3-(2-Carbamoylvinyl)-4,5-dimethylpyrrole-2-carboxylic acids as ligands at the NMDA glycine-binding site: a study on the 2-carbamoylvinyl chain modification

Abstract

Twenty 4,5-dimethylpyrrole-2-carboxylic acids ( 5a– t) with different 2-carbamoylvinyl chains in position 3 were prepared to further investigate the relationships between structure and in vitro affinity for the strychnine-insensitive glycine-binding site. None of these compounds was superior to ( E)-3-( N-phenyl-2-carbamoylvinyl)-4,5-dimethylpyrrole-2-carboxylic acid III (p K i=6.70), which was taken as a reference standard, but overall the results obtained indicate that the N-phenyl-2-carbamoylvinyl substituent of III may be replaced with the N-(1-adamantyl)-2-carbamoylvinyl group as in 5h (p K i=6.20) without considerable loss of affinity. This finding adds to previous knowledge.