5-Phosphonomethylquinoxalinediones as competitive NMDA receptor antagonists with a preference for the human 1A/2A, rather than 1A/2B receptor composition

Bioorg Med Chem Lett. 2002 Apr 8;12(7):1099-102. doi: 10.1016/s0960-894x(02)00074-4.


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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Binding, Competitive
  • Electric Stimulation
  • Humans
  • Mice
  • Molecular Structure
  • Quinoxalines / chemical synthesis
  • Quinoxalines / chemistry*
  • Quinoxalines / pharmacology*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*


  • Anticonvulsants
  • NMDA receptor A1
  • NR2B NMDA receptor
  • Quinoxalines
  • Receptors, N-Methyl-D-Aspartate
  • N-methyl D-aspartate receptor subtype 2A