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The phosphoramidate ProTide approach greatly enhances the activity of beta-2'-C-methylguanosine against hepatitis C virus.

Abstract：

:Beta-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 beta-2'-methylguanosine containing the benzyl ester (20) was the most active at 0.12microM, 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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

McGuigan C,Perrone P,Madela K,Neyts J

doi

10.1016/j.bmcl.2009.05.122

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

4316-20

issue

15

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(09)00759-8

journal_volume

19

pub_type

杂志文章

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