QSAR Study and Molecular Design of Isoquinolone Derivative JNK1 Inhibitors

作     者：TONG Jian-Bo XIAO Xue-Chuna LUO Ding XU Hai-Yin WANG Jie 仝建波;肖雪纯;罗钉;徐海音;王杰

作者机构：College of Chemistry and Chemical EngineeringShaanxi University of Science and TechnologyXi'an 710021China Shaanxi Key Laboratory of Chemical Additives for IndustryXi'an 710021China 

出 版 物：《Chinese Journal of Structural Chemistry》 (结构化学（英文）)

年 卷 期：2021年第40卷第12期

页      面：1586-1594,1551页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：This work was supported by the National Natural Science Funds of China(21475081) Innovation Supporting Plan of Shaanxi Province-Innovation Research Team(No.2018TD-015) the Graduate Innovation Fund of Shaanxi University of Science and Technology 

主　　题：Topomer CoMFA HQSAR molecular docking isoquinolone derivatives molecular design 

摘      要：JNK1 is a drug target for the treatment of type 2 diabetes,and it plays a key mediator role in metabolic *** this paper,holographic quantitative structure-activity relationship(HQSAR)technology and Topomer comparative molecular field analysis(Topomer CoMFA)technology are used to analyze the quantitative structure-activity relationship(QSAR)of 39 isoquinolone *** cross validation correlation coefficient(q^(2))is 0.696(Topomer CoMFA)and 0.826(HQSAR),and the non-cross validation correlation coefficient(r^(2))is 0.935(Topomer CoMFA)and 0.987(HQSAR).The results showed that the models have good stability and predictive *** Topomer search module was applied to define high contribution fragments in the ZINC database,designing 20 new isoquinolone compounds with theoretically high inhibitory *** molecular docking was carried out to explore the interaction between the ligand and target JNK1 *** study can provide a theoretical basis for the design of new JNK1 inhibitors.