有机化学 ›› 2012, Vol. 32 ›› Issue (09): 1719-1724.DOI: 10.6023/cjoc1203131 上一篇    下一篇

研究论文

2-(4-取代苄基-1,4-高哌嗪-1-基)-N-(5-溴喹喔啉-6-基)乙酰胺衍生物的合成及正性肌力活性研究

吴妍a, 马龙旭a, 牛天巍a, 孟凡领a, 崔勋b, 朴虎日a   

  1. a 延边大学药学院 长白山生物资源与功能分子教育部重点实验室 延吉 133002;
    b 延边大学基础医学院 延吉 133002
  • 收稿日期:2012-03-13 修回日期:2012-05-11 发布日期:2012-04-09
  • 通讯作者: 崔勋, 朴虎日 E-mail:piaohuri@yahoo.com.cn
  • 基金资助:

    国家自然科学基金(No.81160381)资助项目

Synthesis and Positive Inotropic Evaluation of 2-(4-Substituted benzyl-1,4-diazepan-1-yl)-N-(5-bromoquinoxalin-6-yl)acetamides

Wu Yana, Ma Longxua, Niu Tianweia, Meng Fanlinga, Cui Xunb, Piao Huria   

  1. a Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002;
    b College of Medicine, Yanbian University, Yanji 133002
  • Received:2012-03-13 Revised:2012-05-11 Published:2012-04-09
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No.81160381)

设计合成了一系列2-(4-取代苄基-1,4-高哌嗪-1-基)-N-(5-溴喹喔啉-6-基)乙酰胺化合物,测定其对家兔离体左心房搏出量的影响,对化合物的正性肌力活性进行了初步评价.结果显示,一些衍生物在测试浓度下显示出比上市药物米力农更好的正性肌力活性,其中活性最好的化合物是3f,在浓度为3×105mol·L-1时,增强左心房搏出量的强度达(6.18±0.06)%[米力农:(2.46±0.07)%].实验中所合成的化合物通过IR,1H NMR,MS和元素分析测试进行了确证.

关键词: 喹喔啉, 高哌嗪, 正性肌力活性, 搏出量

A series of 2-(4-substituted benzyl-1,4-diazepan-1-yl)-N-(5-bromoquinoxalin-6-yl)acetamides were synthesized and evaluated for their positive inotropic activity by measuring left atrium stroke volume on isolated rabbit-heart preparations. Some of these derivatives exhibited better activity in vitro compared with the existing drug, milrinone, among which N-(5-bromoquinoxalin-6-yl)-2-[4-(4-chlorobenzyl)-1,4-diazepan-1-yl]acetamide (3f) proved to be the most potent, increasing stroke volume by with (6.18±0.06)% [milrinone, (2.46±0.07)%] at a concentration of 3×105mol·L-1. The compounds synthesized were characterized by IR,1H NMR, MS techniques and elemental analysis.

Key words: quinoxaline, 1,4-diazepane, positive inotropic activity, stroke volume