Tricyclic quinoxalinediones, aza-kynurenic acids, and indole-2-carboxylic acids as in vivo active NMDA-glycine antagonists.

This review article describes the development of in vivo active antagonists for the glycine binding site of the N-Methyl-D-Aspartate (NMDA) receptor. There were several difficulties in identifying a class of antagonists with in vivo efficacy and only a few compounds succeeded in emerging with activity in vivo. A series of tricyclic quinoxalinediones was highly potent glycine antagonists in vitro and the derivatives having a zwitterionic moiety including SM-18400 indeed showed in vivo activity. Similarly, tricyclic indole-2-carboxylic acids having a zwitterionic moiety such as SM-31900 were also active in vivo. In fact, SM-18400 and SM-31900 exhibited efficacy in several animal stroke models using intravenous infusion protocols. The practical syntheses of SM-18400 and SM-31900 as well as the novel synthesis of moderately active glycine antagonists, tricyclic azakynurenic acids, were also developed.
AuthorsRyu Nagata, Seiji Katayama, Ken-Ichi Ohtani, Hiroyasu Tanaka, Kozo Shimago
JournalCurrent topics in medicinal chemistry (Curr Top Med Chem) Vol. 6 Issue 7 Pg. 733-45 ( 2006) ISSN: 1568-0266 [Print] Netherlands
PMID16719813 (Publication Type: Journal Article, Review)
Chemical References
  • Indoles
  • Quinoxalines
  • Receptors, Glycine
  • indole-2-carboxylic acid
  • Kynurenic Acid
  • Indoles (chemical synthesis, chemistry, pharmacology)
  • Kynurenic Acid (chemical synthesis, chemistry, pharmacology)
  • Models, Molecular
  • Quinoxalines (chemical synthesis, chemistry, pharmacology)
  • Receptors, Glycine (antagonists & inhibitors)
  • Structure-Activity Relationship

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: