Antithrombotic properties of XXXX , a new, orally active @entity7102 inhibitor.

@entity95 @entity49 @entity72234 @entity2613 @entity7102 @entity35 @entity715
N-[3-[[[(1S)-4-(5-Amino-2-pyridinyl)-1-[[4-difluoromethylene)-1-piperidinyl]carbonyl]butyl]amino]sulfonyl][1,1'-biphenyl]-2-yl]acetamide hydrochloride ( @entity72234 ) is a novel, potent, and selective @entity7102 inhibitor. We have examined the antithrombotic properties of @entity72234 administered by i.v. and p.o. routes in several different animal @entity715 models in comparison with reference antithrombotic agents. Oral administration of @entity72234 produced dose-related antithrombotic effects in the following models; @entity35 @entity49 ( @entity2613 (50) 0.9 mg/kg p.o.), @entity35 silk thread arterio-venous (AV) shunt ( @entity2613 (50) 3.8 mg/kg p.o.), @entity35 thromboplastin-induced AV shunt ( @entity2613 (50) 3.1 mg/kg p.o.), @entity35 carotid artery @entity715 ( @entity2613 (200) 5.9 mg/kg p.o.), and @entity95 @entity49 ( @entity2613 (50) 7.5 mg/kg p.o.). Administered as an i.v. bolus, @entity72234 showed antithrombotic activity in the above models with @entity2613 (50)/ @entity2613 (200) values in the range of 0.2 to 1.9 mg/kg i.v. @entity72234 increased @entity35 tail transection bleeding time at doses > or =10 mg/kg p.o. In the @entity35 thromboplastin-induced AV shunt model, @entity72234 10 mg/kg p.o. produced marked antithrombotic effects at 30, 60, 120, and 240 min after administration. Hence, @entity72234 demonstrates potent oral antithrombotic properties in animal venous, AV-shunt, and @entity715 models.
