A novel series of 2-((-1-substituted pheny1-1H-tetrazol-5-ypthio)-2,3-dihydro-1H-inden-1-one compounds were designed, synthesized, and evaluated as multi-potent anti-Alzheimer drug candidates. First, treatment of various organic isothiocyanates with sodium azide in the presence of pyridine gave corresponding 1-substituted phenyl-1H-tetrazol-5-thiol compounds. Then, novel 2-((-1-substituted pheny1-1H-tetrazol-5-ypthio)-2,3-dihydro-1H-inden-1-one compounds were synthesized by treatment of 2,3-dihydro-1H-inden-1 -one with the 1-substituted phenyl-1H-tetrazol-5-thiol in the presence of I-2. The synthesized compounds were characterized by spectroscopic methods. The inhibitory effects of the synthesized compounds on the acetyl cholinesterase enzyme (AChE) were then tested. An o-iodo substituent displayed higher activity compared to the other analogs. The o-iodo substituent showed a mixed-type of the AChE with an IC50 value of 1.75 mu M. For the studied compunds all IC50 values for AChE were in the micromolar range.