GluN2B-containing NMDARs are related to neurodegenerative diseases, making the GluN2B-selective antagonist a promising drug candidate.
The development of positive allosteric modulators targeting GluN1/2A is a new avenue for neuroprotection.
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.
Pregnenolone C-20 oxime ethers are highly potent NMDAR PAM neurosteroids, outperforming pregnenolone sulfate in efficacy, potency, and drug-like properties, validating D-ring bioisosteric design as a promising strategy.
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.