Discovery and synthesis of novel benzofurazan derivatives as inhibitors of influenza A virus

Bioorg Med Chem Lett. 2013 Oct 15;23(20):5575-7. doi: 10.1016/j.bmcl.2013.08.048. Epub 2013 Aug 17.

Abstract

The identification of a novel hit compound inhibitor of the protein-protein interaction between the influenza RNA-polymerase PA and PB1 subunits has been accomplished by means of high-throughput screening. A small family of structurally related molecules has been synthesized and biologically evaluated with most of the compounds showing micromolar potency of inhibition against viral replication.

Keywords: Antiviral agents; Benzofurazan; H1N1; Influenza virus; Viral RNA polymerase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / toxicity*
  • Benzoxazoles / chemical synthesis
  • Benzoxazoles / chemistry*
  • Benzoxazoles / toxicity
  • DNA-Directed RNA Polymerases / chemistry
  • DNA-Directed RNA Polymerases / metabolism*
  • Dogs
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / toxicity
  • Influenza A virus / drug effects*
  • Influenza A virus / enzymology
  • Madin Darby Canine Kidney Cells
  • Protein Interaction Domains and Motifs / drug effects
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Benzoxazoles
  • Enzyme Inhibitors
  • Protein Subunits
  • benzofurazan
  • DNA-Directed RNA Polymerases