Synthesis of new 2-styryl-3-nitroimidazo[1,2-a]pyridine derivatives via base-induced elimination of 2-N-tosyl intermediates and in vitro antileishmanial evaluation.

To explore the antileishmanial structure-activity relationships in a 3-nitroimidazo[1,2-a]pyridine series, we developed a previously undescribed olefination strategy at position 2 via elimination of intermediates bearing an N-tosyl group, giving access to E-configured alkenes. Subsequent modulation at position 8 was performed through nucleophilic aromatic substitutions and Suzuki-Miyaura cross-coupling reactions. This work resulted in 21 original compounds, whose antileishmanial activity, cytotoxicity, and nitro group reduction potential were evaluated. These results provide a new synthetic access to unexplored 2-substituted derivatives and deepen our understanding of the reactivity at position 2 in relation to biological activity.