The reference compounds and the N10 series mostly exhibit a safe profile. In contrast, aromatic modifications to the compound tail region, for instance in 3d, 4j and 5f (PABA, Tail and Merged series, respectively) were associated with notable hERG liabilities. Increasing the hydrophobicity of the compounds further led to liabilities against some CYP isoforms, in particular, 2C9 and 2C19. The shortened tails of 3c and 3d resulted in a strong effect on CYP isoform 2D6. Finally, several of the bulky, more hydrophobic compounds resulted in a cytostatic or cytotoxic effect on A549 cells. Overall, the liability assessment suggests that increasing hydrophobicity is associated with greater compound liabilities. In line with these observations, two of the best inhibitors of T. brucei bloodstream forms, 5e and 5f show 54% and 81% hERG inhibition, respectively. 5e and, in many cases also 5f, affects various CYP isoforms. Finally, 5f is cytostatic with A549 cell growth reduced to 15%