US 11,993,602 B2
PRMT5 inhibitors
David Witter, Norfolk, MA (US); Shuhei Kawamura, Cambridge, MA (US); Michelle Machacek, Belmont, MA (US); Ryan Quiroz, Boston, MA (US); Michael H. Reutershan, Brighton, MA (US); Sebastian Schneider, Boston, MA (US); Phieng Siliphaivanh, Newton, MA (US); Yingchun Ye, Belmont, MA (US); and Charles S. Yeung, Dedham, MA (US)
Assigned to Merck Sharp & Dohme LLC, Rahway, NJ (US)
Appl. No. 17/266,474
Filed by Merck Sharp & Dohme LLC, Rahway, NJ (US); David Witter, Norfolk, MA (US); Shuhei Kawamura, Cambridge, MA (US); Michelle Machacek, Belmont, MA (US); Ryan Quiroz, Boston, MA (US); Michael H. Reutershan, Brighton, MA (US); Sebastian Schneider, Boston, MA (US); Phieng Siliphaivanh, Newton, MA (US); Yingchun Ye, Belmont, MA (US); and Charles S. Yeung, Dedham, MA (US)
PCT Filed Aug. 5, 2019, PCT No. PCT/US2019/045040
§ 371(c)(1), (2) Date Feb. 5, 2021,
PCT Pub. No. WO2020/033282, PCT Pub. Date Feb. 13, 2020.
Claims priority of provisional application 62/715,324, filed on Aug. 7, 2018.
Prior Publication US 2021/0277009 A1, Sep. 9, 2021
Int. Cl. C07D 487/04 (2006.01); C07D 519/00 (2006.01)
CPC C07D 487/04 (2013.01) [C07D 519/00 (2013.01)] 17 Claims
 
1. A compound having formula I

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
A is O or CH2;
R1 is halogen, NH2, OC1-6alkyl, NHCH3, CHF2, C1-6alkyl, cyclopropyl, CH2OH, or C(CH3)2OH;
R2 is H, C1-6alkyl, CF3 or CHF2;
R3 is H, halogen, CH3, CF3, or CHF2, and R4 is H or NHR5, or R3 and R4 together with the atom to which they are attached form a 5-membered saturated ring containing zero or one N atom, wherein the ring is unsubstituted or substituted with CH3;
R5 is H, CH3, C2H5, CH2CH2CH3, CH(CH3)2, CH2CHF2, CH2CF3, or CH2—C3-8cycloalkyl;
R6 is H, C1-4alkyl, or halogen;
R7 is H, NH2, or C1-6alkyl;
Z1 is CH or N;
Z2 is CH or N;
Z3 is CH or N;
Z4 is CH or N; and
Z5 is CR 3 or N.