Synthesis of 2-substituted primaquine analogues as potential antimalarials

A series of 2-substituted primaquine analogues has been synthesized and evaluated against Plasmodium berghei in the mouse and Leishmania donovani in the hamster. Three members (3a,d,e) of the series were evaluated against Plasmodium cynomolgi in the rhesus monkey. One analogue (3d) was evaluated against Trypanosoma rhodesiense in the mouse, and two (3b,e) were evaluated against Schistosoma mansoni in the mouse. Several analogues possessed significant activity against P. berghei (3e,f) and L. donovani (3a,e).