Synthesis and Study of Psychotropic Activity of 1-Substituted 4-Amino-5-oxoprolines

Abstract

1-Substituted (2S,4S)-4-amino-5-oxoprolines have been obtained by nucleophilic substitution of bromine in dimethyl (2S,4RS)-4-bromo-N-phthaloylglutamate followed by isolation of the predominant (2S,4S)-diastereomer and removal of protecting groups. The psychotropic activity of the obtained compounds has been studied after a single administration in experimental animals. 4-Amino-1-(4-bromophenyl)-5-oxoproline and especially 4-amino-1-(4-aminophenyl)-5-oxoproline showed pronounced anxiolytic activity in the Elevated plus maze test. (2S,4S)-4-Amino-5-oxoprolines containing 4-methylphenyl, 4-bromophenyl, 4‑aminophenyl, and 2,3-dimethyl-5-oxo-1-phenyl-3-pyrazolin-4-yl substituents at the 1-position exhibited nootropic activity: they improved the formation and retention of the memory trace in the Passive avoidance test and the Active avoidance test (Extrapolation escape test).