Novel 1,2,4-oxadiazoles and trifluoromethylpyridines related to natural products: synthesis, structural analysis and investigation of their antitumor activity

• Published in: Tetrahedron 2016-03, Vol.72 (9), p.1185-1199
• Main Authors: Maftei, Catalin V., Fodor, Elena, Jones, Peter G., Daniliuc, Constantin G., Franz, M. Heiko, Kelter, Gerhard, Fiebig, Heinz-Herbert, Tamm, Matthias, Neda, Ion
• Format: Article
• Language: English
• Subjects: 1,2,4-Oxadiazoles; Anti-tumor activity; Anticancer properties; Biocompatibility; Bioisosteres; Derivatives; Design analysis; Diffraction; Medical; Panels; Pyrazoles; Pyrazolo[3,4-d]pyrimidine; Structural analysis; Trifluoromethylpyridine
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2016.01.011

The design, structural characterization and potential medical application of novel 1,2,4-oxadiazole and trifluoromethylpyridine derivatives are described. Starting from two readily available compounds, 4-(3-(tert-butyl)-1,2,4-oxadiazol-5-yl)aniline (1) and 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethanamine (10), other bioactive moieties were incorporated (such as pyrazole, pyrazolo[3,4-d]pyrimidine), in order to modify the lipophilicity of the molecules, so that the transport of the bioactive units though the cell wall barrier could be improved. In vitro anti-cancer activity of these compounds was assessed by a monolayer proliferation assay in a panel of 12 cell lines. A good potency was found for 17, which exhibited a mean IC50 value of 5.66 μM, while the other compounds exhibit minor or no activity. The solid state structures of compounds 3, 5, 7–9, 11, 12 and 17 were established by X-ray diffraction analyses. [Display omitted]