Synthesis and structure ― activity study of protease inhibitors. IV: Amidinonaphthols and related acyl derivatives

Various amidinonaphthols and their acyl derivatives were synthesized and evaluated for inhibitory activities against trypsin, plasmin, kallikrein, thrombin, Clr and Cls, as well as against in vitro complement-mediated hemolysis. 6-Amidino-2-naphthyl 4-guanidinobenzoate (74, FUT-175) was found to have potent inhibitory activities, particularly against trypsin (IC50 : 0.02 μM), Clr (IC50 : 0.1 μM) and Cls (IC50 : 0.02 μM), and to be highly effective in inhibiting the complement-mediated hemolysis (IC50 : 0.03μM). FUT-175, furthermore, showed considerable effectiveness in the systemic Forssman shock reaction, in which involvement of the complement system as the pathogenetic factor is well established.