Arylcyanoacrylamides as inhibitors of the Dengue and West Nile virus proteases
The 3-aryl-2-cyanoacrylamide scaffold was designed as core pharmacophore for inhibitors of the Dengue and West Nile virus serine proteases (NS2B-NS3). A total of 86 analogs was prepared to study the structure-activity relationships in detail. Thereby, it turned out that the electron density of the a...
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| Hauptverfasser: | , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
25 October 2011
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| In: |
Bioorganic & medicinal chemistry
Year: 2011, Jahrgang: 19, Heft: 24, Pages: 7318-7337 |
| ISSN: | 1464-3391 |
| DOI: | 10.1016/j.bmc.2011.10.061 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.bmc.2011.10.061 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0968089611008881 
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| Verfasserangaben: | Christoph Nitsche, Christian Steuer, Christian D. Klein |
| Zusammenfassung: | The 3-aryl-2-cyanoacrylamide scaffold was designed as core pharmacophore for inhibitors of the Dengue and West Nile virus serine proteases (NS2B-NS3). A total of 86 analogs was prepared to study the structure-activity relationships in detail. Thereby, it turned out that the electron density of the aryl moiety and the central double bond have a crucial influence on the activity of the compounds, whereas the influence of substituents of the amide residue is less relevant. The para-hydroxy substituted analog was found to be the most potent inhibitor in this series with a Ki-value of 35.7μM at the Dengue and 44.6μM at the West Nile virus protease. The aprotinin competition assay demonstrates a direct interaction of the inhibitor molecule with active centre of the Dengue virus protease. The target selectivity was studied in a counterscreen with thrombin and found to be 2.8:1 in favor of DEN protease and 2.3:1 in favor of WNV protease, respectively. |
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| Beschreibung: | Gesehen am 28.09.2022 |
| Beschreibung: | Online Resource |
| ISSN: | 1464-3391 |
| DOI: | 10.1016/j.bmc.2011.10.061 |