文献类型：期刊文献

英文题名：3D-QSAR Studies on the Biological Activity of Imidazolidinylpiperidinyl-benzoic Acids as Chemokine Receptor Antagonists

作者：Hu, Chunqi[1];Li, Tao[1];Du, Wenting[2,3]

机构：[1]Shaoxing Univ, Chem & Chem Engn Inst, Dept Pharm, Shaoxing 312000, Peoples R China;[2]Zhejiang Med Coll, Dept Pharm, 481 Binwen Rd, Hangzhou 310053, Zhejiang, Peoples R China;[3]Wenzhou Med Univ, Wenzhou 325035, Peoples R China

年份：2016

卷号：12

期号：1

起止页码：42

外文期刊名：CURRENT COMPUTER-AIDED DRUG DESIGN

收录：SCI-EXPANDED(收录号：WOS:000372550900005)、、EI(收录号：20223012426450)、Scopus(收录号：2-s2.0-84963998072)、WOS

基金：This study was financially supported by Zhejiang Provincial Natural Science Foundation (No. LY16H300004 and LQ13H300001), the Natural Science Foundation of China (No. 81502926) and the Education Department of Zhejiang Province, and the general research project (No. Y201431886). We are also grateful to the support provided by Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents (2014) and The 151 Talents Project in new century in Zhejiang Province (the third level, 2011).

语种：英文

外文关键词：CCR5 inhibitor; 3D-QSAR; HIV; CoMFA; CoMSIA and drug design

外文摘要：Background: Human immunodeficiency virus type 1 (HIV-1) infection ultimately leading to acquired immunodeficiency syndrome (AIDS), remains a significant problem. CCR5 is a member of the chemokine receptor family that is utilized in the early stage of the replication cycle by the most commonly transmitted M-tropic strains of HIV-1. In this study, we developed 3D-QSAR models using CoMFA and CoMSIA methods on a series of 71 imidazolidinylpiperidinylbenzoic acid CCR5 antagonists, in order to better understand the substituent requirements and get more potent antagonists of CCR5. Methods: The research of 3D-QSAR modeling of imidazolidinylpiperidinylbenzoic acids as chemokine receptor 5 (CCR5) antagonists was conducted using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Results: For this study, a dataset containing 71 imidazolidinyl-piperidinyl-benzoic acids was divided into a training set of 22 compounds and a test set of 49 compounds. The results obtained from the CoMFA/CoMSIA model exhibited a statistical significance r(2) of 0.996 (0.984) with an estimated standard error of 0.109 (0.209). Conclusion: Both CoMFA and CoMSIA models provided valuable insight into the structural requirements for improving the activity of then CCR5 antagonists.