Therapeutic compounds

Abstract

Compounds of formula I′: or salts thereof are provided. 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 are also provided.

What is claimed is: 
     
         1 . A compound of formula I′: 
       
         
           
           
               
               
           
         
         wherein:
 R 4  is selected from aryl, heterocycle and heteroaryl, wherein any aryl, heterocycle and heteroaryl of R 4  is optionally substituted with one or more groups each independently selected from halo, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )cycloalkyl, —(C 1 -C 6 )alkyl-(C 3 -C 7 )cycloalkyl, —OH, —O(C 1 -C 6 )alkyl, —SH, —S(C 1 -C 6 )alkyl, NH 2 , —NH(C 1 -C 6 )alkyl and —N((C 1 -C 6 )alkyl) 2 , wherein (C 1 -C 6 )alkyl is optionally substituted with hydroxy, —O(C 1 -C 6 )alkyl, cyano or oxo; 
 A is phenyl, monocyclic heteroaryl or monocyclic heterocycle, wherein any phenyl, monocyclic heteroaryl or monocyclic heterocycle of A is optionally substituted with one or more Z 1a  groups, and B is aryl, heteroaryl or hetereocycle, wherein any aryl, heteroaryl or hetereocycle of B is optionally substituted with one or more Z 1b  groups; or A and B together form a bicyclic aryl, bicyclic heteroaryl or bicyclic heterocycle, wherein bicyclic aryl, bicyclic heteroaryl or bicyclic heterocycle is optionally substituted with one or more Z 1b  groups; 
 each Z 1a  is independently selected from 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  and —C(O)NR c R d , wherein any (C 3 -C 7 )carbocycle or heterocycle of Z 1a  is optionally substituted with one or more halogen or (C 1 -C 6 )alkyl; 
 each Z 1b  is independently selected from 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, 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 a C(O)R a , —C(O)OR b  and —C(O)NR c R d , wherein any (C 3 -C 7 )carbocycle or heterocycle of Z 1b  is optionally substituted with one or more 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; 
 or a salt thereof. 
 
       
     
     
         2 . The compound of  claim 1  wherein A is phenyl, monocyclic heteroaryl or monocyclic heterocycle wherein any phenyl, monocyclic heteroaryl or monocyclic heterocycle of A is optionally substituted with one or more Z 1a  groups, and B is aryl, heteroaryl or hetereocycle wherein any aryl, heteroaryl or hetereocycle of B is optionally substituted with one or more Z 1b  groups. 
     
     
         3 . The compound of  claim 1  wherein A is phenyl, monocyclic N-heteroaryl or monocyclic heterocycle wherein any phenyl, monocyclic N-heteroaryl or monocyclic heterocycle of A is optionally substituted with one or more Z 1a  groups, and B is aryl, heteroaryl or hetereocycle wherein any aryl, heteroaryl or hetereocycle of B is optionally substituted with one or more Z 1b  groups. 
     
     
         4 . The compound of  claim 1  wherein A is monocyclic N-heteroaryl, wherein monocyclic N-heteroaryl is optionally substituted with one or more Z 1a  groups, and B is aryl, heteroaryl or hetereocycle wherein any aryl, heteroaryl or hetereocycle of B is optionally substituted with one or more Z 1b  groups. 
     
     
         5 . The compound of  claim 1  wherein A is pyridinyl, pyrimidinyl, pyrazinyl, pyridinyl-2-one, tetrahydropyrimidinyl-2-one, imidazolidinyl-2-one, pyrrolidinyl-2-one or pyrrolidinyl, wherein pyridinyl, pyrimidinyl, pyrazinyl, pyridinyl-2-one, tetrahydropyrimidinyl-2-one, imidazolidinyl-2-one, pyrrolidinyl-2-one or pyrrolidinyl is optionally substituted with one or more Z 1a  groups, and B is aryl, heteroaryl or hetereocycle wherein any aryl, heteroaryl or hetereocycle of B is optionally substituted with one or more Z 1b  groups. 
     
     
         6 . The compound of  claim 1  wherein B is phenyl, pyridinyl, pyrazolyl, pyrimidinyl, indazolyl, pyrazolopyridine or benzimidazolyl, wherein any phenyl, pyridinyl, pyrazolyl, pyrimidinyl, indazolyl, pyrazolopyridine or benzimidazolyl, of B is optionally substituted with one or more Z 1b  groups. 
     
     
         7 . The compound of  claim 1  wherein B is phenyl or indazolyl, wherein any phenyl or indazolyl of B is optionally substituted with one or more Z 1b  groups. 
     
     
         8 . The compound of  claim 1  wherein A and B together form a bicyclic aryl, bicyclic heteroaryl or bicyclic heterocycle wherein bicyclic aryl, bicyclic heteroaryl or bicyclic heterocycle is optionally substituted with one or more Z 1b  groups. 
     
     
         9 . The compound of  claim 1  wherein A and B together form a bicyclic heteroaryl, wherein bicyclic heteroaryl is optionally substituted with one or more Z 1b  groups. 
     
     
         10 . The compound of  claim 1  wherein A and B together form a pyrrolopyridinyl, pyrazolopyridine or indazolyl wherein pyrrolopyridinyl or indazolyl is optionally substituted with one or more Z 1b  groups. 
     
     
         11 . The compound of  claim 1  wherein A is phenyl, wherein phenyl is optionally substituted with one or more Z 1a  groups, and B is aryl, heteroaryl or hetereocycle wherein any aryl, heteroaryl or hetereocycle of B is optionally substituted with one or more Z 1b  groups. 
     
     
         12 . The compound of  claim 1  wherein each Z 1b  is independently selected from methyl, isobutyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, N-methylpiperazinyl, morpholinyl, tetrazolyl, —OCH 3 , t-butyl, —C(O)OH, —NH 2 , —N(CH 3 ) 2 , —OH, —C(O)NH 2 , benzyl and CN. 
     
     
         13 . The compound of  claim 1  wherein A-B is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         14 . The compound of  claim 1  wherein R 4  is selected from aryl and heterocycle, wherein any aryl and heterocycle of R 4  is optionally substituted with one or more chloro, fluoro or methyl. 
     
     
         15 . The compound of  claim 1  wherein R 4  is: 
       
         
           
           
               
               
           
         
       
     
     
         16 . The compound of  claim 1  wherein R 4  is: 
       
         
           
           
               
               
           
         
       
     
     
         17 . The compound of  claim 1  which is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         and salts thereof. 
       
     
     
         18 . A pharmaceutical composition comprising a compound of formula I′ as described in  claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         19 . A method of treating an HIV infection in a mammal comprising administering a compound of formula I′ as described in  claim 1 , or a pharmaceutically acceptable salt thereof, to the mammal. 
     
     
         20 . A method for treating an HIV infection in a mammal comprising administering to the mammal in need thereof a therapeutically effective amount of a compound of formula I′ as described in  claim 1 , or a pharmaceutically acceptable salt thereof, in combination with a therapeutically effective amount of one or more additional therapeutic agents selected from the group consisting HIV protease inhibiting compounds, HIV non-nucleoside inhibitors of reverse transcriptase, HIV nucleoside inhibitors of reverse transcriptase, HIV nucleotide inhibitors of reverse transcriptase, HIV integrase inhibitors, gp41 inhibitors, CXCR4 inhibitors, gp120 inhibitors, CCR5 inhibitors, capsid polymerization inhibitors, and other drug for treating HIV, and combinations thereof.