US 12,391,687 B2
Five-and-six-membered heterocyclic compound and use thereof as protein receptor kinase inhibitor
Lei Jiang, Shanghai (CN); Zhiyong Feng, Shanghai (CN); Xian Jin, Shanghai (CN); Zhi Qiao, Shanghai (CN); Jianyong Shou, Shanghai (CN); Ke Shang, Shanghai (CN); Danyi Wu, Shanghai (CN); Lingling Xu, Shanghai (CN); Yuan Xu, Shanghai (CN); Shuyun Zhang, Shanghai (CN); Yi Zhang, Shanghai (CN); and Yuxing Zhang, Shanghai (CN)
Assigned to SHANGHAI ENNOVABIO PHARMACEUTICALS CO., LTD., Shanghai (CN)
Appl. No. 17/439,012
Filed by SHANGHAI ENNOVABIO PHARMACEUTICALS CO., LTD., Shanghai (CN)
PCT Filed Nov. 13, 2019, PCT No. PCT/CN2019/118198
§ 371(c)(1), (2) Date Sep. 14, 2021,
PCT Pub. No. WO2020/098720, PCT Pub. Date May 22, 2020.
Claims priority of application No. 201811346840.8 (CN), filed on Nov. 13, 2018.
Prior Publication US 2022/0144827 A1, May 12, 2022
Int. Cl. C07D 471/04 (2006.01)
CPC C07D 471/04 (2013.01) 8 Claims
 
1. A compound of Formula I:

OG Complex Work Unit Chemistry
wherein the compound of Formula I has a structure according to Formula Ia:

OG Complex Work Unit Chemistry
wherein
L1 is

OG Complex Work Unit Chemistry
 wherein n is 0, 1 or 2; and R2 is each independently H or halogen;
L2 is a substituted or unsubstituted —(X4)z—, wherein each of the X4 is independently selected from the group consisting of a substituted or unsubstituted C1-C8 alkylene, —O—, —C(═O)—, —S—, —S(═O)—, —S(═O)2—, —NH—, —CONH—, —NHCO—, —NHCONH—, —NHS(═O)—, and —NHS(═O)2—; and z is 0, 1 or 2;
RA is selected from the group consisting of, phenyl, which is substituted or unsubstituted by one or more halogens, and pyridyl, which is substituted or unsubstituted by one or more groups selected from halogen and C1-C6 alkoxyl;
RB is selected from the group consisting of H, NH2, OH, —COOH, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted C1-C8 alkoxyl, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted C1-C6 amino, substituted or unsubstituted 5-10 membered heteroaryl comprising 1-3 hetero atoms selected from N, S and O, and substituted or unsubstituted 5-12 membered heterocyclic group comprising 1-3 hetero atoms, each of which is N, S or O;
unless otherwise specified, the “substituted” means that a group is substituted by one or more substituents selected from the group consisting of a halogen, C1-C6 alkoxyl, halogenated C1-C6 alkyl, halogenated C1-C6 alkoxyl, halogenated C3-C8 cycloalkyl, benzyloxy, methyl sulfuryl, —S(═O)2NH2, oxo (═O), —CN, hydroxy, —NH2, carboxyl, C1-C6 amido, C1-C6 alkyl-(C1-C6 amido),

OG Complex Work Unit Chemistry
 and a substituted or unsubstituted group selected from the group consisting of C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 amino, C6-C10 aryl, 5-10 membered heteroaryl comprising 1-3 heteroatoms selected from N, S and O, 3-12 membered heterocyclic group comprising 1-3 heteroatoms selected from N, S and O, —(CH2)-C6-C10 aryl, and —(CH2)-(5-10 membered heteroaryl comprising 1-3 heteroatoms selected from N, S and O), wherein the substituent is selected from the group consisting of a halogen, C1-C6 alkoxyl, halogenated C1-C6 alkyl, halogenated C1-C6 alkoxyl, halogenated C3-C8 cycloalkyl, methyl sulfuryl, —S(═O)2NH2, oxo (═O), —CN, hydroxyl, —NH2, carboxyl, C1-C6 amido,

OG Complex Work Unit Chemistry
 C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 amino, C6-C10 aryl, 5-10 membered heteroaryl comprising 1-3 heteroatoms selected from N, S and O, 3-12 membered heterocyclic group comprising 1-3 heteroatoms selected from N, S and O, —(CH2)-C6-C10 aryl, and —(CH2)-(5-10 membered heteroaryl comprising 1-3 heteroatoms selected from N, S, and O);
custom character is the connection site of the group;
with the proviso that the compound of formula I is a chemical stable structure.