US 12,145,923 B2
Tetrahydroisoquinoline compound, preparation method therefor, pharmaceutical composition containing same, and use thereof
Yechun Xu, Shanghai (CN); Hong Liu, Shanghai (CN); Wei Tang, Shanghai (CN); Xianglei Zhang, Shanghai (CN); Zhanni Gu, Shanghai (CN); Heng Li, Shanghai (CN); Xu Han, Shanghai (CN); Fenghua Zhu, Shanghai (CN); Chunlan Feng, Shanghai (CN); Guangyu Dong, Shanghai (CN); Tiantian Chen, Shanghai (CN); Wuyan Chen, Shanghai (CN); Hualiang Jiang, Shanghai (CN); and Kaixian Chen, Shanghai (CN)
Assigned to SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES, Shanghai (CN)
Appl. No. 16/967,721
Filed by SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES, Shanghai (CN)
PCT Filed Feb. 3, 2019, PCT No. PCT/CN2019/074704
§ 371(c)(1), (2) Date Aug. 5, 2020,
PCT Pub. No. WO2019/154395, PCT Pub. Date Aug. 15, 2019.
Claims priority of application No. 201810118038.7 (CN), filed on Feb. 6, 2018.
Prior Publication US 2021/0040066 A1, Feb. 11, 2021
Int. Cl. C07D 401/14 (2006.01); C07D 217/08 (2006.01); C07D 401/06 (2006.01); C07D 401/12 (2006.01); C07D 403/04 (2006.01); C07D 405/14 (2006.01); C07D 409/06 (2006.01); C07D 413/06 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01)
CPC C07D 401/14 (2013.01) [C07D 217/08 (2013.01); C07D 401/06 (2013.01); C07D 401/12 (2013.01); C07D 403/04 (2013.01); C07D 405/14 (2013.01); C07D 409/06 (2013.01); C07D 413/06 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01)] 8 Claims
 
1. A tetrahydroisoquinoline compound represented by general formula (I), or a pharmaceutically acceptable salt, enantiomer, diastereomer or racemate thereof:

OG Complex Work Unit Chemistry
wherein,
the chiral carbon atom C* is independently of S type or R type;
n=1;
X is —CH2—;
Y is a linking group selected from a C1-C6 linear or branched alkylene, —CH2O—, —CH2NH—,

OG Complex Work Unit Chemistry
R1 is selected from the group consisting of substituted or unsubstituted C1-C6 linear or branched alkoxy, COOR5 or CONR5R6;
R2 is selected from the group consisting of substituted or unsubstituted C1-C6 linear or branched alkoxy, substituted or unsubstituted C3-C7 cycloalkoxy, substituted or unsubstituted C3-C7 cycloalkylmethoxy, benzyloxy, C1-C6 acyloxy, carboxy substituted C2-C8 linear alkoxy, N, N-dimethylamino substituted C2-C8 linear alkoxy, COOR5 or CONR5R6; the substitutent is selected from deuterium or halogen;
R3 is selected from the following groups that are unsubstituted or substituted with 1-3 substituents: —C(O)—(5 to 7-membered heteroaryl), —C(O)—(4 to 7-membered heterocyclic group), —C1-C4 acyl, —CHO, R7SO2—, R7SO2(CH2)m—, R7O(CH2)mCO—, R7OCO(CH2)m—, difluoromethyl, trifluoromethyl; wherein each of the heterocyclic groups or heteroaryl groups contains 1 to 3 heteroatoms selected from oxygen, sulfur or nitrogen; and the substituents are each independently selected from a deuterium, halogen, C1-C6 linear or branched alkoxy, C1-C4 sulfonyl;
R5, R6 and R7 are each independently selected from a hydrogen, substituted or unsubstituted C1-C4 linear or branched alkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C6-C10 aryl; wherein the substituent is selected from deuterium or halogen;
m is selected from 0, 1, 2, 3 or 4;
R4 is an unsubstituted or substituted heteroaryl group selected from the group consisting of indole, imidazopyridine, benzothiophene, quinoxaline, benzofuran, indazole, benzimidazole, and quinoline, wherein the substitution means substitution with 1-3 groups independently selected from a deuterium, halogen, C1-C6 linear or branched alkyl, C1-C6 linear or branched alkoxy, C1-C6 linear or branched alkylcarbonyloxy, cyano, nitro, hydroxy, amino, hydroxymethyl, trifluoromethyl, trifluoromethoxy, difluoromethyl, difluoromethoxy, or COOR5.