| Autor: |
Tamiz, A. P., Cai, S. X., Zhou, Z.-L., Yuen, P.-W., Schelkun, R. M., Whittemore, E. R., Weber, E., Woodward, R. M., Keana, J. F. W. |
| Zdroj: |
Journal of Medicinal Chemistry; August 26, 1999, Vol. 42 Issue: 17 p3412-3420, 9p |
| Abstrakt: |
A novel series of N-(phenylalkyl)cinnamides related to N-(4-phenylbutyl)-3,4-dihydroxy-β-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 IC50 value of 77 nM and >1000-fold selectivity with respect to NR1a/2A and NR1a/2C receptors. Potency at α1 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. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
