The phosphoramidate ProTide approach greatly enhances the activity of β-2′-C-methylguanosine against hepatitis C virus

C McGuigan, P Perrone, K Madela, J Neyts

Index: McGuigan, Christopher; Perrone, Plinio; Madela, Karolina; Neyts, Johan Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 15 p. 4316 - 4320

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Citation Number: 34

Abstract

β-2′-C-Methyl purines (1, 2) are known inhibitors of hepatitis C virus (HCV). We herein report the synthesis, biological and enzymatic evaluation of their 5′-phosphoramidate ProTides. Described herein are seven l-alanine phosphoramidate derivatives with variations to the amino acid ester. The 1-naphthyl phosphoramidate of β-2′-methylguanosine containing the benzyl ester (20) was the most active at 0.12 μM, an 84-fold of increase in ...