Designing Hypothesis of Some 2,4 – Disubstituted - Phenoxy Acetic Acid Derivatives as A Crth{sub}2 Receptor Antagonist: A QSAR Approach

摘要

In pursuit of better CRTh{sub}2 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 Q{sup}2, 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 2k nearest neighbor to evaluate activity of new molecule.