US 12,304,915 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., Princeton, NJ (US)
Filed by Mirati Therapeutics, Inc., San Diego, CA (US)
Filed on Nov. 29, 2022, as Appl. No. 18/071,384.
Application 18/071,384 is a division of application No. 17/127,582, filed on Dec. 18, 2020, granted, now 11,702,418.
Claims priority of provisional application 63/044,802, filed on Jun. 26, 2020.
Claims priority of provisional application 62/975,645, filed on Feb. 12, 2020.
Claims priority of provisional application 62/951,812, filed on Dec. 20, 2019.
Prior Publication US 2023/0137886 A1, May 4, 2023
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 471/10 (2006.01); C07D 487/08 (2006.01); C07D 487/10 (2006.01); C07D 498/10 (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)] 81 Claims
 
1. A method for inhibiting SOS1 activity in a cell, comprising contacting the cell in which inhibition of SOS1 activity is desired with an effective amount of a compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein:
R1 is 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;
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,
or a pharmaceutical composition comprising the compound of Formula (I) or a pharmaceutically acceptable salt thereof.