A class of novel N-(1-methyl-β-carboline-3-carbonyl)-N'-(aminoacid-acyl)-hydrazines: aromatization leaded design, synthesis, in vitro anti-platelet aggregation/in vivo anti-thrombotic evaluation and 3D QSAR analysis.

High anti-thrombotic activity of aminoacid modified tetrahydro-β-carbolines was generally correlated with a small proximity of the side chain of the aminoacid residue to the carboline-cycle. This paper explored that the aromatization of the tetrahydro-β-carboline-cycle of N-(1-methyl-β-tetrahydrocarboline-3-carbonyl)-N'-(aminoacid-acyl)-hydrazines leaded to N-(1-methyl-β-carboline-3-carbonyl)-N'-(aminoacid-acyl)-hydrazines and decreased the proximity of the side chain of the aminoacid residue to the carboline-cycle. The in vitro activities of inhibiting pig platelet aggregation induced by PAF, ADP, and AA, as well as the in vivo anti-thrombotic activities of inhibiting rat thrombosis of these aromatized derivatives were generally higher than that of N-(1-methyl-β-tetrahydrocarboline-3-carbonyl)-N'-(aminoacid-acyl)-hydrazines. The understanding was also obtained from the 3D QSAR analysis.