Inhibitors of kinin-forming enzymes

The typical trypsin-like protease in animals were plasmin, kallikrein, thrombin, factor X, XI, XII, cathepsin B, plasminogen tissue activator and urokinase, and so on. Among them plasmin and kallikrein have kinin-forming activity. A synthetic reversible inhibitor of plasmin, and anticoagulant factor of blood, has been extensively studied. The first effective fibrinolytic inhibitor, e-aminocaproic acid (eACA) was discovered by Okamoto, et al. in 1958 (1). This discovery was followed several years later in 1964 by an announcement of two additional inhibitors which were shown to possess greater potency; trans-4-aminomethyl-cyclohexanecarboxylic acid (trans-AMCHA [2]) and p-aminomethyl-benzoic acid (3).