2-PYRIDYLARYLHYDRAZONE DERIVATIVES, A NEW CLASS OF PLATELET-AGGREGATION INHIBITORS

A series of 2-pyridylarylhydrazone derivatives was synthesized and com pared with a previously reported pyrazole series, i.e., 4-acylpyrazoly larylhydrazone and 5-pyrazolylarylhydrazone, which present antiplatele t aggregation activity. The structures of these pyridylarylhydrazone d erivatives were designed on the basis of the known bioisosteric relati onship of the heteroaromatic ring. The antiplatelet aggregation activi ty was measured in vitro on citrated platelet-rich rabbit plasma in wh ich aggregation was induced with 5 mu M ADP, 5 mu g/ml collagen and 20 0 mu M arachidonic acid. Eighteen compounds belonging to the pyridine series were tested at 1 mM concentration and none inhibited ADP-induce d rat,bit platelet aggregation. 2-(2-Formylfurane)pyridylhydrazone exh ibited a highly potent inhibitory activity on arachidonic acid-induced aggregation, with an IC50 of 0.35 mu M These results suggest that the hydrazone unit and the 2-furyl moiety of the arylhydrazone framework are important pharmacophores for antiplatelet activity.