Design, synthesis, and biological activity of thiazole derivatives as novel influenza neuraminidase inhibitors

J Enzyme Inhib Med Chem. 2011 Aug;26(4):506-13. doi: 10.3109/14756366.2010.534732. Epub 2010 Dec 14.

Abstract

A series of novel influenza neuraminidase (NA) inhibitors based on thiazole core were synthesized and evaluated for their ability to inhibit NA of influenza A virus (H(3)N(2)). All compounds were synthesized in good yields starting from commercially available 2-amino-4-thiazole-acetic ester using a suitable synthetic strategy. These compounds showed moderate inhibitory activity against influenza A NA. The most potent compound of this series is compound 4d (IC(50) = 3.43 μM), which is about 20-fold less potent than oseltamivir, and could be used to design novel influenza NA inhibitors that exhibit increased activity based on thiazole ring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology*
  • Influenza A Virus, H3N2 Subtype / enzymology*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / metabolism
  • Stereoisomerism
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Thiazoles
  • Neuraminidase