title: NR2B selective NMDA receptor antagonists.
abstract: NR2B antagonists have received considerable attention in recent years. In this class of excitatory amino acid receptor antagonists NR2B antagonists have shown efficacy in neuroprotection, anti-hyperalgesic and anti-Parkinson animal models. Several groups are involved in developing these compounds as therapeutic agents and evaluating newer therapeutic targets for these agents. Until recently benzylpiperidine and phenylpiperidine templates, which were based on the structures of Ifenprodil and Eliprodil, formed the basis of most SAR in this area. A few chemical leads in this class such as CP-101,606, Ro25,6981 and PD0196860 have been identified as possible development leads which have generated significant interest in this area. In addition to the efforts of Pfizer (Parke-Davis), Roche and E.Merck, several other industrial and academic research groups have continued to work in the NR2B area and recently Merck and Roche have reported new chemical leads as NR2B antagonists with significantly different biaryl templates. These new advances have raised hope, for potential success of the NR2B antagonists as new therapeutic agents, for the treatment of several pathophysiological indications.
authors.affiliation: Department of Chemistry, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. sham.nikam@pfizer.com
authors.forename: Sham S
authors.initials: SS
authors.lastname: Nikam
authors.forename: Leonard T
authors.initials: LT
authors.lastname: Meltzer
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy; D002490:Central Nervous System / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D020521:Stroke / Q000188:drug therapy
chemical_list: D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate