Novel 1,3‐Benzenedisulfonamides as Antiplatelet Agents: Design, Synthesis, Biological Evaluation, and In Vitro Cytotoxicity Study

Abstract 1,3‐Benzenedisulfonamide analogues with obvious antiplatelet and cytotoxicity restricted these compounds as candidate drugs. This article modified the side chains of 1,3‐benzenedisulfonamide analogues by introducing less bulky groups substituted with benzene or heterocycles to reduce their toxicity. Target compounds were synthesized by etherification, chlorosulfonation, and amination reactions. All the derivatives were assessed for their antiplatelet activity effects induced by arachidonic acid and adenosine diphosphate, respectively. The cell toxicity data of six compounds with excellent antiplatelet activity were evaluated，and compound 9a displayed lower cytotoxicity than picotamide in four test concentrations. In addition, 9a was selected to dock with the receptor P 2 Y 12 , and each of the synthesized compounds in silico molecular properties were predicted. Comparing the data obtained with other trisubstituted series of 1,3‐benzenedisulfonamides, tetra‐substituted compounds could have obvious antiplatelet activity and low cytotoxicity, and their structural direction is worthy of exploration.