论文部分内容阅读
目的建立可以提示高活性的选择性5-羟色胺再摄取抑制剂(SSRIs)3-苯基-1-茚胺类化合物分子结构信息的三维定量构效关系模型,研究结构与活性间的关系,为进一步提高药物的选择性、指导新化合物的设计提供理论依据。方法通过确定34个茚胺类化合物分子的药效构象,与模板分子进行分子叠加,利用比较分子力场分析方法(CoMFA),建立了一个选择性SSRIs的三维定量构效模型。结果该模型的交叉验证相关系数R2CV=0.660,非交叉验证相关系数R2=0.976,标准偏差SEE=0.196,F=181.916。用此模型预测了4个SSRIs的活性,结果与试验值相符。结论该模型解释了已有的构效关系,且有较高的预测能力,系数等势图映射的受体结合部位的性质对进一步提高该类药物活性的设计具有一定的指导意义。
OBJECTIVE: To establish a three-dimensional quantitative structure-activity-relationship model that can indicate the molecular structure information of 3-phenyl-1-indanamine compounds with high activity of selective serotonin reuptake inhibitors (SSRIs), and to study the relationship between structure and activity, To further improve the selectivity of drugs, to guide the design of new compounds to provide a theoretical basis. Methods By determining the pharmacodynamic conformations of 34 indenine compounds, molecular stacking was performed with the template molecules. A three-dimensional quantitative structure-activity model of selective SSRIs was established by comparative molecular force field analysis (CoMFA). Results The correlation coefficient R2CV of this model was 0.660, the correlation coefficient of non-cross validation was R2 = 0.976, the standard deviation was SEE = 0.196, F = 181.916. The activity of four SSRIs was predicted by this model and the results were consistent with the experimental values. CONCLUSIONS This model explains the existing structure-activity relationship and has high predictive power. The properties of the receptor binding sites mapped by the iso-potential diagram of the coefficients are of guiding significance for further improving the design of such drugs.