Carbocyclic analogs of 5-fluorouracil nucleosides

The carbocyclic analogues of 5-fluoro-2'-deoxyuridine (5-FdUrd, 1), 5-fluorouridine, and 5-fluoro-3 alpha-deoxyuridine were prepared by fluorination of the uracil nucleoside analogues with elemental fluorine. The 5-FdUrd analogue (C-5-F-2'-dUrd, 6) was enzymatically phosphorylated to the a...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1981-09, Vol.24 (9), p.1083-1086
Main Authors: Shealy, Y. Fulmer, Frye, Jerry L, DuBois, Nancy F, Shaddix, Sue C, Brockman, R. Wallace
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - chemical synthesis
Fluorouracil - chemical synthesis
Fluorouracil - pharmacology
Leukemia L1210 - drug therapy
Leukemia P388 - drug therapy
Mice
Nucleosides - chemical synthesis
Nucleosides - pharmacology
Thymidine - metabolism
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Summary:The carbocyclic analogues of 5-fluoro-2'-deoxyuridine (5-FdUrd, 1), 5-fluorouridine, and 5-fluoro-3 alpha-deoxyuridine were prepared by fluorination of the uracil nucleoside analogues with elemental fluorine. The 5-FdUrd analogue (C-5-F-2'-dUrd, 6) was enzymatically phosphorylated to the analogue of 5-FdUrd 5'-phosphate and inhibited the incorporation of 2'-deoxyuridine into DNA of murine colon 26 tumor cells and L-1210 cells in culture. Biochemical studies also indicated that C-5-F-2'-Urd (6) was a less potent inhibitor of DNA synthesis in tumor cells than was 5-FdUrd (1). C-5-F-2'-dUrd was cytotoxic (ED50 = 2.5 mcg/mL) to L-1210 cells in culture; the other two analogues were less cytotoxic. C-5-F-2'-dUrd was inactive--or, at best, borderline active--in tests against P-388 leukemia in vivo.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00141a013