中文摘要：

目的：建立小分子化合物毒性的三维定量构效关系模型，探索化合物毒性数据和三维结构参数之间关系的方法。方法：利用比较分子力场分析方法（CoMFA），建立了一组对发光菌有急性毒性的小分子的三维定量构效模型。结果：模型的交叉验证相关系数q^2=0．731，非交叉验证相关系数r^2=0．973，标准偏差SE=0．122，F=70．910。结论：该模型具有较好的预测能力，表明在甲基的邻对位减小取代基体积或电负性可以降低化合物毒性。

英文摘要：

Objective： To predict the relationship between the toxicity and the structural parameters of Benzene drugs, a 3D - QSAR （three dimensional quantitative structure - activity relationship） model was established. Methods ： By determining their lowest energy conformation, molecules are aligned aceording to one specific rule and the scope of the molecular field is defined around the aligned molecules. The characters of the molecule field such as the electrostatic and steric interaction energies are calculated. Then Partial Least Square （PLS） method is exploited to analyze the relationship between the toxicity of compounds and characters of the molecular field and finally Comparative Molecular Field Analysis （CoMFA） model was built. Results： The crossvalidated q^2 of the model is 0.731 and the cross- validated r^2 is 0.973, so the predictive abilities of these models are considerable. Conclusion： This model has a good predictive ability. To reduce the bulk of substitutent in the paraposition and ortho - position of methyl or decrease the negative charge of substitutent in the para - position and ortho - position of methyl can increase the toxicity.