A novel series of benzimidazole NR2B-selective NMDA receptor antagonists

A series of novel benzimidazoles are discussed as NR2B-selective N-methyl-d-aspartate (NMDA) receptor antagonists. High throughput screening (HTS) efforts identified a number of potent and selective NR2B antagonists such as 1. Exploration of the substituents around the core of this template identified a number of compounds with high potency for NR2B (pIC50 >7) and good selectivity against the NR2A subunit (pIC50 <4.3) as defined by FLIPR-Ca2+ and radioligand binding studies. These agents offer potential for the development of therapeutics for a range of nervous system disorders including chronic pain, neurodegeneration, migraine and major depression.

Graphical abstractDiscovery of a novel series of benzimidazole-derived NR2B selective NMDA receptor antagonists is described.Figure optionsDownload full-size imageDownload as PowerPoint slide