkyl, —(C 2 -C 6 )alkynyl-(C 1 -C 6 )haloalkyl, —(C 3 -C 7 )halocarbocycle, —NR a SO 2 NR c R d , —NR a SO 2 O(C 3 -C 7 )carbocycle, —NR a SO 2 O(C 6 -C 20 aryl, —(C 2 -C 6 )alkenyl-(C 3 -C 7 )carbocycle, —(C 2 -C 6 )alkenyl-(C 6 -C 20 )aryl, —(C 2 -C 6 )alkenyl-heteroaryl, —(C 2 -C 6 )alkenyl-heterocycle,

Assignees

• Babaoglu Kerim
• Bjornson Kyla
• Guo Hongyan
• Halcomb Randall L
• Link John O
• Liu Hongtao
• Mitchell Michael L
• Sun Jianyu
• Taylor James
• Vivian Randall W
• Xu Lianhong
• Gilead Sciences Inc

Inventors

• Babaoglu Kerim
• Bjornson Kyla
• Guo Hongyan
• Halcomb Randall L
• Link John O
• Liu Hongtao
• Mitchell Michael L
• Sun Jianyu
• Taylor James
• Vivian Randall W
• Xu Lianhong

Classifications

• A61P31/18

  for HIV · CPC title

• C07D498/04 Primary

  Ortho-condensed systems · CPC title

• C07D215/18 Primary

  Halogen atoms or nitro radicals · CPC title

• C07D215/38

  Nitrogen atoms (nitro radicals C07D215/18) · CPC title

• C07D215/227

  only one oxygen atom which is attached in position 2 · CPC title