Synthesis and Structure-Activity Study of Protease Inhibitors. V.1) Chemical Modification of 6-Amidino-2-naphthyl 4-Guanidinobenzoate

Abstract

By developing 6-amidino-2-naphthyl 4-guanidinobenzoate (I, FUT-175) as a basic structure, its various derivatives were synthesized and their inhibitory activities on trypsin, plasmin, kallikrein, thrombin, Clr and Cls as well as on complement-mediated hemolysis were examined. The protective effect of these compounds on complement-mediated Forssman shock was also examined in guinea pigs. 6-Amidino-2-naphthyl 4-[(4,5-dihydro-l//-imidazol-2-yl)amino]-benzoate (41, FUT-187) was found to be a suitable compound for oral administration with anti-complement activity superior to that of compound I. © 1993, The Pharmaceutical Society of Japan. All rights reserved.