Tricyclic Quinoxalinediones, Aza-kynurenic Acids, and Indole-2- Carboxylic Acids as In Vivo Active NMDA-Glycine Antagonists

Title: Tricyclic Quinoxalinediones, Aza-kynurenic Acids, and Indole-2- Carboxylic Acids as In Vivo Active NMDA-Glycine Antagonists

Volume: 6 Issue: 7

Author(s): Ryu Nagata, Seiji Katayama, Ken-ichi Ohtani, Hiroyasu Tanaka and Kozo Shimago

Affiliation:

Keywords: N-Methyl-D-Aspartate, NMDA-glycine antagonist, SM-18400, SM-31900, tricyclic quinoxalinedione, tricyclic indole-2-carboxylic acid

Abstract: This review article describes the development of in vivo active antagonists for the glycine binding site of the NMethyl- 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.

Cite this article as:

Nagata Ryu, Katayama Seiji, Ohtani Ken-ichi, Tanaka Hiroyasu and Shimago Kozo, Tricyclic Quinoxalinediones, Aza-kynurenic Acids, and Indole-2- Carboxylic Acids as In Vivo Active NMDA-Glycine Antagonists, Current Topics in Medicinal Chemistry 2006; 6 (7) . https://dx.doi.org/10.2174/156802606776894500