Identification of thieno[3,2-b]pyrroles as allosteric inhibitors of hepatitis C virus NS5B polymerase.
Thieno[3,2-b]pyrroles are a novel class of allosteric inhibitors of HCV NS5B RNA-dependent RNA polymerase which show potent affinity for the NS5B enzyme. Introduction of a polar substituent in the position N1 led to a compound that efficiently blocks subgenomic HCV RNA replication in HUH-7 cells with an EC50 of 2.9 microM.
Ontoria
Jesus M
JM
Department of Medicinal Chemistry, IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia (Rome), Italy. jesus_ontoria@merck.com
Martìn Hernando
Jose I
JI
Malancona
Savina
S
Attenni
Barbara
B
Stansfield
Ian
I
Conte
Immacolata
I
Ercolani
Caterina
C
Habermann
Jörg
J
Ponzi
Simona
S
Di Filippo
Marcello
M
Koch
Uwe
U
Rowley
Michael
M
Narjes
Frank
F
D000494:Allosteric Regulation; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
D011480:Protease Inhibitors; D011758:Pyrroles; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase