GluN2B-containing NMDARs are related to neurodegenerative diseases, making the GluN2B-selective antagonist a promising drug candidate.
Nucleophilic opening of aryloxiranes with benzylpiperidine and subsequent rearrangement under Mitsunobu conditions led regioselectively to α-aryl-β-piperidinoalcohols and -amines. Amino-ifenprodil and indazole bioisosteres show high GluN2B affinity.
The development of positive allosteric modulators targeting GluN1/2A is a new avenue for neuroprotection.
Photoaffinity labels (PALs) for sulfated steroid binding sites on GABAA and NMDA receptors. The PALs have varying profiles of positive and negative modulatory (PAM and NAM) actions.
ShakeIt quantifies binding stability by clustering ligand conformations during MD simulations, showing that dynamic conformational matching is critical for stable ligand–protein recognition and drug design.