1993
DOI: 10.1021/jm00055a004
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Potent quinoxaline-spaced phosphono .alpha.-amino acids of the AP-6 type as competitive NMDA antagonists: synthesis and biological evaluation

Abstract: A series of alpha-amino-3-(phosphonoalkyl)-2-quinoxalinepropanoic acids was synthesized and evaluated for NMDA receptor affinity using a [3H] CPP binding assay. Functional antagonism of the NMDA receptor complex was evaluated in vitro using a stimulated [3H]TCP binding assay and in vivo by employing an NMDA-induced seizure model. Some analogues also were evaluated in the [3H]-glycine binding assay. Several compounds of the AP-6 type show potent and selective NMDA antagonistic activity both in vitro and in vivo… Show more

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Cited by 50 publications
(20 citation statements)
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“…Compound a1 was synthesized in accordance with literature procedures (Baudy et al, 1993;Li et al, 2005). Pink powder, total yield: 55%; M.p.…”
Section: Chemistrymentioning
confidence: 99%
“…Compound a1 was synthesized in accordance with literature procedures (Baudy et al, 1993;Li et al, 2005). Pink powder, total yield: 55%; M.p.…”
Section: Chemistrymentioning
confidence: 99%
“…In the approach to 87 [75], the 2,3-bis(bromomethyl) quinoxaline electrophilic template 138 was constructed via condensation of the relevant 1,2-phenylenediamine with 1,4-dibromo-2,3-butanedione [75,76]; subsequently appending the phosphonate and protected aminocarboxylate functions by standard treatments with trialkyl phosphite (Arbuzov reaction) and sodium diethyl acetamidomalonate reagents respectively (cf. 140, Scheme 21).…”
Section: • Synthesismentioning
confidence: 99%
“…The addition of a cyclohexane ring (NPC 17742), a biphenyl group (EAB 515;URWYLER et al 1996), a methyl group plus a double bond (CGP 37849;FAGG et al 1990), a quinoxaline ring (BAUDY et al 1993) all yield compounds of increased affinity for NMDA receptors. NMDA receptor antagonists with a benzene ring include a variety of phenylglycine and phenylalanine derivatives that have a wide range of potencies .…”
Section: Glutamate Recognition Site Competitive Antagonistsmentioning
confidence: 99%
“…For example, there are cases in which a six bond length between the acidic groups is preferred for optimal activity. The insertion of a chlorinated quinoxaline ring (BAUDY et al 1993) into the D-AP6 structure results in a-amino-6,7-dichloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid which is a highly potent NMDA receptor antagonist. Likewise, the addition of a cyclobutane ring into D-AP6 yields two l-aminocyclobutanecarboxylic acid derivatives which are antagonists (GAONI et al 1994).…”
Section: Glutamate Recognition Site Competitive Antagonistsmentioning
confidence: 99%