基于Topomer CoMFA方法对芳基硫代吲哚衍生物的分子建模与设计

采用Topomer CoMFA方法对30个芳基硫代吲哚衍生物进行三维定量关系研究,建立了3D-QSAR模型,所得模型的交叉验证相关系数q~2,非交叉验证相关系数r~2,外部验证的复相关系数Q_(ext)~2分别为0.562,0.878,0.985,结果表明该模型具有较好的稳定性和预测能力.Topomer CoMFA模型等势面提供的立体场与静电场可视化图像,直观的揭示了这一系列化合物中不同取代基结构对其生物活性的影响,运用这些信息进行分子设计,在理论上获得了5个具有较高活性的新化合物,该QSAR的实验结果可为合成新药提供理论参考.

Molecular Modeling and Design of Arylthiothioindole Derivatives Based on Topomer CoMFA

A three-dimensional quantitative relationship study of 30 Arylthioindole derivatives was studied by Topomer CoMFA method, and a 3D-QSAR model was established. The cross validation coefficient q2, the non-cross validation coefficient r2, and the external validation coefficient Q2ext were 0.878, 0.562 and 0.985 respectively. The result showed that this model had good stability and predictive ability. Contour maps of Topomer CoMFA model provide visual field of steric and field of electrostatic , it reveals that structure of compounds of different substituent have effected on its biological activity. Based on the above informations, we designed 5 new compounds with higher activity, the QSAR Results can offer a theoretical reference for the pharmaceutical synthesis.