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 (pIC(50) > 7) and good selectivity against the NR2A subunit (pIC(50) < 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. (C) 2012 Elsevier Ltd. All rights reserved.