Synthesis and anti-platelet activities of nitric oxide-releasing derivatives of 3-butylphthalide

Aim:To study the synthesis and anti-platelet activities of nitric oxide-releasing derivatives of 3-butylphthalide and search for novel anti-ischemia agents.Methods:Compounds 6a-6c,10a-10c and 12a-12c were synthesized by connecting a NO-donating moiety to 2-(1-acetoxypentyl) benzoic acid,the ring-opening form of 3-butylphthalide,through different linkers.Results:Nine compounds were synthesized and their structures were determined by IR,1H NMR,MS and elemental analysis.All these compounds exhibited anti-platelet activities and released NO to different extents.It was found that compound 10b was the most potent and even stronger than those of aspirin and 3-butylphthalide(P0.01).The maximal level of NO release for the most potent compound 10b and the weakest compound 6c was 0.05 μmol/L and 0.01 μmol/L,respectively.Conclusion:NO-donating derivatives of 3-butylphthalide possess potent anti-platelet activities,which might be partly due to the NO release.