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| [[Image:2fvc.jpg|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_2fvc| PDB=2fvc | SCENE= }} | | {{STRUCTURE_2fvc| PDB=2fvc | SCENE= }} |
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| '''Crystal structure of NS5B BK strain (delta 24) in complex with a 3-(1,1-Dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinone'''
| | ===Crystal structure of NS5B BK strain (delta 24) in complex with a 3-(1,1-Dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinone=== |
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| ==Overview==
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| Recently, we disclosed a new class of HCV polymerase inhibitors discovered through high-throughput screening (HTS) of the GlaxoSmithKline proprietary compound collection. This interesting class of 3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones potently inhibits HCV polymerase enzymatic activity and inhibits the ability of the subgenomic HCV replicon to replicate in Huh-7 cells. This report will focus on the structure-activity relationships (SAR) of substituents on the quinolinone ring, culminating in the discovery of 1-(2-cyclopropylethyl)-3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-6-fluor o-4-hydroxy-2(1H)-quinolinone (130), an inhibitor with excellent potency in biochemical and cellular assays possessing attractive molecular properties for advancement as a clinical candidate. The potential for development and safety assessment profile of compound 130 will also be discussed.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16451063}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16451063 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16451063}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Hcv polymerase]] | | [[Category: Hcv polymerase]] |
| [[Category: Thiadiazin inhibitor]] | | [[Category: Thiadiazin inhibitor]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:20:43 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:56:55 2008'' |