A series of 1-(quinoliloxypropyl)-4-aryl-piperazines has been synthesized and the target compounds evaluated for atypical antipsychotic activity in apomorphine induced mesh climbing and stereotypic behaviour in mice. The 8-hydroxyquinoline ether derivative 14 has emerged as an important lead compound showing a potential atypical antipsychotic profile. Employing appropriate physicochemical properties, the similarity of the compounds was assessed with respect to some atypical antipsychotic drugs as clozapine, ketanserine, ziprasidone and risperidone.