title: Aryl uracil inhibitors of hepatitis C virus NS5B polymerase: synthesis and characterization of analogs with a fused 5,6-bicyclic ring motif.
abstract: The synthesis and structure-activity relationships of a novel aryl uracil series which contains a fused 5,6-bicyclic ring unit for HCV NS5B inhibition is described. Several analogs display replicon cell culture potencies in the low nanomolar range along with excellent rat pharmacokinetic values.
authors.affiliation: AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA. a.chris.krueger@abbvie.com
authors.forename: A Chris
authors.initials: AC
authors.lastname: Krueger
authors.forename: John T
authors.initials: JT
authors.lastname: Randolph
authors.forename: David A
authors.initials: DA
authors.lastname: DeGoey
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Donner
authors.forename: Charles A
authors.initials: CA
authors.lastname: Flentge
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Hutchinson
authors.forename: Dachun
authors.initials: D
authors.lastname: Liu
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Motter
authors.forename: Todd W
authors.initials: TW
authors.lastname: Rockway
authors.forename: Rolf
authors.initials: R
authors.lastname: Wagner
authors.forename: David W A
authors.initials: DW
authors.lastname: Beno
authors.forename: Gennadiy
authors.initials: G
authors.lastname: Koev
authors.forename: Hock B
authors.initials: HB
authors.lastname: Lim
authors.forename: Jill M
authors.initials: JM
authors.lastname: Beyer
authors.forename: Rubina
authors.initials: R
authors.lastname: Mondal
authors.forename: Yaya
authors.initials: Y
authors.lastname: Liu
authors.forename: Warren M
authors.initials: WM
authors.lastname: Kati
authors.forename: Kenton L
authors.initials: KL
authors.lastname: Longenecker
authors.forename: Akhteruzzaman
authors.initials: A
authors.lastname: Molla
authors.forename: Kent D
authors.initials: KD
authors.lastname: Stewart
authors.forename: Clarence J
authors.initials: CJ
authors.lastname: Maring
mesh_terms: D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D016174:Hepacivirus / Q000201:enzymology; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship; D014498:Uracil / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001643:Bridged Bicyclo Compounds; D004791:Enzyme Inhibitors; D017361:Viral Nonstructural Proteins; D014498:Uracil; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase