IRREVERSIBLE ENZYME INHIBITORS .165. PROTEOLYTIC ENZYMES .15. INHIBITION OF GUINEA PIG COMPLEMENT BY DERIVATIVES OF M-PHENOXYPROPOXYBENZAMIDINE

A series of 28 derivatives of m-phenoxypropoxybenzamidine (2) with substituents on the phenoxy moiety were synthesized, then evaluated as inhibitors of the guinea pig complement-sheep red blood cell-antibody system. Small substituents such as Cl, NO2, OCH3, NH2, AcNH, or COOCH3 give at best only fourfold more effective inhibition. Larger substituents such as substituted benzamido or substituted phenylureido gave 6-30-fold better inhibition. The best inhibitor of the series was m-[m-(p-nitrophenylureido)phenoxypmpoxy]benzamidine (29) which at 62μM showed 95% inhibition of guinea pig complement and 60% inhibition at 16μM. Thus 29 was 30-fold more effective than 2 and about 400-fold more effective than benzamidine. © 1969, American Chemical Society. All rights reserved.