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  • Title: Design and synthesis of novel carbocyclic versions of 2'-spirocyclopropyl ribonucleosides as potent anti-HCV agents.
    Author: Oh CH, Kim E, Hong JH.
    Journal: Nucleosides Nucleotides Nucleic Acids; 2011 Jun; 30(6):423-39. PubMed ID: 21780908.
    Abstract:
    The discovery of 2'-spirocyclopropyl-ribocytidine as a potent inhibitor of RNA synthesis by NS5B (IC(50) = 7.3 μM), the RNA polymerase encoded by hepatitis C virus (HCV), has led to the synthesis and biological evaluation of carbocyclic versions of 2'-spiropropyl-nucleosides from cyclopentenol 6. Spirocyclopropylation of enone 7 was completed by using (2-chloroethyl)-dimethylsulfonium iodide and potassium t-butoxide to form the desired intermediate 9a. The synthesized nucleoside analogues, 18, 19, 26, and 27, were assayed for their ability to inhibit HCV RNA replication in a subgenomic replicon Huh7 cell line. The synthesized cytosine nucleoside 19 showed moderate anti-HCV activity (IC(50) = 14.4 μM).
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