Synthesis and biological activity of 5-fluoro-2'-deoxyuridine 5'-phosphorodiamidates.

doi:10.1021/JM00185A016

Paper

Synthesis and biological activity of 5-fluoro-2'-deoxyuridine 5'-phosphorodiamidates.

Published Nov 1, 1980 · M. Phelps, P. W. Woodman, P. Danenberg

Journal of medicinal chemistry

Q1 SJR score

11

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0

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Abstract

Three 5'-phosphorodiamidate derivatives of 5-fluoro-2'-deoxyuridine (FdUrd), 5-fluoro-2'-deoxyuridine 5'-phosphorodiamidate (4a), 5'-phosphorodiimidazolidate (4b), and 5'-phosphorodimorpholidate (4c), were synthesized by aminolysis of 5-fluoro-2'-deoxyuridine 5'-phosphorodichloridate with the respective amine. In culture, these 5'-phosphorodiamidates inhibited the growth of murine leukemia (L5178Y) cells. 5-Fluoro-2'-deoxyuridine 5'-phosphorodiamidate (4a) was the most active derivative and, on a molar basis, produced a cytostatic effect comparable to that of FdUrd and 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUrd-5'-P). Compounds 4b and 4c were less active than 4a, with relative rates of activity 4a > 4b > 4c that corresponded to their rates of hydrolysis to FdUrd-5'-P. None of the 5'-phosphorodiamidates inhibited thymidylate synthetase of concentrations up to 1 mM.

In Vitro Study

Study Snapshot

5-fluoro-2'-deoxyuridine 5'-phosphorodiamidates effectively inhibit murine leukemia cell growth, with the most active compound being 5-fluoro-2'-deoxyuridine 5'-phosphorodiamidate (4a).

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Synthesis and biological activity of 5-fluoro-2'-deoxyuridine 5'-phosphorodiamidates.

References

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