Subtype Selective NMDA Receptor Antagonists: Evaluation of Some Novel Alkynyl Analogues.

Abstract A benzylpiperidine analogue with an acetylenic linker, 5-{3-[4-(4-fluorobenzyl)-piperidin-1-yl]-prop-1-ynyl}-1,3-dihydrobenzimidazol-2-one (3), was identified as a chemical lead with excellent activity at the NR1A/2B receptor (IC50=3 nM). Efforts to optimize this activity led to focused modifications around the structural motif of 3. The synthesis and SAR studies are discussed.