IRREVERSIBLE ENZYME INHIBITORS .152. PROTEOLYTIC ENZYMES .X. INHIBITION OF GUINEA PIG COMPLEMENT BY SUBSTITUTED BENZAMIDINES

The inhibition of guinea pig complement was investigated with 54 amidines, alkylamines, aralkylamines, and guanidines previously synthesized for inhibition of trypsin: based on these results, 15 new candidate inhibitors were synthesized. The I test inhibitors were derived from benzamidine, the hitter being a fair inhibitor. Inhibition by benzamidine was considerably enhanced by meta substituents such as isoamyloxy (18), phenoxypropyloxy (22), and p-acetamiduphenylbutyl (27). Of 28 paw-substituted benzamidines, only the benzamidine with an O(CH2)4OC6H4-p-NHCONHC6H3-2-OMe-5-SO2F substituent (37) showed good inhibition. The most potent inhibitor in the literature, maleopimaric acid (2), showed about 50% inhibition at 0.5 m.M; the same concentration of 18, 22, and 27 showed 50%, inhibition, whereas only 0.062 m.M of 37 was required. However, maleopimaric acid showed better total inhibition than the three benzamidines when the concentrations of the four compounds were increased. © 1969, American Chemical Society. All rights reserved.