Discovery of novel 1-phenyl-cycloalkane carbamides as potent and selective influenza fusion inhibitors

A novel class of HA inhibitors (4a) was identified based on ligand similarity search of known HA inhibitors. Parallel synthesis and further structural modifications resulted in 1-phenyl-cyclopentanecarboxylic acid (4-cyano-phenyl)-methyl-amide 4t as a potent and selective inhibitor to phylogenetic H1 influenza viruses with an EC50 of 98 nM against H1N1 A/Weiss/43 strain and over 1000-fold selectivity against host MDCK cells.