title: Discovery of fluorobenzimidazole HCV NS5A inhibitors.
abstract: Research toward a next-generation HCV NS5A inhibitor has identified fluorobenzimidazole analogs that demonstrate potent, broad-genotype in vitro activity against HCV genotypes 1-6 replicons as well as HCV NS5A variants that are orders of magnitude less susceptible to inhibition by first-generation NS5A inhibitors in comparison to wild-type replicons. The fluorobenzimidazole inhibitors have improved pharmacokinetic properties in comparison to non-fluorinated benzimidazole analogs. Discovery of these inhibitors was facilitated by exploring SAR in a structurally simplified inhibitor series.
authors: AbbVie Inc., North Chicago, IL, USA.
authors: John T
authors: JT
authors: Randolph
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Charles A
authors: CA
authors: Flentge
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Pamela
authors: P
authors: Donner
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Todd W
authors: TW
authors: Rockway
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Sachin V
authors: SV
authors: Patel
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Lissa
authors: L
authors: Nelson
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Douglas K
authors: DK
authors: Hutchinson
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Rubina
authors: R
authors: Mondal
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Neeta
authors: N
authors: Mistry
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Thomas
authors: T
authors: Reisch
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Tatyana
authors: T
authors: Dekhtyar
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Preethi
authors: P
authors: Krishnan
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Tami
authors: T
authors: Pilot-Matias
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Deanne F
authors: DF
authors: Stolarik
authors: AbbVie Inc., North Chicago, IL, USA.
authors: David W A
authors: DWA
authors: Beno
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Rolf
authors: R
authors: Wagner
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Clarence
authors: C
authors: Maring
authors: AbbVie Inc., North Chicago, IL, USA.
authors: Warren M
authors: WM
authors: Kati
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004285:Dogs; D005838:Genotype; D054879:Halogenation; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D051379:Mice; D051381:Rats; D012093:Replicon / Q000187:drug effects; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D017361:Viral Nonstructural Proteins; C031000:benzimidazole; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: Antiviral; HCV; NS5A inhibitor