【摘要】 目的:建立可提示高活性5-HT重摄取抑制剂分子结构信息的三维定量构效关系模型,深入研究结构-活性间的关系,指导新化合物的设计。方法和结果:通过确定分子的药效构象,与选定的模板分子(sertraline)进行atom to atom叠合,采用比较分子立场分析法建立67个5-HT重摄取抑制剂的3D-QSAR模型,模型的交叉验证相关系数Rcv2=0.614,传统相关系数R2=0.988,F=456.172,标准偏差SEE=0.134。结论:该模型在一定程度上反映了结合部位的性质要求,解释了已有的构效关系,并对同类化合物的预测能力较好,系数等势图映射的受体结合部位的性质对新化合物的设计具有一定的指导意义。更多还原

【Abstract】 AIM to quatitatively disclose the relationship between structure and activety of a series of serotonin reuplake inhibitors and direct the design of novel potent selective serotonin reuptake inhibitors. METHODS AND RESULTS Sixty 5-HT reuplake inhibitors from literature as a training set were investigated with the aim of developing a 3D-QSAR model using the comparative molecular field analysis (CoMFA) . The predictive pharmacophore model shows a higher ability to explain and predict the activity of serotonin reuptake inhibitors, with the cross-validation Rcv2 = 0.614, non cross-validation R2 = 0.988, F = 456.172, and SEE (standard err of estimate) =0.134. Seven Compounds were selected as a predicting set, the low deviations of calculated values from the measured ones suggesting a powerful predictive ability of the model. CONCLUSION The 3D-QSAR explains the dependence of upon the structures of the compounds. Some structure information for design of new 5-HT reuptake inhibitors with higher activity has been given.更多还原