X-ray structure and chemical behaviour of three oxadiazole derivatives, as potential Stat3 inhibitors

Signal transduction and activator for transcription factor 3 (Stat3) is a latent cytosolic protein member of Stat family. It is a transcription factor that transmits cytoplasmic signals (e.g. from growth factors, poly-peptide cytokines etc.) to the nucleus. Blocking constitutively activated Stat3 signalling leads to apoptosis of tumour cells but has no effects on normal cells suggesting that its inhibition could be a leading target for cancer therapy[1]. In our research, focused on the discovery of new oxadiazole Stat3 inhibitors, [2] during the synthesis of compounds 2 and 3 we noted an interesting chemical behaviour. Through X-Ray analysis we established that 2 exists in the cyclic form, while in the general conditions applied to obtain the ureidic derivatives,[2] the synthesis of 3 led to a mixture of two symmetric ureas.The results of the crystallographic studies and the biological activity of the compounds will be presented.