Non-nucleoside inhibitors of HCV polymerase NS5B. Part 2: Synthesis and structure-activity relationships of benzothiazine-substituted quinolinediones

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 13, 2009, Pages 3642-3646

  de Vicente, Javier ^a   Hendricks, Robert T ^a   Smith, David B ^a   Fell, Jay B ^a   Fischer, John ^b   Spencer, Stacey R ^b   Stengel, Peter J ^b   Mohr, Peter ^b   Robinson, John E ^b   Blake, James F ^b   Hilgenkamp, Ramona K ^a   Yee, Calvin ^a   Adjabeng, George ^a   Elworthy, Todd R ^a   Tracy, Jahari ^a   Chin, Elbert ^a   Li, Jim ^a   Wang, Beihan ^a   Bamberg, Joe T ^a   Stephenson, Rebecca ^a   Oshiro, Connie ^a   Harris, Seth F ^a   Ghate, Manjiri ^a   Leveque, Vincent ^a   Najera, Isabel ^a   Pogam, Sophie Le ^a   Rajyaguru, Sonal ^a   Ao Ieong, Gloria ^a   Alexandrova, Ludmila ^a   Larrabee, Susan ^a   Brandl, Michael ^a   Briggs, Andrew ^a   Sukhtankar, Sunil ^a   Farrell, Robert ^a   Xu, Brian ^a   more..

^a ROCHE BIOSCIENCE   (United States)

^b ARRAY BIOPHARMA INC   (United States)

Author keywords

Benzothiazine; DMPK properties; HCV polymerase NS5B; Non nucleoside inhibitors; Pharmacokinetic studies; X ray co crystal structures

Indexed keywords

BENZOTHIAZINE DERIVATIVE; MONOSULFONYLATED BENZOTHIAZINE; NON NUCLEOSIDE HEPATITIS C VIRUS NONSTRUCTURAL PROTEIN 5B POLYMERASE INHIBITOR; NONSTRUCTURAL PROTEIN 5B; NUCLEOTIDYLTRANSFERASE INHIBITOR; QUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; DOG; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG METABOLISM; DRUG POTENCY; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG SYNTHESIS; FEMALE; HEPATITIS C VIRUS; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; RAT; REACTION ANALYSIS; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ANIMALS; ANTIVIRAL AGENTS; COMPUTER SIMULATION; CRYSTALLOGRAPHY, X-RAY; DNA-DIRECTED RNA POLYMERASES; DOGS; ENZYME INHIBITORS; HEPACIVIRUS; HUMANS; QUINOLINES; QUINOLONES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZINES; VIRAL NONSTRUCTURAL PROTEINS; VIRUS REPLICATION;

HEPATITIS C VIRUS;

EID: 66349098029     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.05.004     Document Type: Article

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17. A representative number of benzothiazine-substituted quinolinediones were also evaluated in a GT-1a replicon assay. This class of compounds had a minimal loss in inhibitory activity of 2-10 fold relative to our standard GT-1b replicon assay.
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