title: Synthesis and biological activity of heteroaryl 3-(1,1-dioxo-2H-(1,2,4)-benzothiadizin-3-yl)-4-hydroxy-2(1H)-quinolinone derivatives as hepatitis C virus NS5B polymerase inhibitors.
abstract: Modification of the benzo rings of 3-(1,1-dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones into heteroaromatic systems was investigated to enhance physicochemical properties and potency profile of this class of inhibitors. The synthesis and biological activity of the derived compounds is discussed.
authors.affiliation: Department of Medicinal Chemistry, GlaxoSmithKline Pharmaceuticals, Collegeville, PA 19426, USA. Rosanna_2_Tedesco@gsk.com
authors.forename: Rosanna
authors.initials: R
authors.lastname: Tedesco
authors.forename: Deping
authors.initials: D
authors.lastname: Chai
authors.forename: Michael G
authors.initials: MG
authors.lastname: Darcy
authors.forename: Dashyant
authors.initials: D
authors.lastname: Dhanak
authors.forename: Duke M
authors.initials: DM
authors.lastname: Fitch
authors.forename: Adam
authors.initials: A
authors.lastname: Gates
authors.forename: Victor K
authors.initials: VK
authors.lastname: Johnston
authors.forename: Richard M
authors.initials: RM
authors.lastname: Keenan
authors.forename: Juili
authors.initials: J
authors.lastname: Lin-Goerke
authors.forename: Robert T
authors.initials: RT
authors.lastname: Sarisky
authors.forename: Antony N
authors.initials: AN
authors.lastname: Shaw
authors.forename: Klara L
authors.initials: KL
authors.lastname: Valko
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Wiggall
authors.forename: Michael N
authors.initials: MN
authors.lastname: Zimmerman
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Duffy
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D005838:Genotype; D016174:Hepacivirus / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure; D011485:Protein Binding; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D015363:Quinolones; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase