Abstract
In an attempt to identify novel nucleoside phosphoramidate analogues for improving the anti-HCV activity of 2'-C-Me-uridine, we have synthesized for the first time a series of l-glutamic acid, l-serine, l-threonine and l-tyrosine containing aryloxyphosphoramidate prodrugs of 2'-C-Me-uridine. Evaluation of their activity against HCV revealed that they displayed very potent anti-HCV activity, with EC50 values that are in the same range as of Sofosbuvir.
MeSH terms
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Amides / chemical synthesis
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Amides / chemistry
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Amides / metabolism
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Amides / pharmacology
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Antiviral Agents / chemical synthesis
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Antiviral Agents / chemistry*
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Antiviral Agents / metabolism
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Antiviral Agents / pharmacology*
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Chemistry Techniques, Synthetic
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Hepacivirus / drug effects*
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Hepacivirus / physiology
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Hepatitis C / drug therapy
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Hepatitis C / virology
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Humans
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Microsomes, Liver / metabolism
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Phosphoric Acids / chemical synthesis
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Phosphoric Acids / chemistry
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Phosphoric Acids / metabolism
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Phosphoric Acids / pharmacology
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Prodrugs / chemical synthesis
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Prodrugs / chemistry*
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Prodrugs / metabolism
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Prodrugs / pharmacology*
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Uridine / analogs & derivatives*
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Uridine / chemical synthesis
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Uridine / chemistry
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Uridine / metabolism
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Uridine / pharmacology
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Virus Replication / drug effects
Substances
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Amides
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Antiviral Agents
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Phosphoric Acids
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Prodrugs
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O(4)-methyluridine
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phosphoramidic acid
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Uridine