ONO-5046, A NOVEL INHIBITOR OF HUMAN NEUTROPHIL ELASTASE

ONO-5046, N-[2-[4-(2,2-Dimethylpropionyloxy)phenylsulfonylamino]benzoyl] aminoacetic acid, competitively inhibited human neutrophil elastase (IC50=0.044 μM, Ki = 0.2μM). It also inhibited leukocyte elastase obtained from rabbit, rat, hamster and mouse. However, ONO-5046 did not inhibit trypsin, thrombin, plasmin, plasma kallikrein, pancreas kallikrein, chymotrypsin and cathepsin G even at 100μM. In in vivo studies, ONO-5046 suppressed lung hemorrhage in hamster (ID50 = 82 μg/kg) by intratracheal administration and increase of skin capillary permeability in guinea pig (ID50 = 9.6 mg/kg) by intravenous administration, both of which were induced by human neutrophil elastase. © 1991.