Substituted 1,4,10-triazadibenzo[cd,f]azulenes, substituted 1,4,5,10-tetraazadibenzo[cd,f]azulenes and substituted 1,4,5,7,10-pentaazadibenzo[cd,f]azulenes as bromodomain inhibitors

Patent metadata

Field	Value
Publication number	US-10035800-B2
Application number	US-201414774866-A
Country	US
Kind code	B2
Filing date	Mar 12, 2014
Priority date	Mar 12, 2013
Publication date	Jul 31, 2018
Grant date	Jul 31, 2018

Abstract

The present invention provides for compounds of formula (I) wherein R 1 , R 2 , R 6 , Y 1 , 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).

First claim

The invention claimed is:

1. A compound of formula (I),

or a pharmaceutically acceptable salt thereof,
wherein:
formula (I) is selected from the group consisting of:

wherein:
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;
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 optionally and independently substituted with one or two 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 )S(O) 2 R 3d , N(R 3b )C(O)OR 3d , N(R 3b )C(O)NR 3b R 3c , N(R 3b )S(O) 2 NR 3b R 3c and N(R 3b )C(NR 3b R 3c )═NR 3b R 3c ;
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 optionally and independently substituted with one or two 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 )S(O) 2 R 5d , N(R 5b )C(O)OR 5d , N(R 5b )C(O)NR 5b R 5c , N(R 5b )S(O) 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, heterocyclyl, cycloalkyl or cycloalkenyl, wherein each G 1 is optionally substituted with one, two, three, four or five 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 optionally and independently substituted with one or two 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 )S(O) 2 R 6d , N(R 6b )C(O)OR 6d , N(R 6b )C(O)NR 6b R 6c , N(R 6b )S(O) 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, heterocyclyl, cycloalkyl or cycloalkenyl, wherein each G 2 is optionally substituted with one, two, three, four or five R 2g groups;
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, heterocyclyl, cycloalkyl or cycloalkenyl, wherein each G 3 group is optionally substituted with one, two, three, four or five 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(

Assignees

• Abbvie Inc

Inventors

• Fidanze Steven D
• Liu Dauchun
• Mantei Robert A
• Mcdaniel Keith F
• PRATT John
• Sheppard George S
• Wang Le
• Bogdan Andrew
• Holms James H
• Dietrich Justin D
• Marjanovic Jasmina
• Hasvold Lisa A
• Dai Yujia

Classifications

• A61P15/16

  Masculine contraceptives · CPC title

• A61P13/12

  of the kidneys · CPC title

• A61P31/18

  for HIV · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D471/22 Primary

  in which the condensed systems contains four or more hetero rings · CPC title