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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.
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•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.