Discovery of thiophene-2-carboxylic acids as potent inhibitors of HCV NS5B polymerase and HCV subgenomic RNA replication. Part 1: Sulfonamides.
The discovery of a novel class of HCV NS5B polymerase inhibitors, 3-arylsulfonylamino-5-phenyl-thiophene-2-carboxylic acids is described. SAR studies have yielded several potent inhibitors of HCV polymerase as well as of HCV subgenomic RNA replication in Huh-7 cells.
Chan
Laval
L
Shire BioChem Inc., 275 Armand-Frappier, Laval, Quebec, Canada H7V 4A7. lchan@ca.shire.com
Das
Sanjoy K
SK
Reddy
T Jagadeeswar
TJ
Poisson
Carl
C
Proulx
Mélanie
M
Pereira
Oswy
O
Courchesne
Marc
M
Roy
Caroline
C
Wang
Wuyi
W
Siddiqui
Arshad
A
Yannopoulos
Constantin G
CG
Nguyen-Ba
Nghe
N
Labrecque
Denis
D
Bethell
Richard
R
Hamel
Martine
M
Courtemanche-Asselin
Philippe
P
L'Heureux
Lucille
L
David
Maud
M
Nicolas
Olivier
O
Brunette
Stéphanie
S
Bilimoria
Darius
D
Bédard
Jean
J
D002264:Carboxylic Acids; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000201:enzymology / Q000821:virology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D016679:Genome, Viral; D016174:Hepacivirus / Q000201:enzymology*; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000821:virology; D012367:RNA, Viral / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D012093:Replicon / Q000187:drug effects; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects
D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D012367:RNA, Viral; D013449:Sulfonamides; D013876:Thiophenes; D017361:Viral Nonstructural Proteins; C550746:2-thiophene carboxylic acid; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase