[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.5012/bkcs.2009.30.11.2626

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)

Publication Information

Bulletin of the Korean Chemical Society / v.30, no.11, 2009 , pp. 2626-2630 More about this Journal

Abstract

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.

Keywords

Carbodine; Anti-HCV agent; Substituted carbocyclic nucleoside;

Citations & Related Records

Times Cited By Web Of Science : 2 (Related Records In Web of Science)
Times Cited By SCOPUS : 2

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