Abstract: AIM: To study the effects and mechanisms of a novel sulfonylureous compound 1-{4-[2-(4-bromobenzenesulfonaminoethyl) phenylsufonyl}-3-(trans-4-methylcyclohexyl) urea, G004, on antithrombosis. METHODS: The influence of compound G004 on the vasoconstrictor action, platelet aggregation and thrombosis formation was studied.The effects of compound G004 on the tail vein bleeding time in mice was examined.The influence of compound G004 on the release of prostanglandin I2 and thromboxan A2 from ECV304 cells was investigated.The measurement of cytosolic free Ca²⁺ in attached ECV304 cells loaded with Fluo3/AM was carried out. RESULTS: Compound G004 did not inhibit the contraction of rat aorta rings induced by norepinephrine or potassium chloride, but potently inhibit human platelet aggregation challenged by arachidonic acid and adenosine diphosphate.Compound G004 significantly prolonged the tail vein bleeding time in mice and occlusion time of carotid artery in experimentally thrombotic rats.Compound G004 reduced mice mortality induced by the collagen plus epinephrine in a dose-dependent manner.Compound G004 enhanced PGI₂ release and reduced TXA₂ secretion from ECV304 cells.G004 had no effect on the increase of cytosolic free Ca²⁺ induced by patassium chloride.CONCLUSION: The compound G004 has a remarkable antithrombotic effect in vivo.Its active mechanism may be attributed to inhibition of platelet aggregation, enhancing PGI₂ generation and decreasing TXA₂ secretion from human umbilical vein endothelium.

Key words: G004, platelet aggregation, thrombosis, PGI₂, TXA₂, Fluo3/AM