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

@article{Niedzwicki19825benzylacyclouridineA5,
  title={5-benzylacyclouridine and 5-benzyloxybenzylacyclouridine, potent inhibitors of uridine phosphorylase.},
  author={J G Niedzwicki and Shih Hsi Chu and Mahmoud H. el Kouni and Elizabeth C. Rowe and Sungman Cha},
  journal={Biochemical pharmacology},
  year={1982},
  volume={31 10},
  pages={
          1857-61
        }
}
5-phenylthioacyclouridine: a potent and specific inhibitor of uridine phosphorylase.
Synthesis of enantiomers of 2′-aminomethyl-5-benzylacyclouridine (AM-BAU) and 2′-aminomethyl-5-benzyloxybenzylacyclouridine (AM-BBAU). Potent inhibitors of uridine phosphorylase
Racemic 2′-aminomethyl-5-benzyl-acyclouridine (AM-BAU, 5) and 2′-aminomethyl-5-benzyloxybenzyla-cyclouridine (AM-BBAU, 6) have been found to be very active inhibitors of uridine phosphorylase [1].
Enhancement of 5-fluoro-2'-deoxyuridine antitumor efficacy by the uridine phosphorylase inhibitor 5-(benzyloxybenzyl)barbituric acid acyclonucleoside.
TLDR
The effect of BBBA on modulating the antitumor efficacy of FdUrd was evaluated in vitro, against the human colon carcinomas D LD-1 and HCT-15 grown in culture, and in vivo, against DLD-1 grown as xenografts in anti-thymocyte serum immunosuppressed mice.
Synthesis of (R - and (S)-1-[[2-Hydroxy-1-(aminomethyl)ethoxy]methyl]-5- benzyluracil, Potent Inhibitors of Uridine Phosphorylase
TLDR
These acyclic pyrimidine amino nucleoside analogues represent a new class of potent uridine phosphorylase inhibitors, which has a bulky hydrophobic substituent at the 5-position in the uracil base, yet has remarkably high water solubility.
Phase I clinical and pharmacological studies of benzylacyclouridine, a uridine phosphorylase inhibitor.
  • G. Pizzorno, L. Yee, P. Calabresi
  • Biology, Chemistry
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 1998
TLDR
On the basis of this clinical study, the suggested Phase II starting dose of BAU in combination with 5-FU is 800 mg/m2 and studies combining BAU with5-FU and incorporating appropriate molecular and biochemical end points to assess the effects of this drug combination on tumor and/or surrogate tumor tissue are under way.
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References

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Synthesis of pyrimidine acyclonucleosides
Nucleoside analogues of uridine, 5-bromo-, 5-iodo-, and 5-fluorouridines, thymidine and cytidine were prepared by condensing appropriately substituted 2,4-dimethoxypyrimidines with an acyclic side
SPECIFICITY OF MOUSE URIDINE PHOSPHORYLASE. CHROMATOGRAPHY, PURIFICATION, AND PROPERTIES.
TLDR
This investigation provides evidence in support of three hypotheses explaining the pyrimidine deoxyribonucleoside phosphorolytic activity of mammalian uridine phosphorylase preparations: contamination by thymidine phosphate, contamination by a distinct enzyme, deoxyuridine phosphORYlase, and nonspecificity of some mammalian uridines for the pentose moiety, in contrast to an analogous bacterial enzyme.
Salvage of circulating pyrimidine nucleosides in the rat.
TLDR
These studies permitted an estimation of the contribution of circulating pyrimidine nucleoside to the nucleotide pools of various rat tissues, and the implication for chemotherapy based on inhibition of pyridine synthesis de novo is discussed.
Lethality of adenosine for cultured mammalian cells by interference with pyrimidine biosynthesis.
TLDR
The toxic effect of adenosine in concentrations up to 2 x 10 -4 M was completely prevented by the addition of uridine or of pyrimidines potentially convertible to uridine, suggesting that theadenosine was interfering with endogenous synthesis of uridylate.
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