Abstract: AimTo design and synthesize novel AchE inhibitors. MethodsThe condensation of 2-bromo-5,6-dimethoxy-indan-1-one with various aminoalkyl phenols in the presence of K₂CO₃ and acetonitrile gave the corresponding title compounds, and the in vitro AchE and BchE inhibitory activities were evaluated by the modified Ellman method. ResultsSixteen novel target compounds 8a-p were synthesized, their structures were confirmed by ¹H NMR, MS, IR and elemental analysis. Preliminary pharmacological test demonstrated that most of these compounds displayed high AchE inhibitory activities, the IC₅₀ of the most potent inhibitor 8h was 50.0 nmol·L^-1, similar to that of Huperzine A (IC₅₀=53.0 nmol·L^-1), while all the compounds were almost inactive against BchE. Conclusion2-Phenoxy-indan-1-one derivatives exhibit high activities of AchE inhibition and are worthy of further investigation.