N,N-二甲基-2-溴苯乙胺类衍生物对大鼠生物活性的三维构效关系研究

Study of Three-Dimensional Quantitative Structure-Activity Relationship of the Bioactivity of N,N-Dimethyl-2-bromo-2-phenyl-ethylamine Derivatives to Rat

N,N-二甲基-2-溴苯乙胺类衍生物是一类有效的肾上腺素阻断剂,具有较高的生物活性.通过比较分子力场分析(CoMFA)方法,建立了22个标题化合物对大鼠阻断活性的三维定量结构-活性关系(3D-QSAR)模型.该模型显示立体场、静电场对生物活性贡献分别为67.3%,32.7%,其中立体场与受体之间的相互作用是造成阻断剂生物活性差别的主要因素.此3D-QSAR模型的交叉验证系数q2=0.862,传统的相关系数(非交互验证系数)R2=0.962.该模型给出的预测值与实验值非常接近,其方差比F=503.7,估计标准误差(S)为0.11.根据CoMFA模型的立体场、静电场三维等值线图不仅直观地解释了结构与活性的关系,而且为进一步设计高活性的标题化合物提供一定的理论依据.

The three-dimensional quantitative structure-activity relationship between the structure of 22 title compounds and their retardant activity to rat has been set up by comparative molecular field analysis （CoMFA）. The results based on the CoMFA model showed that the contributions of steric and electrostatic fields to the bioactivity were 67.3% and 32.7%, respectively, and this difference was attributed to interaction between the steric field and acceptors. The coefficient q^2 of cross validation and the relation coefficient R^2 of non-cross validation for the 3D-QSAR model are 0.862 and 0.962, respectively. The activity of such compounds predicted by this model was agreed with experimental results, and its F value was 503.7 and the standard deviation was 0.11. The contour maps based on the analysis of steric and electrostatic CoMFA coefficients can not only explain the relationship between the structures and biological activity, but also lead to insight into the further design of highly active title compounds.