Abstract
A series of 6-hydrazinopurine 2'-methyl ribonucleosides was synthesized and tested for its inhibitory activity against the hepatitis C virus (HCV). The lack of antiviral activity of these nucleosides was associated with a poor affinity for adenosine kinase, which prompted us to synthesize several of their 5'-monophosphate prodrugs. Some of these prodrugs exhibited more than 1000-fold improvement in anti-HCV activity when compared to their parent nucleosides (EC(50) of 24 nM vs 92 microM for the parent).
MeSH terms
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / pharmacology*
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Chemistry, Pharmaceutical / methods
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Drug Design
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Hepacivirus / genetics*
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Hepatitis C / drug therapy*
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Humans
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Models, Chemical
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Molecular Conformation
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Phosphates / chemistry*
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Prodrugs
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Ribonucleosides / chemistry*
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Viral Nonstructural Proteins / antagonists & inhibitors*
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Virus Replication / drug effects*
Substances
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Antiviral Agents
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Phosphates
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Prodrugs
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Ribonucleosides
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Viral Nonstructural Proteins
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NS-5 protein, hepatitis C virus