Novel N1-(benzyl)cinnamamidine derived NR2B subtype-selective NMDA receptor antagonists.
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.
Curtis
Neil R
NR
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
Diggle
Helen J
HJ
Kulagowski
Janusz J
JJ
London
Clare
C
Grimwood
Sarah
S
Hutson
Peter H
PH
Murray
Fraser
F
Richards
Pawel
P
Macaulay
Alison
A
Wafford
Keith A
KA
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
D000578:Amidines; D001550:Benzamidines; C121001:NR2B NMDA receptor; D009281:Naphthalenes; D016194:Receptors, N-Methyl-D-Aspartate; C018609:beta-naphthamidine