Further, integration of transport-related considerations in the design , or using, for instance, structurally related scaffolds reported in the literature, which show inhibition of the Leishmania parasite, and a similar property-based correlation concept to that presented here, may help to overcome the current limitations of the pteridine-based compounds as inhibitors of intracellular parasites. Our data show that, overall, optimization for increased lipophilicity leads to more potent pteridine-based T. brucei inhibitors. However, increased lipophilicity can also introduce compound liabilities, e.g. for hERG and CYPs. Strategies to avoid these, for instance by making use of a similar property-based optimization strategy, should thus be incorporated in future design efforts. Interdipartimentale Grandi Strumenti, CIGS UniMoRe). The purity of the reported compounds is >95%. Exact monoisotopic masses are reported in "Supporting information" along with the melting point intervals of all compounds, which were measured on a Stuart SMP3 instrument.