Synthesis and influenza virus sialidase inhibitory activity of analogues of 4-Guanidino-Neu5Ac2en (Zanamivir) modified in the glycerol side-chain

Eur J Med Chem. 1999 Jul-Aug;34(7-8):563-74. doi: 10.1016/s0223-5234(00)80026-4.

Abstract

Analogues of 4-Guanidino-Neu5Ac2en (Zanamivir) have been prepared containing carbamate substituents at the 7-hydroxy position. (4S,5R,6R)-5-Acetylamino-6-[1R-[(6-aminohexyl)carbamoyloxy]-2R,3-dihydroxypropyl]-4-guanidino-5,6-dihydro-4H-pyran-2carboxylic acid and (4S,5R,6R)-5-Acetylamino-6-[1R-[heptylcarbamoyloxy]-2R,3-dihydroxypropyl]-4-guanidino-5,6-dihydro4H-pyran2-carboxylic acid were the two analogues possessing activity comparable to Zanamivir, showing potent inhibition of influenza virus sialidases and good antiviral activity in vitro.

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology*
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Glycerol / chemistry
  • Guanidines
  • Humans
  • Influenza A virus / drug effects
  • Influenza A virus / enzymology*
  • Influenza B virus / drug effects
  • Influenza B virus / enzymology*
  • Neuraminidase / antagonists & inhibitors*
  • Pyrans
  • Sialic Acids / chemical synthesis*
  • Sialic Acids / pharmacology*
  • Viral Plaque Assay
  • Zanamivir

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Guanidines
  • Pyrans
  • Sialic Acids
  • Neuraminidase
  • Zanamivir
  • Glycerol