US 12,152,040 B2
Tert-butyl (s)-2-(4-(phenyl)-6H-thieno[3, 2-f][1, 2, 4]triazolo[4, 3-a] [1,4]diazepin-6-yl) acetate derivatives and related compounds as bromodomain BRD4 inhibitors for treating cancer
Robert Anthony Blake, South San Francisco, CA (US); Peter Dragovich, South San Francisco, CA (US); Lewis J. Gazzard, South San Francisco, CA (US); Susan Kaufman, South San Francisco, CA (US); Tracy Kleinheinz, South San Francisco, CA (US); Thomas Pillow, South San Francisco, CA (US); Steven T. Staben, South San Francisco, CA (US); and Binqing Wei, South San Francisco, CA (US)
Assigned to Genentech, Inc., South San Francisco, CA (US)
Filed by Genentech, Inc., South San Francisco, CA (US)
Filed on Mar. 10, 2021, as Appl. No. 17/198,240.
Application 17/198,240 is a continuation of application No. PCT/US2019/050576, filed on Sep. 11, 2019.
Claims priority of provisional application 62/729,679, filed on Sep. 11, 2018.
Prior Publication US 2021/0221821 A1, Jul. 22, 2021
Int. Cl. C07D 495/14 (2006.01); A61P 35/00 (2006.01); C07D 495/16 (2006.01)
CPC C07D 495/14 (2013.01) [A61P 35/00 (2018.01); C07D 495/16 (2013.01)] 31 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or an enantiomer thereof, wherein:
X1 is S or C(R11);
X2 is absent or C(R12);
X3 is N or O;
custom character is a single or a double bond;
wherein when X1 is C(R11), custom character is a double bond between X1 and X2, and when X3 is N, custom character is a double bond between X3 and the rest of the molecule;
ring A is phenyl or a 6-membered heteroaryl, wherein ring A is optionally further substituted with one or more substituents selected from the group consisting of halo, hydroxy, —C1-3-alkyl, —O—C1-3-alkyl, and —NH2;
R1 is —O—C1-C6-alkyl, or —N(R8)(R9), wherein
R8 and R9 are independently selected from the group consisting of H, C1-C4-alkyl, and phenyl, wherein the phenyl is optionally substituted with R10, wherein R10 is hydroxyl;
R2 is methyl;
R3, R4, R11, and R12 are each independently selected from the group consisting of H, methyl, and methoxy;
L is C1-C4 alkylene, C2-C4 alkenylene or C2-C4 alkynylene; and
R5 is selected from the group consisting of —N(R6)(R7); —C(H)(CH3)—NH2; —C(CH3)2—NH2; methyl; and hydroxyl, wherein R6 and R7 are independently selected from the group consisting of H, methyl, —C(NH)—NH2, hydroxy, and —C(O)CH3.