Synthesis of bicyclic 1,4-thiazepines as novel anti-Trypanosoma brucei brucei agents

Abstract

1,4-Thiazepines derivatives are pharmacologically important heterocycles with different applications in medicinal chemistry. In the present work, we describe the preparation of new bicyclic thiazolidinyl-1,4-thiazepines 3 by reaction between azadithiane compounds and Michael acceptors. The reaction scope was explored and the yields were optimized. The activity of the new compounds was evaluated against Nippostrongylus brasiliensis and Caenorhabditis elegans as anthelmintic models and Trypanosoma brucei brucei. The most active compound was 3l, showing an EC₅₀ = 2.8 ± 0.7 μM against T. b. brucei and a selectivity index >71.