3D-QSAR STUDIES OF INDENOPYRAZOLE AS CDK4 INHIBITORS WITH COMFA AND COMSIA METHODS

Three-dimensional quantitative structure–activity relationship (3D-QSAR) studies were performed for a series of indenopyrazole inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. A training set containing 69 molecules served to establish the models. The optimum CoMFA and CoMSIA models obtained for the training set were all statistically significant with cross-validated coefficients (q2 ) of 0.845 and 0.763 and conventional coefficients (r2 ) of 0.946 and 0.952, respectively. The predictive capacities of both models were successfully validated by calculating a test set of 24 molecules that were not included in the training set. The CoMFA and CoMSIA field contour maps agree well with the structural characteristics of the binding pocket of CDK4 inhibitor, which suggests that the 3D-QSAR models constructed in this paper can be used to guide the development of novel indenopyrazole inhibitors of CDK4 receptor. Keywords: Indenopyrazole derivatives, Test set, Training set, CoMFA, CoMSI