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ID: ALA1147866

Journal: Bioorg Med Chem Lett

Title: Cyclic monophosphate prodrugs of base-modified 2'-C-methyl ribonucleosides as potent inhibitors of hepatitis C virus RNA replication.

Authors: Gunic E, Girardet JL, Ramasamy K, Stoisavljevic-Petkov V, Chow S, Yeh LT, Hamatake RK, Raney A, Hong Z.

Abstract: A new series of heterobase-modified 2'-C-methyl ribonucleosides was synthesized and tested as inhibitors of hepatitis C virus (HCV) RNA replication. The nucleosides showed a weak inhibitory activity in a HCV replicon system (EC(50)=92 microM) and did not exhibit any cytotoxicity (CC(50)>300 microM). Cyclic monophosphate (cMP) prodrugs of the same nucleosides were synthesized and also tested in the HCV replicon system. Prodrugs exhibited strong potency (EC(50)=0.008 microM) without significant cytotoxicity (CC(50)>50 microM).

CiteXplore: 17331721

DOI: 10.1016/j.bmcl.2007.02.030