一氧化氮供体型3-丁基苯酞衍生物的合成及抗血小板活性  

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

作　　者：闵真立[1] 张奕华[1] 庄佩[2] 季晖[2] 赖宜生[1] 彭司勋[1] 

机构地区：[1]中国药科大学新药研究中心,南京210009 [2]中国药科大学药理学教研室,南京210009

出　　处：《中国药科大学学报》2008年第5期392-397,共6页Journal of China Pharmaceutical University

摘　　要：目的:研究一氧化氮(NO)供体型3-丁基苯酞衍生物的合成和生物活性,寻找新型抗脑缺血药物。方法:使用不同的连接基团将3-丁基苯酞的开环衍生物2-(1-乙酰氧戊基)苯甲酸与一氧化氮供体连接,合成了目标化合物6a-6c、10a-10c和12a-12c,同时测定它们在体外释放NO的量。结果:合成了9个未见文献报道的目标化合物,其结构均经IR、1HNMR、MS和元素分析确证。它们均有一定的抗血小板活性且有不同程度的NO释放,其中化合物10b活性最强,明显优于阿司匹林和3-丁基苯酞(P<0.01),其NO最大释放量为0.05μmol/L,而活性最弱的化合物6c仅为0.01μmol/L。结论:NO供体型3-丁基苯酞衍生物具有较强抗血小板活性,其作用机制可能与NO释放有关。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-aeetoxypentyl） 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（ P 〈 0.01）. The maximal level of NO release for the most potent compound 10b and the weakest compound 6c was 0. 05 μmol/L and 0. 01μmol/L, respectively. Conclusion： NO-donating derivatives of 3-butylphthalide possess potent anti-platelet activities, which might be partly due to the NO release.

关 键 词：NO供体 3-丁基苯酞 合成 抗血小板活性 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]