Biomedical subjects
Publications and source records attributed to P Acklin.
N-Substituted 5-aminomethylquinoxalinediones containing carboxy or phosphonic acids yield potent and selective AMPA and/or NMDA (glycine-binding site) antagonists. Phosphonic acid derivatives are particularly water-soluble and display potent anticonvulsant effects in the electroshock-induced convulsion assay in mice.
An exceptionally stable 1:2 complex [FeL(2)](3-) is formed from the ligand H(3)L and Fe(III). In contrast, the affinity of this ligand for other biometals is relatively small. These properties make H(3)L a highly promising candidate for medical applications (e.g. for the treatment of iron overload).
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.
Potent antagonists at the glycine-binding site of NMDA receptors, as well as dual antagonists acting also at AMPA receptors have been identified in a series of 5-arylaminomethylquinoxaline-2,3-diones. A study of the structure-activity relationship of these compounds is reported here.