Design, synthesis, and biological evaluation of Pamicogrel derivatives as potential antiplatelet agents.

According to the bioisosterism principle and activity substructure splicing strategy, new pamicogrel derivatives were designed, synthesized, and evaluated for their antiplatelet aggregation activities in vitro. Bioassay results showed that compound SZ displayed superior in vitro antiplatelet aggregation activities induced by Arachidonic Acid (AA) and Collagen (COL) with the IC50 values of 3.44 and 2.23 mg/mL, respectively. Compound BMPA showed apparent antiplatelet aggregation towards Adenosine Diphosphate (ADP) with a IC50 value of 2.79 mg/mL. Significantly, compound K-10 exhibited the most antiplatelet aggregation activity to the aggregation of platelet induced by AA, ADP, and COL, representing a promising lead compound for further study.