US 11,655,248 B2
Pyridone-pyrimidine derivative acting as KRAS G12C mutein inhibitor
Yaxian Cai, Shanghai (CN); Zhaobing Xu, Shanghai (CN); Hailong Yang, Shanghai (CN); Shiqi Han, Shanghai (CN); Guoping Hu, Shanghai (CN); Lihong Hu, Shanghai (CN); Charles Z. Ding, Shanghai (CN); Jian Li, Shanghai (CN); and Shuhui Chen, Shanghai (CN)
Assigned to MEDSHINE DISCOVERY INC., Jiangsu (CN)
Filed by MEDSHINE DISCOVERY INC., Jiangsu (CN)
Filed on Jan. 27, 2021, as Appl. No. 17/159,928.
Application 17/159,928 is a continuation of application No. 16/962,951, granted, now 11,453,667, previously published as PCT/CN2019/072393, filed on Jan. 18, 2019.
Claims priority of application No. 201810055396.8 (CN), filed on Jan. 19, 2018; and application No. 201810712103.9 (CN), filed on Jun. 29, 2018.
Prior Publication US 2021/0147418 A1, May 20, 2021
Int. Cl. C07D 471/04 (2006.01); C07D 519/00 (2006.01); A61P 35/00 (2006.01)
CPC C07D 471/04 (2013.01) [A61P 35/00 (2018.01); C07D 519/00 (2013.01)] 18 Claims
 
1. A compound of formula (I), a pharmaceutically acceptable salt thereof, or a stereoisomer thereof,

OG Complex Work Unit Chemistry
wherein
ring A is selected from 3-8 membered heterocycloalkyl, and the 3-8 membered heterocycloalkyl is optionally substituted with 1, 2 or 3 R;
R1, R2, R3, R4 and R5 are each independently selected from H, halogen, OH, NH2, CN, C1-6 alkyl and C1-6 heteroalkyl, and the C1-6 alkyl and C1-6 heteroalkyl are optionally substituted with 1, 2 or 3 R;
or R1 and R2 are connected together to form ring B;
or R2 and R3 are connected together to form ring B;
or R3 and R4 are connected together to form ring B;
or R4 and R5 are connected together to form ring B;
ring B is selected from phenyl, C5-6 cycloalkenyl, 5-6 membered heterocycloalkenyl and 5-6 membered heteroaryl, and the phenyl, C5-6 cycloalkenyl, 5-6 membered heterocycloalkenyl and 5-6 membered heteroaryl are optionally substituted with 1, 2 or 3 Ra;
Ra is selected from halogen, OH, NH2, CN, C1-6 alkyl and C1-6 heteroalkyl, and the C1-6 alkyl and C1-6 heteroalkyl are optionally substituted with 1, 2 or 3 R;
R6 is selected from H, halogen, CF3, CHF2 and CH2F;
R7 is selected from H;
L is selected from a single bond;
L is selected from a single bond and —NH—;
R8 is selected from H, C1-6 alkyl and C1-6 heteroalkyl, and the C1-6 alkyl and C1-6 heteroalkyl are optionally substituted with 1, 2 or 3 R;
R is selected from halogen, OH, NH2, CN, C1-6 alkyl, C1-6 heteroalkyl and C3-6 membered cycloalkyl, and the C1-6 alkyl, C1-6 heteroalkyl and C3-6 membered cycloalkyl are optionally substituted with 1, 2 or 3 R′;
R′ is selected from F, Cl, Br, I, OH, NH2, CN, CH3, CH3CH2, CH3O, CF3, CHF2, CH2F, cyclopropyl, n-propyl, isopropyl, N(CH3)2 and NH(CH3);
“hetero” means a heteroatom or a heteroatomic group, the “hetero” in the 3-8 membered heterocycloalkyl, C1-6 heteroalkyl, 5-6 membered heterocycloalkenyl and 5-6 membered heteroaryl is each independently selected from —C(═O)N(R)—, —N(R)—, —NH—, N, —O—, —S—, —C(═O)O—, —C(═O)—, —C(═S)—, —S(═O)—, —S(═O)2— and —N(R)C(═O)N(R)—;
in any of the cases above, the number of heteroatoms or heteroatomic groups is each independently selected from 1, 2 and 3.