1,5-Benzodiazepine inhibitors of HCV NS5B polymerase.
Optimization through parallel synthesis of a novel series of hepatitis C virus (HCV) NS5B polymerase inhibitors led to the identification of (R)-11-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl-10-(6-methylpyridine-2-carbonyl)-2,3,4,5,10,11-hexahydro-dibenzo[b,e][1,4]diazepin-1-one 11zc and (R)-11-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl-10-(2,5-dimethyloxazol-4-carbonyl)-2,3,4,5,10,11-hexahydro-dibenzo[b,e][1,4]diazepin-1-one 11zk as potent (replicon EC(50)=400nM and 270nM, respectively) and selective (CC(50)>20muM) inhibitors of HCV replication. These data warrant further lead-optimization efforts.
McGowan
David
D
Tibotec BVBA, Gen. De Wittelaan L11 B3, B-2800 Mechelen, Belgium.
Nyanguile
Origène
O
Cummings
Maxwell D
MD
Vendeville
Sandrine
S
Vandyck
Koen
K
Van den Broeck
Walter
W
Boutton
Carlo W
CW
De Bondt
Hendrik
H
Quirynen
Ludo
L
Amssoms
Katie
K
Bonfanti
Jean-François
JF
Last
Stefaan
S
Rombauts
Klara
K
Tahri
Abdellah
A
Hu
Lili
L
Delouvroy
Frédéric
F
Vermeiren
Katrien
K
Vandercruyssen
Geneviève
G
Van der Helm
Liesbet
L
Cleiren
Erna
E
Mostmans
Wendy
W
Lory
Pedro
P
Pille
Geert
G
Van Emelen
Kristof
K
Fanning
Gregory
G
Pauwels
Frederik
F
Lin
Tse-I
TI
Simmen
Kenneth
K
Raboisson
Pierre
P