Synthesis and inhibitory activity on hepatitis C virus RNA replication of 4-(1,1,1,3,3,3-hexafluoro-2-hydroxy-2-propyl)aniline analogs

Kenji Matsuno, Youki Ueda, Miwa Fukuda, Kenji Onoda, Minoru Waki, Masanori Ikeda, Nobuyuki Kato, Hiroyuki Miyachi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Using our recently developed assay system for full-genome-length hepatitis C virus (HCV) RNA replication in human hepatoma-derived Li23 cells (ORL8), we identified 4-(1,1,1,3,3,3-hexafluoro-2-hydroxy-2-propyl)aniline analog 1a as a novel HCV inhibitor. Structural modifications of 1a provided a series of sulfonamides 7 with much more potent HCV RNA replication-inhibitory activity than ribavirin. Compound 7a showed an additive anti-HCV effect in combination with standard anti-HCV therapy (IFN-α plus ribavirin). Since 7a generated reactive oxygen species (ROS) in the ORL8 system and its anti-HCV activity was blocked by vitamin E, its anti-HCV activity may be mediated at least in part by ROS.

Original languageEnglish
Pages (from-to)4276-4280
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number17
DOIs
Publication statusPublished - Sep 1 2014

Fingerprint

Virus Replication
Viruses
Hepacivirus
RNA
Ribavirin
Reactive Oxygen Species
Sulfonamides
aniline
Vitamin E
Hepatocellular Carcinoma
Assays
Genes
Genome

Keywords

  • Anti-HCV agent
  • Full genome length
  • HCV RNA replication
  • Hepatitis C virus
  • ORL8

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Medicine(all)

Cite this

Synthesis and inhibitory activity on hepatitis C virus RNA replication of 4-(1,1,1,3,3,3-hexafluoro-2-hydroxy-2-propyl)aniline analogs. / Matsuno, Kenji; Ueda, Youki; Fukuda, Miwa; Onoda, Kenji; Waki, Minoru; Ikeda, Masanori; Kato, Nobuyuki; Miyachi, Hiroyuki.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 24, No. 17, 01.09.2014, p. 4276-4280.

Research output: Contribution to journalArticle

Matsuno, Kenji ; Ueda, Youki ; Fukuda, Miwa ; Onoda, Kenji ; Waki, Minoru ; Ikeda, Masanori ; Kato, Nobuyuki ; Miyachi, Hiroyuki. / Synthesis and inhibitory activity on hepatitis C virus RNA replication of 4-(1,1,1,3,3,3-hexafluoro-2-hydroxy-2-propyl)aniline analogs. In: Bioorganic and Medicinal Chemistry Letters. 2014 ; Vol. 24, No. 17. pp. 4276-4280.
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