Synthesis and antifungal activity of 3-(1,3,4-oxadiazol-5-yl)-indoles and 3-(1,3,4-oxadiazol-5-yl)methyl-indoles

On the basis of the principle of combination of active structural moieties, a modified and efficient synthetic method for three series of novel indole-based 1,3,4-oxadiazoles is described. Bioassays conducted at Syngenta showed that several of the synthesized compounds exhibit higher antifungal activity than pimprinine, the natural product which inspired this synthesis. Two main structural alterations were found to broaden the spectrum of biological activity in most cases. Compounds 3g, 6c, 6e, 6h, 9d, 9e, 9h and 9m (Fig. 1) were identified as the most active on the biological assays, and will be studied further. [Display omitted] We efficiently synthesized three series of indole-based 1,3,4-oxadiazole derivatives, designed as analogues of the antifungal natural product pimprinine, and evaluated their antifungal activities. ► Three series of novel analogues of natural product pimprinine were synthesized. ► Antifungal activity of fifty five analogues of pimprinine were screened. ► Some of the tested compounds showed good antifungal activity or broad spectrum. ► The structure–activity relationships of the pimprinine analogues were summarized.