N-[3-[[[(1S)-4-(5-Amino-2-pyridinyl)-1-[[4-
difluoromethylene)-1-piperidinyl]carbonyl]butyl]amino]sulfonyl][1,1'-
biphenyl]-2-yl]
acetamide hydrochloride (
SSR182289A) is a novel, potent, and selective
thrombin inhibitor. We have examined the antithrombotic properties of
SSR182289A administered by i.v. and p.o. routes in several different animal
thrombosis models in comparison with reference
antithrombotic agents.
Oral administration of
SSR182289A produced dose-related antithrombotic effects in the following models; rat
venous thrombosis (ED(50) 0.9 mg/kg p.o.), rat
silk thread arterio-venous (AV) shunt (ED(50) 3.8 mg/kg p.o.), rat
thromboplastin-induced AV shunt (ED(50) 3.1 mg/kg p.o.), rat
carotid artery thrombosis (ED(200) 5.9 mg/kg p.o.), and rabbit
venous thrombosis (ED(50) 7.5 mg/kg p.o.). Administered as an i.v. bolus,
SSR182289A showed antithrombotic activity in the above models with ED(50)/ED(200) values in the range of 0.2 to 1.9 mg/kg i.v.
SSR182289A increased rat tail transection bleeding time at doses > or =10 mg/kg p.o. In the rat
thromboplastin-induced AV shunt model,
SSR182289A 10 mg/kg p.o. produced marked antithrombotic effects at 30, 60, 120, and 240 min after administration. Hence,
SSR182289A demonstrates potent oral antithrombotic properties in animal venous, AV-shunt, and arterial
thrombosis models.