Bulletin of the Korean Chemical Society

  • 제30권11호
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  • Pages.2626-2630
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  • 2009
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  • 0253-2964(pISSN)
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  • 1229-5949(eISSN)
대한화학회 (Korean Chemical Society)
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Synthesis and Antiviral Activity of 2'(β)-Hydroxymethylated Carbodine Analogues Against Hepatitis C Virus

  • Hong, Joon-Hee (BK-21 Project Team, College of Pharmacy, Chosun University) ;
  • Oh, Chang-Hyun (Biomaterials Research Center, Korea Institute of Science and Technology)
  • 발행 : 2009.11.20
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초록

2'($\beta$)-Hydroxymethylated adenosine is a potent and selective inhibitor of hepatitis C virus (HCV) replication. It targets the RNA-dependent RNA polymerase of HCV, NS5B. Synthesis and antiviral evaluation of carbocyclic versions are described. The cyclopentene intermediate ($9\beta$) was successfully synthesized through sequential Johnson-Claisen orthoester rearrangement and ring-closing metathesis (RCM). Coupling of bases via a Pd(0) catalyst, selective dihydroxylation, and desilylation yielded the target nucleoside analogues. The compounds 17 and 18 were assayed for their ability to inhibit HCV RNA replication in a subgenomic replicon Huh7 cell line and showed moderate antiviral activity with toxicity up to 20.0 and 24.7 ${\mu}g/mL$, respectively.

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피인용 문헌

  1. Nucleoside, Nucleotide, and Non-Nucleoside Inhibitors of Hepatitis C Virus NS5B RNA-Dependent RNA-Polymerase vol.55, pp.6, 2012, https://doi.org/10.1021/jm201384j