Design, synthesis and antiplatelet evaluation of tetramethylpyrazine/chalcone hybrids

In order to search for new antiplatelet agents with higher potency, a series of tetramethylpyrazine(TMP)/chalcone hybrids( 2 - 26 )were synthesized and evaluated based on the principle of bioisostere and hybridization. They exerted inhibitory activity against adenosine diphosphate(ADP)-induced and arachidonic acid(AA)-induced platelet aggregation to varied extent. Among them, compound 8 was the most potent with IC₅₀ of 0. 14 mmol/L on ADP-induced platelet aggregation(9. 1 folds of TMP and 10. 5 folds of chalcone)and 0. 09 mmol/L on AA-induced platelet aggregation(8. 8 folds of TMP and 10. 0 folds of chalcone), which was superior to clinically used anti-platelet drug aspirin(ASP, IC₅₀=0. 15 mmol/L).