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

  • Bioorg Med Chem Lett. 2025 Jul 1:122:130185. doi: 10.1016/j.bmcl.2025.130185.
Lin Yuan  1 ,  Qing-Ru Chu  2 ,  Feng-Xin Li  2 ,  Da-Kui Zhang  2 ,  Ya-Xin Yu  2 ,  Jing-Chang Liu  2
Affiliations
  • 1. Jilin Provincial Institute of Pharmaceutical Research, Changchun 130061, People's Republic of China. Electronic address: [email protected].
  • 2. Jilin Provincial Institute of Pharmaceutical Research, Changchun 130061, People's Republic of China.
PMID: 40086605 DOI: 10.1016/j.bmcl.2025.130185
Abstract

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.

Keywords
Activity substructure splicing strategy; Antiplatelet aggregation activity; Bioisosterism; Pamicogrel; Structure activity relationship.
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