title: Pyrrolo[1,2-b]pyridazin-2-ones as potent inhibitors of HCV NS5B polymerase.
abstract: Pyrrolo[1,2-b]pyridazin-2-one analogs were discovered as a novel class of inhibitors of genotype 1 HCV NS5B polymerase. Structure-based design led to the discovery of compound 3 k, which displayed potent inhibitory activities in biochemical and replicon assays (IC(50) (1b)<10nM; EC(50) (1b)=12 nM) as well as good stability towards human liver microsomes (HLM t(1/2)>60 min).
authors.affiliation: 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: Stephen E
authors.initials: SE
authors.lastname: Webber
authors.forename: Martin T
authors.initials: MT
authors.lastname: Tran
authors.forename: Chinh V
authors.initials: CV
authors.lastname: Tran
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Murphy
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.forename: Peter S
authors.initials: PS
authors.lastname: Dragovich
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Lian-Sheng
authors.initials: LS
authors.lastname: Li
authors.forename: Yuefen
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qing
authors.initials: Q
authors.lastname: Han
authors.forename: Charles R
authors.initials: CR
authors.lastname: Kissinger
authors.forename: Richard E
authors.initials: RE
authors.lastname: Showalter
authors.forename: Matthew
authors.initials: M
authors.lastname: Lardy
authors.forename: Amit M
authors.initials: AM
authors.lastname: Shah
authors.forename: Mei
authors.initials: M
authors.lastname: Tsan
authors.forename: Rupal
authors.initials: R
authors.lastname: Patel
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Lebrun
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: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D011724:Pyridazines; D011758:Pyrroles; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase