Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10596426 | Bioorganic & Medicinal Chemistry Letters | 2009 | 5 Pages |
Abstract
β-2â²-C-Methyl purines (1, 2) are known inhibitors of hepatitis C virus (HCV). We herein report the synthesis, biological and enzymatic evaluation of their 5â²-phosphoramidate ProTides. Described herein are seven l-alanine phosphoramidate derivatives with variations to the amino acid ester. The 1-naphthyl phosphoramidate of β-2â²-methylguanosine containing the benzyl ester (20) was the most active at 0.12 μM, an 84-fold of increase in activity compared to the parent nucleoside (2) with no increase of cytotoxicity. The carboxypeptidase mediated hydrolysis of several ProTides showed a predictive correlation with their activity versus HCV in replicon.
Related Topics
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Authors
Christopher McGuigan, Plinio Perrone, Karolina Madela, Johan Neyts,