📗 In the present work, Different substituted derivatives of 5-substituted-1,3,4-oxadiazole-2-thiols were synthesized by successive conversions of 5-substituted carboxylic acids into respective ester, hydrazide and 1,3,4-oxadiazole. Finally the target compounds were obtained by reaction of 5-substituted-1,3,4-oxadiazole-2-thiols with a series of various electrophiles,in N,N-dimethyl formamide (DMF) in the presence of sodium hydride (NaH)which acts as a base. The structural characterization of these newly synthesized compounds was done by IR, 1H-NMR and EI-MS spectral data. All these compounds were evaluated for their enzyme inhibitory potentials and found to exhibit broad range spectrum against acetylcholinesterase, butyrylcholinestrase and lipoxygenase enzymes and hence are suitable entrants for the treatment of Alzheimer's disease.