New synthetic inhibitors of C1r̄, C1 esterase, thrombin, plasmin, kallikrein and trypsin

Abstract

p-Guanidinobenzoate derivatives were prepared and their inhibitory effects on trypsin, plasmin, pancreatic kallikrein, plasma kallikrein, thrombin, C1r̄ and C1 esterase were examined. Among the various inhibitors tested, 6′-amidino-2-naphthyl-4-guanidinobenzoate dihydrochloride, 4-(β-amidinoethenyl)phenyl-4-guanidinobenzoate dimethanesulfonate and 4-amidino-2-benzoylphenyl-4-guanidinobenzoate dimethanesulfonate were the most effective inhibitors of trypsin, plasmin, pancreatic kallikrein, plasma kallikrein and thrombin and they strongly inhibited the esterolytic activities of C1r̄ and C1 esterase, and then strongly inhibited complement-mediated hemolysis.