Abstract
A new synthesis of the thiepino[2,3-b]pyridine ring system 4 was achieved via intramolecular condensation of the 2-thiobutyrate ester nicotinonitrile derivative 6 with sodium hydride. Compound 6 was provided by alkylation of the nicotinonirile-2-thiol derivative 5 with ethyl 4-bromobutyrate in the presence of sodium carbonate. On attempting the previous alkylation in the presence of sodium hydride afforded the pyridoazepine 11 instead of thiepinopyridine 4 in one-pot synthesis. Computational quantum chemistry was utilized to explore the reaction route at the level of DFT. Data of the computational studies indicated that both anions of compounds 8 and 9 have the same stabilization energies. Antitumor activity evaluation, in vitro, of compound 4 showed high affinity as a potential novel antitumor lead.
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Acknowledgments
We are indebted to Ms Hebatallh M. Waly (M.Sc., Biochemistry Department, Faculty of Science, Damietta, Mansoura University, Egypt) for evaluation of in vitro antitumor activity in this work.
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Waly, M.A., Elhawary, I.I. & Elgogary, T.M. Utilization of nicotinonitrile-2-thiol in the synthesis of new thiepino[2,3-b]pyridine derivative as an in vitro novel antitumor potent. Med Chem Res 22, 1674–1678 (2013). https://doi.org/10.1007/s00044-012-0161-4
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DOI: https://doi.org/10.1007/s00044-012-0161-4