In continuation to our previous findings on amidoximes' antiparasitic activities, a new series of 23 original derivatives was designed and obtained by convergent synthesis. First, new terminal alkenes were synthesized by cross-coupling reaction. Then, cyclization was performed between terminal alkenes and beta-ketosulfones using manganese(III) acetate reactivity. Twenty-three amidoximes were tested for their in vitro activity against Leishmania amazonensis promastigotes and their toxicity on murine macrophages. Seven of the tested compounds exhibited an antileishmanial activity at lower than 10 mu M with moderate to low toxicity. Six of these molecules showed activity at lower than 10 41 A against promastigotes and toxicity at higher than 50 mu M were selected and evaluated for their activity against intracellular Leishmania amazonensis amastigotes. Modulating chemical substituents in position 2 of dihydrofuran highly influenced their antileishmanial activitie s. The introduction of a methyl or trifluoromethyl group on the benzene ring of the benzyl group had a positive influence on activity without significantly increasing toxicity (52, 59, 60). (C) 2018 Elsevier Masson SAS. All rights reserved.