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6-Hydrazinopurine 2′-methyl ribonucleosides and their 5′-monophosphate prodrugs as potent hepatitis C virus inhibitors

2007; Elsevier BV; Volume: 17; Issue: 9 Linguagem: Inglês

10.1016/j.bmcl.2007.02.029

1464-3405

Esmir Gunić, Suetying Chow, Frank Rong, Kanda S. Ramasamy, Anneke K. Raney, David Yunzhi Li, Jingfan Huang, Robert Hamatake, Zhi Hong, Jean‐Luc Girardet,

Biochemical and Molecular Research

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).