Antithrombotic Activity of a Potent, New Agent, 6,7-Dichloro-1,2,3,5-Tetrahydroimidazo[2,1-B] Quinazolin-2-One Hydrochloride Monohydrate
A potent, new anti-thrombotic agent, 6 ,7-dichloro-l,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-one hydrochloride monohydrate (BL-4162A) has been evaluated for activity against induced platelet aggregation in a series of in vitro and ex vivo experiments using platelet rich plasma (PRP) from various species including man. In addition, the compound’s potential utility as an antithrombotic agent has been tested in various in vivo animal models including two models of induced thrombosis involving both large and small vessels. Aggregometry was employed to test the ability of BL-4162A to inhibit platelet aggregation induced by aggregating agents such as ADP, collagen, thrombin and antigen-antibody complexes. The compound’s antithrombotic activity was evaluated in small vessels using the biolaser-rabbit ear chamber technique while the effect of BL-4162A on large vessel thrombosis was assessed against electrically-induced carotid artery thrombosis in dogs. Results indicate that BL-4162A inhibits platelet aggregation in the range of 0.08 to 0.68 pg/ml. Platelet antiaggregating activity was also observed in ex vivo aggregometry studies in dogs and rats at oral doses in the range of 1 to 10 mg/kg. Of particular interest, is the fact that BL-4162A effectively inhibited thrombosis in both animal models employed over the same oral dosage range. Results of the above investigations as well as an appreciable duration of action suggest that BL-4162A may be an important candidate for clinical evaluation in thromboembolism.