IRREVERSIBLE ENZYME INHIBITORS .150. PROTEOLYTIC ENZYMES .9. (3,4-DICHLOROPHENOXYACETAMIDO)PYRIDINES BRIDGED BY A QUATERNARY SALT TO A TERMINAL SULFONYL FLUORIDE . POTENT IRREVERSIBLE INHIBITORS OF ALPHA-CHYMOTRYPSIN

Six candidate irreversible inhibitors (18-23) for α-chymotrypsin were synthesized by quaternization of N-(β-pyridyl)-(25) and N-(β-pyridylmethyl)-3,4-dichlorophenoxyacetamide (26) with m-and p-bromomethylbenzenesulfonyl fluoride and N-bromoacetylsulfanilyl fluoride (29); all six were excellent irreversible inhibitors at a Ki, concentration, inactivating the enzyme with a half-life of <2 min. One of the best inhibitors was the quaternary salt (20) formed between 26 and 29; at a Ki, = 7 μM concentration, 20 showed 89% inactivation of the enzyme in 2 min and 100% in 4 min at 24°. © 1969, American Chemical Society. All rights reserved.