Therapeutic compounds

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.

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: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         37 . A method of treating an HIV infection in a patient in need thereof comprising administering a compound, or a pharmaceutically acceptable salt thereof, having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         38 . A method of treating an HIV infection in a patient in need thereof comprising administering a compound, or a pharmaceutically acceptable salt thereof, having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         39 . A method of treating an HIV infection in a patient in need thereof comprising administering a compound, or pharmaceutically acceptable salt thereof, having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         40 . A method of treating an HIV infection in a patient in need thereof comprising administering a compound, or a pharmaceutically acceptable salt thereof, having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         41 . A method of treating an HIV infection in a patient in need thereof comprising administering a compound, or a pharmaceutically acceptable salt thereof, having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         42 . A method of treating an HIV infection in a patient in need thereof comprising administering a compound, or a pharmaceutically acceptable salt thereof, having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         43 . A method of treating an HIV infection in a patient in need thereof comprising administering a compound, or a pharmaceutically acceptable salt thereof, having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         44 . A method for treating an HIV infection in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound as described in  claim 25 , 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 of 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 drugs for treating HIV.