Synthesis and biological evaluation of (acyl)hydrazones and thiosemicarbazones obtained via in situ condensation of iminium salts with nitrogen-containing nucleophiles

Abstract

An unprecedented, highly convergent, high-yielding, one-pot synthesis of (acyl)hydrazones and thiosemicarbazones was carried out by the in situ condensation of isolable iminium chlorides of imidazolidin-2-(thio)one, tetrahydropyrimidin-2-thione and indole derivatives with nitrogen nucleophiles in the presence of a base. The developed reaction procedure is largely advantageous. It is highly parallelizable, no intermediates need to be isolated and minimal sample handling is required during the purification steps. Some relevant reaction parameters including reaction temperature and p[Formula: see text] of the base are discussed. NMR analysis was carried out to assess the stereochemistry of the obtained compounds. The stereochemical outcome of the reaction was found to be affected by the nature of the nitrogen-containing nucleophile being the majority of the derivatives isolated as single geometric isomers. The cytotoxicity and antiviral activities of the prepared compounds have been preliminary assessed. In cell-based screenings some of the derivatives proved to be cytotoxic at low micromolar concentrations and interesting anti-Reo-1 properties have been detected.

Mono- and di-acylated imidazolidine-2-thione derivatives: synthesis, cytotoxicity evaluation and computational studies

“…1) that was isolated and fully characterized by IR and NMR spectroscopy in our previous work [20]. Im1 represented a key intermediate for the synthesis of pharmacologically relevant compounds endowed with antiproliferative, chelating and GPER-agonistic properties [27][28][29].…”