New Excitatory Amino Acid Receptor Antagonists

Excitatory amino acid is a predominant excitatory neurotransmitter of the central nervous system(CNS). The increasing evidences show that abnormal activation of excitatory amino acid receptor may associated with several disorders of the central nervous system. Excitatory amino acid receptor antagonist may have important therapeutic potential in the treatment of certain disease states.Two new types of EAA receptor antagonists have been designed, the structures featuring quinolinones with annexed lactonic or lactamic functions respectively. Eleven different synthetic routes have been performed to prepare these compounds. So far forty compounds have been synthesized, among them thirty-eight compounds are unknown. The antagonist activities of twenty compounds have been evaluated by the radio-labeling ligand binding test. Some of them are superior in the activity to those published from the recent literature. The energies of all compounds have been minimized by molecular mechanics in SGI workstation. The structure-activity relationships have been analyzed.