Abstract:

In order to explore the influence of methoxy substitution in benzene ring, methylation of tyramine hydroxyl and cinnamoyl-tyramine amines, on anti-platelet aggregation activities analogues, cinnamoyl-tyramine amide analogues were synthesized via condensation and methylation with eight benzaldehyde derivatives as raw materials. The structures of synthesized compounds were characterized by nuclear magnetic resonance spectroscopy(NMR), mass spectrometry(MS) and single crystal diffraction. Based on variable-temperature NMR, rotational isomerization based on amide C—N bond was studied for compounds 4a~4h. Their anti-platelet aggregation activities were tested in vitro and assayed by Born test. The results show that nine analogues are more active than podocarpamide. Specifically, compounds 2c, 4c and 4f show inhibition rates of 50.03%, 60.87% and 53.33%, respectively, at 200 μmol/L. The preliminary structure-activity relationship studies on these compounds indicate that 4-methoxy substituent is the most favorable for anti-ADP(adenosine-diphosphate) induced platelet aggregation, and methylated hydroxyl group on ring B and the amide nitrogen also increase the activities to some extent.

Key words: thrombus, variable-temperature nuclear magnetic resonance spectroscopy, rotational isomerization, antiplatelet aggregation