Effects of subacute treatment with benzopyranopyrimidines in hemostasis and experimental thrombosis in mice

The antithrombotic activity of a series of benzopyranopyrimidine derivatives was investigated in plateletdependentand independent pulmonary thromboembolism in mice. Intraperitoneal subacute treatment with 2-morpholino derivative 3c significantly prevented paralysis due to collagen plus epinephrine-induced pulmonarythrombosis while 2-piperidino substituted derivative 3h significantly protected mice from paralysis caused bythrombin-induced intravascular fibrin formation at dosage not affecting bleeding time. These compounds,previously proved to be effective as antiplatelet agents in vitro, were in vivo more potent as antithrombotics thanlysine acetylsalicylate and possessed lower prohemorrhagic activity than the reference drug. Although theirineffectiveness on clotting times, PT and APTT, allows the involvement of coagulation pathways to be ruled out,the mechanisms underlying the favourable benefit risk ratio for these two compounds remain to be further clarified.