Receptor-based QSAR studies of non-peptide human oxytocin receptor antagonists

In the present study, QSAR calculations were performed on the receptor-based alignment of 58 non-peptide human oxytocin receptor antagonists. With the aid of different scoring functions (AutoDock 3.05 built-in and X-Score 1.2) the evolved receptor–ligand complexes were characterized. By means of various datasets it was confirmed that the scoring functions were not capable to predict the biological activity correctly in compounds containing a rigid derivative in the variable region. To improve the pKi prediction 3D-QSAR calculation was performed. The regions related to the biological activity were determined by using cross-validated r2(q2)-guided region selection (q2-GRS) method. The predictive power of the CoMFA model [rpred2=0.89, q2(LMO, five groups) = 0.695 ± 0.034] allowed prediction of the biological activities of newly synthesized compounds and confirmed the receptor-based alignment.