In present investigation, a series of substituted phenyl-5,6-dimethoxy-1-oxo-2,3-dihydro-1H-2-indenylmethanone analogues were synthesized and were tested for their potential for treating AD disease. All the newly synthesized compounds were showing moderate to high AChE inhibitory activities, with compound 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-2-indenyl-3,4,5-trimethoxyphenylmethanone (5f) produced significant activities with 2.7+/-0.01 micromol/L.