Novel N1-(benzyl)cinnamamidine derived NR2B subtype-selective NMDA receptor antagonists

Neil R Curtis; Helen J Diggle; Janusz J Kulagowski; Clare London; Sarah Grimwood; Peter H Hutson; Fraser Murray; Pawel Richards; Alison Macaulay; Keith A Wafford

doi:10.1016/s0960-894x(02)01060-0

Novel N1-(benzyl)cinnamamidine derived NR2B subtype-selective NMDA receptor antagonists

Bioorg Med Chem Lett. 2003 Feb 24;13(4):693-6. doi: 10.1016/s0960-894x(02)01060-0.

Authors

Neil R Curtis¹, Helen J Diggle, Janusz J Kulagowski, Clare London, Sarah Grimwood, Peter H Hutson, Fraser Murray, Pawel Richards, Alison Macaulay, Keith A Wafford

Affiliation

¹ 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

PMID: 12639560
DOI: 10.1016/s0960-894x(02)01060-0

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.

MeSH terms

Amidines / chemical synthesis*
Amidines / metabolism
Benzamidines / chemical synthesis
Benzamidines / metabolism
Drug Evaluation, Preclinical
Humans
Naphthalenes / chemical synthesis
Naphthalenes / metabolism
Protein Binding
Radioligand Assay
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
Receptors, N-Methyl-D-Aspartate / metabolism
Structure-Activity Relationship

Substances

Amidines
Benzamidines
NR2B NMDA receptor
Naphthalenes
Receptors, N-Methyl-D-Aspartate
beta-naphthamidine