US2019389861A1PendingUtilityA1
Tetracyclic bromodomain inhibitors
Est. expiryMar 12, 2033(~6.6 yrs left)· nominal 20-yr term from priority
Inventors:Steven D. FidanzeDachun LiuRobert A. ManteiKeith F. McdanielJohn K. PrattGeorge S. SheppardLe WangAndrew BogdanJames H. HolmsJustin D. DietrichJasmina MarjanovicLisa A. HasvoldYujia Dai
A61P 35/00A61P 13/12A61P 15/16A61P 31/18C07D 498/14C07D 471/22C07D 471/16C07D 498/04C07D 498/16
63
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Claims
Abstract
wherein R1, R2, R6, Y1, Y2, Y3, A1, A2, A3, and A4 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-modified1 . A compound of formula (I) or a pharmaceutically acceptable salt thereof,
wherein
Y 1 is N or CH;
R 1 is CD3, 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 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 2 , —(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 4 , —(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 2 a, —(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 4 , or —(C 1 -C 6 alkylenyl)-G 2 a;
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 2 ), —(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 CD3, 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 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 4 , —(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 2 a, —(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 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 2 ), —(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 CD3, 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 5b ), —(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 2 , —(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 2 a, —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 R d , —N(R e )S(O) 2 NR c R d , —(C 1 -C 6 alkylenyl)-CN, —(C 1 -C 6 alkylenyl)-G 2 a, —(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 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.
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