Derivatives of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-phenyluracil and 5-benzyluracil synthesis and biological properties

Article abstract of DOI:10.1080/15257779408013228

A number of 1-(2-deoxy-2-fluoro-β-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 o-nitrophenyl, p-nitrophenyl, p- nitrobenzyl or p-aminobenzyl substituent were found to be toxic (even at 1 μM) 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 K(i) value of 0.01 μM.

Full text of DOI:10.1080/15257779408013228

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Derivatives of 1-(2-Deoxy-2-fluoro-β-D-
arabinofuranosyl)-5-phenyluracil and 5-
Benzyluracil. Synthesis and Biological
Properties
Krzysztof Dziewiszek a , Raymond F. Schinazi b , Ting-Chao Chou a ,
Tsann-Long Su a , Jolanta M. Dzik c , Wojciech Rode c & Kyoichi A.
Watanabe a
a Sloan-Kettering Institute for Cancer Research, Memorial Sloan-
Kettering Cancer Center, Sloan-Kettering Division of Graduate School
of Medical Sciences, New York, NY, 10021
b Laboratory of Biochemical Pharmacology, Department of
Pediatrics, Emory University School of Medicine and the Veterans
Affairs Medical Center, Decatur, GA, 30033
c M. Nencki Institute of Experimental Biology, Polish Academy of
Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland
Version of record first published: 23 Sep 2006.
To cite this article: Krzysztof Dziewiszek , Raymond F. Schinazi , Ting-Chao Chou , Tsann-Long
Su , Jolanta M. Dzik , Wojciech Rode & Kyoichi A. Watanabe (1994): Derivatives of 1-(2-Deoxy-2-
fluoro-β-D-arabinofuranosyl)-5-phenyluracil and 5-Benzyluracil. Synthesis and Biological Properties,
Nucleosides and Nucleotides, 13:1-3, 77-94
To link to this article: http://dx.doi.org/10.1080/15257779408013228
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