CoMFA and docking studies on triazolopyridine oxazole derivatives as p38 MAP kinase inhibitors.

摘要

With the objective to design new chemical entities with enhanced inhibitory potencies against p38 MAP alpha kinase, the 3D-QSAR and Comparative Molecular Field Analysis (CoMFA) studies were carried out on triazolopyridine oxazole compounds as inhibitors of these kinase is presented here. The developed model gave q(2) value of 0.707 and r(2) value of 0.942 for CoMFA. The high leave-one-out (LOO) cross-validated correlation coefficient q(2) reveals that the model is a useful tool for the prediction of test set of 19 compounds that were not included in the training set of 55 compounds. The results not only lead to better understanding of structural requirements of p38 alpha inhibitors but also can help in the design of new potent inhibitors. The binding mode of the compounds at the active site of p38 MAP alpha kinase was explored using Glide docking program and hydrogen-bonding interactions were observed between the inhibitors and the target. The details of amino acid interactions of the active site are discussed briefly and correlated with the contour plots.