| Literature DB >> 10464027 |
A P Tamiz1, S X Cai, Z L Zhou, P W Yuen, R M Schelkun, E R Whittemore, E Weber, R M Woodward, J F Keana.
Abstract
A novel series of N-(phenylalkyl)cinnamides related to N-(4-phenylbutyl)-3,4-dihydroxy-beta-cyanocinnamide (6, an EGFR-K inhibitor with high antiproliferative activity) was synthesized and tested for antagonism at N-methyl-D-aspartate (NMDA) receptor subtypes. Potency and subunit selectivity were assayed by electrical recordings in Xenopus oocytes expressing three binary combinations of cloned rat NMDA receptor subunits: NR1A expressed in combination with either NR2A, NR2B, or NR2C. The N-(phenylalkyl)cinnamides are selective antagonists of NR1A/2B receptors. Assayed under steady-state conditions, N-(4-phenylbutyl)-4-hydroxycinnamide (16) has an IC(50) value of 77 nM and >1000-fold selectivity with respect to NR1A/2A and NR1A/2C receptors. Potency at alpha(1) adrenergic receptors is low for the four cinnamides tested. Inhibition of NR1A/2B receptors does not correlate with EGFR and ErbB2/neu tyrosine kinase inhibitor activity. The N-(phenylalkyl)cinnamide series we describe provides a novel and structurally diverse framework for designing new NR2B-selective NMDA antagonists as potential CNS therapeutics.Entities:
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Year: 1999 PMID： 10464027 DOI： 10.1021/jm990199u
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446