US 12,252,493 B2
Imidazo[1,2-c]pyrimidine derivatives as PRC2 inhibitors for treating cancer
Matthew Arnold Marx, San Diego, CA (US); John Michael Ketcham, San Diego, CA (US); and Aaron Craig Burns, San Diego, CA (US)
Assigned to MIRATI THERAPEUTICS, INC., Princeton, NJ (US)
Appl. No. 17/615,778
Filed by Mirati Therapeutics, Inc., San Diego, CA (US)
PCT Filed Jun. 3, 2020, PCT No. PCT/US2020/035891
§ 371(c)(1), (2) Date Dec. 1, 2021,
PCT Pub. No. WO2020/247475, PCT Pub. Date Dec. 10, 2020.
Claims priority of provisional application 62/857,515, filed on Jun. 5, 2019.
Prior Publication US 2022/0274990 A1, Sep. 1, 2022
Int. Cl. C07D 487/04 (2006.01)
CPC C07D 487/04 (2013.01) 27 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein:
custom character represents a single or a double bond;
Z is O or S;
X is O, CR11, CR11OH, or C(R11)2, wherein:
when X is O custom character is a single bond;
when X is C(R11)2, custom character is a single bond;
when X is CR11OH, custom character is a single bond; or
when X is CR11, custom character is a double bond;
R1 is aryl, heteroaryl, -L-cycloalkyl, or -L-heterocyclyl, wherein the aryl, and the heteroaryl and cyclyl portions of the L -cycloalkyl and -L-heterocyclyl are optionally substituted with one or more R4;
R2 is —C(R5aR5b)R7 or heteroaryl;
each R3 is independently C1-C3 alkyl or halogen;
each R4 is independently cyano, halogen, alkoxy, hydroxyalkyl, heteroalkyl, haloalkyl, —Y2-haloalkyl; —Y1—C1-C6 alkyl, —Y2—C1-C6 alkyl, -L-cycloalkyl, -L-heteroaryl, -L-heterocyclyl,—Y1-heterocyclyl, -L-N(R11)2,—Y1—N(R11)2, or —Y2—N(R11)2
wherein the ring of the -L-cycloalkyl, -L-heteroaryl, -L-heterocyclyl, or —Y1-heterocyclyl is optionally substituted with one or more R9;
L is a bond or C1-C4 alkylene;
Y1 is a bond, —C(O)—, or —NHC(O)—;
Y2 is a bond, —S—, —SO—, —SO2—, or —NR10SO2—,
R5a and R5b are each independently hydrogen, C1-C3 alkyl, haloalkyl, cycloalkyl, or aryl, wherein at least one of R5a or R5b is hydrogen;
R6 is hydrogen, C1-C3 alkyl, halogen, haloalkyl, hydroxyalkyl, or heteroalkyl;
R7 is —NR8aR8b wherein R8a and R8b together with the nitrogen atom to which each is attached form a 4-8 membered saturated or partially saturated heterocyclyl optionally containing 1, 2, or 3 heteroatoms selected from —O—, —N—, or —S— and optionally substituted with one or more R10; or
R7 is —OR8a or —NHR8a wherein R8a is hydrogen, C1-C3 alkyl, cycloalkyl, aralkyl, or halosulfonylalkyl;
each R9 is independently oxo, cyano, hydroxyl, alkoxy, halogen, haloalkyl, hydroxyalkyl, heteroalkyl, cycloalkyl, -L-N(R11)2, C1-C6 alkyl, or —Y1-heterocyclyl,
wherein the —Y1-heterocyclyl is optionally substituted with one or more R10,
each R10 is independently oxo, cyano, hydroxyl, alkoxy, halogen, haloalkyl, hydroxyalkyl, or heteroalkyl;
each R11 is independently hydrogen or C1-C3 alkyl; and
n is 1 or 2.