Designing hypothesis of some 2,4 -disubstituted-phenoxy acetic acid derivatives as a Crth2 receptor antagonist: A QSAR approach

Abstract

In pursuit of better CRTh2 receptor antagonist agents, 2D-QSAR, 3D- QSAR studies were performed on a series of 2,4-disubstituted-phenoxy acetic acid derivatives. The best QSAR model was selected, having correlation coefficient R = 0.904, standard error of estimation SEE = 0.456 and cross validated squared correlation coefficient Q2 = 0.739. The predictive ability of the selected model was also confirmed by leave one out cross validation and by leave 33% out Q2 = 688. The QSAR model indicates that the descriptors (logP, SI3, LM, and DVZ). play an important role for the CRTh2 receptor antagonist activities. The kNN-MFA approach was used to generate models by all three different methods and predict the activity of test molecules through each of these models. The Q2, pred_r2, Vn and k value of kNN-MFA with SW, SA & GA were (0.8392, 0.7059, 2/2 ) (0.6725, 0.6716, 2/4 ) and (0.6832, 0.6716, 2/4 ) SW kNN-MFA method have better q2 (0.8392) and pred_r2 (0.7059) than other two methods, model validation correctly predicts activity 83.9% and 70.5% for the training and test set respectively. It uses 2 steric descriptors with 2 k nearest neighbor to evaluate activity of new molecule.