А series of novel 6,6,7-trisubstituted thiopyrano[2,3-d][1,3]thiazoles-based molecules have been synthesized and evaluated as potential antitrypanosomal agents. The most active analogue 3b inhibited Trypanosoma brucei brucei and Trypanosoma brucei gambiense with an IC(50) of 0.26 and 0.42 μМ, respectively. They could be considered as potent hits for further antitrypanosomal drug discovery efforts.