Derivatives of l-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)-5-phenyluracil and 5-benzyluracil. Synthesis and biological properties Journal Article
| Authors: | Dziewiszek, K.; Schinazi, R. F.; Chou, T. C.; Su, T. L.; Dzik, J. M.; Rode, W.; Watanabe, K. A. |
| Article Title: | Derivatives of l-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)-5-phenyluracil and 5-benzyluracil. Synthesis and biological properties |
| Abstract: | A number of l-(2-deoxy-2-fluoro-j3-D-arabinofuranosyl)uracil and -cytosine nucleosides substituted at the 5 position with a nitrophenyl or nitrobenzyl group were synthesized from 5-phenyl- and 5-benzyluracil via condensation of the fluorinated sugar, followed by nitration. The corresponding amino analogues were also prepared by reduction of the nitro nucleosides. The uracil nucleosides were converted into the corresponding cytosine nucleosides by way of the triazole intermediates. None of these nucleosides exhibited significant activity against herpes simplex virus type 1 in Vero cells. However, cytosine nucleosides containing the p-nitrophenyl, p-nitrophenyl, o-nitrobenzyl or p-aminobenzyl substituent were found to be toxic (even at 1 pM) to uninfected Vero cells, although they were essentially nontoxic in HL-60 cells. The 5,-monophosphates of the uracil nucleosides were inhibitors of the reaction catalyzed by purified Ehrlich ascites carcinoma thymidylate synthase, the 5-phenyluracil nucleotides causing a strong inhibition, competitive vs dUMP, described by the Kj value of 0.01 pM. © 1994, Taylor & Francis Group, LLC. All rights reserved. |
| Keywords: | unclassified drug; cytotoxicity; drug synthesis; structure activity relation; thymidylate synthase; reaction analysis; antiviral activity; vero cell; growth inhibition; competitive inhibition; pyrimidine nucleoside derivative; cell strain hl 60; article; 2' deoxy 2' fluoro 5 phenylcytarabine; 2' deoxy 2' fluoro 5 phenyluracil arabinoside; 5 benzyl 2' deoxy 2' fluorocytarabine; 5 benzyl 2' deoxy 2' fluorouracil arabinoside |
| Journal Title: | Nucleosides & Nucleotides |
| Volume: | 13 |
| Issue: | 1-3 |
| ISSN: | 0732-8311 |
| Publisher: | Taylor & Francis Inc. |
| Date Published: | 1994-01-01 |
| Start Page: | 77 |
| End Page: | 94 |
| Language: | English |
| DOI: | 10.1080/15257779408013228 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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