R基团搜索技术用于2-氨基-6-磺酰苯甲腈衍生物的分子设计

Application of an R-group search technology into molecular design of 2-amino-6-arylsulfonylbenzonitrile derivatives

艾滋病对人类的健康构成了很大的威胁,因此,抗艾滋病药物的研究设计成为了当今社会的重要任务之一.本文采用基于R基团搜索技术的Topomer CoMFA方法,对60个2-氨基-6-磺酰苯甲腈衍生物分子进行了三维定量构效关系分析.所得优化模型的拟合、交互验证及外部验证的复相关系数分别为0.851、0.601和0.671;并采用Topomer Search技术对ZINC数据库进行R基团的虚拟筛选,最终得到5个Ra基团和2个Rb基团,并设计出了10个新化合物.研究结果表明:所建立的Topomer CoMFA模型具有良好的稳定性和预测能力;基于R基团的Topomer Search技术可以有效地筛选并设计出新的化合物,这为抗艾滋病新药设计提供了依据.

Acquired Immunodeficiency Syndrome （AIDS） has been threatening human health , the study of anti‐HIV drug design has become one of the important tasks of today＆#39;s society . In this paper ,a three‐dimensional quantitative structure‐activity relationship （3D‐QSAR） study for 60 2‐amino‐6‐arylsulfonylbenzonitrile derivatives was established using Topomer CoMFA .The multiple correlation coefficient of fitting ,cross validation and external valida‐tion were 0 .851 ,0 .601 and 0 .671 ,respectively .Topomer Search was used to search R groups from ZINC database .As the result ,5 Ra groups and 2 Rb groups were selected .Finally ,we designed 10 new compounds .The results indicated that Topomer CoMFA model had both fa‐vorable estimation stability and good predictive capability .Topomer Search technology could be effectively used to screen and design new compound ,and had good predictive capability to guide the design of new Anti‐HIV drugs .