4-乙氧基-N,N'-二(取代苯基)酰胺类化合物的合成及其抗血小板聚集活性  

Design,synthesis and in vitro activities on anti-platelet aggregation of 4-ethoxy-N,N'-two( substituted phenyl)isophthalamides

作　　者：林永彬 李旭[1] 史天恩 李贵良[1] 刘秀杰[1] 

机构地区：[1]天津理工大学化学化工学院,天津300384

出　　处：《中国药物化学杂志》2015年第5期355-360,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(21342014);天津市自然科学基金项目(15JCZDJC33100)

摘　　要：目的寻找活性更好的抗血小板聚集化合物。方法基于吡考他胺的抗血小板聚集机制和生物电子等排原理,以2,3-二甲基苯酚为原料,经Williamson反应、氧化、氯代和胺解反应合成了13个未见文献报道的4-乙氧基-N,N'-二(取代苯基)酰胺类化合物。以吡考他胺和阿司匹林为阳性对照药物,采用Born比浊法对目标化合物进行活性筛选。结果与结论目标化合物的结构经MS、IR和1H-NMR谱确证,其中,4个目标化合物(7、9、10和12)的抗血小板聚集活性明显高于阳性对照药吡考他胺,有进一步研究的价值。在活性筛选结果的基础上对目标化合物的构效关系作了初步的推测和总结,以期为今后开展相关研究提供借鉴。The purpose of the present study was to search for better anti-platelet drugs. Based on the antiplatelet aggregation mechanism of picotamide and its corresponding principle of bioisosterism,2,4-dimethyl phenol was employed as a main rawmaterial for the synthesis and ultimately 13 derivatives of 4-ethoxy isophthalamides,which had not been reported in any previous articles,were successfully designed and obtained via Williamson reaction,oxidation,chlorination and ammonolysis. All the compounds were characterized by utilizing M S,IR and1H-NM R. Additionally,their anti-platelet aggregation activities in vitro were assessed by adopting the Born test with pictotamide and aspirin as reference drugs. The results indicated that most of the synthesized compounds possessed anti-platelet aggregation activities and especially compounds7,9,10 and 12 exhibited higher activities than that of picotamide. It was noteworthy that forgoing compounds7,9,10 and 12 even performed slightly better than picotamide,which meat further investigation on these newproducts should be explored. In viewof the tested data,the preliminary structure-activity relationships of the synthesized compounds were conjectured and summarized,which should be useful for the follow-up studies as promising references.

关 键 词：4-乙氧基-1 3-苯二甲酰胺 构效关系 吡考他胺 抗血小板聚集 合成 

分 类 号：R914.5[医药卫生—药物化学] R96[医药卫生—药学]