Synthesis of bioactive 2-aza-analogues of ipecac and alangium alkaloids.

License to kill: Substitution of the methine carbon C2 in the ipecac or alangium alkaloids by nitrogen yields functional mimetics with low micromolar to high naonomolar IC50 values against Trypanosoma brucei, the parasite that causes African trypanosomiasis. 2-Azaemetine shows an improved selectivity ratio between its antiparasitic activity and its cytotoxicity against mammalian cells compared to the parent compound. The chosen isomorphous replacement permits a modular synthesis and facilitates the combinatorial variation of the products.