Concerning the aliphatic derivatives 11, saturated chains and cycles were inserted by reductive amination on the piperazine moiety. All compounds except the one containing a cyclopropyl function, 11b gave no improved activities. However, 11b was very promising owning a satisfactory antitrypanosomal activity with an IC50 value around 3.65 µM. More importantly, it presented better pharmacokinetic properties, all series considered, with low cytotoxicity, thus meaning a greater selectivity, an acceptable molecular weight (ca. 400 g/mol) and a lipophilicity slightly over 5. With these new observations, it was for the first time possible to demonstrate that the benzyl ring Bn2 was not essential to display a suitable activity against T.