5-Aminomethylquinoxaline-2,3-diones, Part III: Arylamide derivatives as highly potent and selective glycine-site NMDA receptor antagonists

P Acklin; H Allgeier; Y P Auberson; S Bischoff; S Ofner; D Sauer; M Schmutz

doi:10.1016/s0960-894x(98)00055-9

5-Aminomethylquinoxaline-2,3-diones, Part III: Arylamide derivatives as highly potent and selective glycine-site NMDA receptor antagonists

Bioorg Med Chem Lett. 1998 Mar 3;8(5):493-8. doi: 10.1016/s0960-894x(98)00055-9.

Authors

P Acklin¹, H Allgeier, Y P Auberson, S Bischoff, S Ofner, D Sauer, M Schmutz

Affiliation

¹ Novartis Pharma AG, Basel, Switzerland. acklin@fmi.ch

PMID: 9871605
DOI: 10.1016/s0960-894x(98)00055-9

Abstract

A series of quinoxaline-2,3-diones with very high affinity to the glycine site of the NMDA receptor has been discovered. In contrast to the 7-nitro derivatives, the most potent 7-bromo substituted compounds were highly selective for the glycine site. Although none of the described compounds were active in the electroshock model in mice, 1a displayed significant protection in the quinolinic acid-induced excitotoxicity model in vivo.

MeSH terms

Animals
Excitatory Amino Acid Antagonists / chemistry
Excitatory Amino Acid Antagonists / pharmacology*
Glycine / metabolism*
Mice
Quinoxalines / chemistry
Quinoxalines / pharmacology*
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
Receptors, N-Methyl-D-Aspartate / metabolism
Structure-Activity Relationship

Substances

Excitatory Amino Acid Antagonists
Quinoxalines
Receptors, N-Methyl-D-Aspartate
Glycine