Rational Design and Synthesis of 1‐(Arylideneamino)‐4‐aryl‐1 H ‐imidazole‐2‐amine Derivatives as Antiplatelet Agents

Based on previous studies indicating the pharmacophoric role of a hydrazone group and azole rings for antiplatelet aggregation activity, a few series of compounds with both hydrazone and an azole (imidazole) ring in their structures were synthesized, and their platelet aggregation inhibitory effects were evaluated. Two of these 1‐(arylideneamino)‐4‐aryl‐1 H ‐imidazole‐2‐amine derivatives, compounds 4 a [( E )‐1‐(benzylideneamino)‐4‐phenyl‐1 H ‐imidazol‐2‐amine] and 4 p [( E )‐4‐phenyl‐1‐((thiophen‐2‐ylmethylene)amino)‐1 H ‐imidazol‐2‐amine], exhibited IC 50 values similar to that of acetylsalicylic acid against collagen as a platelet aggregation inducer. Structural comparison of the synthesized compounds revealed that those with a para ‐substituted phenyl ring on the imidazole were among the most active compounds against platelet aggregation induced by arachidonic acid (AA), and the presence of a thiophene ring in these compounds maximized their antiplatelet activity.