Modeling VEGFR kinase inhibition of aminopyrazolopyridine urea derivatives using topological and physicochemical descriptors: a quantitative structure activity analysis study

Abstract

A QSAR study has been performed on a series of aminopyrazolopyridine urea derivatives with potent VEGFR kinase inhibitory activity. Structural features responsible for the activity of the compounds were characterized by using physicochemical, topological, and electrotopological descriptors, calculated from the Molecular Design Suite software (V-life MDSTM 3.5). Correlations between the inhibitory activities (KDR and KDRcell) of aminopyrazolopyridine urea derivatives and the calculated descriptors were established through simulated annealing method. The best QSAR models generated from the study explain 89 and 88% of the variation in KDR and KDRcell inhibitory activities, respectively. Internal and external validation methods were used to evaluate the predictive capacity of the generated models. The significant cross-validated correlation coefficient (Q 2 > 0.6) and other statistical parameters suggest that the models exhibited considerable predictivity. The generated QSAR models divulge that factors related to lipophilicity and topological state of atoms in the molecule influences KDR and KDRcell inhibitory activities of aminopyrazolopyridine urea derivatives. A QSAR study has been performed on aminopyrazolopyridine urea derivatives which exhibited VEGFR kinase inhibitory activity, and the results derived show that the lipophilicity and the topological state of atoms in the molecule influences KDR and KDRcell inhibitory activities.