Based on the evidence that 5-HT4R, 5-HT6R and AChE are all valuable therapeutic targets in AD treatment, the present work aimed at designing, starting from our dual compound 4 and the benzyl analog of donecopride 5a (Rochais et al., 2015), novel MTDLs associating 5-HT4R agonist, 5-HT6R antagonist and AChE inhibitory balanced activities (Figure 2). Here, ACHE is linked to Alzheimer disease.