Cyclic phosphoramidates as prodrugs of 2′-C-methylcytidine
| Autor: | Cristina Gardelli, Uwe Koch, Odalys Gonzalez-Paz, Barbara Pacini, Claudio Giuliano, Renzo Bazzo, Vincenzo Pucci, Joseph F. Leone, Kenneth A. Koeplinger, Michael Rowley, Frank Narjes, Sergio Altamura, Fabrizio Fiore, Malte Meppen, Ralph Laufer, Annalise Di Marco |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
viruses
Hepatitis C virus Hepacivirus Cytidine medicine.disease_cause Antiviral Agents Structure-Activity Relationship chemistry.chemical_compound Drug Stability Pegylated interferon Cricetinae Drug Discovery medicine Animals Humans Prodrugs Pharmacology biology Ribavirin Organic Chemistry virus diseases Nucleoside inhibitor General Medicine Hepatitis C Prodrug medicine.disease biology.organism_classification Virology digestive system diseases chemistry Hepatocytes Viral load medicine.drug |
| Zdroj: | European Journal of Medicinal Chemistry. 44:3765-3770 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2009.04.043 |
| Popis: | The currently approved treatment for hepatitis C virus infections is a combination of Ribavirin and pegylated Interferon. It leads to a sustained virologic response in approximately only half of the patients treated. For this reason there is an urgent need of new therapeutic agents. 2'-C-Methylcytidine is the first nucleoside inhibitor of the HCV NS5B polymerase that was efficacious in reducing the viral load in patients infected with HCV. The application of a monophosphate prodrug approach based on unprecedented cyclic phosphoramidates is reported. Our SAR studies led to compounds that are efficiently converted to the active triphosphate in human hepatocytes. |
| Databáze: | OpenAIRE |
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