847442-84-6Relevant articles and documents
Inhibitors of hepatitis C virus polymerase: Synthesis and biological characterization of unsymmetrical dialkyl-hydroxynaphthalenoyl-benzothiadiazines
Wagner, Rolf,Larson, Daniel P.,Beno, David W. A.,Bosse, Todd D.,Darbyshire, John F.,Gao, Yi,Gates, Bradley D.,He, Wenping,Henry, Rodger F.,Hernandez, Lisa E.,Hutchinson, Douglas K.,Jiang, Wen W.,Kati, Warren M.,Klein, Larry L.,Koev, Gennadiy,Kohlbrenner, William,Krueger, A. Chris,Liu, Jinrong,Liu, Yaya,Long, Michelle A.,Maring, Clarence J.,Masse, Sherie V.,Middleton, Tim,Montgomery, Debra A.,Pratt, John K.,Stuart, Patricia,Molla, Akhteruzzaman,Kempf, Dale J.
experimental part, p. 1659 - 1669 (2010/01/07)
The hepatitis C virus (HCV) NS5B polymerase is essential for viral replication and has been a prime target for drug discovery research. Our efforts directed toward the discovery of HCV polymerase inhibitors resulted in the identification of unsymmetrical dialkyl-hydroxynaphthalenoyl-benzothiadiazines 2 and 3. The most active compound displayed activity in genotypes 1a and 1b polymerase and replicon cell culture inhibition assays at subnanomolar and low nanomolar concentrations, respectively. It also displayed an excellent pharmacokinetic profile in rats, with a plasma elimination half-life after intravenous dosing of 4.5 h, oral bioavailability of 77%, and a peak liver concentration of 21.8 μg/mL.
Inhibitors of HCV NS5B polymerase: Synthesis and structure-activity relationships of unsymmetrical 1-hydroxy-4,4-dialkyl-3-oxo-3,4-dihydronaphthalene benzothiadiazine derivatives
Krueger, A. Chris,Madigan, Darold L.,Green, Brian E.,Hutchinson, Douglas K.,Jiang, Wen W.,Kati, Warren M.,Liu, Yaya,Maring, Clarence J.,Masse, Sherie V.,McDaniel, Keith F.,Middleton, Tim R.,Mo, Hongmei,Molla, Akhteruzzaman,Montgomery, Debra A.,Ng, Teresa I.,Kempf, Dale J.
, p. 2289 - 2292 (2008/02/13)
Substituted 1-hydroxy-4,4-dialkyl-3-oxo-3,4-dihydronaphthalene benzothiadiazine derivatives were investigated as inhibitors of genotype 1 HCV polymerase. Structure-activity relationship patterns for this class of compounds are discussed. It was found that
ANTI-INFECTIVE AGENTS
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Page/Page column 203, (2010/02/11)
Compounds having the formula (I) are hepatitis C (HCV) polymerase inhibitors. Also disclosed are a composition and method for inhibiting hepatitis C (HCV) polymerase, processes for making the compounds, and synthetic intermediates employed in the processes.
