| |  Online-Ressource |
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| Verfasst von: | Steuer, Christian [VerfasserIn]  |
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| | Gege, Christian [VerfasserIn] |
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| | Fischl, Wolfgang [VerfasserIn] |
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| | Heinonen, Karl H. [VerfasserIn] |
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| | Bartenschlager, Ralf [VerfasserIn] |
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| | Klein, Christian D. [VerfasserIn] |
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| Titel: | Synthesis and biological evaluation of α-ketoamides as inhibitors of the Dengue virus protease with antiviral activity in cell-culture |
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| Verf.angabe: | Christian Steuer, Christian Gege, Wolfgang Fischl, Karl H. Heinonen, Ralf Bartenschlager, Christian D. Klein |
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| E-Jahr: | 2011 |
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| Jahr: | 18 May 2011 |
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| Umfang: | 8 S. |
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| Fussnoten: | Gesehen am 21.10.2022 |
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| Titel Quelle: | Enthalten in: Bioorganic & medicinal chemistry |
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| Ort Quelle: | Amsterdam [u.a.] : Elsevier, 1993 |
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| Jahr Quelle: | 2011 |
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| Band/Heft Quelle: | 19(2011), 13, Seite 4067-4074 |
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| ISSN Quelle: | 1464-3391 |
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| Abstract: | The development of small molecule inhibitors of the viral protease is of considerable interest for the treatment of emergent flaviviral diseases such as Dengue or West Nile fever. Until today little progress has been made in finding drug-like compounds that inhibit the protease and provide a starting point for lead optimization. We describe here the initial steps of a drug discovery effort that focused on the styryl pharmacophore, combined with a ketoamide function to serve as electrophilic trap for the catalytic serine. This resulted in a fragment-like lead compound with reasonable target affinity and good ligand efficiency, which was extensively modified to explore structure-activity relationships. Selected compounds were cross-tested against the West Nile virus protease and thrombin, indicating that selectivity for one or more flaviviral proteases can be achieved. Finally, the antiviral activity of several protease inhibitors was confirmed in a cell-culture model of Dengue virus replication. The SAR presented here may serve as starting point for further drug discovery efforts with the aim of targeting flaviviral proteases. |
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| DOI: | doi:10.1016/j.bmc.2011.05.015 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.bmc.2011.05.015 |
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| | Volltext: https://www.sciencedirect.com/science/article/pii/S0968089611003609 |
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| | DOI: https://doi.org/10.1016/j.bmc.2011.05.015 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Dengue virus |
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| | Flavivirus |
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| | Ketoamides |
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| | NS2B-NS3 protease |
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| | Protease inhibitors |
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| K10plus-PPN: | 1819634752 |
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| Verknüpfungen: | → Zeitschrift |
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Synthesis and biological evaluation of α-ketoamides as inhibitors of the Dengue virus protease with antiviral activity in cell-culture / Steuer, Christian [VerfasserIn]; 18 May 2011 (Online-Ressource)
