The worldwide diffusion of resistance in malaria parasite, especially the Plasmodium falciparum, towards currently available drugs has become a major health and development challenges to human society. Isoquine, an isomeric analogue of amodiaquine, has been reported recently as a second generation lead compound for development of cost-effective and potentially safer alternative to amodiaquine which cause adverse effects including agranulocytosis and liver damage. In this study, a series of seven analogues of isoquine have been synthesized and subjected to in vitro antimalarial activity screening against the chloroquine sensitive 3D7 strain of Plasmodium falciparum. A simple two-step Mannich reaction was used to synthesize the compounds. All the seven compounds possessed little to moderate antimalarial activity. However, the analogues with aliphatic alcoholic amino group side chain having promising activity than the compounds with substituted aromatic ring side chain and compounds substituted with urea while analogues with heterocyclic ring side chain exhibits moderate antimalarial activity.