Tricyclic Quinoxalinediones, Aza-kynurenic Acids, and Indole-2- Carboxylic Acids as In Vivo Active NMDA-Glycine Antagonists
| Autor: | Ken-ichi Ohtani, Seiji Katayama, Ryu Nagata, Kozo Shimago, Hiroyasu Tanaka |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular Indole test chemistry.chemical_classification Indoles Chemistry Stereochemistry Carboxylic Acids General Medicine Glycine receptor antagonist Pharmacology Kynurenic Acid In vitro Structure-Activity Relationship Receptors Glycine Glycine binding In vivo Quinoxalines Drug Discovery NMDA receptor Moiety Tricyclic |
| Zdroj: | Current Topics in Medicinal Chemistry. 6:733-745 |
| ISSN: | 1568-0266 |
| DOI: | 10.2174/156802606776894500 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|