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

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(CV)(2) = 0.672, r(pred)(2) = 0.503, Delta r(m)(2) = 0.197, r(mtest)(2) = 0.520, r(Y-rand)(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.