Pyrrolidinobenzoic acid inhibitors of influenza virus neuraminidase: the hydrophobic side chain influences type A subtype selectivity.

Academic Article

Abstract

  • Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A series of influenza neuraminidase inhibitors with the pyrrolidinobenzoic acid scaffold containing lipophilic side chains at the C3 position have been synthesized and evaluated for influenza neuraminidase inhibitory activity. The size and geometry of the C3 side chains have been modified in order to investigate structure-activity relationships. The results indicated that size and geometry of the C3-side chain are important for selectivity of inhibition against N1 versus N2 NA, important type A influenza variants that infect man, including the highly lethal avian influenza.
  • Published In

    Keywords

  • Antiviral Agents, Benzoic Acid, Enzyme Inhibitors, Hydrophobic and Hydrophilic Interactions, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Influenza A virus, Neuraminidase, Pyrrolidinones, Structure-Activity Relationship
  • Digital Object Identifier (doi)

    Author List

  • Li Y; Silamkoti A; Kolavi G; Mou L; Gulati S; Air GM; Brouillette WJ
  • Start Page

  • 4582
  • End Page

  • 4589
  • Volume

  • 20
  • Issue

  • 14