Irreversible enzyme inhibitors. 202. Candidate active-site-directed irreversible inhibitors of 5-fluoro-2'-deoxyuridine phosphorylase from Walker 256 rat tumor derived from 1-benzyl-5-(3-ethoxybenzyl)uracil.

Six candidate irreversible inhibitors of uridine--deoxyuridine phosphorylase (EC 2.4.2.3) from Walker 256 rat tumor were synthesized. These compounds connect a terminal sulfonyl fluoride group to the 1-benzyl moiety of 1-benzyl-5-(3-ethoxybenzyl)uracil (9). Although none of the compounds were irreversible inhibitors, the four 3-[(fluorosulfonyl)benzamido] analogues (14-17) of 9 were good reversible inhibitors of the enzyme which were complexed from 125- to 360-fold better than the substrate, 5-fluoro-2'-deoxyuridine.