Identification of N,N-disubstituted phenylalanines as a novel class of inhibitors of hepatitis C NS5B polymerase.
The HCV NS5B RNA dependent RNA polymerase plays an essential role in viral replication. The discovery of a novel class of inhibitors based on an N,N-disubstituted phenylalanine scaffold and structure-activity relationships studies to improve potency are described.
Chan
Laval
L
Shire BioChem Inc., 275 Armand-Frappier Boulevard, Laval, Quebec H7V 4A7, Canada. lchan@ca.shire.com
Reddy
T Jagadeeswar
TJ
Proulx
Mélanie
M
Das
Sanjoy K
SK
Pereira
Oswy
O
Wang
Wuyi
W
Siddiqui
Arshad
A
Yannopoulos
Constantin G
CG
Poisson
Carl
C
Turcotte
Nathalie
N
Drouin
Alexandre
A
Alaoui-Ismaili
M Hicham
MH
Bethell
Richard
R
Hamel
Martine
M
L'Heureux
Lucille
L
Bilimoria
Darius
D
Nguyen-Ba
Nghe
N
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D016174:Hepacivirus / Q000201:enzymology*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D017361:Viral Nonstructural Proteins; D010649:Phenylalanine; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase