9- and 11-substituted 4-azapaullones are potent and selective inhibitors of African trypanosoma

•4-Azapaullones with α,β-unsaturated carbonyl side chains were synthesized.•Some derivatives inhibited Trypanosoma brucei brucei parasites in submicromolar concentrations.•Trypanothione synthetase was eliminated as intracellular target.

Trypanosomes from the “brucei” complex are pathogenic parasites endemic in sub-Saharan Africa and causative agents of severe diseases in humans and livestock. In order to identify new antitrypanosomal chemotypes against African trypanosomes, 4-azapaullones carrying α,β-unsaturated carbonyl chains in 9- or 11-position were synthesized employing a procedure with a Heck reaction as key step. Among the so prepared compounds, 5a and 5e proved to be potent antiparasitic agents with antitrypanosomal activity in the submicromolar range.

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