US 11,708,353 B2
Inhibitors of prolyl-tRNA-synthetase
Ralph Mazitschek, Belmont, MA (US); Sofia A. Santos, Saugus, MA (US); Mark A. Tye, San Ramon, CA (US); N. Connor Payne, Cambridge, MA (US); and Dyann F. Wirth, Boston, MA (US)
Assigned to The General Hospital Corporation, Boston, MA (US); and President and Fellows of Harvard College, Cambridge, MA (US)
Appl. No. 16/973,080
Filed by The General Hospital Corporation, Boston, MA (US); and PRESIDENT AND FELLOWS OF HARVARD COLLEGE, Cambridge, MA (US)
PCT Filed Jun. 10, 2019, PCT No. PCT/US2019/036411
§ 371(c)(1), (2) Date Dec. 8, 2020,
PCT Pub. No. WO2019/237125, PCT Pub. Date Dec. 12, 2019.
Claims priority of provisional application 62/682,294, filed on Jun. 8, 2018.
Prior Publication US 2021/0253558 A1, Aug. 19, 2021
Int. Cl. C07D 241/28 (2006.01); C07D 403/12 (2006.01); C07D 405/12 (2006.01); A61P 33/02 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01)
CPC C07D 403/12 (2013.01) [A61P 33/02 (2018.01); C07D 241/28 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 405/12 (2013.01)] 19 Claims
 
1. A compound of Formula Ia:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
each Y is N;
Z is selected from the group consisting of CH2, NH, and Cy;
Cy is selected from the group consisting of C3-10 carbocyclyl, C6-10 aryl, 4-10 membered heterocyclyl, and 5-10 membered heteroaryl;
each R3 is independently selected from the group consisting of H, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C3-6 carbocyclyl, —C(═O)ORA1, —ORA1, —N(RA2)2, and —NRA2C(═O)ORA1, wherein the C1-6 alkyl is optionally substituted with —C(═O)ORA1 or —NHC(═O)RA2;
each RA1 is independently selected from the group consisting of H and C1-6 alkyl;
each RA2 is independently selected from the group consisting of H, C1-6 alkyl, and 4-6 membered heterocyclyl;
each RA4 is independently selected from the group consisting of H and an amino protecting group; and
n1 is 0, 1, 2, 3, or 4;
provided that when Z is NH or CH2, then n1 is not 0; and
provided that the compound of Formula Ia is not 3-(cyclohexanecarboxamido)-N-(2,3-dihydro-1H-inden-2-yl)pyrazine-2-carboxamide.