C-6 aryl substituted 4-quinolone-3-carboxylic acids as inhibitors of hepatitis C virus

Yue Lei Chen, Jeana Zacharias, Robert Vince, Robert J. Geraghty, Zhengqiang Wang

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Quinolone-3-carboxylic acid represents a highly privileged chemotype in medicinal chemistry and has been extensively explored as antibiotics and antivirals targeting human immunodeficiency virus (HIV) integrase (IN). Herein we describe the synthesis and anti-hepatitis C virus (HCV) profile of a series of C-6 aryl substituted 4-quinlone-3-carboxylic acid analogues. Significant inhibition was observed with a few analogues at low micromolar range against HCV replicon in cell culture and a reduction in replicon RNA was confirmed through an RT-qPCR assay. Interestingly, evaluation of analogues as inhibitors of NS5B in a biochemical assay yielded only modest inhibitory activities, suggesting that a different mechanism of action could operate in cell culture.

Original languageEnglish (US)
Pages (from-to)4790-4800
Number of pages11
JournalBioorganic and Medicinal Chemistry
Issue number15
StatePublished - Aug 1 2012

Bibliographical note

Funding Information:
This research was supported by the Center for Drug Design at the University of Minnesota. We thank Dr. Guangxiang Luo at University of Kentucky for providing the Huh-7/HCV1b-Rluc replicon cells and Matthew Kesler for technical assistance.


  • 6-Aryl-4-quinolone-3-carboxylic acids
  • Hepatitis C virus inhibitors
  • NS5B polymerase


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