Utilization of nicotinonitrile-2-thiol in the synthesis of new thiepino[2,3-b]pyridine derivative as an in vitro novel antitumor potent

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.