Therapeutic compounds

Patent metadata

Field	Value
Publication number	US-2016015690-A1
Application number	US-201514615333-A
Country	US
Kind code	A1
Filing date	Feb 5, 2015
Priority date	Apr 20, 2012
Publication date	Jan 21, 2016
Grant date	—

Abstract

Compounds disclosed herein including compounds of formula I′:

and salts thereof are provided. Pharmaceutical compositions comprising compounds disclosed herein, processes for preparing compounds disclosed herein, intermediates useful for preparing compounds disclosed herein and therapeutic methods for treating an HIV infection using compounds disclosed herein are also provided.

First claim

1 - 24 . (canceled)

25 . A method of treating an HIV infection in a patient in need thereof comprising administering a compound, or a pharmaceutically acceptable salt thereof, of formula I′ to the patient:

wherein:
R 4 is:

A is phenyl, 6-membered N-heteroaryl, thiazolyl, pyridinyl-2(1H)-one, tetrahydropyrimidin-2(1H)-one, imidazolidinyl-2-one, pyrrolidinyl-2-one, pyrrolidinyl, pyrazin-2(1H)-one, piperazinyl-2-one, piperazinyl, morpholinyl, or piperidinyl, wherein A is optionally substituted with 1 to 5 Z 1a groups;
B is (C 6 -C 20 )aryl, heteroaryl or heterocycle, wherein B is optionally substituted with 1 to 5 Z 1b groups; or A and B together form a bicyclic (C 9 -C 14 )aryl, bicyclic heteroaryl or bicyclic heterocycle, wherein bicyclic (C 9 -C 14 )aryl, bicyclic heteroaryl or bicyclic heterocycle is optionally substituted with 1 to 5 Z 1b groups;
each Z 1a is independently halo, (C 1 -C 3 )alkyl, (C 2 -C 3 )alkenyl, (C 2 -C 3 )alkynyl, (C 1 -C 3 )haloalkyl, (C 3 -C 7 )carbocycle, heterocycle, —O(C 1 -C 3 )alkyl, —O(C 2 -C 3 )alkenyl, —O(C 2 -C 3 )alkynyl, —NR c R d , —NR a C(O)R a , —C(O)OR b or —C(O)NR c R d , wherein any (C 3 -C 7 )carbocycle and heterocycle of Z 1a is optionally substituted with 1 to 5 halogen or (C 1 -C 6 )alkyl;
each Z 1b is independently halo, CN, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )carbocycle, heteroaryl, heterocycle, (C 6 -C 20 )aryl(C 1 -C 6 )alkyl-, —OH, —O(C 1 -C 6 )alkyl, —O(C 2 -C 6 )alkenyl, —O(C 2 -C 6 )alkynyl, —NR c R d , —NR a C(O)R a , —C(O)OR b or —C(O)NR c R d , wherein any (C 3 -C 7 )carbocycle and heterocycle of Z 1b is optionally substituted with 1 to 5 halogen or (C 1 -C 6 )alkyl; and
R a , R b , R c and R d are each independently H or (C 1 -C 6 )alkyl;
wherein each heteroaryl, as a monocyclic ring or portion of a 2 to 3 ring system, has 1 to 6 carbon atoms and 1 to 4 heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, and each heterocycle, as a monocyclic ring or portion of a 2 to 3 ring system, has 1 to 6 carbon atoms and 1 to 3 heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur.

26 . The method of claim 25 , wherein:
A is pyridinyl, pyrimidinyl or pyrazinyl, optionally substituted with 1 to 5 Z 1a groups; and B is (C 6 -C 20 )aryl, heteroaryl or heterocycle, optionally substituted with 1 to 5 Z 1b groups.

27 . The method of claim 25 , wherein:
A is pyridinyl, pyrimidinyl or pyrazinyl; and B is heteroaryl or heterocycle, optionally substituted with 1 to 5 Z 1b groups.

28 . The method of claim 25 , wherein:
A is pyridinyl, pyrimidinyl or pyrazinyl; and B is a 4-6 membered monocyclic heterocycle optionally substituted with 1 to 5 Z 1b groups.

29 . The method of claim 25 , wherein:
A is pyridinyl, pyrimidinyl or pyrazinyl; and B is phenyl, pyridinyl, indazolyl, pyrazolo[4,3-b]pyridinyl, pyrimidinyl, pyrazolyl, benzo[d]imidazolyl, indazolyl, 1H-benzo[d]imidazolyl-2(3H)-one, 2H-pyrido[3,2-b][1,4]oxazinyl-3(4H)-one, 2,6-naphthyridin-1(2H)-one, 1,7-naphthyridinyl-8(7H)-one, 1H-indazolyl-3(2H)-one, quinolinyl-2(1H)-one, quinolinyl, pyrrolo[2,3-b]pyridinyl, pyrrolidinyl, piperazinyl, phenyl, imidazolyl, piperidinyl, morpholinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, pyrimidinyl-2,4(1H,3H)-dionyl, pyridinyl-2(1H)-one, 1H-pyrazolo[3,4-c]pyridinyl, indolinyl-2-one, 1H-pyrrolo[3,4-c]pyridinyl-3(2H)-one, 2,3-dihydro-1H-pyrrolo[3,2-c]pyridinyl, pyrazolyl, pyrimidinyl-2(1H)-one, azetidinyl, tetrahydro-2H-pyranyl, 3,6-dihydro-2H-pyranyl, 1,2,3,6-tetrahydropyridine, 1H-pyrazolo[3,4-b]pyridinyl, 2H-benzo[b][1,4]oxazinyl-3(4H)-one, 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, indolinyl, 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one, 3H-imidazo[4,5-b]pyridinyl or 1H-benzo[d][1,2,3]triazolyl, wherein B is optionally substituted with 1 to 5 Z 1b groups.

30 . The method of claim 25 , wherein A is pyridinyl, pyrimidinyl or pyrazinyl, and B is piperazinyl or azetidinyl, optionally substituted with 1 to 5 Z 1b groups.

31 . The method of claim 25 , wherein A is not substituted with Z 1a .

32 . The method of claim 25 , wherein Z 1b is (C 1 -C 6 )alkyl.

33 . The method of claim 25 , wherein A is not substituted with Z 1a ; and Z 1b is (C 1 -C 6 )alkyl.

34 . The method of claim 25 , wherein A and B together form a bicyclic (C 9 -C 14 )aryl, bicyclic heteroaryl or bicyclic heterocycle, wherein bicyclic (C 9 -C 14 )aryl, bicyclic heteroaryl or bicyclic heterocycle is optionally substituted with 1 to 5 Z 1b groups.

35 . The method of claim 25 , wherein each Z 1b is independently CN, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )carbocycle, heteroaryl, heterocycle, (C 6 -C 20 )aryl(C 1 -C 6 )alkyl-, —OH, —O(C 1 -C 6 )alkyl, —O(C 2 -C 6 )alkenyl, —O(C 2 -C 6 )alkynyl, —NR c R d , —NR a C(O)R a , or —C(O)NR c R d .

36 . The method of claim 25 , wherein the compound of formula I′, or a pharmaceutically acceptable salt thereof, is selected from the group consisting of:

Assignees

• Gilead Sciences Inc

Inventors

• Babaoglu Kerim
• Brizgys Gediminas
• Cha Jake
• Chen Xiaowu
• Guo Hongyan
• Halcomb Randall L
• Han Xiaochun
• Huang Richard
• Liu Hongtao
• Mcfadden Ryan
• Mitchell Michael L
• Qi Yingmei
• Roethle Paul A
• Xu Lianhong
• Yang Hong

Classifications

• A61P31/18

  for HIV · CPC title

• A61K31/497

  containing further heterocyclic rings · CPC title

• A61K31/553

  having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine · CPC title

• A61K31/444

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

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title