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.

• Authors: J L Kelley, B R Baker
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 25 Issue 5 Pg. 600-3 (May 1982) ISSN: 0022-2623 [Print] United States
• PMID: 6211547 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Floxuridine
• Uracil
• Pentosyltransferases
• Uridine Phosphorylase

Topics

• Animals
• Antineoplastic Agents (chemical synthesis)
• Binding Sites
• Carcinoma 256, Walker (enzymology)
• Chemical Phenomena
• Chemistry
• Floxuridine (metabolism)
• Pentosyltransferases (antagonists & inhibitors)
• Rats
• Uracil (analogs & derivatives, chemical synthesis, pharmacology)
• Uridine Phosphorylase (antagonists & inhibitors)