3D-QSAR study on VEGFR kinase inhibition of aminopyrazolopyridine urea derivatives by CoMFA and CoMSIA

Abstract

Three-dimensional quantitative structure–activity relationship has been performed on 28 aminopyrazolopyridine ureas derivatives to correlate their chemical structures with their observed VEGFR kinase inhibitory activity. The studies include comparative molecular field analysis (CoMFA), CoMFA region focusing and comparative molecular similarity indices analysis (CoMSIA). An alignment rule for the compounds was defined using Distill in SYBYL. Data set was divided into training and test sets using diversity to validate the models. The constructed CoMFA, CoMFA region-focusing and CoMSIA models produced statistically significant results with the cross-validated correlation coefficients (q2) of 0.858, 0.884, and 0.794, noncross-validated correlation coefficients (r2) of 0.990, 0.991, and 0.930 and predicted correlation coefficients \((r_{\text{pred}}^{2} )\) of 0.796, 0.785, and 0.910, respectively. These results ensure the CoMFA and CoMSIA models as a tool to guide the design of series of new potent VEGFR kinase inhibitors.