2. Academic Validation
  3. Novel 2-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,3,4-oxadiazole and 3-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,2,4-oxadiazole derivatives as dengue virus inhibitors targeting NS5 polymerase

Novel 2-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,3,4-oxadiazole and 3-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,2,4-oxadiazole derivatives as dengue virus inhibitors targeting NS5 polymerase

  • Eur J Med Chem. 2016 Feb 15:109:146-56. doi: 10.1016/j.ejmech.2015.12.046.
Fatiha Benmansour 1,  Cécilia Eydoux 1,  Gilles Querat 2,  Xavier de Lamballerie 2,  Bruno Canard 1,  Karine Alvarez 1,  Jean-Claude Guillemot 1,  Karine Barral 3
Affiliations

Affiliations

  • 1 Aix-Marseille Université, AFMB, AD2P, UMR 7257, 163 Avenue de Luminy, 13288 Marseille Cedex 09, France; CNRS, AFMB UMR 7257, 163 Avenue de Luminy, 13288 Marseille Cedex 09, France.
  • 2 UMR190, Emergence des Pathologies Virales, Aix-Marseille University, IRD French Institute of Research for Development, EHESP French School of Public Health, 27 Boulevard Jean Moulin, Marseille 13005, France.
  • 3 Aix-Marseille Université, AFMB, AD2P, UMR 7257, 163 Avenue de Luminy, 13288 Marseille Cedex 09, France; CNRS, AFMB UMR 7257, 163 Avenue de Luminy, 13288 Marseille Cedex 09, France. Electronic address: karine.barral@inserm.fr.
PMID: 26774922 DOI: 10.1016/j.ejmech.2015.12.046
Abstract

Using a functional high-throughput screening (HTS) and subsequent SAR studies, we have discovered a novel series of non-nucleoside dengue viral polymerase inhibitors. We report the elaboration of SAR around hit compound 1 as well as the synthesis and Antiviral evaluation of 3-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,2,4-oxadiazole and 5-phenyl-2-[2-(2-thienyl)ethenyl]-1,3,4-oxadiazole analogues derived from a rapid and easily accessible chemical pathway. A large number of compounds prepared by this method were shown to possess in vitro activity against the polymerase of Dengue virus. The most potent inhibitors were tested against Dengue virus clinical isolates on infected cells model and exhibit submicromolar activity on the four Dengue virus serotypes.

Keywords

2-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,3,4-oxadiazole; 3-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,2,4-oxadiazole; Antiviral activity; Dengue virus; NS5 RdRp inhibitors.

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