乙酰水杨酰对羟基桂皮酸与呋咱氮氧化物和硝酸酯偶联物的合成及其抗血栓作用  

Synthesis and Antithrombotic Activity of Acetylsalicyl p-Coumaric Acid Coupled with Furoxans and Nitrates

作　　者：周洲[1] 蒋丽媛[1] 张奕华[1] 季晖[2] 孙易[2] 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：《有机化学》2006年第10期1403-1408,共6页Chinese Journal of Organic Chemistry

摘　　要：对羟基桂皮酸酚羟基经保护后与相应的羟基呋咱氮氧化物酯化,酯化物脱保护,再与阿司匹林缩合得II1～II3;对羟基桂皮酸与相应二溴烷烃作用,再经阿司匹林酯化,得到的溴代烷基酯与硝酸银反应得II4～II7;酚羟基保护的对羟基桂皮酸与异山梨醇单硝酸酯酯化,脱保护后与阿司匹林缩合得II8.目标物II1～II8均经MS,IR,1HNMR和元素分析确证,并通过大小鼠体内外抗血栓活性初筛,结果表明,多数目标物显示与阿司匹林相当的抗血栓活性,II6活性优于阿司匹林.The protected p-coumaric acid was esterified with corresponding hydroxyfuroxan, and the resuited ester was deprotected and condensed with aspirin to give Ⅱ1～Ⅱ3, respectively. Treatment of p-coumaric acid with dibromoalkane, followed by esterification with aspirin offered acetylsalicyl p-coumaric acid bromoalkyl ester, and then reacted with silver nitrate to give Ⅱ4～Ⅱ7, respectively. Ⅱ8 was obtained by esterification of the protected p-coumaric acid with isosorbide mononitrate, subsequent deprotection and condensation with aspirin. Ⅱ1-Ⅱ8 were identified by MS, IR, ^1H NMR spectra and elemental analysis, and screened for in vitro and in vivo thrombosis inhibitory activities in mice and rats. Most of tested compounds are comparable to aspirin in antithrombotic activity, and Ⅱ6 is more potent than aspirin.

关 键 词：乙酰水杨酰对羟基桂皮酸 呋咱氮氧化物 阿司匹林 合成 抗血栓活性 

分 类 号：TQ463.2[化学工程—制药化工]