3-Hydroxy-quinolin-2-ones: Inhibitors of [3H]-glycine binding to the site associated with the NMDA receptor

✍ Scribed by Sing-Yuen Sit; Frederick J. Ehrgott; Jinnian Gao; Nicholas A. Meanwell

• Publisher: Elsevier Science
• Year: 1996
• Tongue: English
• Weight: 294 KB
• Volume: 6
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/0960-894x(96)00031-5

✦ Synopsis

A series of substituted 3-hydroxy-quinolin-2-one derivatives 6 was synthesized and evaluated as inhibitors of [3H]-glycine and [3H]-AMPA binding to rat cortical membranes. These compounds were generally found to be more potent ligands for the NMDA-associated glycine binding site than the AMPA receptor. Affinity for the glycine site was found to be influenced by both the electronic and steric properties associated with the C-4 substituent and the nature and pattern of substitution of the aromatic ring. The most active compound in this series, 6y, displaces [3H]-glycine with an IC50 of 29 nM.

Excitatory amino acids have been implicated in the pathophysiology of acute neurodegenerative disorders including stroke, head trauma, and spinal cord injury, as well as the more chronic processes associated with Alzheimer's and Huntington's diseases. 1 The elucidation of the spectrum of excitatory amino acid receptor subtypes and their inherent complexity, particularly with respect to the NMDA receptor, has characterized