title: 5,6-Dihydro-1H-pyridin-2-ones as potent inhibitors of HCV NS5B polymerase.
abstract: 5,6-Dihydro-1H-pyridin-2-one analogs were discovered as a novel class of inhibitors of genotype 1 HCV NS5B polymerase. Among these, compound 4ad displayed potent inhibitory activities in biochemical and replicon assays (IC(50) (1b)<10nM; IC(50) (1a)<25nM, EC(50) (1b)=16nM), good in vitro DMPK properties, as well as moderate oral bioavailability in monkeys (F=24%).
authors.affiliation: Department of Medicinal Chemistry, Anadys Pharmaceuticals, Inc., 3115 Merryfield Row, San Diego, CA 92121, USA. fruebsam@anadyspharma.com
authors.forename: Frank
authors.initials: F
authors.lastname: Ruebsam
authors.forename: Chinh V
authors.initials: CV
authors.lastname: Tran
authors.forename: Lian-Sheng
authors.initials: LS
authors.lastname: Li
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Alan X
authors.initials: AX
authors.lastname: Xiang
authors.forename: Yuefen
authors.initials: Y
authors.lastname: Zhou
authors.forename: Julie K
authors.initials: JK
authors.lastname: Blazel
authors.forename: Zhongxiang
authors.initials: Z
authors.lastname: Sun
authors.forename: Peter S
authors.initials: PS
authors.lastname: Dragovich
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.forename: Helen M
authors.initials: HM
authors.lastname: McGuire
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Murphy
authors.forename: Martin T
authors.initials: MT
authors.lastname: Tran
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Stankovic
authors.forename: David A
authors.initials: DA
authors.lastname: Ellis
authors.forename: Alberto
authors.initials: A
authors.lastname: Gobbi
authors.forename: Richard E
authors.initials: RE
authors.lastname: Showalter
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Webber
authors.forename: Amit M
authors.initials: AM
authors.lastname: Shah
authors.forename: Mei
authors.initials: M
authors.lastname: Tsan
authors.forename: Rupal A
authors.initials: RA
authors.lastname: Patel
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Lebrun
authors.forename: Huiying J
authors.initials: HJ
authors.lastname: Hou
authors.forename: Ruhi
authors.initials: R
authors.lastname: Kamran
authors.forename: Maria V
authors.initials: MV
authors.lastname: Sergeeva
authors.forename: Darian M
authors.initials: DM
authors.lastname: Bartkowski
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Nolan
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Norris
authors.forename: Leo
authors.initials: L
authors.lastname: Kirkovsky
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000882:Haplorhini; D011728:Pyridones / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D012321:DNA-Directed RNA Polymerases; D004791:Enzyme Inhibitors; D011728:Pyridones; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase