中文摘要：

目的本文针对51个具有CCR5拮抗剂作用的咪唑并吡啶衍生化合物进行构效关系研究,希望能够为设计此类小分子药物提供依据。方法运用比较分子力场分析（Co MFA）和比较分子相似性指数分析（Co MSIA）这2种经典的三维定量构效关系（3D-QSAR）方法,分别建立了相应的模型,进行分子结构和抗病毒活性彼此关系的分析。结果 Co MFA模型的交叉验证系数q^2和相关系数r^2分别为0.617和0.825,立体场和静电场对活性的贡献为62%和38%;Co MSIA模型的交叉验证系数q^2和相关系数r^2分别为0.599和0.810,立体场、静电场、疏水场、氢键供体场和受体场对活性的贡献分别为9.8%、12.5%、33.8%、30.8%和13.1%。结论这2种模型都显示出了较好的预测性和稳定性,其三维等势图也证实了这些化合物拮抗CCR5的构效关系。

英文摘要：

The CC chemokine receptor 5（CCR5） has been identified as a critical determinant in the pathwayof infection and inflammation of HIV-1,which makes it an attractive target for anti-HIV drugs design.In this work,comparative molecular field analysis（Co MFA） and comparative molecular similarity indices analysis（Co MSIA） wereperformed on a group of 51 CCR5 antagonistic derivatives,and the Co MFA and Co MSIA models were built for thethree-dimensional quantitative structure-activity relationship（3D-QSAR） analyses.The coefficients ofcross-validation q^2 and non cross-validation r^2 for Co MFA model were 0.617 and 0.825（S%=0.617,E%=0.825）,forCo MSIA model were 0.559 and 0.810 respectively（S%=9.8%,E%=12.5%,H%=33.8%,D%=30.8%,A%=13.1%）.Both of the two models display enough predictive ability and stability,and their contour maps also demonstrate thestructure-activity relationship of the compounds.