Study on the Biological Activity of 3-Aroyl-5-substituted Thiophene Derivatives Based on the CoMFA Method  

作　　者：FENG Hui FENG Chang-Jun CAO Jing-Pei 

机构地区：[1]Key Laboratory of Coal Processing and Efficient Utilization(Ministry of Education),Xuzhou 221116,China [2]School of Chemistry&Chemical Engineering,Xuzhou University of Technology,Xuzhou 221018,China

出　　处：《Chinese Journal of Structural Chemistry》2020年第11期1978-1984,共7页结构化学（英文）

基　　金：supported by the National Natural Science Foundation of China (21676292,21075138);special fund of State Key Laboratory of Structure Chemistry (2016028)。

摘　　要：A three-dimensional quantitative structure-activity relationship(3 D-QSAR) study was conducted to analyze the A1 AR density(Bmax) of 56 3-aroyl-5-substituted thiophene derivatives(ASTDs) in human A1 Chinese hamster ovary(hA1 CHO) membranes by the comparative molecular field analysis(CoMFA) method. A training set of 45 compounds was used to establish the predictive model, which was verified by the test set of 17 compounds containing template molecule and 5 newly designed molecules. The cross-validation(R2 cv) and non-cross-validation(R2) coefficients of the training set were 0.655 and 0.959, respectively. The model was used to predict the activities of the compounds of the training and test sets, and the results indicated that the models had strong stability and good prediction ability. According to model analysis, the contribution of steric and electrostatic fields was 51.4% and 48.6%, respectively. Based on the 3 D contour maps, five excellent ASTDs agonists were designed, which need to be further verified by biomedical experiments.

关 键 词：3-aroyl-5-substituted thiophene derivatives(ASTDs) A1AR density(Bmax) three-dimensional quantitative structure-activity relationship comparative molecular field analysis 

分 类 号：TQ460.1[化学工程—制药化工]