IRREVERSIBLE ENZYME INHIBITORS .161. PROTEOLYTIC ENZYMES .13. INHIBITORS OF GUINEA PIG COMPLEMENT DERIVED BY QUATERNIZATION OF 3-ACYLAMIDOPYRIDINES WITH ALPHA-BROMOMETHYLBENZENESULFONYL FLUORIDES .2.

Twenty quaternary salts (26) derived from N-(3-pyridyl)- or N-(3-pyridylmethyl)-3,4-dichlorophenoxyacetamide (24) by reaction with substituted fluorosulfonylbenzyl bromides (25) were evaluated as inhibitors of the lysis of sheep red blood cells by hemolysin and complement. The most effective compound was 3-(3,4-dichlorophenoxyacetamido)-N-(6-chloro-2-fluorosulfonylbenzyl)pyridimum bromide (16): at 62 and 31 μM, 16 showed 84 and 45%, inhibition, respectively. A number of these compounds were excellent irreversible inhibitors of α-chymotrypsin: for example, 16 had an I50 ∼ Ki of 3.7 μM and at this Concentration gave 98% inactivation in 2 min. © 1969, American Chemical Society. All rights reserved.