Molecular modeling studies on imidazo[4,5-b]pyridine derivatives as Aurora A kinase inhibitors using 3D-QSAR and docking approaches.

3D-QSAR and docking studies were performed on sixty imidazo[4,5-b]pyridine derivatives as Aurora A kinase inhibitors. The CoMFA and CoMSIA models using forthy-eight molecules in the training set, gave r(cv)(2) values of 0.774 and 0.800, r(2) values of 0.975 and 0.977, respectively. The external validation indicated that both CoMFA and CoMSIA models possessed high predictive powers with r(pred)(2) values of 0.933 and 0.959, r(m)(2) values of 0.883 and 0.915, respectively. 3D contour maps generated from the two models along with docking binding structures have identified several key structural requirements responsible for the activity. A set of thirty new analogues were proposed by utilizing the results revealed in the present study, and were predicted with significantly improved potencies in the developed models.