| Synthesis and biological activity of 5-fluoro-2'-deoxyuridine 5'-phosphorodiamidates. | |
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MedLine Citation:
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PMID: 6779007 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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M E Phelps; P W Woodman; P V Danenberg |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 23 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 1980 Nov |
Date Detail:
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Created Date: 1981-03-17 Completed Date: 1981-03-17 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1229-32 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / chemical synthesis* Cells, Cultured Chemical Phenomena Chemistry Deoxyuracil Nucleotides / chemical synthesis* Fluorodeoxyuridylate / analogs & derivatives, chemical synthesis*, pharmacology Lactobacillus casei / enzymology Leukemia, Experimental / drug therapy Mice Thymidylate Synthase / antagonists & inhibitors |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Deoxyuracil Nucleotides; 134-46-3/Fluorodeoxyuridylate; EC 2.1.1.45/Thymidylate Synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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