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

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 and in most cases its C1 component. The most active compounds were 3-(4-phenylphenylbutyl)-N-(6-choro-2-fluorosulfonylbenzyl) pyridinium bromide (43) and 3-(4-phenylphenylbutyl)-N-(2-fluorosulfonylbenzyl) pyridinium bromide (44), each showing 50% inhibition at 7.8 muM. The most effective irreversible inhibitor of the C1 component was N-(6-chloro-2-fluorosulfonylbenzyl)-5,6-benzoquinolinium bromide (87), which showed 50% inhibition at 4 muM.