A three-dimensional quantitative structure-activity relationship (3D QSAR) of 44 structurally and functionally diverse series of 1- (Naphthylalkylimidazoles) as antiepileptic agents was studied using the Comparative molecular similarity indices analysis (CoMSIA) method. A training set containing 34 molecules served to establish the models. The optimum CoMSIA model obtained for the training set were all statistically significant, with cross-validated coefficients (q(2)) of 0.725 and conventional coefficients (r(2) (ncv)) of 0.998. The predictive capacities of the model were successfully validated by using a test set of 10 molecules that were not included in the training set. CoMSIA model (Model 1) obtained from the hydrophobic and Hbond acceptor field was found to have the best predictivity, with a predictive correlation coefficient (r(2) (pred)) of 0.67. The information obtained from this 3D-QSAR model can be used to guide the development of imidazoles as novel antiepileptic agents.
Keywords: 3D QSAR; CoMSIA; antiepileptic agents; epilepsy; imidazole.