title: 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.
abstract: 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.
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001665:Binding Sites; D002279:Carcinoma 256, Walker / Q000201:enzymology*; D055598:Chemical Phenomena; D002621:Chemistry; D005467:Floxuridine / Q000378:metabolism; D010430:Pentosyltransferases / Q000037:antagonists & inhibitors*; D051381:Rats; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014543:Uridine Phosphorylase / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D005467:Floxuridine; D014498:Uracil; D010430:Pentosyltransferases; D014543:Uridine Phosphorylase