ANTITHROMBOTIC EFFECTS OF THE NOVEL INHIBITOR OF THROMBIN-INDUCED PLATELET-AGGREGATION AND THROMBUS FORMATION, 3-[2-([1,1' 2',1'']-TERPHENYL-4'-YL)ETHYL]PHENOXYACETIC ACID/

The new compound 1,1,1':2',1'']-terphenyl-4'-yl)ethyl]phenoxyacetic ac id (F1070) was synthesized and its effects on platelet aggregation ind uced by thrombin, thrombin receptor agonist peptide (TRAP), ADP and co llagen were evaluated in humans, guinea pigs and rats, and were compar ed with the effects of the thrombin antagonists argipidine and (D)Phe- Pro-Arg-CH2Cl (FPR). F1070 inhibited the platelet aggregation induced by these agonists and was highly selective in its inhibition of thromb in. F1070 inhibited fibrin formation induced by thrombin, but far less effectively than argipidine. In a guinea pig model of extracorporeal circulation thrombosis, F1070 (10 mg/kg p.o.) significantly inhibited the development of a thrombus. F1070 is thus a key compound that shoul d facilitate the development of new orally active antithrombotic drugs that are specific for thrombin.