The naphthylisoquinoline alkaloids (NIQs) represent a class of natural products with manifold activities against various tropical diseases. They are isolated from rare and difficult-to-cultivate tropical plants. In order to find novel, more easily accessible analogs and to study structure-activity relationships, a variety of simplified analogs were produced, which bear the functional groups typical of the NIQs, but avoid the synthetically difficult elements of chirality, stereogenic centers and rotationally hindered axes. Their syntheses and activities against Plasmodium falciparum, Trypanosoma cruzi, and Leishmania donovani are described and compared with those of the natural NIQs. Remarkably, quite good activities were found for naphthalene-devoid halogenated isoquinolinic analogs.