Irreversible enzyme inhibitors. Inhibitors of guinea pig complement derived by quaternization of substituted pyridines with benzyl halides

Abstract

A series of 83 compounds derived from hydrocarbon-substituted pyridines by quaternization with PhCH2Br usually containing a 2-SO2F or 6-Cl-2-SO2F group was synthesized and evaluated as inhibitors of guinea pig complement [C] and in most cases its C.hivin.1 component [activated 1st C component]. The most active compounds were 3-(4-phenylphenylbutyl)-N-(6-chloro-2-fluorosulfonylbenzyl)pyridinium bromide and 3-(4-phenylphenylbutyl)-N-(2-fluorosulfonylbenzyl)pyridinium bromide, each showing 50% inhibition at 7.8 .mu.M. The most effective irreversible inhibitor of the C.hivin.1 component was N-(6-chloro-2-fluorosulfonylbenzyl)-5,6-benzoquinolinium bromide, which showed 50% inhibition at 4 .mu.M.