An approach to the identification of potent inhibitors of influenza virus fusion using parallel synthesis methodology.

Academic Article

Abstract

  • Structure-activity studies associated with the salicylic acid-derived inhibitor of influenza fusion, BMY-27709, were examined using a parallel synthesis approach. This SAR survey led to the discovery of potent influenza inhibitory activity in a series of aromatic amides and thioamides derived from 1,3,3-trimethyl-5-hydroxycyclohexylmethylamine. Select compounds were characterized as inhibitors of the H1 subtype of influenza A viruses that act by preventing the pH-induced fusion process, thereby blocking viral entry into host cells. In a plaque-reduction assay, the most potent inhibitors displayed EC(50) values of 0.02-0.14 microg/mL.
  • Keywords

  • Amines, Antiviral Agents, Cells, Cultured, Drug Evaluation, Preclinical, Hemolysis, Humans, Influenza A virus, Magnetic Resonance Spectroscopy, Membrane Fusion, Molecular Structure, Quinolizines, Stereoisomerism, Structure-Activity Relationship, Thioamides
  • Digital Object Identifier (doi)

    Author List

  • Deshpande MS; Wei J; Luo G; Cianci C; Danetz S; Torri A; Tiley L; Krystal M; Yu KL; Huang S
  • Start Page

  • 2393
  • End Page

  • 2396
  • Volume

  • 11
  • Issue

  • 17