IRREVERSIBLE ENZYME INHIBITORS .164. PROTEOLYTIC ENZYMES .14. INHIBITION OF GUINEA PIG COMPLEMENT BY META-SUBSTITUTED BENZAMIDINES

A series of 33 meta-substituted benzamidines were evaluated as inhibitors of guinea pig complement-sheep red blood cell-antibody system in order to determine the optimum substituents for inhibition. Since some of the benzamidines with meta-hydrocarbon substituents caused severe lysis of the red blood cells in the absence of complement, optimum hydrophobic interaction with minimal lysis was determined. The activity peaked at n-amyloxy (15) and isoamyloxy (16) which showed 50% inhibition at 0.5 mM; n-butoxy (14) showed less inhibition and n-hexyloxy (17) caused extensive lysis of the red blood cells. m-Alkyl substituents were less effective than m-alkoxy. Similar results were seen with phenylalkyl and phenylalkoxy substituents; m-phenylbutyl (30) and m-phenylbutyloxy (20) showed extensive lysis of the red blood cells, but m-phenylpropoxy (19) was an effective inhibitor at 0.5 mM. The best inhibitor showing no lysis was still the previously described m-phenoxypropyloxybenzamidine (21)4 which at 0.5 m.M showed 50%. inhibition of complement. © 1969, American Chemical Society. All rights reserved.