847442-91-5Relevant academic research and scientific papers
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.
Synthesis and SAR of novel 1,1-dialkyl-2(1H)-naphthalenones as potent HCV polymerase inhibitors
Bosse, Todd D.,Larson, Daniel P.,Wagner, Rolf,Hutchinson, Doug K.,Rockway, Todd W.,Kati, Warren M.,Liu, Yaya,Masse, Sherie,Middleton, Tim,Mo, Hongmei,Montgomery, Debra,Jiang, Wen,Koev, Gennadiy,Kempf, Dale J.,Molla, Akhter
, p. 568 - 570 (2008/09/17)
A series of gem-dialkyl naphthalenone derivatives with varied alkyl substitutions were synthesized and evaluated according to their structure-activity relationship. This investigation led to the discovery of potent inhibitors of the hepatitis C virus at l
ANTI-INFECTIVE AGENTS
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Page/Page column 217, (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.
