title: Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1',4'-dihydro-1'lambda(6)-benzo[1',2',4']thiadiazin-3'-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 2: Variation of the 2- and 6-pyridazinone substituents.
abstract: 5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as inhibitors of genotype 1 HCV NS5B polymerase. The structure-activity relationship (SAR) associated with variation of the pyridazinone 2- and 6-substituents is discussed. The synthesis and metabolic stability of this new class of compounds are also described.
authors.affiliation: Anadys Pharmaceuticals, Inc., 3115 Merryfield Row, San Diego, CA 92121, USA.
authors.forename: Yuefen
authors.initials: Y
authors.lastname: Zhou
authors.forename: Lian-Sheng
authors.initials: LS
authors.lastname: Li
authors.forename: Peter S
authors.initials: PS
authors.lastname: Dragovich
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Murphy
authors.forename: Chinh V
authors.initials: CV
authors.lastname: Tran
authors.forename: Frank
authors.initials: F
authors.lastname: Ruebsam
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: April
authors.initials: A
authors.lastname: Averill
authors.forename: Richard E
authors.initials: RE
authors.lastname: Showalter
authors.forename: Rupal
authors.initials: R
authors.lastname: Patel
authors.forename: Qing
authors.initials: Q
authors.lastname: Han
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.forename: Thomas
authors.initials: T
authors.lastname: Hermann
authors.forename: Charles R
authors.initials: CR
authors.lastname: Kissinger
authors.forename: Laurie
authors.initials: L
authors.lastname: Lebrun
authors.forename: Maria V
authors.initials: MV
authors.lastname: Sergeeva
mesh_terms: D018360:Crystallography, X-Ray; D015195:Drug Design; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008862:Microsomes, Liver / Q000378:metabolism; D008958:Models, Molecular; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013829:Thiadiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011724:Pyridazines; D013829:Thiadiazines; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase