摘要
目的设计并合成4-乙氧基-1,3-苯二甲酰胺类化合物并进行体外抗血小板聚集活性测试。方法以2,4-二甲基苯酚为原料,经Williamson反应、氧化、氯代和胺解反应制得化合物1a^1h,8个目标化合物结构均经1H-NMR、13C-NMR、IR和MS谱确证。1a^1h分别以ADP和collagen为诱导剂,以吡考他胺和阿司匹林为对照药物,用Born比浊法进行体外抗血小板聚集活性初筛。结果以ADP为诱导剂时化合物1g的活性和以collagen为诱导剂时化合物1a的活性均高于对照药吡考他胺和阿司匹林。结论大多数目标化合物具有较高的体外抗血小板聚集活性,其中,侧链苯环4-位引入位阻较大的烷基正丁基和叔丁基时,活性明显高于位阻较小的烷基取代的目标化合物。
In order to achieve more active and selective anti-platelet candidate drugs,eight target compounds(1 a-1 h)were designed and synthesized.With 2,4-dimethylphenol as the starting material,the target compounds were obtained by Williamson reaction,oxidation,chlorination and amine hydrolysis reaction.The structures of the target compounds were confirmed by 1H-NMR,13C-NMR,IR and MS.Using ADP and collagen as inducers,respectively,the anti-platelet aggregation activities in vitro of the target compounds were evaluated by Born test method with picotamide and aspirin as reference drugs.The results of pharmacological experiments at a concentration of 1.3μmol·L-1 indicated that the activity of compound 1 g(ADP as an inducer)and 1 a(collagen as an inducer)were superior to picotamide and aspirin.Most of the newly prepared target compounds showed higher in vitro anti-platelet aggregation activities.When two side chain benzene rings were introduced by large hindrance alkyl groups like(CH2)3CH3 and C(CH3)3,the activities of the target compounds were higher than the previous prepared compound(2 a*-2 c*)which having small hindrance alkyl group on the 4-posation of the benzene on the side chain.
作者
张志豪
刘秀杰
许祥
ZHANG Zhi-hao;LIU Xiu-jie;XU Xiang(School of Chemistry and Chemical Engineering,Tianjin University of Technology,Tianjin 300384,China)
出处
《中国药物化学杂志》
CAS
CSCD
北大核心
2019年第5期352-356,共5页
Chinese Journal of Medicinal Chemistry
基金
国家自然科学基金主任基金项目(21342014)
天津市高等学校大学生创新创业训练计划项目(201710060142).
