title: Discovery of novel 1-phenyl-cycloalkane carbamides as potent and selective influenza fusion inhibitors.
abstract: 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 EC(50) of 98 nM against H1N1 A/Weiss/43 strain and over 1000-fold selectivity against host MDCK cells.
authors.affiliation: Roche R&D Center China, Shanghai, China. gordon.tang@roche.com
authors.forename: Guozhi
authors.initials: G
authors.lastname: Tang
authors.forename: Zongxing
authors.initials: Z
authors.lastname: Qiu
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Lin
authors.forename: Wentao
authors.initials: W
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Shaohua
authors.initials: S
authors.lastname: Li
authors.forename: Haodong
authors.initials: H
authors.lastname: Li
authors.forename: Lisha
authors.initials: L
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Jim Z
authors.initials: JZ
authors.lastname: Wu
authors.forename: Wengang
authors.initials: W
authors.lastname: Yang
mesh_terms: D000818:Animals; D002460:Cell Line; D003516:Cycloparaffins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D055808:Drug Discovery; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000187:drug effects*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D003516:Cycloparaffins; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014508:Urea