title: Novel N1-(benzyl)cinnamamidine derived NR2B subtype-selective NMDA receptor antagonists.
abstract: Novel (E)-N(1)-(benzyl)cinnamamidines were prepared and evaluated as NR2B subtype NMDA receptor ligands. Excellent affinity was achieved by appropriate substitution of either phenyl ring. The 2-methoxybenzyl compound 1h had approximately 1,000-fold lower IC(50) in NR2B than NR2A-containing cells. Replacement of the styryl unit by 2-naphthyl was well tolerated.
authors.affiliation: Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. neil_curtis@merck.com
authors.forename: Neil R
authors.initials: NR
authors.lastname: Curtis
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Diggle
authors.forename: Janusz J
authors.initials: JJ
authors.lastname: Kulagowski
authors.forename: Clare
authors.initials: C
authors.lastname: London
authors.forename: Sarah
authors.initials: S
authors.lastname: Grimwood
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hutson
authors.forename: Fraser
authors.initials: F
authors.lastname: Murray
authors.forename: Pawel
authors.initials: P
authors.lastname: Richards
authors.forename: Alison
authors.initials: A
authors.lastname: Macaulay
authors.forename: Keith A
authors.initials: KA
authors.lastname: Wafford
mesh_terms: D000578:Amidines / Q000138:chemical synthesis* / Q000378:metabolism; D001550:Benzamidines / Q000138:chemical synthesis / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009281:Naphthalenes / Q000138:chemical synthesis / Q000378:metabolism; D011485:Protein Binding; D011869:Radioligand Assay; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000578:Amidines; D001550:Benzamidines; C121001:NR2B NMDA receptor; D009281:Naphthalenes; D016194:Receptors, N-Methyl-D-Aspartate; C018609:beta-naphthamidine