Background and Objective: Resistance to chloroquine (CQ) in Plasmodium falciparum malaria has become a major health concern in the developing countries. This problem has prompted investigators for finding alternative antimalarials that may be effective against resistant strains. Amodiaquine (AQ) is an antimalarial which is effective against many chloroquine-resistant strains of P. falciparum. However, clinical use of AQ has severely been restricted because of its hepatotoxicity and agranulocytosis side effects. The aim of this study was to design and examine the effects of new analogues of amodiaquine. Materials and Methods: A successful four-step synthesis of a new series of 4-fluoro analogues was designed and applied to the synthesis of an array of 10 analogues. Antimalarial activity of these agents was assessed against chloroquine-resistant (TM6) and sensitive strains (3D7) of P. falciparum. Results: Several analogues have shown potent antimalarial activity against sensitive 3D7 strain of the parasite. The 6h analogue was superior to the pyrollidino analogue 6b against all of the strains examined. The N-tert butyl analogue 6b was potent against chloroquine resistant strains, though it was not quite as active as amodiaquine (AQ) against both chloroquine sensitive and resistant parasites. Conclusion: From the different analogues made, it was shown that the analogue 6h was more potent than the others. However, this analogue has equal or slightly less potent than amodiaquine and chloroquine against P. falciparum. Further studies on the metabolism and pharmacokinetics of 6h are recommended.