Tetrahydrobenzothiophene inhibitors of hepatitis C virus NS5B polymerase

A series of tetrahydrobenzothiophenes have been prepared and identified as potent inhibitors of HCV NS5B polymerase. R = 6,6-Dimethyl, R′ = CONHSO 2Ar. A novel series of selective HCV NS5B RNA dependent RNA polymerase inhibitors has been disclosed. These compounds contain an appropriately substitute...

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 16; no. 1; pp. 100 - 103
Main Authors:	LaPorte, M.G., Lessen, T.A., Leister, L., Cebzanov, D., Amparo, E., Faust, C., Ortlip, D., Bailey, T.R., Nitz, T.J., Chunduru, S.K., Young, D.C., Burns, C.J.
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 2006 Elsevier
Subjects:	Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences Caco-2 Cells Chemistry, Pharmaceutical - methods Drug Design Drug Evaluation, Preclinical Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology HCV polymerase inhibitors Hepacivirus - enzymology Humans Medical sciences Models, Chemical Pharmacology. Drug treatments Protein Structure, Tertiary RNA-Dependent RNA Polymerase - antagonists & inhibitors Structure-Activity Relationship Sulfonamides - chemistry Tetrahydrobenzothiophenes Thiophenes - chemistry Thiophenes - pharmacology Viral Nonstructural Proteins - antagonists & inhibitors HCV polymerase inhibitors Tetrahydrobenzothiophenes Sulfonamide Enzyme Transferases Enzyme inhibitor Selectivity In vitro RNA-directed RNA polymerase Virus Benzothiophene derivatives Imide Nucleotidyltransferases Structure activity relation Antiviral Ureas Flaviviridae Chemical synthesis Hepatitis C virus Hepacivirus
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Summary:	A series of tetrahydrobenzothiophenes have been prepared and identified as potent inhibitors of HCV NS5B polymerase. R = 6,6-Dimethyl, R′ = CONHSO 2Ar. A novel series of selective HCV NS5B RNA dependent RNA polymerase inhibitors has been disclosed. These compounds contain an appropriately substituted tetrahydrobenzothiophene scaffold. This communication will detail the SAR and activities of this series.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2005.09.047