磺酰脲类乙酰羟基酸合成酶抑制剂的拓扑物比较分子力场分析

Topomer-CoMFA of Sulfonylureas Acetohydroxyacidsynthase Inhibitors

磺酰脲类除草剂是一类高选择性、广谱、低毒的化合物,在世界范围内得到了广泛的应用。本文采用拓扑物比较分子力场分析(Topomer-CoMFA)对75个磺酰脲类化合物与植物源野生型拟南芥AHAS酶的离体相互作用进行了三维定量构效关系研究,构建了Topomer CoMFA模型,该模型具有较强的预测能力(交叉验证相关系数q2为0.890,非交叉验证相关系数r2为0.967)。此模型对测试集的10个化合物的pKi值进行预测,其预测值与实际值基本一致。

As one kind of aeetohydroxyacidsynthase inhibitors, the sulfonylureas herbicide has been widely used throughout the world. For designing more potent acetohydroxyaeidsynthase inh^bitors, three-dimensional quantitative structure-activity relationship （3D-QSAR） studies were carried out on 85 sulfonylureas derivatives using topomer comparative molecular field analysis （Topomer CoMFA ）. The predictive capability of established model was validated, whose correlation coefficient of cross-validation q2 is 0. 890 and non cross-validation r2 is 0. 967, respectively.