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 EC(50) of 98 nM against H1N1 A/Weiss/43 strain and over 1000-fold selectivity against host MDCK cells.
Tang
Guozhi
G
Roche R&D Center China, Shanghai, China. gordon.tang@roche.com
Qiu
Zongxing
Z
Lin
Xianfeng
X
Li
Wentao
W
Zhu
Lei
L
Li
Shaohua
S
Li
Haodong
H
Wang
Lisha
L
Chen
Li
L
Wu
Jim Z
JZ
Yang
Wengang
W
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
D003516:Cycloparaffins; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014508:Urea