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.
D000818:Animals; D003174:Complement C1 Inactivator Proteins; D003169:Complement Inactivator Proteins; D004791:Enzyme Inhibitors / Q000032:analysis / Q000138:chemical synthesis*; D006168:Guinea Pigs; D011726:Pyridinium Compounds / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D003174:Complement C1 Inactivator Proteins; D003169:Complement Inactivator Proteins; D004791:Enzyme Inhibitors; D011726:Pyridinium Compounds