A novel series of 2-carboxytetrahydroquinolines provides new insights intothe eastern region of glycine site NMDA antagonists

A series of potent 4-substituted tetrahydroquinolines has been synthesized and biologically tested in order to refine the eastern region of the pharma cophore model for glycine site NMDA antagonists concerning the assessment o f lipophilicity, flexibility, and hydrogen bonding. Displacement studies on rat cortical membranes using [H-3]-5,7-dichlorokynurenic acid as a radioli gand indicated that binding affinities are markedly enhanced when additiona l hydrogen-accepting groups are introduced into the eastern region of the 2 -carboxytetrahydroquinolines. Among the most potent ligands were some urea, sulfonylurea, and crown ether compounds as interesting leads for new diagn ostics, especially for the evaluation of PET tracers, which allow biodistri bution studies and NMDA receptor studies in the living organism.