新型[(吡嗪-3-基)甲氧基]芳酸衍生物的合成及其抗血小板聚集活性  

Synthesis of New ((pyrazin-3-yl)methoxy)aryl Acid Derivatives and Their Anti-platelet Aggregation Activities

作　　者：马逢时 李家明[2] MA Feng-shi;LI Jia-ming(Anqing Medical and Pharmaceutical College, Anqing 246052, China;Anhui University of Chinese Medicine, Hefei 230012, China)

机构地区：[1]安庆医药高等专科学校,安徽安庆246052 [2]安徽中医药大学,安徽合肥230012

出　　处：《合成化学》2019年第9期698-703,共6页Chinese Journal of Synthetic Chemistry

基　　金：国家科技重大专项重大新药创制项目(2009ZX09103-123);安徽省高等专科学校自然科学研究项目(KJ2016A443)

摘　　要：以具有活血化瘀作用的中药有效成分阿魏酸为先导物,利用基于受体结构的理性药物设计方法,设计并合成了6个新化合物[(吡嗪-3-基)甲氧基]芳酸衍生物(6a^6f)。以2-甲基吡嗪和不同取代的芳香酸甲酯为起始原料,经自由基卤代反应、醚化反应和水解反应合成6a^6f,其结构经1H NMR,13C NMR, IR和MS表征。体外药效筛选结果显示:6a^6f具有明显的抗血小板聚集活性,其中(E)-3-甲氧基-4-(吡嗪-2-甲氧基)-苯丙烯酸(6a)和3-(2-吡嗪甲氧基)-4-甲氧基-苯甲酸(6e)的活性优于奥扎格雷和阿魏酸。(E)-3-甲氧基-4-(吡嗪-2-甲氧基)-苯丙烯酸(6a)的抗血小板聚集活性,优于化合物(E)-3-(4-(吡啶-3-基)甲氧基)-3-甲氧基苯基)丙烯酸。Six new ((pyrazin-3-yl)methoxy)aromatic acids( 6a^6f ) were designed and synthesized based on receptor structure using ferulic acid as the lead compound, which is active ingredient of traditional Chinese medicine with blood circulation and phlegm. The target compounds were obtained by free radical halogenation, etherification and hydrolysis using 2-methylpyrazine and different substituted aromatic acid methyl esters as raw materials. The structures were characterized by 1 H NMR, 13 C NMR , IR and and MS. The results of in vitro pharmacodynamic screening showed that the title compounds had significant anti-platelet aggregation activity, and the activities of( E)-3-methoxy-4-(pyrazine-2-methoxy)-phenylacrylic acid( 6a ) and 3-(2-pyrazinemethoxy)-4-methoxy-benzoic acid( 6e ) were due to ozagrel and ferulic acid. The anti-platelet aggregation activity of 6a is superior to( E)-3-(4-(pyridin-3-yl)methoxy)-3- methoxyphenyl) acrylic acid.

关 键 词：阿魏酸 2-甲基吡嗪 [(吡嗪-3-基)甲氧基]芳酸 合成 血栓 抗血小板聚集 

分 类 号：O621.3[理学—有机化学] O625[理学—化学]