Hepatitis C NS5B polymerase inhibitors: 4,4-Dialkyl-1-hydroxy-3-oxo-3,4-dihydronaphthalene-3-yl benzothiadiazine derivatives.
4,4-Dialkyl-1-hydroxy-3-oxo-3.4-dihydronaphthalene-3-yl benzothiadiazine derivatives were synthesized and evaluated as inhibitors of genotypes 1a and 1b HCV NS5B polymerase. A number of these compounds exhibited potent activity against genotypes 1a and 1b HCV polymerase in both enzymatic and cell culture activities. A representative compound also showed favorable pharmacokinetics in the rat.
Hutchinson
Douglas K
DK
Department of Antiviral Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. douglas.hutchinson@abbott.com
Rosenberg
Teresa
T
Klein
Larry L
LL
Bosse
Todd D
TD
Larson
Daniel P
DP
He
Wenping
W
Jiang
Wen W
WW
Kati
Warren M
WM
Kohlbrenner
William E
WE
Liu
Yaya
Y
Masse
Sherie V
SV
Middleton
Tim
T
Molla
Akhteruzzaman
A
Montgomery
Debra A
DA
Beno
David W A
DW
Stewart
Kent D
KD
Stoll
Vincent S
VS
Kempf
Dale J
DJ
D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D005838:Genotype; D007262:Infusions, Intravenous; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D051381:Rats; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase