Abstract
Synthesis of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracils containing a vinyl (4a), 2-halovinyl (4b-d), or ethyl substituent at C-5 was achieved. These nucleosides were found to be about a log order less active than 2'-fluoro-5-iodo-ara-C (FIAC) against HSV-1, but they are much less cytotoxic against normal human lymphocytes than FIAC. Nucleosides 4a and 4e showed good activity against HSV-1 (ED50 = 0.16 and 0.24 microM, respectively) and HSV-2 (ED50 = 0.69 and 0.65 microM) with very little cytotoxicity (ID50 greater than 100 microM).
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antiviral Agents / chemical synthesis*
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Arabinofuranosyluracil / analogs & derivatives*
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Arabinofuranosyluracil / chemical synthesis
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Arabinofuranosyluracil / therapeutic use
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Cell Line
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Chlorocebus aethiops
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Drug Evaluation, Preclinical
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Humans
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Indicators and Reagents
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Kidney
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Lymphocyte Activation / drug effects
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Lymphocytes / drug effects
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Lymphocytes / immunology
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Magnetic Resonance Spectroscopy
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Simplexvirus / drug effects*
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Structure-Activity Relationship
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Uridine / analogs & derivatives*
Substances
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Antiviral Agents
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Indicators and Reagents
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Arabinofuranosyluracil
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Uridine