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.
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.
Tedesco
Rosanna
R
Department of Medicinal Chemistry, GlaxoSmithKline Pharmaceuticals, Collegeville, PA 19426, USA. Rosanna_2_Tedesco@gsk.com
Chai
Deping
D
Darcy
Michael G
MG
Dhanak
Dashyant
D
Fitch
Duke M
DM
Gates
Adam
A
Johnston
Victor K
VK
Keenan
Richard M
RM
Lin-Goerke
Juili
J
Sarisky
Robert T
RT
Shaw
Antony N
AN
Valko
Klara L
KL
Wiggall
Kenneth J
KJ
Zimmerman
Michael N
MN
Duffy
Kevin J
KJ
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
D000998:Antiviral Agents; D015363:Quinolones; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase