US 11,884,680 B2
Bromodomain inhibitors
Amogh Boloor, San Diego, CA (US)
Assigned to Celgene Quanticel Research, Inc., San Diego, CA (US)
Filed by CELGENE QUANTICEL RESEARCH, INC., San Diego, CA (US)
Filed on Dec. 31, 2020, as Appl. No. 17/139,963.
Application 16/744,080 is a division of application No. 15/990,576, filed on May 25, 2018, granted, now 10,562,915.
Application 15/436,340 is a division of application No. 14/789,881, filed on Jul. 1, 2015, granted, now 9,598,372.
Application 17/139,963 is a continuation of application No. 16/744,080, filed on Jan. 15, 2020, granted, now 10,941,160.
Application 15/990,576 is a continuation of application No. 15/436,340, filed on Feb. 17, 2017, granted, now 10,023,592.
Application 14/789,881 is a continuation of application No. 14/658,048, filed on Mar. 13, 2015, granted, now 9,115,114.
Application 14/658,048 is a continuation of application No. 14/517,705, filed on Oct. 17, 2014, granted, now 9,034,900.
Claims priority of provisional application 61/931,467, filed on Jan. 24, 2014.
Claims priority of provisional application 61/893,133, filed on Oct. 18, 2013.
Prior Publication US 2022/0315601 A1, Oct. 6, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 498/04 (2006.01); C07D 217/24 (2006.01); C07D 413/04 (2006.01); C07D 401/04 (2006.01); C07D 471/04 (2006.01); C07D 405/04 (2006.01); C07D 487/04 (2006.01); C07D 211/94 (2006.01); C07D 401/14 (2006.01); C07D 213/64 (2006.01); C07D 213/73 (2006.01); C07D 213/74 (2006.01); C07D 237/14 (2006.01); C07D 239/54 (2006.01); C07D 239/56 (2006.01); C07D 241/20 (2006.01); C07D 403/04 (2006.01); C07D 405/12 (2006.01); C07D 409/04 (2006.01); C07D 413/06 (2006.01); C07D 417/14 (2006.01); C07D 491/048 (2006.01); C07D 495/04 (2006.01); C07D 213/69 (2006.01); C07D 213/70 (2006.01); C07D 401/12 (2006.01); C07D 405/06 (2006.01)
CPC C07D 498/04 (2013.01) [C07D 211/94 (2013.01); C07D 213/64 (2013.01); C07D 213/69 (2013.01); C07D 213/70 (2013.01); C07D 213/73 (2013.01); C07D 213/74 (2013.01); C07D 217/24 (2013.01); C07D 237/14 (2013.01); C07D 239/54 (2013.01); C07D 239/56 (2013.01); C07D 241/20 (2013.01); C07D 401/04 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/04 (2013.01); C07D 405/04 (2013.01); C07D 405/06 (2013.01); C07D 405/12 (2013.01); C07D 409/04 (2013.01); C07D 413/04 (2013.01); C07D 413/06 (2013.01); C07D 417/14 (2013.01); C07D 471/04 (2013.01); C07D 487/04 (2013.01); C07D 491/048 (2013.01); C07D 495/04 (2013.01)] 14 Claims
 
1. A method of treating prostate cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of compound having the structure of Formula (I), or a pharmaceutically acceptable salt thereof,

OG Complex Work Unit Chemistry
wherein:
R2 is selected from CH3, CH2CH3, CH2CF3, CH2F, CHF2, CF3, CH2D, CHD2, or CD3;
X5 is C—R5 or N;
X6 is C—R6 or N;
X7 is C—R7 or N;
X8 is C—R8 or N; wherein no more than two of X5, X6, X7, or X8 may be N;
R5 is hydrogen, halogen, —CN, —NHR61, —N(R61)2, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl, wherein each R61 is independently selected from alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;
R6 is hydrogen, halogen, —CN, —NHR61, —N(R61)2, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl, wherein each R61 is independently selected from alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;
R7 is hydrogen, halogen, —CN, —NHR61, —N(R61)2, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl, wherein each R61 is independently selected from alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;
R8 is hydrogen, halogen, or alkyl;
RA is

OG Complex Work Unit Chemistry
X2 is N or C—R12, wherein R12 is hydrogen, halogen, alkyl, or alkoxy;
R13 is —Y—Z;
Y is selected from a bond, —CH2—, or —CH(C1-C4 alkyl)-;
Z is selected from —SO2R21, —N(R22)SO2R21, —SO2N(R22)2, —N(R22)SO2N(R22)2, —CON(R22)2, —N(R22)CO2R21, —N(R22)CON(R22)2, —N(R22)COR21, —COR21, —OC(O)N(R22)2, —OSO2N(R22)2, or —N(R22)SO3R21;
X3 is N or C—R14, wherein R14 is hydrogen, halogen, —CN, alkyl, cycloalkyl, or alkoxy;
X4 is N or C—R15, wherein R15 is hydrogen, halogen, alkyl, —CN, or alkoxy;
R16 is hydrogen, halogen, —N(H)COX, or —W—X, wherein W is a bond, —O—, —S—, or —NH—, and X is selected from alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, alkynyl, cycloalkylalkynyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;
each R21 is independently selected from alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl; and
each R22 is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl.