Details

Autor(en) / Beteiligte

• Benmansour, Fatiha
• Eydoux, Cécilia
• Querat, Gilles
• de Lamballerie, Xavier
• Canard, Bruno
• Alvarez, Karine
• Guillemot, Jean-Claude
• Barral, Karine

Titel

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

Ist Teil von

• European journal of medicinal chemistry, 2016-02, Vol.109, p.146-156

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Identification and optimization of new dengue virus polymerase inhibitors.•A rapid synthesis of new 1,2,4-oxadiazole and 1,3,4-oxadiazole derivatives.•Validation of dengue virus polymerase inhibition by fluorescent assay.•Antiviral evaluation on dengue virus infected cells.•Five inhibitors exhibit submicromolar activity on the four dengue virus serotypes.