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

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.