Based on the antiplatelet aggregation mechanism and the bioisosterism principle of the reference drug picotamide, thirteen novel derivatives of arylamide and arylsulfonamide were designed and prepared. The biological activities of these derivatives were investigated. The chemical structures of the target compounds were confirmed by 1 H NMR and IR. The in vitro activities of antiplatelet aggregation of the thirteen target compounds were assessed by Born's method. Compounds 2b and 8h have significant antiplatelet aggregation activities, which are superior to the corresponding activity of Picotamide.