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5-benzylacyclouridine and 5-benzyloxybenzylacyclouridine, potent inhibitors of uridine phosphorylase.

Authors
  • Niedzwicki, J G
  • Chu, S H
  • el Kouni, M H
  • Rowe, E C
  • Cha, S
Type
Published Article
Journal
Biochemical Pharmacology
Publisher
Elsevier
Publication Date
May 15, 1982
Volume
31
Issue
10
Pages
1857–1861
Identifiers
PMID: 7104017
Source
Medline
License
Unknown

Abstract

Various pyrimidine acyclonucleosides (1-(2'-hydroxyethoxymethyl)uracils) are specific inhibitors of uridine phosphorylase[Niedzwicki et al., Biochem. Pharmac. 30, 2097 (1981) )). 5-Benzyluracils have also been shown to inhibit this enzyme[Baker and Kelley, J. med. Chem. 13, 461 (1970); Woodman et al., Biochem. Pharmac. 29, 1059 (1980) )). We have synthesized the acyclonucleoside analogs of 5-benzyluracil (BU) and 5-benzyloxybenzyluracil (BBU). These compounds, 5-benzyl-1-(2'-hydroxyethoxymethyl)uracil (BAU) and 5-(m-benzyloxybenzyl)-1-(2'-hydroxyethoxymethyl)uracil (BBAU), are potent inhibitors of uridine phosphorylase. K1 values of 98 and 32 nM were estimated for BAU and BBAU respectively. These compounds are better inhibitors of uridine phosphorylase than BU (K1= 1575 nM), BBU (K1=270 nM), and all other compounds previously tested, and they have no effect on thymidine phosphorylase, uridine-cytidine kinase, or thymidine kinase. Potential chemotherapeutic applications of BAU and BBAU are discussed.

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