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

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.

• Authors: M S Deshpande, J Wei, G Luo, C Cianci, S Danetz, A Torri, L Tiley, M Krystal, K L Yu, S Huang, Q Gao, N A Meanwell
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 11 Issue 17 Pg. 2393-6 (Sep 03 2001) ISSN: 0960-894X [Print] England
• PMID: 11527739 (Publication Type: Journal Article)

Chemical References

• Amines
• Antiviral Agents
• BMY 27709
• N-((3-hydroxy-1,5,5-trimethylcyclohexyl)methyl)-3-chlorophenylmethanethioamide
• Quinolizines
• Thioamides

Topics

• Amines (chemistry)
• Antiviral Agents (chemistry, pharmacology)
• Cells, Cultured (virology)
• Drug Evaluation, Preclinical
• Hemolysis (drug effects)
• Humans
• Influenza A virus (drug effects, pathogenicity)
• Magnetic Resonance Spectroscopy
• Membrane Fusion (drug effects)
• Molecular Structure
• Quinolizines (chemistry, pharmacology)
• Stereoisomerism
• Structure-Activity Relationship
• Thioamides (chemistry, pharmacology)