Docking and 3D-QSAR Studies on the Imidazo[1,5-c]pyrimidine Derivative as EED Inhibitors  

作　　者：CHEN Xiao-Zhong LI Guang-Ping SHEN Yan HU Yong WANG Juan WANG Yuan-Qiang LIN Zhi-Hua 陈小中;李广平;沈燕;胡勇;王娟;王远强;林治华(Department of Pharmacy and Bioengineering,Chongqing University of Technology,Chongqing 400054,China)

机构地区：[1]Department of Pharmacy and Bioengineering,Chongqing University of Technology,Chongqing 400054,China

出　　处：《Chinese Journal of Structural Chemistry》2021年第6期689-702,683,共15页结构化学（英文）

基　　金：supported by the National Natural Science Foundation of China (81171508);Key project of Chongqing

摘　　要：Embryonic ectoderm development(EED)has become a novel target for cancer treatment.In this study,a series of EED inhibitors was subjected to a three-dimensional quantitative structure-activity relationship(3D-QSAR)and molecular docking.Accordingly,this is the first of such 3D-QSAR studies in a series of EED inhibitors displaying anti-cancer pharmacological profiles.The CoMFA(q^(2)=0.792,r^(2)=0.994,r^(2)pred=0.74)and CoMSIA(q^(2)=0.873,r2=0.994,r^(2)pred=0.81)models demonstrated good robustness and predictive ability.Moreover,molecular docking suggested that cation-π,π-π stacking and hydrogen bonding interactions were the main factors affecting the activity of these inhibitors.Five new small molecules were designed based on the CoMFA and CoMSIA contour maps.These molecules were then submitted to further ADME studies,in which the ADME properties of the five designed molecules were found to be within a reasonable range.In view of the corresponding findings,this study may provide theoretical guidance for the rational design of novel EED inhibitors.

关 键 词：embryonic ECTODERM development COMFA COMSIA molecular DOCKING 

分 类 号：TQ460.1[化学工程—制药化工]