Quantitative Structure-Activity Relationship Studies for Potential Rho-Associated Protein Kinase Inhibitors

Abstract EN

A series of pyridylthiazole derivatives developed by Lawrence et al.

as Rho-associated protein kinase inhibitors were subjected to four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis.

The models were generated applying genetic algorithm (GA) optimization combined with partial least squares (PLS) regression.

The best model presented validation values of r 2 = 0.773 , q C V 2 = 0.672 , r p r e d 2 = 0.503 , Δ r m 2 = 0.197 , r m t e s t 2 = 0.520 , r Y - r a n d 2 = 0.19 , and R p 2 = 0.590 .

Furthermore, analyzing the descriptors it was possible to propose new compounds that predicted higher inhibitory concentration values than the most active compound of the series.