• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.91-100
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• 1990

The benzylacycoluridines (BAU and BBAU) are potent and specific inhibitors of uridine phosphorylase (UrdPase). In contrast to the report that benzylacyclouridines potentiated 5-fluoro-2'-deoxyuridine (FdUrd) cytotoxicity against human solid tumor cells (Cancer Res., 44:1852, 1984), continuous exposure of mouse lymphoma L5178Y cells, to FdURd, 5-fluorouridine (FUrd), 5'-deoxy-5-fluorouridine (5'-dFUrd), or 5-fluorouracil (FUra) showed no potentiation of cytotoxicity by benzylacyclouridines. In fact, under the conditions employed, benzylacycoluridines protected the cells from the cytotoxicity of FdUrd, FUrd, or 5'-dFUrd, but not FUra in a dose dependent manner. Intraperitoneal coadministration of BAU or BBAU and a 5-fluorinated pyrimidine (i.e., FdUrd, FUrd, or FUra), to mice bearing L5178Y cells also did not significantly increase the life span compared to those treated with the antimetabolites alone. Anabolism of these nucleosides through the sequential action of UrdPase and orotate phosphoribosyltransferase (OPRTase), inhibition of nucleoside transport by benzylacyclouridines, or both could be responsible for the ineffectiveness of UrdPase inhibitors to potentiate the antineoplastic activity of fluoropvrimidines in L5178Y cells.

• Bulletin of the Korean Chemical Society
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• v.31 no.8
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• pp.2235-2241
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• 2010

A reverse-phase HPLC method with detection by mass spectrometry is described for the simultaneous determination of doxifluridine and its two active metabolites, 5-fluorouracil (5-FU) and 5-fluorouridine (5-FUrd), in beagle dog plasma. The optimal chromatographic separation was achieved on a Waters $Xterra^{(R)}$ $C_{18}$ column ($4.6{\times}250\;mm$ i.d., $5\;{\mu}m$ particle size) with a mobile phase of 0.1% formic acid in a mixture of 99% methanol and purified water (99:1, v/v). The developed method was validated in beagle dog plasma with a lowest limit of quantification of $0.05\;{\mu}g/mL$ for both doxifluridine and 5-FU, and $0.2\;{\mu}g/mL$ for 5-FUrd. Doxifluridine and its two metabolites were stable under the analysis conditions, and intra- and inter-day accuracies exceeded 92.87%, with a precision variability ${\leq}11.34%$ for each analyte. Additionally, the method for quantifying doxifluridine and its two metabolites, 5-FU and 5-FUrd, in beagle dog plasma was applied successfully to the analysis of pharmacokinetic samples.

• Journal of the Korean Chemical Society
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• v.19 no.6
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• pp.438-442
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• 1975

The syntheses of anomeric mixtures of 1-(4-thio-${\alpha},{\beta}$-D-ribofuranosyl)-5-fluoro-and 5-chlorouracils from their corresponding bis(trimethylsilyl) derivatives of 5-halogenouracils and 2,3,5-tri-O-acetyl-4-thio-${\alpha},{\beta}$-D-ribofuranosyl chloride are described. Preliminary biochemical studies showed that in leukemia 1210 cells and Streptococcus faecium, the ${\beta}$-anomeric 5-chloro-4'-thionucleoside is not greatly different from the corresponding 4'-oxygen analog. However, the 5-fluoro-4'-thionucleoside showed a growth inhibitory effect more than that of the oxygen counterpart. The potential chemotherapeutic use of the analog is to warrant further study.