A series of 13 novel pyrimidine-based sulfonamides 6a-m were synthesized in short periods of time under microwave conditions in good to excellent yield (54-86%). The chemical structures of these heterocycles consist of a central pyrimidine ring having a phenyl group and pyrimidine groups with sulfonamide motifs. The enzyme inhibitory potential of these compounds was investigated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) because these enzymes play a crucial role in the treatment of Alzheimer's disease. As compared to the reference compound eserine (IC50=0.04 +/- 0.0001 mu M for AChE and IC50=0.85 +/- 0.0001 mu M for BChE), the IC50 values of the synthesized compounds ranged from 3.73 +/- 0.61 mu M to 57.36 +/- 0.22 mu M for AChE and 4.81 +/- 0.16 mu M to 111.61 +/- 0.53 mu M for BChE. Among these tested compounds, 6j having a -CH3 group was found to be the most potent one against both enzymes (AChE, IC50=3.73 +/- 0.61 mu M; BChE, IC50=4.81 +/- 0.16 mu M). Quantitative structure-activity relationship (QSAR) and molecular docking studies of the synthesized compounds were also performed.