Synthesis and structure-activity study of protease inhibitors. V. Chemical modification of 6-amidino-2-naphthyl 4-guanidinobenzoate.
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, C1r and C1s 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-1H-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.
Nakayama
T
T
Research Laboratories, Torii & Co., Ltd., Chiba, Japan.
Taira
S
S
Ikeda
M
M
Ashizawa
H
H
Oda
M
M
Arakawa
K
K
Fujii
S
S
D000818:Animals; D001550:Benzamidines; D003169:Complement Inactivator Proteins / Q000138:chemical synthesis; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001550:Benzamidines; D003169:Complement Inactivator Proteins; D006146:Guanidines; D011480:Protease Inhibitors; C032855:nafamostat