An efficient method to develop novel dihydropyrido[3,2-e][1,3]selenazines iminium salts. A comparative study of the key reagent selenourea towards thiourea and urea was carried out to assess the contribution of chalcogen to the pathway. DFT (density functional theory) calculations have predicted the optimized minimum energy structure for the hybrid compounds. Molecular docking envisaged the inhibition of the main protease of SARS-CoV-2.

Abstract

Functionalizing organic molecules with selenium-containing fragments is a strategy to increase the biological properties of natural products and biomolecules. Therefore, in the present study, this strategy was followed to develop a new series in which the 1,3-selenazine ring is condensed with a 1,4-dihydropyridine, a nitrogen-containing six-membered heterocycle, as both entities are known to have proven biological activity. The 2-iminium chloride salts of 5,8-dihydro-2H-pyrido[3,2-e][1,3]selenazine derivatives were easily synthesized in one step from the corresponding o-chloroformyl-1,4-dihydropyridine and selenourea in good yields. Also, a comparative study of selenourea towards thiourea and urea was carried out to assess the contribution of chalcogen to the reaction pathway. All derivatives have been fully characterized by a whole set of instrumental techniques to determine their chemical structure. Further, theoretical calculations at the DFT level have predicted the optimized minimum energy structure for the hybrid compounds. Molecular docking was used to predict the potential application of the new compounds as inhibitors of the main protease of SARS-CoV-2, paving the way to study the possible application of these compounds in medicinal chemistry.