title: Receptor-based QSAR studies of non-peptide human oxytocin receptor antagonists.
abstract: 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 [r(pred)2=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.
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, University of Szeged, H-6720 Szeged, Eötvös u. 6, Hungary. jojartb@pharm.u-szeged.hu
authors.forename: Balázs
authors.initials: B
authors.lastname: Jójárt
authors.forename: Arpád
authors.initials: A
authors.lastname: Márki
mesh_terms: D048588:Benzoxazines / Q000737:chemistry* / Q000494:pharmacology*; D003198:Computer Simulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008958:Models, Molecular; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D012984:Software; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D048588:Benzoxazines; D018045:Receptors, Oxytocin