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Visualizing Dengue Virus through Alexa Fluor Labeling
Published on: July 9, 2011
Discovery of Indole Derivatives as Novel and Potent Dengue Virus Inhibitors
Dorothée Bardiot1, Mohamed Koukni1, Wim Smets1
1Cistim Leuven vzw , Bioincubator 2, Gaston Geenslaan 2 , 3001 Leuven , Belgium.
Abstract:
3-Acyl-indole derivative 1 was identified as a novel dengue virus (DENV) inhibitor from a DENV serotype 2 (DENV-2) phenotypic antiviral screen. Extensive SAR studies led to the discovery of new derivatives with improved DENV-2 potency as well as activity in nanomolar to micromolar range against the other DENV serotypes. In addition to the potency, physicochemical properties and metabolic stability in rat and human microsomes were improved during the optimization process. Chiral separation of the racemic mixtures showed a clear preference for one of the two enantiomers. Furthermore, rat pharmacokinetics of two compounds will be discussed in more detail, demonstrating the potential of this new series of pan-serotype-DENV inhibitors.
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