US 11,981,701 B2
PRMT5 inhibitors
Jongwon Lim, Lexington, MA (US); Michelle Machacek, Belmont, MA (US); Michael H. Reutershan, Brighton, MA (US); and Sebastian Schneider, Boston, MA (US)
Assigned to Merck Sharp & Dohme LLC, Rahway, NJ (US)
Appl. No. 17/266,507
Filed by Merck Sharp & Dohme LLC, Rahway, NJ (US)
PCT Filed Aug. 5, 2019, PCT No. PCT/US2019/045042
§ 371(c)(1), (2) Date Feb. 5, 2021,
PCT Pub. No. WO2020/033284, PCT Pub. Date Feb. 13, 2020.
Claims priority of provisional application 62/715,341, filed on Aug. 7, 2018.
Prior Publication US 2021/0309688 A1, Oct. 7, 2021
Int. Cl. C07H 19/167 (2006.01); A61P 35/00 (2006.01); C07D 471/04 (2006.01); C07D 473/00 (2006.01); C07D 473/34 (2006.01); C07D 487/04 (2006.01); C07H 19/04 (2006.01)
CPC C07H 19/167 (2013.01) [A61P 35/00 (2018.01); C07D 471/04 (2013.01); C07D 473/00 (2013.01); C07D 473/34 (2013.01); C07D 487/04 (2013.01); C07H 19/04 (2013.01)] 14 Claims
 
1. A compound of the formula

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
X is O or CH2;
Y is O or CH2;
R1 is H or —NHR3;
R2 is

OG Complex Work Unit Chemistry
R3 is H, CH3, C2H5, CH2CH2CH3, CH(CH3)2, CH2CHF2, CH2CF3, or CH2—C3-8 cycloalkyl;
R4 is H, C1-6alkyl, CF3 or CHF2;
R5 is H, halogen, CH3, CF3, or CHF2;
R6 is NH2 or C1-6alkyl;
Z1 is CH or N;
Z2 is CH or N;
Z3 is CH or N;
Z4 is CR5 or N;
Z is CH or N; and
A is CH, N or C—NH2.