title: 5-Phosphonomethylquinoxalinediones as competitive NMDA receptor antagonists with a preference for the human 1A/2A, rather than 1A/2B receptor composition.
abstract: NMDA antagonists derived from 5-phosphonomethyl-1,4-dihydroquinoxaline-2,3-dione (3a) are potent anticonvulsant agents, and display strong protective effects in the electroshock-induced convulsion assay in mice. Their preference for the human NMDAR 1A/2A over 1A/2B subunit composition was optimized, leading to (1RS,1'S)-PEAQX (9r), which shows a >100-fold selectivity.
authors.affiliation: Novartis Pharma AG, Klybeckstrasse 141, 4002 Basel, Switzerland. yves.auberson@pharma.novartis.com
authors.forename: Yves P
authors.initials: YP
authors.lastname: Auberson
authors.forename: Hans
authors.initials: H
authors.lastname: Allgeier
authors.forename: Serge
authors.initials: S
authors.lastname: Bischoff
authors.forename: Kurt
authors.initials: K
authors.lastname: Lingenhoehl
authors.forename: Robert
authors.initials: R
authors.lastname: Moretti
authors.forename: Markus
authors.initials: M
authors.lastname: Schmutz
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001667:Binding, Competitive; D004558:Electric Stimulation; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D000927:Anticonvulsants; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor