US 12,234,232 B2
Aromatic heterocyclic compound with kinase inhibitory activity
Lei Jiang, Shanghai (CN); Jianwen Deng, Shanghai (CN); Zhiyong Feng, Shanghai (CN); Shengyang Liu, Shanghai (CN); Xudong Mao, Shanghai (CN); Ke Shang, Shanghai (CN); Jianyong Shou, Shanghai (CN); Danyi Wu, Shanghai (CN); Xiaoping Xie, Shanghai (CN); Yuan Xu, Shanghai (CN); Haixia Zhao, Shanghai (CN); Jianhua Zhang, Shanghai (CN); and Mingwei Zheng, Shanghai (CN)
Assigned to SHANGHAI ENNOVABIO PHARMACEUTICALS CO., LTD., Shanghai (CN)
Appl. No. 17/278,405
Filed by SHANGHAI ENNOVABIO PHARMACEUTICALS CO., LTD., Shanghai (CN)
PCT Filed Sep. 23, 2019, PCT No. PCT/CN2019/107381
§ 371(c)(1), (2) Date Mar. 22, 2021,
PCT Pub. No. WO2020/057669, PCT Pub. Date Mar. 26, 2020.
Claims priority of application No. 201811109355.9 (CN), filed on Sep. 21, 2018; and application No. 201811110497.7 (CN), filed on Sep. 21, 2018.
Prior Publication US 2021/0371415 A1, Dec. 2, 2021
Int. Cl. C07D 471/04 (2006.01); C07D 487/04 (2006.01); C07D 519/00 (2006.01)
CPC C07D 471/04 (2013.01) [C07D 487/04 (2013.01); C07D 519/00 (2013.01)] 9 Claims
 
1. A compound according to Formula I:

OG Complex Work Unit Chemistry
wherein, X1 is N, X2, X3, and X4 are each independently CH; and

OG Complex Work Unit Chemistry
ring is phenyl or pyrazol R1 is independently selected from the group consisting of H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted 3-6 membered heterocyclyl, and —S(═O)2R7, wherein the heterocyclyl including 1-3 heteroatoms selected from N, S and O;
R2, and R3 are independently selected from the group consisting of H, halogen, CN, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxyl, substituted or unsubstituted 3-6 membered heterocyclyl, —S(═O)2R7, and —NHS(═O)2R7, wherein the heterocyclyl including 1-3 heteroatoms selected from N, S and O;
R4 is H, R5 is selected from the group consisting of H, halogen, CN, and substituted or unsubstituted C1-C6 alkyl;
R6 is selected from the group consisting of R7—C(═O)—, R9R10N—C(═O)—, substituted or unsubstituted 5-12 membered heterocyclyl with 1-3 heteroatoms selected from N, S and O, substituted or unsubstituted C6-C10 aryl, and substituted or unsubstituted 5-10 membered heteroaryl with 1-3 heteroatoms selected from the group consisting of N, S and O;
R7, R9, and R10 are each independently selected from the group consisting of H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxyl, substituted or unsubstituted C3-C8 cycloalkyl, and substituted or unsubstituted 5-12 membered heterocyclyl with 1-3 heteroatoms selected from the group consisting of N, S and O;
unless otherwise specified, “substituted” refers to being substituted by one or more substituents selected from the group consisting of halogen, C1-C6 alkoxyl, halogenated C1-C6 alkoxyl, C3-C8 cycloalkyl, halogenated C3-C8 cycloalkyl, methyl sulfone, oxo(═O), —CN, hydroxy, —NH2, C1-C6 amine, carboxy, C1-C6 amide, and substituted or unsubstituted groups selected from the group consisting of C1-C6 alkyl, C6-C10 aryl, 5-10 membered heteroaryl with 1-3 heteroatoms selected from N, S, and_O, —(CH2)-C6-C10 aryl,—(CH2)-(5-10 membered heteroaryl with 1-3 heteroatoms selected from N, S and O), -(5-10 membered heteroarylene with 1-3 heteroatoms selected from N, S and O)-(C1-C6 alkyl), 5-12 membered heterocyclyl with 1-3 heteroatoms selected from N, S and O, and the substituents thereof are selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 alkylene-OH, C1-C6 alkoxyl, oxo, —S(O)2CH3, —CN, —OH, C6-C10 aryl, 3-10 membered heteroaryl with 1-3 heteroatoms selected from N, S and O, —C(O) CH2NH2, and —C(O)CH2OH;
and in the compound of Formula I, each chiral center is in R configuration or S configuration.