US 12,312,324 B2
Fluorine-containing substituted benzothiophene compound, and pharmaceutical composition and application thereof
Ao Zhang, Shanghai (CN); Meiyu Geng, Shanghai (CN); Chunyong Ding, Shanghai (CN); Zuoquan Xie, Shanghai (CN); Jian Ding, Shanghai (CN); Yan Zhang, Shanghai (CN); Ancheng Shen, Shanghai (CN); and Xiyuan Wang, Shanghai (CN)
Assigned to SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES, Shanghai (CN)
Appl. No. 17/420,389
Filed by Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (CN)
PCT Filed Dec. 31, 2019, PCT No. PCT/CN2019/130605
§ 371(c)(1), (2) Date Jul. 1, 2021,
PCT Pub. No. WO2020/140894, PCT Pub. Date Jul. 9, 2020.
Claims priority of application No. 201910002749.2 (CN), filed on Jan. 2, 2019.
Prior Publication US 2022/0089561 A1, Mar. 24, 2022
Int. Cl. C07D 333/64 (2006.01); C07D 409/12 (2006.01)
CPC C07D 333/64 (2013.01) [C07D 409/12 (2013.01)] 10 Claims
 
1. A compound of formula I, or its isomer, prodrug, solvate, hydrate or pharmaceutically acceptable salt thereof,

OG Complex Work Unit Chemistry
wherein,
R1 and R2 are independently selected from the substituted or unsubstituted group consisting of halogen, amino, hydroxyl, carboxyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, C1-C6 alkoxy, C3-C8 cycloalkoxy, 3-8 membered heterocycloalkyl containing 1 to 3 heteroatoms selected from N, O or S, 3-8 membered heterocycloalkoxy containing 1 to 3 heteroatoms selected from N, O or S, C6-C10 aryl, and 3-10 membered heteroaryl containing 1 to 3 heteroatoms selected from N, O or S; or R1 and R2 together with the carbon atoms to which they are attached form a 5-14 membered heterocyclic group;
the substituted in R1 and R2 refers to be independently substituted by one or more substituents selected from the group consisting of halogen, amino, hydroxy, carboxy, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkoxy, C3-C8 cycloalkoxy, 3-8 membered heterocyclic group containing 1 to 3 heteroatoms selected from N, O or S, C6-C10 aryl, and 3-10 membered heteroaryl containing 1 to 3 heteroatoms selected from N, O or S;
X1 and X2 are independently selected from the group consisting of H, D, halogen, unsubstituted or halogen-substituted C1-C6 alkyl, unsubstituted or halogen-substituted C1-C6 alkoxy, and cyano;
X3 is selected from the group consisting of hydrogen, halogen, hydroxy, C1-C3 alkyl, C1-C3 alkoxy;
n is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7 or 8;
Y is selected from the group consisting of —OR3, and —N(X4R4) R5,
wherein,
X4 is selected from the group consisting of O, S, and NH;
R3 is selected from the substituted or unsubstituted group consisting of H, carboxy, sulfonic acid group, phosphoryl group, C1-C6 alkyl, C3-C8 cycloalkyl, C6-C10 aryl, 3-10 membered heteroaryl containing 1 to 3 heteroatoms selected from N, O or S, and 3-8 membered heterocycloalkyl containing 1 to 3 heteroatoms selected from N, O or S;
R4 and R5 are independently selected from the substituted or unsubstituted group consisting of H, carboxy, sulfonic acid group, phosphoryl group, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, C1-C6 alkoxy, C3-C8 cycloalkoxy, C6-C10 aryloxy, C6-C10 aryl, 3-8 membered heterocycloalkyl containing 1 to 3 heteroatoms selected from N, O or S, and 3-10 membered heteroaryl containing 1 to 3 heteroatoms selected from N, O or S;
the substituted in R3, R4 and R5 refers to be independently substituted by one or more substituents selected from the group consisting of halogen, hydroxyl, amino, carboxyl, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkoxy, C3-C8 cycloalkoxy, 3-8 membered heterocyclic group containing 1 to 3 heteroatoms selected from N, O or S, C6-C10 aryl, and 3-10 membered heteroaryl containing 1 to 3 heteroatoms selected from N, O or S.