title: Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1',4'-dihydro-1'lambda6-benzo[1',2',4']thiadiazin-3'-yl)-5-hydroxy-2H-pyridazin-3-ones: Part 4. Optimization of DMPK properties.
abstract: 5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as potent inhibitors of genotype 1 HCV NS5B polymerase focusing on the optimization of their drug metabolism and pharmacokinetics (DMPK) profiles. This investigation led to the discovery of potent inhibitors with improved DMPK properties.
authors.affiliation: Anadys Pharmaceuticals, Inc., Medicinal Chemistry, 3115 Merryfield Row, San Diego, CA 92121, USA.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Sergeeva
authors.forename: Yuefen
authors.initials: Y
authors.lastname: Zhou
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: Ellen
authors.initials: E
authors.lastname: Okamoto
authors.forename: Leo
authors.initials: L
authors.lastname: Kirkovsky
authors.forename: Ruhi
authors.initials: R
authors.lastname: Kamran
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Lebrun
authors.forename: Mei
authors.initials: M
authors.lastname: Tsan
authors.forename: Rupal
authors.initials: R
authors.lastname: Patel
authors.forename: Amit M
authors.initials: AM
authors.lastname: Shah
authors.forename: Matthew
authors.initials: M
authors.lastname: Lardy
authors.forename: Alberto
authors.initials: A
authors.lastname: Gobbi
authors.forename: Lian-Sheng
authors.initials: LS
authors.lastname: Li
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.forename: Thomas
authors.initials: T
authors.lastname: Bertolini
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Stankovic
authors.forename: Zhongxiang
authors.initials: Z
authors.lastname: Sun
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Murphy
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Webber
authors.forename: Peter S
authors.initials: PS
authors.lastname: Dragovich
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D000882:Haplorhini; D016174:Hepacivirus / Q000201:enzymology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D011724:Pyridazines; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase