2-Alkyloxazoles as potent and selective PI4KIIIβ inhibitors demonstrating inhibition of HCV replication

Bioorg Med Chem Lett. 2014 Aug 15;24(16):3714-8. doi: 10.1016/j.bmcl.2014.07.015. Epub 2014 Jul 12.

Abstract

Synthesis and SAR of 2-alkyloxazoles as class III phosphatidylinositol-4-kinase beta (PI4KIIIβ) inhibitors is described. These compounds demonstrate that inhibition of PI4KIIIβ leads to potent inhibition of HCV replication as observed in genotype (GT) 1a and 1b replicon and GT2a JFH1 virus assays in vitro.

Keywords: HCV; PI4K.

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Hepacivirus / drug effects*
  • Hepacivirus / enzymology
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Oxazoles / chemical synthesis
  • Oxazoles / chemistry
  • Oxazoles / pharmacology*
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents
  • Oxazoles
  • Protein Kinase Inhibitors
  • Phosphotransferases (Alcohol Group Acceptor)