infantum intracellular amastigotes in vitro. We found that increased lipophilicity correlated with improved inhibitory effects on T. brucei. We were able to prioritize compounds for synthesis from a designed combinatorial in silico library by using predicted properties, which suggested a likely improvement of the trypanocidal effect. In this way, we identified three improved compounds, 5d, 5e and 5f, with low micromolar inhibition of T. brucei brucei (EC 50 0.66 -4.53 μM).