title: Studies on acyl pyrrolidine inhibitors of HCV RNA-dependent RNA polymerase to identify a molecule with replicon antiviral activity.
abstract: The SAR development is described for a series of N-acyl pyrrolidine inhibitors of the Hepatitis C virus RNA-dependent RNA polymerase, NS5B, from tractable Delta21 enzyme inhibitors to an example with antiviral activity in a cellular assay (HCV replicon).
authors.affiliation: GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA 19426-0989, USA. george.burton@gsk.com
authors.forename: George
authors.initials: G
authors.lastname: Burton
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Ku
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Carr
authors.forename: Terry
authors.initials: T
authors.lastname: Kiesow
authors.forename: Robert T
authors.initials: RT
authors.lastname: Sarisky
authors.forename: Juili
authors.initials: J
authors.lastname: Lin-Goerke
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Hofmann
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Slater
authors.forename: David
authors.initials: D
authors.lastname: Haigh
authors.forename: Dashyant
authors.initials: D
authors.lastname: Dhanak
authors.forename: Victor K
authors.initials: VK
authors.lastname: Johnson
authors.forename: Nigel R
authors.initials: NR
authors.lastname: Parry
authors.forename: Pia
authors.initials: P
authors.lastname: Thommes
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016174:Hepacivirus / Q000737:chemistry* / Q000235:genetics*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008968:Molecular Conformation; D011759:Pyrrolidines / Q000037:antagonists & inhibitors*; D012367:RNA, Viral / Q000737:chemistry; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D012093:Replicon / Q000235:genetics*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C032519:pyrrolidine