Novel hybrids of 3-n-butylphthalide and edaravone: Design, synthesis and evaluations as potential anti-ischemic stroke agents

Article abstract of DOI:10.1016/j.bmcl.2015.06.090

Abstract Fourteen hybrids (10a-g, 11a-g) of 3-n-butylphthalide (NBP) and edaravone (Eda) analogues have been designed and synthesized as potential anti-ischemic stroke agents. In vitro biological studies showed that compounds 10d and 10g exhibited more potent anti-platelet aggregation than ticlopidine (Ticlid), aspirin (ASP) and NBP. Compound 10g more significantly prevented H₂O₂-mediated neuronal cell (PC12) death than NBP, Eda or NBP together with Eda. Meanwhile, 10g also possessed potent radical scavenging effects on hydroxyl radical (·OH) and superoxide anion radical (·O₂^-). Our findings may provide new insights into the development of these hybrids, like 10g, for the intervention of ischemic stroke.