Design, synthesis, inhibitory activity, and SAR studies of pyrrolidine derivatives as neuraminidase inhibitors

Bioorg Med Chem. 2007 Apr 1;15(7):2749-58. doi: 10.1016/j.bmc.2007.01.020. Epub 2007 Jan 19.

Abstract

A series of pyrrolidine derivatives 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 4-hydroxy-L-proline using a suitable synthetic strategy. These compounds showed potent inhibitory activity against influenza A neuraminidase. Within this series, five compounds, 6e, 9c, 9e, 9f, and 10e, have good potency (IC(50)=1.56-2.71 microM) which are compared to that the NA inhibitor Oseltamivir (IC(50)=1.06 microM), and could be used as lead compoundS in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Diclofenac / pharmacology
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Hydroxyproline / chemistry
  • Hydroxyproline / pharmacology
  • Indicators and Reagents
  • Influenza A Virus, H3N2 Subtype / drug effects
  • Influenza A Virus, H3N2 Subtype / enzymology*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Neuraminidase / antagonists & inhibitors*
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / pharmacology*
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Ultraviolet
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Enzyme Inhibitors
  • Indicators and Reagents
  • Pyrrolidines
  • Diclofenac
  • Neuraminidase
  • Hydroxyproline