A new class of agonists and antagonists of N-methyl-D-aspartic acid receptors: Derivatives of imidazole-4,5- and pyrazole-3,4-dicarboxylic acids

Abstract

Studies of imidazole-4,5- and pyrazole-3,4-dicarboxylic acid derivatives revealed a number of new agonists and antagonists of N-methyl-D-aspartic acid (NMDA) receptors. Studies were based on whole-cell patch-clamp methods applied to rat hippocampus pyramidal cells. Increases in the lipophilicity of the environment of the nitrogen atom, keeping the distance between the terminal acid functions constant, led to a weakening of NMDA antagonism and increases in NMDA antagonism. Increases in the lipophilicity around the nitrogen atom could also lead to less of selectivity in the interaction with NMDA receptors and the appearance of non-NMDA antagonist properties.

Unexpected formation of imidazole-4,5-dicarboxylic acid in the oxidation of 2-substituted benzimidazoles with hydrogen peroxide

“…On the other hand, 4,5-IDC derivatives are interesting for pharmacology [4][5][6]. Amides derived from 4,5-IDC stimulate the central nervous system and exhibit antiproliferative activity [5], while 2-alkyl-substituted derivatives are NMDA receptor ligands [6]. …”