Synthesis and Biological Evaluation of Bridged Analogues of the Platelet Aggregation Inhibitor Trifenagrel

The synthesis and preliminary biological investigation of three methylene bridged heterocyclic analogues of trifenagrel, a potent inhibitor of arachidonate-induced aggregation of platelets, is reported. The synthesis of the compounds is based on the cyclocondensation reaction of a tricyclic 1,2-diketone with an appropriate aldehyde, hydrazide or a diamine to form an imidazole, a 1,2,4-triazine or a pyrazine moiety respectively. In comparison to trifenagrel, its methylene- bridged analogue had much reduced activity, while its pyrazine analogue was devoid of activity.