4-alkyl- and 4-cinnamylglutamic acid analogues are potent GluR5 kainate receptor agonists

Citation
C. Pedregal et al., 4-alkyl- and 4-cinnamylglutamic acid analogues are potent GluR5 kainate receptor agonists, J MED CHEM, 43(10), 2000, pp. 1958-1968
Citations number
25
Categorie Soggetti
Chemistry & Analysis
Journal title
JOURNAL OF MEDICINAL CHEMISTRY
ISSN journal
00222623 → ACNP
Volume
43
Issue
10
Year of publication
2000
Pages
1958 - 1968
Database
ISI
SICI code
0022-2623(20000518)43:10<1958:4A4AAA>2.0.ZU;2-I
Abstract
Enantiomerically pure (2S,4R)-4-substituted glutamic acids were prepared an d tested for homomeric GluR5 and GluR6 kainate subtype receptor affinity. S ome of the 4-cinnamyl analogues showed high selectivity and potency (K-i < 25 nM) for the GluR5 receptors. The greatest selectivity and potency were a chieved with the 3-(2-naphthyl)prop-2-enyl compound. This compound, LY33943 4, has negligible activity at the AMPA and kainate receptors GluR1, -2, -4 and -6. Although, LY339434 shows agonist activity at NMDA receptors in cult ural hippocampal neurons (approximate EC50 of 2.5 mu M), we consider that L Y339434 should be a useful pharmacological tool for the investigation of th e functional role of GluR5 kainate receptors.