A novel series of diphenylbutylpiperidine derivatives in which a benzo-five or six membered heterocycle was linked at the 4-position of the piperidine moiety were designed and synthesized. Structure–activity relationship (SAR) studies of these compounds indicated that some molecules show promising autophagy inducing activity. Replacement of the fluorine atom by a CF₃ group on the diphenyl part resulted in significant enhancement of the autophagy inducing effect. In the addition, a group of diphenylpentyl nitriles also showed similar bioactivities.