title: Discovery of thienoimidazole-based HCV NS5A inhibitors. Part 2: non-symmetric inhibitors with potent activity against genotype 1a and 1b.
abstract: The discovery of non-symmetric thienoimidazole-containing HCV NS5A inhibitors is described. The inhibitors herein reported display high potencies against both genotype 1a and 1b. In this follow-up manuscript, we discuss the importance of the linker aromaticity to achieve high potency, particularly against genotype 1a.
authors.affiliation: Vertex Pharmaceuticals Inc., 50 Northern Avenue, Boston, MA 02210, USA. Electronic address: simon_giroux@vrtx.com.
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: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017361:Viral Nonstructural Proteins / Q000187:drug effects*; 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