双吗啉类PI3Kα抑制剂的自组织分子场分析

基金项目: 教育部博士点新教师基金资助项目(No. 20090181120113)

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

摘要: 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(r²_pred)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。
- PI3Kα /
- 三维定量构效关系 /
- 自组织分子场分析
Abstract: To study the three-dimensional quantitative-structure activity relationship(3D-QSAR)of 39 dimorpholino derivatives as phosphatidylinositol-3-kinases α(PI3Kα)inhibitors, a self-organizing molecular field analysis(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(r²_pred)reached 0. 808. With its obvious statistical significance, this model may provide a way to develop novel dimorpholino derivatives as PI3Kα inhibitors.