双吗啉类PI3Kα抑制剂的自组织分子场分析

Self-organizing molecular field analysis on PI3Kα inhibitors:dimorpholino derivatives

采用自组织分子场分析(SOMFA)构建了39个双吗啉类磷脂酰肌醇-3激酶α(PI3Kα)抑制剂的三维定量构效关系模型。交叉验证相关系数(q2)、非交叉验证相关系数(r2)、标准偏差(SEE)分别为0.636、0.702和0.581,立体场和静电场的贡献分别为0.7和0.3,并用测试集进行了验证。测试集非交叉验证相关系数(r2pred)为0.808。该模型具有显著的统计学意义,为进一步开发新的双吗啉类PI3Kα抑制剂奠定了基础。

To study the three-dimensional quantitative-structure activity relationship （3D-QSAR） of 39 dimor- pholino derivatives as phosphatidylinositol-3-kinases α （ PI3Kα） inhibitors, a self-organizing molecular field anal- ysis （SOMFA） model has been established. The cross-validated correlation coefficient （q2）, non-cross-validated correlation coefficient （ r2） and standard error of estimate （SEE） reached 0. 636, 0. 702 and 0. 581, respectively. The contribution coefficient of the shape and electrostatic potential reached 0. 7 and 0. 3, respectively. This model was validated by a group of compounds as test set. The predicted non-cross-validated correlation coefficient （r2ped） reached 0. 808. With its obvious statistical significance, this model may provide a way to develop novel dimorpho- lino derivatives as PI3Kα inhibitors.