US 11,702,418 B2
SOS1 inhibitors
Matthew Arnold Marx, San Diego, CA (US); John Michael Ketcham, Carlsbad, CA (US); Christopher Ronald Smith, San Diego, CA (US); John David Lawson, San Diego, CA (US); Aaron Craig Burns, San Diego, CA (US); Xiaolun Wang, San Diego, CA (US); Svitlana Kulyk, Redwood City, CA (US); and Anthony Ivetac, San Diego, CA (US)
Assigned to MIRATI THERAPEUTICS, INC., San Diego, CA (US)
Filed by Mirati Therapeutics, Inc., San Diego, CA (US)
Filed on Dec. 18, 2020, as Appl. No. 17/127,582.
Claims priority of provisional application 62/951,812, filed on Dec. 20, 2019.
Claims priority of provisional application 62/975,645, filed on Feb. 12, 2020.
Claims priority of provisional application 63/044,802, filed on Jun. 26, 2020.
Prior Publication US 2021/0188857 A1, Jun. 24, 2021
Int. Cl. C07D 487/04 (2006.01); C07D 237/34 (2006.01); C07D 403/04 (2006.01); C07D 409/12 (2006.01); C07D 409/14 (2006.01); C07D 413/04 (2006.01); C07D 471/04 (2006.01); C07D 471/08 (2006.01); C07D 487/08 (2006.01); C07D 487/10 (2006.01); C07D 498/10 (2006.01); C07D 471/10 (2006.01)
CPC C07D 487/04 (2013.01) [C07D 237/34 (2013.01); C07D 403/04 (2013.01); C07D 409/12 (2013.01); C07D 409/14 (2013.01); C07D 413/04 (2013.01); C07D 471/04 (2013.01); C07D 471/08 (2013.01); C07D 471/10 (2013.01); C07D 487/08 (2013.01); C07D 487/10 (2013.01); C07D 498/10 (2013.01)] 72 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein:
R1 is hydrogen, hydroxyl, C1-C6 alkyl, alkoxy, —N(R6)2, —NR6C(O)R6, —C(O)N(R6)2, —SO2alkyl, —SO2NR6alkyl, cycloalkyl, -Q-heterocyclyl, aryl, or heteroaryl, wherein the cycloalkyl, the heterocyclyl, the aryl, and the heteroaryl are each optionally substituted with one or more R2 or L-R2;
each Q is independently a bond, O, or NR6;
X is N;
each R2 is independently C1-C3 alkyl, oxo, hydroxy, halogen, cyano, hydroxyalkyl, haloalkyl, alkoxy, —C(O)N(R6)2, —N(R6)2, —SO2alkyl, —NR6C(O)C1-C3 alkyl, —C(O)cycloalkyl, —C(O)C1-C3 alkyl, —C(O)heterocyclyl, aryl, heteroaryl or heterocyclyl,
wherein the cycloalkyl, the heterocyclyl, the aryl, the heteroaryl or the heterocyclyl are each optionally substituted with one or more R11;
R3 is hydrogen, C1-C6 alkyl, alkoxy, —N(R10)2, -L-N(R10)2, cycloalkyl, haloalkyl or heterocyclyl, wherein the C1-C6 alkyl, the cycloalkyl and the heterocyclyl, are each optionally substituted with one or more R9;
Y is a bond or heteroarylene;
R4 is aryl or heteroaryl, each optionally substituted with one or more R5;
each R5 is independently hydroxy, halogen, cyano, hydroxyalkyl, alkoxy, C1-C3 alkyl, haloalkyl, haloalkyl-OH, —N(R6)2, -L-N(R6)2 or —SO2alkyl;
L is C1-C3 alkylene;
each R6 is independently hydrogen, C1-C3 alkyl, haloalkyl, or cycloalkyl;
R7 is hydrogen, cyano, CF3, F, or alkoxy;
R8 is C1-C2 alkyl or halo-C1-C2 alkyl;
each R9 is independently hydroxy, halogen, amino, cyano, alkoxy, or C1-C3 alkyl;
each R10 is independently hydrogen, C1-C3 alkyl or cycloalkyl;
each R11 is independently C1-C3 alkyl, halogen or haloalkyl; and
R12 is hydrogen, halogen or C1-C3 alkyl.