143154-28-3Relevant articles and documents
Potent Quinoxaline-Spaced Phosphono α-Amino Acids of the AP-6 Type as Competitive NMDA Antagonists: Synthesis and Biological Evaluation
Baudy, Reinhardt B.,Greenblatt, Lynne P.,Jirkovsky, Ivo L.,Conklin, Mary,Russo, Ralph J.,et al.
, p. 331 - 342 (2007/10/02)
A series of α-amino-3-(phosphonoalkyl)-2-quinoxalinepropanoic acids was synthesized and evaluated for NMDA receptor affinity using a CPP binding assay.Functional antagonism of the NMDA receptor complex was evaluated in vitro using a stimulated TCP binding assay and in vivo by empolying an NMDA-induced seizure model.Some analogues also were evaluated in the -glycine binding assay.Several compounds of the AP-6 type show potent and selective NMDA antagonistic activity both in vitro and in vivo.In particular α-amino-7-chloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid (1) d isplayed an ED50 of 1.1 mg/kg ip in the NMDA lethality model.Noteworthy is α-amino-6,7-dichloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid (3) with a unique dual activity, displaying in the NMDA receptor binding assay an IC50 of 3.4 nM and in the glycine binding assay an IC50 of 0.61 μM.
