Abstract
Nucleoside analogs are widely used for the treatment of viral diseases (Hepatitis B/C, herpes and human immunodeficiency virus, HIV) and various malignancies. ALS-8176, a prodrug of the 4'-chloromethyl-2'-deoxy-2'-fluoro nucleoside ALS-8112, was evaluated in hospitalized infants for the treatment of respiratory syncytial virus (RSV), but was abandoned for unclear reasons. Based on the structure of ALS-8112, a series of novel 4'-modified-2'-deoxy-2'-fluoro nucleosides were synthesized. Newly prepared compounds were evaluated against RSV, but also against a panel of RNA viruses, including Dengue, West Nile, Chikungunya, and Zika viruses. Unfortunately, none of the compounds showed marked antiviral activity against these viruses.
Keywords:
Chikungunya; Dengue; West Nile; Zika; nucleoside; polymerase inhibitors; respiratory syncytial virus; virus.
MeSH terms
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Animals
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / pharmacology
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Cell Line, Tumor
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Chikungunya virus / drug effects
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Chikungunya virus / growth & development
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Cricetulus
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Dengue Virus / drug effects
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Dengue Virus / growth & development
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Deoxycytidine / analogs & derivatives*
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Deoxycytidine / chemical synthesis
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Deoxycytidine / pharmacology
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Deoxyribonucleosides / chemical synthesis*
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Deoxyribonucleosides / pharmacology
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Epithelial Cells / drug effects
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Epithelial Cells / virology
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Hepatocytes / drug effects
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Hepatocytes / virology
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Humans
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Leukocytes, Mononuclear / drug effects
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Leukocytes, Mononuclear / virology
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Microbial Sensitivity Tests
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Primary Cell Culture
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Prodrugs / chemical synthesis*
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Prodrugs / pharmacology
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Respiratory Syncytial Virus, Human / drug effects
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Respiratory Syncytial Virus, Human / growth & development
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T-Lymphocytes / drug effects
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T-Lymphocytes / virology
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Treatment Failure
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Virus Replication / drug effects
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West Nile virus / drug effects
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West Nile virus / growth & development
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Zika Virus / drug effects
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Zika Virus / growth & development
Substances
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Antiviral Agents
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Deoxyribonucleosides
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Prodrugs
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Deoxycytidine
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4'-chloromethyl-2'-deoxy-3',5'-di-O-isobutyryl-2'-fluorocytidine