Abstract: A series of sulfonamide (ester) derivatives were designed and synthesized by using 2,4-dimethylaniline as the starting material. The in vitro inhibitory activities of the target compounds against aldose reductase were evaluated. Docking studies were performed to examine the manner by which newly prepared compounds interact with ALR2. It was found that sulfonyl compounds 8a-d, 12a-b, 16a-b show moderate inhibitory activities against aldose reductase and they interact with the ALR2 active site pocket in a good way. Compounds 8a-d are found as a new type of aldose reductase inhibitors with moderate activity and they can be used as lead compounds to explore ARIs with higher activity.