title: Novel bis(benzamidino) compounds with an aromatic central link. Inhibitors of thrombin, pancreatic kallikrein, trypsin, and complement.
abstract: A series of novel aromatic diamidines was synthesized and evaluated for antiproteolytic activity. The compounds were distignuished by inclusion of an aromatic ring structure--either benzene or bisbenzene or naphthalene--in the link between two amidinobenzene moieties. A highly potent inhibitor of bovine thrombin was discovered in alph, alph'-bis(4-amidino-2-iodophenoxy)-p-xylene with a Ki value of 1.1 X 10(-7) M (pH 8.1, 37 degrees), while alpha, alpha'-bis(4-amidino-2-iodophenoxy)-m-xylene was found to be an outstanding inhibitor of porcine pancreatic kallikrein (Ki = 3.1 X 10(-8) M). Several of the compounds investigated also demonstrated a considerable blocking effect on typsin and on the complement-dependent immune lysis of red cells.
mesh_terms: D000578:Amidines / Q000138:chemical synthesis*; D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000818:Animals; D001550:Benzamidines / Q000138:chemical synthesis* / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D003169:Complement Inactivator Proteins; D003864:Depression, Chemical; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D010179:Pancreas / Q000201:enzymology; D051381:Rats; D013552:Swine; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013925:Thromboplastin; D014361:Trypsin Inhibitors / Q000138:chemical synthesis*
chemical_list: D000578:Amidines; D001550:Benzamidines; D003169:Complement Inactivator Proteins; D014361:Trypsin Inhibitors; D013925:Thromboplastin; D007610:Kallikreins; D013917:Thrombin; D000581:Amidohydrolases