Discovery of Indole Derivatives as Novel and Potent Dengue Virus Inhibitors

Journal of Medicinal Chemistry
Dorothée BardiotArnaud Marchand

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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Citations

Sep 9, 2020·Antiviral Research·Li-Hsin LiKai Dallmeier
Jan 23, 2021·RSC Medicinal Chemistry·Fumiaki Yokokawa
Jun 8, 2021·RSC Medicinal Chemistry·Atukuri Dorababu
Oct 8, 2021·Nature·Suzanne J F KapteinJohan Neyts
Oct 8, 2021·Nature·Scott B Biering, Eva Harris
Jan 1, 2019·Antiviral Research·Siew Pheng Lim

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