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

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 substitutent 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.