Discovery of novel effective and safe antimalarials has been traditionally focused on targeting erythrocytic parasite stages that cause clinical symptoms. However, elimination of malaria parasites from the human population will be facilitated by intervention at different life-cycle stages of the parasite, including the obligatory developmental phase in the liver, which precedes the erythrocytic stage. We have previously reported that N-Mannich-based quinolon-4(1H)-imines are potent antiplasmodial agents but present several stability liabilities. We now report our efforts to optimize quinolon-4(1H)-imines as dual-stage antiplasmodial agents endowed with chemical and metabolic stability. We report compounds active against both the erythrocytic and exoerythrocytic forms of malaria parasites, such as the quinolon-4(1H)-imine 5p (IC50 values of 54 and 710 nM against the erythrocytic and exoerythrocytic forms), which constitute excellent starting points for further lead optimization as dual-stage antimalarials.