US2021070756A1PendingUtilityA1

Tetracyclic bromodomain inhibitors

Assignee: ABBVIE INCPriority: Mar 12, 2013Filed: Nov 16, 2020Published: Mar 11, 2021
Est. expiryMar 12, 2033(~6.6 yrs left)· nominal 20-yr term from priority
A61P 15/16C07D 498/04C07D 498/14A61P 13/12C07D 471/22A61P 31/18A61P 35/00C07D 498/16C07D 471/16
70
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Claims

Abstract

The present invention provides for compounds of formula (I) wherein R 1 , R 2 , R 6 , Y 1 , Y 2 , Y 3 , A 1 , A 2 , A 3 , and A 4 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).

Claims

exact text as granted — not AI-modified
1 . A compound of formula (I) or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
         wherein 
         Y 1  is N or CH; 
         R 1  is CD 3 , C 1 -C 3  alkyl, or C 1 -C 3  haloalkyl; 
         R 2  is H or C 1 -C 3  alkyl; 
         Y 3  is N or CR 3 ; 
         R 3  is H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —CN, —C(O)R 3a , —C(O)OR 3a , —C(O)NR 3b R 3c , —S(O)R 3d , —S(O) 2 R 3a , —S(O) 2 NR 3b R 3c , or G 1 ; wherein the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, and C 2 -C 6  alkynyl are each independently unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of G 1 , —CN, —C(O)R 3a , —C(O)OR 3a , —C(O)NR 3b R 3c , —C(O)N(R 3b )NR 3b R 3c , —S(O)R 3d , —S(O) 2 R 3a , —S(O) 2 NR 3b R 3c , —OR 3a , —OC(O)R 3d , —NR 3b R 3c , N(R 3b )C(O)R 3d , N(R 3b )SO 2 R 3d , N(R 3b )C(O)OR 3d , N(R 3b )C(O)NR 3b R 3c , N(R 3b )SO 2 NR 3b R 3c , and N(R 3b )C(NR 3b R 3c )═NR 3b R 3c ; 
         Y 2  is C(O), S(O) 2 , or CR 4 R 5 ; 
         R 4  is H, deuterium, C 1 -C 6  alkyl, halogen, or C 1 -C 6  haloalkyl; 
         R 5  is H, deuterium, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —C(O)R 5a , —C(O)OR 5a , —C(O)NR 5b R 5c , —S(O)R 5d , —S(O) 2 R 5a , —S(O) 2 NR 5b R 5c , or G 1 ; wherein the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, and C 2 -C 6  alkynyl are each independently unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of G 1 , —CN, —C(O)R 5a , —C(O)OR 5a , —C(O)NR 5b R 5c , —C(O)N(R 5b )NR 5b R 5c , —S(O)R 5d , —S(O) 2 R 5a , —S(O) 2 NR 5b R 5c , —OR 5a , —OC(O)R 5d , —NR 5b R 5c , N(R 5b )C(O)R 5d , N(R 5b )SO 2 R 5d , N(R 5b )C(O)OR 5d , N(R 5b )C(O)NR 5b R 5c , N(R 5b )SO 2 NR 5b R 5c , and N(R 5b )C(NR 5b R 5c )═NR 5b R 5c ; 
         R 3a , R 3b , R 3c , R 5a ,and R 5b , at each occurrence, are each independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 1 , or —(C 1 -C 6  alkylenyl)-G 1 ; 
         R 5c , at each occurrence, is independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 1 , —(C 1 -C 6  alkylenyl)-G 1 , —(C 1 -C 6  alkylenyl)-CN, —(C 1 -C 6  alkylenyl)-OR a , or —(C 1 -C 6  alkylenyl)-C(O)OR a ; 
         R 3d , at each occurrence, is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 1 , or —(C 1 -C 6  alkylenyl)-G 1 ; 
         R 5d , at each occurrence, is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 1 , —(C 1 -C 6  alkylenyl)-G 1 , —(C 1 -C 6  alkylenyl)-NR c R d , or —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ); 
         G 1 , at each occurrence, is independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl; and each G 1  is optionally substituted with 1, 2, 3, 4, or 5 R 1g  groups; 
         R 6  is H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —C(O)R 6a , —C(O)OR 6a , —C(O)NR 6b R 6c , —S(O) 2 R 6a , —S(O) 2 NR 6b R 6c , or G 2 ; wherein the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, and C 2 -C 6  alkynyl are each independently unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of G 2 , —CN, —C(O)R 6a , —C(O)OR 6a , —C(O)NR 6b R 6c , —C(O)N(R 6b )NR 6b R 6c , —S(O)R 6d , —S(O) 2 R 6a , —S(O) 2 NR 6b R 6c , —OR 6a , —OC(O)R 6d , —NR 6b R 6c , N(R 6b )C(O)R 6d , N(R 6b )SO 2 R 6d , N(R 6b )C(O)OR 6d , N(R 6b )C(O)NR 6b R 6c , N(R 6b )SO 2 NR 6b R 6c , and N(R 6b )C(NR 6b R 6c )—NR 6b R 6c ; 
         R 6a , R 6b , and R 6c , at each occurrence, are each independently H, alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, haloalkyl, G 2 , —(C 1 -C 6  alkylenyl)-G 2 , —(C 1 -C 6  alkylenyl)-OR a , —(C 1 -C 6  alkylenyl)-S(O) 2 R a , —(C 1 -C 6  alkylenyl)-S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-C(O)R a , —(C 1 -C 6  alkylenyl)-C(O)OR a , —(C 1 -C 6  alkylenyl)-C(O)NR c R d , —(C 1 -C 6  alkylenyl)-NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )C(O)R b , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 R b , —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ), —(C 1 -C 6  alkylenyl)-N(R e )C(O)NR c R d , or —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 NR c R d ; 
         R 6d , at each occurrence, is independently alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, haloalkyl, G 2 , —(C 1 -C 6  alkylenyl)-G 2 , —(C 1 -C 6  alkylenyl)-OR a , —(C 1 -C 6  alkylenyl)-S(O) 2 R a , —(C 1 -C 6  alkylenyl)-S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-C(O)R a , —(C 1 -C 6  alkylenyl)-C(O)OR a , —(C 1 -C 6  alkylenyl)-C(O)NR c R d , —(C 1 -C 6  alkylenyl)-NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )C(O)R b , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 R b , —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ), —(C 1 -C 6  alkylenyl)-N(R e )C(O)NR c R d , or —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 NR c R d ; 
         G 2 , at each occurrence, is independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl; and each G 2  is optionally substituted with 1, 2, 3, 4, or 5 R 2  groups; 
         A 1  is C(R 7 ) or N; A 2  is C(R 8 ) or N; A 3  is C(R 9 ) or N; and A 4  is C(R 10 ) or N; wherein zero, one, or two of A 1 , A 2 , A 3 , and A 4  are N; 
         R 7 , R 8 , and R 9 , are each independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —CN, NO 2 , —OR y1 , —OC(O)R y2 , —OC(O)NR y3 R y4 , —SR y1 , —S(O) 2 R y1 , —S(O) 2 NR y3 R y4 , —C(O)R y1 , —C(O)OR y1 , —C(O)NR y3 R y4 , —NR y3 R y4 , —N(R y3 )C(O)R y2 , —N(R y3 )S(O) 2 R y2 , —N(R y3 )C(O)O(R y2 ), —N(R y3 )C(O)NR y3 R y4 , —N(R y3 )S(O) 2 NR y3 R y4 , G 3 , —(C 1 -C 6  alkylenyl)-CN, —(C 1 -C 6  alkylenyl)-OR y1 , —(C 1 -C 6  alkylenyl)-OC(O)R y2 , —(C 1 -C 6  alkylenyl)-OC(O)NR y3 R y4 , —(C 1 -C 6  alkylenyl)-S(O) 2 R y1 , —(C 1 -C 6  alkylenyl)-S(O) 2 NR y3 R y4 , —(C 1 -C 6  alkylenyl)-C(O)R y1 , —(C 1 -C 6  alkylenyl)-C(O)OR y1 , —(C 1 -C 6  alkylenyl)-C(O)NR y3 R y4 , —(C 1 -C 6  alkylenyl)-NR y3 R y4 , —(C 1 -C 6  alkylenyl)-N(R y3 )C(O)R y2 , —(C 1 -C 6  alkylenyl)-N(R y3 )S(O) 2 R y2 , —(C 1 -C 6  alkylenyl)-N(R y3 )C(O)O(R y2 ), —(C 1 -C 6  alkylenyl)-N(R y3 )C(O)NR y3 R y4 , —(C 1 -C 6  alkylenyl)-N(R y3 )S(O) 2 NR y3 R y4 , —(C 1 -C 6  alkylenyl)-CN, or —(C 1 -C 6  alkylenyl)-G 3 ; 
         R y1 , R y3 , and R y4 , at each occurrence, are each independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 3 , —(C 1 -C 6  alkylenyl)-G 3 , —(C 1 -C 6  alkylenyl)-OR a , —(C 1 -C 6  alkylenyl)-S(O) 2 R a , —(C 1 -C 6  alkylenyl)-S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-C(O)R a , —(C 1 -C 6  alkylenyl)-C(O)OR a , —(C 1 -C 6  alkylenyl)-C(O)NR c R d , —(C 1 -C 6  alkylenyl)-NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )C(O)R b , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 R b , —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ), —(C 1 -C 6  alkylenyl)-N(R e )C(O)NR c R d , or —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 NR c R d ; 
         R y2 , at each occurrence, is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 3 , —(C 1 -C 6  alkylenyl)-G 3 , —(C 1 -C 6  alkylenyl)-OR a , —(C 1 -C 6  alkylenyl)-S(O) 2 R a , —(C 1 -C 6  alkylenyl)-S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-C(O)R a , —(C 1 -C 6  alkylenyl)-C(O)OR a , —(C 1 -C 6  alkylenyl)-C(O)NR c R d , —(C 1 -C 6  alkylenyl)-NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )C(O)R b , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 R b , —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ), —(C 1 -C 6  alkylenyl)-N(R e )C(O)NR c R d , or —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 NR c R d ; 
         G 3 , at each occurrence, is independently aryl, heteroaryl, cycloalkyl, cycloalkenyl, or heterocycle; and each G 3  group is optionally substituted with 1, 2, 3, 4, or 5 R 4g  groups; 
         R 10  is H, C 1 -C 3  alkyl, halogen, C 1 -C 3  haloalkyl, or —CN; 
         R 1g , R 2g , and R 4g , at each occurrence, is independently selected from the group consisting of oxo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —CN, NO 2 , G 2a , —OR a , —OC(O)R b , —OC(O)NR c R d , —SR a , —S(O) 2 R a , —S(O) 2 NR c R d , —C(O)R a , —C(O)OR a , —C(O)NR c R d , —NR c R d , —N(R e )C(O)R b , —N(R e )S(O) 2 R b , —N(R e )C(O)O(R b ), —N(R e )C(O)NR c R d , —N(R e )S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-CN, —(C 1 -C 6  alkylenyl)-G 2a , —(C 1 -C 6  alkylenyl)-OR a , —(C 1 -C 6  alkylenyl)-OC(O)R b , —(C 1 -C 6  alkylenyl)-OC(O)NR c R d , —(C 1 -C 6  alkylenyl)-S(O) 2 R a , —(C 1 -C 6  alkylenyl)-S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-C(O)R a , —(C 1 -C 6  alkylenyl)-C(O)OR a , —(C 1 -C 6  alkylenyl)-C(O)NR c R d , —(C 1 -C 6  alkylenyl)-NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )C(O)R b , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 R b , —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ), —(C 1 -C 6  alkylenyl)-N(R e )C(O)NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 NR c R d , or —(C 1 -C 6  alkylenyl)-CN; 
         R a , R c , R d , and R e , at each occurrence, are each independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 2a , —(C 1 -C 6  alkylenyl)-OR z1 , —(C 1 -C 6  alkylenyl)-NR z3 R z4 , —(C 1 -C 6  alkylenyl)-C(O)NR z3 R z4 , or —(C 1 -C 6  alkylenyl)-G 2a ; 
         R b , at each occurrence, is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 2a , or —(C 1 -C 6  alkylenyl)-G 2a ; 
         G 2a , at each occurrence, are each independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl; and each G 2a  group is optionally substituted with 1, 2, 3, 4, or 5 R 3g  groups; 
         R 3g , at each occurrence, is independently oxo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —CN, NO 2 , —OR z1 , —OC(O)R z2 , —OC(O)NR z3 R z4 , —SR z1 , —S(O) 2 R z1 , —S(O) 2 NR z3 R z4 , —C(O)R z1 , —C(O)OR z1 , —C(O)NR z3 R z4 , —NR z3 R z4 , —N(R z3 )C(O)R z2 , —N(R z3 )S(O) 2 R z2 , —N(R z3 )C(O)O(R z2 ), —N(R z3 )C(O)NR z3 R z4 , —N(R z3 )S(O) 2 NR z3 R z4 , —(C 1 -C 6  alkylenyl)-OR z1 , —(C 1 -C 6  alkylenyl)-OC(O)R z2 , —(C 1 -C 6  alkylenyl)-OC(O)NR z3 R z4 , —(C 1 -C 6  alkylenyl)-S(O) 2 R z1 , —(C 1 -C 6  alkylenyl)-S(O) 2 NR z3 R z4 , —(C 1 -C 6  alkylenyl)-C(O)R z1 , —(C 1 -C 6  alkylenyl)-C(O)OR z1 , —(C 1 -C 6  alkylenyl)-C(O)NR z3 R z4 , —(C 1 -C 6  alkylenyl)-NR z3 R z4 , —(C 1 -C 6  alkylenyl)-N(R z3 )C(O)R z2 , —(C 1 -C 6  alkylenyl)-N(R z3 )S(O) 2 R z2 , —(C 1 -C 6  alkylenyl)-N(R z3 )C(O)O(R z2 ), —(C 1 -C 6  alkylenyl)-N(R z3 )C(O)NR z3 R z4 , —(C 1 -C 6  alkylenyl)-N(R z3 )S(O) 2 NR z3 R z4  or —(C 1 -C 6  alkylenyl)-CN; 
         R z1 , R z3 , and R z4 , at each occurrence, are each independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, or C 1 -C 6  haloalkyl; and 
         R z2 , at each occurrence, is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, or C 1 -C 6  haloalkyl. 
       
     
     
         2 .- 33 . (canceled) 
     
     
         34 . A compound of formula (I) or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
         wherein 
         Y 1  is N or CH; 
         R 1  is CD 3 , C 1 -C 3  alkyl, or C 1 -C 3  haloalkyl; 
         R 2  is H or C 1 -C 3  alkyl; 
         Y 3  is N or CR 3 ; 
         R 3  is H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —C(O)R 3a , —C(O)OR 3a , —C(O)NR 3b R 3c , —S(O)R 3d , —S(O) 2 R 3a , —S(O) 2 NR 3b R 3c , or G 1 ; wherein the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, and C 2 -C 6  alkynyl are each independently unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of G 1 , —C(O)R 3a , —C(O)OR 3a , —C(O)NR 3b R 3c , —C(O)N(R 3b )NR 3b R 3c , —S(O)R 3d , —S(O) 2 R 3a , —S(O) 2 NR 3b R 3c , —OR 3a , —OC(O)R 3d , —NR 3b R 3c , N(R 3b )C(O)R 3d , N(R 3b )SO 2 R 3d , N(R 3b )C(O)OR 3d , N(R 3b )C(O)NR 3b R 3c , N(R 3b )SO 2 NR 3b R 3c , and N(R 3b )C(NR 3b R 3c )═NR 3b R 3c ; 
         Y 2  is C(O), S(O) 2 , or CR 4 R 5 ; 
         R 4  is H, deuterium, C 1 -C 6  alkyl, halogen, or C 1 -C 6  haloalkyl; 
         R 5  is H, deuterium, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —C(O)R 5a , —C(O)OR 5a , C(O)NR 5b R 5c , —S(O)R 5d , —S(O) 2 R 5a , S(O) 2 NR 5b R 5c , or G 1 ; wherein the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, and C 2 -C 6  alkynyl are each independently unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of G 1 , —C(O)R 5a , —C(O)OR 5a , —C(O)NR 5b R 5c , —C(O)N(R 5b )NR 5b R 5c , —S(O)R 5d , —S(O) 2 R 5a , —S(O) 2 NR 5b R 5c , —OR 5a , —OC(O)R 5d , —NR 5b R 5c , N(R 5b )C(O)R 5d , N(R 5b )SO 2 R 5d , N(R 5b )C(O)OR 5d , N(R 5b )C(O)NR 5b R 5c , N(R 5b )SO 2 NR 5b R 5c , and N(R 5b )C(NR 5b R 5c )═NR 5b R 5c ; 
         R 3a , R 3b , R 3c , R 5a , R 5b , and R 5c , at each occurrence, are each independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 1 , or —(C 1 -C 6  alkylenyl)-G 1 ; 
         R 3d  and R 5d , at each occurrence, are each independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 1 , or —(C 1 -C 6  alkylenyl)-G 1 ; 
         G 1 , at each occurrence, is independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl; and each G 1  is optionally substituted with 1, 2, 3, 4, or 5 R 1g  groups; 
         R 6  is H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —C(O)R 6a , —C(O)OR 6a , —C(O)NR 6b R 6c , —S(O) 2 R 6a , —S(O) 2 NR 6b R 6c , or G 2 ; wherein the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, and C 2 -C 6  alkynyl are each independently unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of G 2 , —C(O)R 6a , —C(O)OR 6a , —C(O)NR 6b R 6c , —C(O)N(R 6b )NR 6b R 6c , —S(O)R 6d , —S(O) 2 R 6a , —S(O) 2 NR 6b R 6c , —OR 6a , —OC(O)R 6d , —NR 6b R 6c , N(R 6b )C(O)R 6d , N(R 6b )SO 2 R 6d , N(R 6b )C(O)OR 6d , N(R 6b )C(O)NR 6b R 6c , N(R 6b )SO 2 NR 6b R 6c , and N(R 6b )C(NR 6b R 6c )═NR 6b R 6c ; 
         R 6a , R 6b , and R 6c , at each occurrence, are each independently H, alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, haloalkyl, G 2 , —(C 1 -C 6  alkylenyl)-G 2 , —(C 1 -C 6  alkylenyl)-OR a , —(C 1 -C 6  alkylenyl)-S(O) 2 R a , —(C 1 -C 6  alkylenyl)-S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-C(O)R a , —(C 1 -C 6  alkylenyl)-C(O)OR a , —(C 1 -C 6  alkylenyl)-C(O)NR c R d , —(C 1 -C 6  alkylenyl)-NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )C(O)R b , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 R b , —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ), —(C 1 -C 6  alkylenyl)-N(R e )C(O)NR c R d , or —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 NR c R d ; 
         R 6d , at each occurrence, is independently alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, haloalkyl, G 2 , —(C 1 -C 6  alkylenyl)-G 2 , —(C 1 -C 6  alkylenyl)-OR a , —(C 1 -C 6  alkylenyl)-S(O) 2 R a , —(C 1 -C 6  alkylenyl)-S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-C(O)R a , —(C 1 -C 6  alkylenyl)-C(O)OR a , —(C 1 -C 6  alkylenyl)-C(O)NR c R d , —(C 1 -C 6  alkylenyl)-NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )C(O)R b , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 R b , —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ), —(C 1 -C 6  alkylenyl)-N(R e )C(O)NR c R d , or —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 NR c R d ; 
         G 2 , at each occurrence, is independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl; and each G 2  is optionally substituted with 1, 2, 3, 4, or 5 R 2  groups; 
         A 1  is C(R 7 ) or N; A 2  is C(R 8 ) or N; A 3  is C(R 9 ) or N; and A 4  is C(R 10 ) or N; wherein zero, one, or two of A 1 , A 2 , A 3 , and A 4  are N; 
         R 7 , R 8 , and R 9 , are each independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —CN, NO 2 , —OR y1 , —OC(O)R y2 , —OC(O)NR y3 R y4 , —SR y1 , —S(O) 2 R y1 , —S(O) 2 NR y3 R y4 , —C(O)R y1 , —C(O)OR y1 , —C(O)NR y3 R y4 , —NR y3 R y4 , —N(R y3 )C(O)R y2 , —N(R y3 )S(O) 2 R y2 , —N(R y3 )C(O)O(R y2 ), —N(R y3 )C(O)NR y3 R y4 , —N(R y3 )S(O) 2 NR y3 R y4 , G 3 , —(C 1 -C 6  alkylenyl)-CN, —(C 1 -C 6  alkylenyl)-OR y1 , —(C 1 -C 6  alkylenyl)-OC(O)R y2 , —(C 1 -C 6  alkylenyl)-OC(O)NR y3 R y4 , —(C 1 -C 6  alkylenyl)-S(O) 2 R y1 , —(C 1 -C 6  alkylenyl)-S(O) 2 NR y3 R y4 , —(C 1 -C 6  alkylenyl)-C(O)R y1 , —(C 1 -C 6  alkylenyl)-C(O)OR y1 , —(C 1 -C 6  alkylenyl)-C(O)NR y3 R y4 , —(C 1 -C 6  alkylenyl)-NR y3 R y4 , —(C 1 -C 6  alkylenyl)-N(R y3 )C(O)R y2 , —(C 1 -C 6  alkylenyl)-N(R y3 )S(O) 2 R y2 , —(C 1 -C 6  alkylenyl)-N(R y3 )C(O)O(R y2 ), —(C 1 -C 6  alkylenyl)-N(R y3 )C(O)NR y3 R y4 , —(C 1 -C 6  alkylenyl)-N(R y3 )S(O) 2 NR y3 R y4 , —(C 1 -C 6  alkylenyl)-CN, or —(C 1 -C 6  alkylenyl)-G 3 ; 
         R y1 , R y3 , and R y4 , at each occurrence, are each independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 3 , —(C 1 -C 6  alkylenyl)-G 3 , —(C 1 -C 6  alkylenyl)-OR a , —(C 1 -C 6  alkylenyl)-S(O) 2 R a , —(C 1 -C 6  alkylenyl)-S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-C(O)R a , —(C 1 -C 6  alkylenyl)-C(O)OR a , —(C 1 -C 6  alkylenyl)-C(O)NR c R d , —(C 1 -C 6  alkylenyl)-NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )C(O)R b , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 R b , —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ), —(C 1 -C 6  alkylenyl)-N(R e )C(O)NR c R d , or —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 NR c R d ; 
         R y2 , at each occurrence, is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 3 , —(C 1 -C 6  alkylenyl)-G 3 , —(C 1 -C 6  alkylenyl)-OR a , —(C 1 -C 6  alkylenyl)-S(O) 2 R a , —(C 1 -C 6  alkylenyl)-S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-C(O)R a , —(C 1 -C 6  alkylenyl)-C(O)OR a , —(C 1 -C 6  alkylenyl)-C(O)NR c R d , —(C 1 -C 6  alkylenyl)-NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )C(O)R b , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 R b , —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ), —(C 1 -C 6  alkylenyl)-N(R e )C(O)NR c R d , or —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 NR c R d ; 
         G 3 , at each occurrence, is independently aryl, heteroaryl, cycloalkyl, cycloalkenyl, or heterocycle; and each G 3  group is optionally substituted with 1, 2, 3, 4, or 5 R 4g  groups; 
         R 10  is H, C 1 -C 3  alkyl, halogen, C 1 -C 3  haloalkyl, or —CN; 
         R 1g , R 2g , and R 4g , at each occurrence, is independently selected from the group consisting of oxo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —CN, NO 2 , G 2a , —OR a , —OC(O)R b , —OC(O)NR c R d , —SR a , —S(O) 2 R a , —S(O) 2 NR c R d , —C(O)R a , —C(O)OR a , —C(O)NR c R d , —NR c R d , —N(R e )C(O)R b , —N(R e )S(O) 2 R b , —N(R e )C(O)O(R b ), —N(R e )C(O)NR c R d , —N(R e )S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-CN, —(C 1 -C 6  alkylenyl)-G 2a , —(C 1 -C 6  alkylenyl)-OR a , —(C 1 -C 6  alkylenyl)-OC(O)R b , —(C 1 -C 6  alkylenyl)-OC(O)NR c R d , —(C 1 -C 6  alkylenyl)-S(O) 2 R a , —(C 1 -C 6  alkylenyl)-S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-C(O)R a , —(C 1 -C 6  alkylenyl)-C(O)OR a , —(C 1 -C 6  alkylenyl)-C(O)NR c R d , —(C 1 -C 6  alkylenyl)-NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )C(O)R b , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 R b , —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ), —(C 1 -C 6  alkylenyl)-N(R e )C(O)NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 NR c R d , or —(C 1 -C 6  alkylenyl)-CN; 
         R a , R c , R d , and R e , at each occurrence, are each independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 2 , or —(C 1 -C 6  alkylenyl)-G 2a ; 
         R b , at each occurrence, is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 2a , or —(C 1 -C 6  alkylenyl)-G 2a ; 
         G 2a , at each occurrence, are each independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl; and each G 2a  group is optionally substituted with 1, 2, 3, 4, or 5 R 3g  groups; 
         R 3g , at each occurrence, is independently oxo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —CN, NO 2 , —OR z1 , —OC(O)R z2 , —OC(O)NR z3 R z4 , —SR z1 , —S(O) 2 R z1 , —S(O) 2 NR z3 R z4 , —C(O)R z1 , —C(O)OR z1 , —C(O)NR z3 R z4 , —NR z3 R z4 , —N(R z3 )C(O)R z2 , —N(R z3 )S(O) 2 R z2 , —N(R z3 )C(O)O(R z2 ), —N(R z3 )C(O)NR z3 R z4 , —N(R z3 )S(O) 2 NR z3 R z4 , —(C 1 -C 6  alkylenyl)-OR z1 , —(C 1 -C 6  alkylenyl)-OC(O)R z2 , —(C 1 -C 6  alkylenyl)-OC(O)NR z3 R z4 , —(C 1 -C 6  alkylenyl)-S(O) 2 R z1 , —(C 1 -C 6  alkylenyl)-S(O) 2 NR z3 R z4 , —(C 1 -C 6  alkylenyl)-C(O)R z1 , —(C 1 -C 6  alkylenyl)-C(O)OR z1 , —(C 1 -C 6  alkylenyl)-C(O)NR z3 R z4 , —(C 1 -C 6  alkylenyl)-NR z3 R z4 , —(C 1 -C 6  alkylenyl)-N(R z3 )C(O)R z2 , —(C 1 -C 6  alkylenyl)-N(R z3 )S(O) 2 R z2 , —(C 1 -C 6  alkylenyl)-N(R z3 )C(O)O(R z2 ), —(C 1 -C 6  alkylenyl)-N(R z3 )C(O)NR z3 R z4 , —(C 1 -C 6  alkylenyl)-N(R z3 )S(O) 2 NR z3 R z4  or —(C 1 -C 6  alkylenyl)-CN; 
         R z1 , R z3 , and R z4 , at each occurrence, are each independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, or C 1 -C 6  haloalkyl; and 
         R z2 , at each occurrence, is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, or C 1 -C 6  haloalkyl. 
       
     
     
         35 . A compound of formula (I) or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
         wherein 
         Y 1  is N or CH; 
         R 1  is CD 3 , C 1 -C 3  alkyl, or C 1 -C 3  haloalkyl; 
         R 2  is H or C 1 -C 3  alkyl; 
         Y 3  is N or CR 3 ; 
         R 3  is H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —CN, —C(O)R 3a , —C(O)OR 3a , —C(O)NR 3b R 3c , —S(O)R 3d , —S(O) 2 R 3a , —S(O) 2 NR 3b R 3c , or G 1 ; wherein the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, and C 2 -C 6  alkynyl are each independently unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of G 1 , —CN, —C(O)R 3a , —C(O)OR 3a , —C(O)NR 3b R 3c , —C(O)N(R 3b )NR 3b R 3c , —S(O)R 3d , —S(O) 2 R 3a , —S(O) 2 NR 3b R 3c , —OR 3a , —OC(O)R 3d , —NR 3b R 3c , N(R 3b )C(O)R 3d , N(R 3b )SO 2 R 3d , N(R 3b )C(O)OR 3d , N(R 3b )C(O)NR 3b R 3c , N(R 3b )SO 2 NR 3b R 3c , and N(R 3b )C(NR 3b R 3c )═NR 3b R 3c ; 
         Y 2  is C(O), S(O) 2 , or CR 4 R 5 ; 
         R 4  is H, deuterium, C 1 -C 6  alkyl, halogen, or C 1 -C 6  haloalkyl; 
         R 5  is H, deuterium, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —C(O)R 5a , —C(O)OR 5a , C(O)NR 5b R 5c , —S(O)R 5d , —S(O) 2 R 5a , S(O) 2 NR 5b R 5c , or G 1 ; wherein the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, and C 2 -C 6  alkynyl are each independently unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of G 1 , —C(O)R 5a , —C(O)OR 5a , —C(O)NR 5b R 5c , —C(O)N(R 5b )NR 5b R 5c , —S(O)R 5d , —S(O) 2 R 5a , —S(O) 2 NR 5b R 5c , —OR 5a , —OC(O)R 5d , —NR 5b R 5c , N(R 5b )C(O)R 5d , N(R 5b )SO 2 R 5d , N(R 5b )C(O)OR 5d , N(R 5b )C(O)NR 5b R 5c , N(R 5b )SO 2 NR 5b R 5c , and N(R 5b )C(NR 5b R 5c )═NR 5b R 5c ; 
         R 3a , R 3b , R 3c , R 5a ,and R 5b , at each occurrence, are each independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 1 , or —(C 1 -C 6  alkylenyl)-G 1 ; 
         R 5c , at each occurrence, is independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 1 , —(C 1 -C 6  alkylenyl)-G 1 , —(C 1 -C 6  alkylenyl)-CN, —(C 1 -C 6  alkylenyl)-OR a , or —(C 1 -C 6  alkylenyl)-C(O)OR a ; 
         R 3d , at each occurrence, is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 1 , or —(C 1 -C 6  alkylenyl)-G 1 ; 
         R 5d , at each occurrence, is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 1 , —(C 1 -C 6  alkylenyl)-G 1 , —(C 1 -C 6  alkylenyl)-NR c R d , or —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ); 
         G 1 , at each occurrence, is independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl; and each G 1  is optionally substituted with 1, 2, 3, 4, or 5 R 1g  groups; 
         R 6  is H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —C(O)R 6a , —C(O)OR 6a , —C(O)NR 6b R 6c , —S(O) 2 R 6a , —S(O) 2 NR 6b R 6c , or G 2 ; wherein the C 1 -C 6  alkyl, C 2 -C 6  alkenyl, and C 2 -C 6  alkynyl are each independently unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of G 2 , —C(O)R 6a , —C(O)OR 6a , —C(O)NR 6b R 6c , —C(O)N(R 6b )NR 6b R 6c , —S(O)R 6d , —S(O) 2 R 6a , —S(O) 2 NR 6b R 6c , —OR 6a , —OC(O)R 6d , —NR 6b R 6c , N(R 6b )C(O)R 6d , N(R 6b )SO 2 R 6d , N(R 6b )C(O)OR 6d , N(R 6b )C(O)NR 6b R 6c , N(R 6b )SO 2 NR 6b R 6c , and N(R 6b )C(NR 6b R 6c )—NR 6b R 6c ; 
         R 6a , R 6b , and R 6c , at each occurrence, are each independently H, alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, haloalkyl, G 2 , —(C 1 -C 6  alkylenyl)-G 2 , —(C 1 -C 6  alkylenyl)-OR a , —(C 1 -C 6  alkylenyl)-S(O) 2 R a , —(C 1 -C 6  alkylenyl)-S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-C(O)R a , —(C 1 -C 6  alkylenyl)-C(O)OR a , —(C 1 -C 6  alkylenyl)-C(O)NR c R d , —(C 1 -C 6  alkylenyl)-NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )C(O)R b , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 R b , —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ), —(C 1 -C 6  alkylenyl)-N(R e )C(O)NR c R d , or —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 NR c R d ; 
         R 6d , at each occurrence, is independently alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, haloalkyl, G 2 , —(C 1 -C 6  alkylenyl)-G 2 , —(C 1 -C 6  alkylenyl)-OR a , —(C 1 -C 6  alkylenyl)-S(O) 2 R a , —(C 1 -C 6  alkylenyl)-S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-C(O)R a , —(C 1 -C 6  alkylenyl)-C(O)OR a , —(C 1 -C 6  alkylenyl)-C(O)NR c R d , —(C 1 -C 6  alkylenyl)-NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )C(O)R b , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 R b , —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ), —(C 1 -C 6  alkylenyl)-N(R e )C(O)NR c R d , or —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 NR c R d ; 
         G 2 , at each occurrence, is independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl; and each G 2  is optionally substituted with 1, 2, 3, 4, or 5 R 2g  groups; 
         A 1  is C(R 7 ) or N; A 2  is C(R 8 ) or N; A 3  is C(R 9 ) or N; and A 4  is C(R 10 ) or N; wherein zero, one, or two of A 1 , A 2 , A 3 , and A 4  are N; 
         R 7 , R 8 , and R 9 , are each independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —CN, NO 2 , —OR y1 , —OC(O)R y2 , —OC(O)NR y3 R y4 , —SR y1 , —S(O) 2 R y1 , —S(O) 2 NR y3 R y4 , —C(O)R y1 , —C(O)OR y1 , —C(O)NR y3 R y4 , —NR y3 R y4 , —N(R y3 )C(O)R y2 , —N(R y3 )S(O) 2 R y2 , —N(R y3 )C(O)O(R y2 ), —N(R y3 )C(O)NR y3 R y4 , —N(R y3 )S(O) 2 NR y3 R y4 , G 3 , —(C 1 -C 6  alkylenyl)-CN, —(C 1 -C 6  alkylenyl)-OR y1 , —(C 1 -C 6  alkylenyl)-OC(O)R y2 , —(C 1 -C 6  alkylenyl)-OC(O)NR y3 R y4 , —(C 1 -C 6  alkylenyl)-S(O) 2 R y1 , —(C 1 -C 6  alkylenyl)-S(O) 2 NR y3 R y4 , —(C 1 -C 6  alkylenyl)-C(O)R y1 , —(C 1 -C 6  alkylenyl)-C(O)OR y1 , —(C 1 -C 6  alkylenyl)-C(O)NR y3 R y4 , —(C 1 -C 6  alkylenyl)-NR y3 R y4 , —(C 1 -C 6  alkylenyl)-N(R y3 )C(O)R y2 , —(C 1 -C 6  alkylenyl)-N(R y3 )S(O) 2 R y2 , —(C 1 -C 6  alkylenyl)-N(R y3 )C(O)O(R y2 ), —(C 1 -C 6  alkylenyl)-N(R y3 )C(O)NR y3 R y4 , —(C 1 -C 6  alkylenyl)-N(R y3 )S(O) 2 NR y3 R y4 , —(C 1 -C 6  alkylenyl)-CN, or —(C 1 -C 6  alkylenyl)-G 3 ; 
         R y1 , R y3 , and R y4 , at each occurrence, are each independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 3 , —(C 1 -C 6  alkylenyl)-G 3 , —(C 1 -C 6  alkylenyl)-OR a , —(C 1 -C 6  alkylenyl)-S(O) 2 R a , —(C 1 -C 6  alkylenyl)-S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-C(O)R a , —(C 1 -C 6  alkylenyl)-C(O)OR a , —(C 1 -C 6  alkylenyl)-C(O)NR c R d , —(C 1 -C 6  alkylenyl)-NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )C(O)R b , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 R b , —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ), —(C 1 -C 6  alkylenyl)-N(R e )C(O)NR c R d , or —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 NR c R d ; 
         R y2 , at each occurrence, is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 3 , —(C 1 -C 6  alkylenyl)-G 3 , —(C 1 -C 6  alkylenyl)-OR a , —(C 1 -C 6  alkylenyl)-S(O) 2 R a , —(C 1 -C 6  alkylenyl)-S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-C(O)R a , —(C 1 -C 6  alkylenyl)-C(O)OR a , —(C 1 -C 6  alkylenyl)-C(O)NR c R d , —(C 1 -C 6  alkylenyl)-NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )C(O)R b , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 R b , —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ), —(C 1 -C 6  alkylenyl)-N(R e )C(O)NR c R d , or —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 NR c R d ; 
         G 3 , at each occurrence, is independently aryl, heteroaryl, cycloalkyl, cycloalkenyl, or heterocycle; and each G 3  group is optionally substituted with 1, 2, 3, 4, or 5 R 4g  groups; 
         R 10  is H, C 1 -C 3  alkyl, halogen, C 1 -C 3  haloalkyl, or —CN; 
         R 1g , R 2g , and R 4g , at each occurrence, is independently selected from the group consisting of oxo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —CN, NO 2 , G 2a , —OR a , —OC(O)R b , —OC(O)NR c R d , —SR a , —S(O) 2 R a , —S(O) 2 NR c R d , —C(O)R a , —C(O)OR a , —C(O)NR c R d , —NR c R d , —N(R e )C(O)R b , —N(R e )S(O) 2 R b , —N(R e )C(O)O(R b ), —N(R e )C(O)NR c R d , —N(R e )S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-CN, —(C 1 -C 6  alkylenyl)-G 2a , —(C 1 -C 6  alkylenyl)-OR a , —(C 1 -C 6  alkylenyl)-OC(O)R b , —(C 1 -C 6  alkylenyl)-OC(O)NR c R d , —(C 1 -C 6  alkylenyl)-S(O) 2 R a , —(C 1 -C 6  alkylenyl)-S(O) 2 NR c R d , —(C 1 -C 6  alkylenyl)-C(O)R a , —(C 1 -C 6  alkylenyl)-C(O)OR a , —(C 1 -C 6  alkylenyl)-C(O)NR c R d , —(C 1 -C 6  alkylenyl)-NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )C(O)R b , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 R b , —(C 1 -C 6  alkylenyl)-N(R e )C(O)O(R b ), —(C 1 -C 6  alkylenyl)-N(R e )C(O)NR c R d , —(C 1 -C 6  alkylenyl)-N(R e )S(O) 2 NR c R d , or —(C 1 -C 6  alkylenyl)-CN; 
         R a , R c , R d , and R e , at each occurrence, are each independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 2a , or —(C 1 -C 6  alkylenyl)-G 2a ; 
         R b , at each occurrence, is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, G 2a , or —(C 1 -C 6  alkylenyl)-G 2a ; 
         G 2a , at each occurrence, are each independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl; and each G 2a  group is optionally substituted with 1, 2, 3, 4, or 5 R 39  groups; 
         R 3g , at each occurrence, is independently oxo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, halogen, C 1 -C 6  haloalkyl, —CN, NO 2 , —OR z1 , —OC(O)R z2 , —OC(O)NR z3 R z4 , —SR z1 , —S(O) 2 R z1 , —S(O) 2 NR z3 R z4 , —C(O)R z1 , —C(O)OR z1 , —C(O)NR z3 R z4 , —NR z3 R z4 , —N(R z3 )C(O)R z2 , —N(R z3 )S(O) 2 R z2 , —N(R z3 )C(O)O(R z2 ), —N(R z3 )C(O)NR z3 R z4 , —N(R z3 )S(O) 2 NR z3 R z4 , —(C 1 -C 6  alkylenyl)-OR z1 , —(C 1 -C 6  alkylenyl)-OC(O)R z2 , —(C 1 -C 6  alkylenyl)-OC(O)NR z3 R z4 , —(C 1 -C 6  alkylenyl)-S(O) 2 R z1 , —(C 1 -C 6  alkylenyl)-S(O) 2 NR z3 R z4 , —(C 1 -C 6  alkylenyl)-C(O)R z1 , —(C 1 -C 6  alkylenyl)-C(O)OR z1 , —(C 1 -C 6  alkylenyl)-C(O)NR z3 R z4 , —(C 1 -C 6  alkylenyl)-NR z3 R z4 , —(C 1 -C 6  alkylenyl)-N(R z3 )C(O)R z2 , —(C 1 -C 6  alkylenyl)-N(R z3 )S(O) 2 R z2 , —(C 1 -C 6  alkylenyl)-N(R z3 )C(O)O(R z2 ), —(C 1 -C 6  alkylenyl)-N(R z3 )C(O)NR z3 R z4 , —(C 1 -C 6  alkylenyl)-N(R z3 )S(O) 2 NR z3 R z4  or —(C 1 -C 6  alkylenyl)-CN; 
         R z1 , R z3 , and R z4 , at each occurrence, are each independently H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, or C 1 -C 6  haloalkyl; and 
         R z2 , at each occurrence, is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, or C 1 -C 6  haloalkyl. 
       
     
     
         36 .- 47 . (canceled)

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