3D-QSAR, ADME-Tox In Silico Prediction and Molecular Docking Studies for Modeling the Analgesic Activity against Neuropathic Pain of Novel NR2B-Selective NMDA Receptor Antagonists

A new class of selective antagonists the N-Methyl-D-Aspartate (NMDA) receptor subunit 2B have been developed using molecular modeling techniques. The three-dimensional quantitative structure–activity relationship (3D-QSAR) study, based on comparative field analysis (CoMFA) and similarity index (CoMSIA) models, indicate that steric, electrostatic hydrogen bond acceptor fields a key function in analgesic activity against neuropathic pain. predictive accuracy CoMFA model (Q2 = 0.540, R2 0.980, pred 0.613) best CoMSIA 0.665, 0.916, 0.701) has successfully examined through external internal validation. Based ADMET silico properties, L1, L2 L3 ligands are non-toxic inhibitors 1A2, 2C19 2C9 cytochromes, predicted to passively cross blood–brain barrier (BBB) highest probability penetrate central nervous system (CNS). Molecular docking results active (L1, L3) interact specifically with Phe176, Glu235, Glu236, Gln110, Asp136 Glu178 amino acids transport protein encoded as 3QEL. Therefore, they could be used drugs for treatment