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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2008-4-15
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pubmed:abstractText |
In our program to discover non-nucleoside, small molecule inhibitors of genotype 1 HCV polymerase, we investigated a series of promising analogs based on a benzothiadiazine screening hit that contains an ABCD ring system. After demonstrating that a methylsulfonylamino D-ring substituent increased the enzyme potency into the low nanomolar range, we explored a minimum core required for activity by truncating to a three-ring system. Described herein are the syntheses and structure-activity relationship of a set of inhibitors lacking the A-ring of an ABCD ring system. We observed that small aromatic rings and alkenyl groups appended to the 5-position of the B-ring were optimal, resulting in inhibitors with low nanomolar potencies.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:DonnerPamela LPL,
pubmed-author:JiangWenW,
pubmed-author:KatiWarrenW,
pubmed-author:KempfDale JDJ,
pubmed-author:KoevGennadiyG,
pubmed-author:LiuYayaY,
pubmed-author:MaringClarence JCJ,
pubmed-author:MasseSherieS,
pubmed-author:MollaAkhterA,
pubmed-author:MontgomeryDebraD,
pubmed-author:PrattJohn KJK,
pubmed-author:XieQinghuaQ
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2735-8
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pubmed:meshHeading |
pubmed-meshheading:18362072-Benzothiadiazines,
pubmed-meshheading:18362072-Enzyme Inhibitors,
pubmed-meshheading:18362072-Genotype,
pubmed-meshheading:18362072-Hepacivirus,
pubmed-meshheading:18362072-Models, Molecular,
pubmed-meshheading:18362072-Molecular Structure,
pubmed-meshheading:18362072-RNA Replicase,
pubmed-meshheading:18362072-Structure-Activity Relationship,
pubmed-meshheading:18362072-Viral Nonstructural Proteins,
pubmed-meshheading:18362072-Virus Replication
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pubmed:year |
2008
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pubmed:articleTitle |
Des-A-ring benzothiadiazines: inhibitors of HCV genotype 1 NS5B RNA-dependent RNA polymerase.
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pubmed:affiliation |
Antiviral Research, Global Pharmaceutical Research, and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. Pamela.l.donner@abbott.com
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pubmed:publicationType |
Journal Article
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