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.
