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

Rosanna Tedesco; Deping Chai; Michael G Darcy; Dashyant Dhanak; Duke M Fitch; Adam Gates; Victor K Johnston; Richard M Keenan; Juili Lin-Goerke; Robert T Sarisky; Antony N Shaw; Klara L Valko; Kenneth J Wiggall; Michael N Zimmerman; Kevin J Duffy

doi:10.1016/j.bmcl.2009.05.080

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

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4354-8. doi: 10.1016/j.bmcl.2009.05.080. Epub 2009 May 27.

Authors

Rosanna Tedesco¹, Deping Chai, Michael G Darcy, Dashyant Dhanak, Duke M Fitch, Adam Gates, Victor K Johnston, Richard M Keenan, Juili Lin-Goerke, Robert T Sarisky, Antony N Shaw, Klara L Valko, Kenneth J Wiggall, Michael N Zimmerman, Kevin J Duffy

Affiliation

¹ Department of Medicinal Chemistry, GlaxoSmithKline Pharmaceuticals, Collegeville, PA 19426, USA. Rosanna_2_Tedesco@gsk.com

PMID: 19505821
DOI: 10.1016/j.bmcl.2009.05.080

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.

MeSH terms

Antiviral Agents / chemical synthesis
Antiviral Agents / pharmacology
Chemistry, Pharmaceutical / methods*
Drug Design
Genotype
Hepacivirus / metabolism
Humans
Inhibitory Concentration 50
Models, Chemical
Molecular Structure
Protein Binding
Quinolones / chemical synthesis*
Quinolones / pharmacology
Structure-Activity Relationship
Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

Antiviral Agents
Quinolones
Viral Nonstructural Proteins
NS-5 protein, hepatitis C virus