Synthesis and study of antiplatelet and antithrombotic activity of 4-substituted pyroglutamic acids

A series of (2 S ,4 S )-4-amino- N -arylpyroglutamic acids was first obtained by the nucleophilic substitution of bromine atom in dimethyl (2 S ,4 RS )-4-bromo- N -phthaloylglutamate under the action of primary arylamines, followed by the separation of diastereomers and removal of protecting groups by acidic hydrolysis. These compounds were studied for anti-platelet and antithrombotic activity in experiments in vitro and in vivo. Some compounds were identified as exhibiting a significant effect on platelet function, which was manifested in slowing down the process of thrombus formation in the model of arterial and deep vein thrombosis. It was established that the most efficient compound is (2 S ,4 S )-4-amino- N -(4-fluoro-phenyl)pyroglutamic acid, with its effect being comparable to that of acetylsalicylic acid.