US 12,473,273 B2
Quinoline compounds and compositions for inhibiting EZH2
Xuan Dai, Shanghai (CN); Michael Dore, Quebec (CA); Xiang-Ju Justin Gu, Shanghai (CN); Ling Li, Shanghai (CN); Kun Chin Liu, Shanghai (CN); Sing Yeung Frankie Mak, Cintech IV (SG); Yuan Mi, Shanghai (CN); Counde Oyang, Sunnyvale, CA (US); Julien Papillon, Cambridge, MA (US); Wei (Vicky) Qi, Shanghai (CN); Xiaoxia Yan, Shanghai (CN); Zhengtian Yu, Shanghai (CN); Ji Yue (Jeff) Zhang, Shanghai (CN); and Kehao Zhao, Newton, MA (US)
Assigned to NOVARTIS AG, Basel (CH)
Appl. No. 17/919,490
Filed by Novartis AG, Basel (CH)
PCT Filed Aug. 10, 2021, PCT No. PCT/CN2021/111910
§ 371(c)(1), (2) Date Oct. 17, 2022,
PCT Pub. No. WO2022/033492, PCT Pub. Date Feb. 17, 2022.
Claims priority of application No. PCT/CN2020/108213 (WO), filed on Aug. 10, 2020.
Prior Publication US 2023/0167100 A1, Jun. 1, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 405/14 (2006.01); A61K 45/06 (2006.01)
CPC C07D 405/14 (2013.01) [A61K 45/06 (2013.01)] 19 Claims
 
1. A compound having the structure of Formula (I):

OG Complex Work Unit Chemistry
or a stereoisomer, enantiomer, enantiomeric mixture or pharmaceutically acceptable salt thereof; wherein:
Y is N or CRa;
Ra, R1, R3, R5, R6, R7, R8 and R9 are independently is H, halogen or —C1-C4 alkyl;
R2 is —CN, —C1-C6 alkyl, -hydroxyC1-C4 alkylene, —C1-C4 alkoxy, —C2-C4 alkoxy substituted with 1-2 hydroxyl;
—(CR13R14)nC(═O) NR11R12, —(CR13R14)nC(═O) NR11R15;
—(CR13R14)nC(═O) R15;
—(CR2) NR11C(═O) R15, —(CR2)nNR11(CR2)2C(═O)R15;
—(CR2)nNR—C(═O)OR11, —(CR2)nNR—C(═O)O—(CR2)—R15;
—NR—C(═O)(CR2)2C(═O)R15, —NR—C(═O) R11;
—(CR2)nNR11R12, —(CR2)nNR11 (CR2)nR15;
—(CR2)nOR15, —(CR2)nR15;

OG Complex Work Unit Chemistry
or a 5- to 6-membered heteroaryl having 1 to 4 heteroatoms independently selected from O, S and N;
R4a, R4b, R4c and R4d are independently H or —C1-C4 alkyl;
R10 is H, halogen, —C1-C4 alkyl, —C1-C4 alkoxy, —C1-C4 haloalkoxy or —NH(C1-C4 alkyl);
R11 is H, —C1-C4 alkyl, -hydroxyC1-C4 alkylene, -cyanoC1-C4 alkylene or —C1-C4 alkyl substituted with —C1-C4 alkoxy;
R12 is H or —C1-C4 alkyl;
R13 is H, halogen, —CN, —OH, —C1-C4 alkyl or -hydroxyC1-C4 alkylene;
R14 is H, halogen or —C1-C4 alkyl;

OG Complex Work Unit Chemistry
R15 is —C3-C6cycloalkyl, or a 4- to 6-membered heterocycoalkyl having 1-2 heteroatoms independently selected from O, S, S(═O)2, and N; wherein said —C3-C6cycloalkyl or 4- to 6-membered heterocycloalkyl of R15 is unsubstituted or substituted with 1-2 substituents selected from —OH, —C1-C4 alkyl, -hydroxyC1-C4 alkylene, —C1-C4 alkoxy, —SO2 (C1-C4 alkyl) and —N(C1-C4 alkyl)2;
R16, if present, is a substituent selected from halogen, —CN, —OH, —C1-C4 alkyl and -hydroxyC1-C4 alkylene;
each R is independently H or —C1-C4 alkyl;
m is 0, 1 or 2; and
each n is independently selected from 0, 1 and 2.