title: Discovery of thienoimidazole-based HCV NS5A inhibitors. Part 1: C2-symmetric inhibitors with diyne and biphenyl linkers.
abstract: The discovery of C2-symmetric bis-thienoimidazoles HCV NS5A inhibitors is herein reported. Two straightforward approaches to access the requisite diyne and biphenyl linker moieties are described. This study revealed the paramount importance of the aromatic character of the linker to achieve high genotype 1a potency.
authors.affiliation: Vertex Pharmaceuticals Inc., 50 Northern Avenue, Boston, MA 02210, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Giroux
authors.affiliation: Vertex Pharmaceuticals Canada Inc., 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
authors.forename: Darius
authors.initials: D
authors.lastname: Bilimoria
authors.affiliation: Vertex Pharmaceuticals Canada Inc., 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Cadilhac
authors.affiliation: Vertex Pharmaceuticals Inc., 50 Northern Avenue, Boston, MA 02210, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Cottrell
authors.affiliation: Vertex Pharmaceuticals Canada Inc., 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
authors.forename: Francois
authors.initials: F
authors.lastname: Denis
authors.affiliation: Vertex Pharmaceuticals Canada Inc., 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Dietrich
authors.affiliation: Vertex Pharmaceuticals Inc., 50 Northern Avenue, Boston, MA 02210, USA.
authors.forename: Nigel
authors.initials: N
authors.lastname: Ewing
authors.affiliation: Vertex Pharmaceuticals Inc., 50 Northern Avenue, Boston, MA 02210, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Henderson
authors.affiliation: Vertex Pharmaceuticals Canada Inc., 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
authors.forename: Lucille
authors.initials: L
authors.lastname: L'Heureux
authors.affiliation: Vertex Pharmaceuticals Inc., 50 Northern Avenue, Boston, MA 02210, USA.
authors.forename: Nagraj
authors.initials: N
authors.lastname: Mani
authors.affiliation: Vertex Pharmaceuticals Inc., 50 Northern Avenue, Boston, MA 02210, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Morris
authors.affiliation: Vertex Pharmaceuticals Canada Inc., 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
authors.forename: Olivier
authors.initials: O
authors.lastname: Nicolas
authors.affiliation: Vertex Pharmaceuticals Canada Inc., 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
authors.forename: T Jagadeeswar
authors.initials: TJ
authors.lastname: Reddy
authors.affiliation: Vertex Pharmaceuticals Canada Inc., 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
authors.forename: Subajini
authors.initials: S
authors.lastname: Selliah
authors.affiliation: Vertex Pharmaceuticals Inc., 50 Northern Avenue, Boston, MA 02210, USA.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Shawgo
authors.affiliation: Vertex Pharmaceuticals Inc., 50 Northern Avenue, Boston, MA 02210, USA.
authors.forename: Jinwang
authors.initials: J
authors.lastname: Xu
authors.affiliation: Vertex Pharmaceuticals Canada Inc., 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chauret
authors.affiliation: Vertex Pharmaceuticals Inc., 50 Northern Avenue, Boston, MA 02210, USA.
authors.forename: Francoise
authors.initials: F
authors.lastname: Berlioz-Seux
authors.affiliation: Vertex Pharmaceuticals Canada Inc., 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
authors.forename: Laval C
authors.initials: LC
authors.lastname: Chan
authors.affiliation: Vertex Pharmaceuticals Canada Inc., 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Das
authors.affiliation: Vertex Pharmaceuticals Inc., 50 Northern Avenue, Boston, MA 02210, USA.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Grillot
authors.affiliation: Vertex Pharmaceuticals Inc., 50 Northern Avenue, Boston, MA 02210, USA.
authors.forename: Youssef L
authors.initials: YL
authors.lastname: Bennani
authors.affiliation: Vertex Pharmaceuticals Inc., 50 Northern Avenue, Boston, MA 02210, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Maxwell
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D007093:Imidazoles; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: HCV; Hepatitis C; NS5a; Thienoimidazole