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

Abstract

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-1H-imidazole-2-amine derivatives, compounds 4 a [(E)-1-(benzylideneamino)-4-phenyl-1H-imidazol-2-amine] and 4 p [(E)-4-phenyl-1-((thiophen-2-ylmethylene)amino)-1H-imidazol-2-amine], exhibited IC₅₀ 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.

Keywords: 2-aminoimidazoles; antiplatelet; arachidonic acid; cyclization; hydrazones.