Design, synthesis, inhibitory activity, and SAR studies of hydrophobic p-aminosalicylic acid derivatives as neuraminidase inhibitors

Bioorg Med Chem. 2008 Apr 1;16(7):3839-47. doi: 10.1016/j.bmc.2008.01.036. Epub 2008 Jan 30.

Abstract

A series of hydrophobic p-aminosalicylic acid derivatives containing a lipophilic side chain at C-2 and an amino or guanidine at C-5 were synthesized and evaluated for their ability to inhibit neuraminidase (NA) of influenza A virus (H3N2). All compounds were synthesized in good yields starting from commercially available p-aminosalicylic acid (PAS) using a suitable synthetic strategy. These compounds showed potent inhibitory activity against influenza A NA. Within this series, six compounds, 11, 12, 13e, 16e, 17c, and 18e, have the good potency (IC(50)=0.032-0.049 microM), which are compared to Oseltamivir (IC(50)=0.021 microM) and could be used as lead compounds in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminosalicylic Acid / chemical synthesis
  • Aminosalicylic Acid / chemistry
  • Aminosalicylic Acid / pharmacology*
  • Aminosalicylic Acids*
  • Binding Sites
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Hydrophobic and Hydrophilic Interactions*
  • Influenza A Virus, H3N2 Subtype / enzymology*
  • Models, Molecular
  • Molecular Structure
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / metabolism
  • Structure-Activity Relationship

Substances

  • Aminosalicylic Acids
  • Enzyme Inhibitors
  • Aminosalicylic Acid
  • Neuraminidase