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

Article abstract of DOI:10.1016/0960-894X(96)00031-5

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.