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A short history of the research work of S. Okamoto and co-workers, for the previous 50 years, is briefly described. In the 1950s, when the physiologic role of fibrinolysis had not been established, they began to seek for compounds that inhibit the action of plasmin. They examined approximately 200 lysine derivatives and discovered epsilon aminocaproic acid(More)
Based on structure-activity relationship studies, we designed and synthesized plasmin (PL) and plasma kallikrein (PK) inhibitors. Trans-(4-aminomethylcyclohexanecarbonyl)-Tyr(O-Pic)-octylamide inhibited PL, PK, urokinase (UK) and thrombin (TH) with IC50 values of 0.53, 30, 5.3 and > 400 microm, respectively.(More)
Based on the structure of Tra-Tyr(O-Pic)-octylamide, a portion of the octylamine was replaced with moieties bearing hydrophobic, basic or acidic groups. Replacement of the C-terminal residue with a moiety bearing a hydrophobic group gave the proper affinity of the inhibitor to both plasmin (PL) and plasma kallikrein (PK). While addition of a basic residue(More)
The molecule of trans-4-aminomethylcyclohexanecarbonylphenylalanine 4-carboxymethylanilide (8), which is a potent and selective inhibitor of plasma kallikrein, can be divided into three parts (P1, P1' and P2'), each of which contains one of the rings. In order to study the role of each part in the manifestation of potent and selective inhibitory activity(More)
With the aim of obtaining selective synthetic inhibitors of plasmin and plasma kallikrein, D-Ile-Phe-Lys-CH2Cl, Ile-Phe-Lys-CH2Cl, D-Ile-Phe-Arg-CH2Cl and Ile-Phe-Arg-CH2Cl were synthesized and their inhibitory activity against plasmin, plasma kallikrein and other trypsin-like serine proteinases was examined. Among them, D-Ile-Phe-Arg-CH2Cl exhibited a(More)