Synthesis and anti-influenza virus activity of 4-guanidino-7-substituted Neu5Ac2en derivatives

Bioorg Med Chem Lett. 2002 Aug 5;12(15):1921-4. doi: 10.1016/s0960-894x(02)00328-1.

Abstract

Substitution of 7-OH by small hydrophobic groups on zanamivir resulted in the retaining of low nanomolar inhibitory activities against not only influenza A virus sialidase but also influenza A virus in cell culture. These compounds were prepared by treatment of the corresponding 7-substituted sialic acids derived from 4-modified N-acetyl-D-mannosamine (ManNAc) using enzyme-catalyzed aldol condensation.

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Guanidine / analogs & derivatives*
  • Guanidine / chemical synthesis
  • Guanidine / pharmacology
  • Influenza A virus / drug effects*
  • Influenza A virus / enzymology
  • Influenza B virus / drug effects*
  • Influenza B virus / enzymology
  • Inhibitory Concentration 50
  • N-Acetylneuraminic Acid / analogs & derivatives*
  • N-Acetylneuraminic Acid / chemistry*
  • N-Acetylneuraminic Acid / pharmacology*
  • Neuraminidase / antagonists & inhibitors
  • Structure-Activity Relationship
  • Viral Plaque Assay

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • 2-deoxy-2,3-dehydro-N-acetylneuraminic acid
  • Neuraminidase
  • N-Acetylneuraminic Acid
  • Guanidine