Design and synthesis of 6-oxo-1,4,5,6-tetrahydropyrimidine-5-carboxylate derivatives as neuraminidase inhibitors

Eur J Med Chem. 2014 Aug 18:83:466-73. doi: 10.1016/j.ejmech.2014.06.059. Epub 2014 Jun 26.

Abstract

A series of 6-oxo-1,4,5,6-tetrahydropyrimidine-5-carboxylate derivatives were prepared to evaluate their ability of inhibiting neuraminidase (NA) of influenza A virus. All the compounds were synthesized in good yields starting from aldehyde by using a suitable synthetic strategy, which showed moderate inhibitory activity against influenza A NA. Compound 6g exhibited the strongest inhibitory activity against influenza virus A NA (IC50 = 17.64 μM), which indicated pyrimidine ring could be used as a core structure to design novel influenza NA inhibitors.

Keywords: 6-oxo-1,4,5,6-tetrahydropyrimidine-5-carboxylate derivatives; Anti-influenza; Neuraminidase inhibitors; SAR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Chemistry Techniques, Synthetic
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Influenza A virus / enzymology*
  • Models, Molecular
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / chemistry
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*

Substances

  • 6-oxo-1,4,5,6-tetrahydropyrimidine-5-carboxylate
  • Enzyme Inhibitors
  • Pyrimidines
  • Neuraminidase