title: N-Acetamideindolecarboxylic acid allosteric 'finger-loop' inhibitors of the hepatitis C virus NS5B polymerase: discovery and initial optimization studies.
abstract: SAR studies at the N(1)-position of allosteric indole-based HCV NS5B inhibitors has led to the discovery of acetamide derivatives with good cellular potency in subgenomic replicons (EC(50) <200 nM). This class of inhibitors displayed improved physicochemical properties and favorable ADME-PK profiles over previously described analogs in this class.
authors.affiliation: Department of Chemistry, Boehringer Ingelheim Canada Ltd, Research and Development, 2100 Cunard Street, Laval, Québec, Canada H7S 2G5. pierre.beaulieu@boehringer-ingelheim.com
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Beaulieu
authors.forename: Eric
authors.initials: E
authors.lastname: Jolicoeur
authors.forename: James
authors.initials: J
authors.lastname: Gillard
authors.forename: Christian
authors.initials: C
authors.lastname: Brochu
authors.forename: René
authors.initials: R
authors.lastname: Coulombe
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dansereau
authors.forename: Jianmin
authors.initials: J
authors.lastname: Duan
authors.forename: Michel
authors.initials: M
authors.lastname: Garneau
authors.forename: Araz
authors.initials: A
authors.lastname: Jakalian
authors.forename: Peter
authors.initials: P
authors.lastname: Kühn
authors.forename: Lisette
authors.initials: L
authors.lastname: Lagacé
authors.forename: Steven
authors.initials: S
authors.lastname: LaPlante
authors.forename: Ginette
authors.initials: G
authors.lastname: McKercher
authors.forename: Stéphane
authors.initials: S
authors.lastname: Perrault
authors.forename: Martin
authors.initials: M
authors.lastname: Poirier
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Poupart
authors.forename: Timothy
authors.initials: T
authors.lastname: Stammers
authors.forename: Louise
authors.initials: L
authors.lastname: Thauvette
authors.forename: Bounkham
authors.initials: B
authors.lastname: Thavonekham
authors.forename: George
authors.initials: G
authors.lastname: Kukolj
mesh_terms: D000081:Acetamides / Q000737:chemistry* / Q000494:pharmacology; D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018938:Caco-2 Cells; D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008862:Microsomes, Liver / Q000201:enzymology; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000081:Acetamides; D000998:Antiviral Agents; D002264:Carboxylic Acids; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; D012321:DNA-Directed RNA Polymerases