高等学校化学学报 ›› 2013, Vol. 34 ›› Issue (12): 2745.doi: 10.7503/cjcu20130298

• 有机化学 • 上一篇    下一篇

N-取代邻苯二甲酰亚胺类衍生物的设计、合成及活性评价

秦思凝1,2, 吕文文3,4, 王铨1,2, 赵庆春4, 许永男1,2   

  1. 1. 沈阳药科大学基于靶点的药物设计与研究教育部重点实验室, 沈阳 110016;
    2. 沈阳药科大学制药工程学院, 沈阳 110016;
    3. 沈阳药科大学药学院, 沈阳 110016;
    4. 沈阳军区总医院药剂科, 沈阳 110840
  • 收稿日期:2013-04-01 出版日期:2013-12-10 发布日期:2013-05-03
  • 作者简介:许永男,男,博士,教授,博士生导师,主要从事活性天然产物及其衍生物合成、有机合成和天然产物化学成分研究. E-mail:ynxu@syphu.edu.cn;赵庆春,男,博士,主任药师,博士生导师,主要从事基于靶点的中药及天然产物、基因多态性与个体化用药研究. E-mail:zhaoqingchun1967@163.com
  • 基金资助:

    教育部创新团队发展计划和辽宁省高校创新团队支持计划资助

Design, Synthesis and Activity Evaluation of N-Substituted Phthalimide Derivatives

QIN Si-Ning1,2, LÜ Wen-Wen3,4, WANG Quan1,2, ZHAO Qing-Chun4, XU Yong-Nan1,2   

  1. 1. Key Laboratory of Sturcture-based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China;
    2. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China;
    3. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;
    4. Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, China
  • Received:2013-04-01 Online:2013-12-10 Published:2013-05-03

摘要:

结合中药脱皮马勃中分离得到的3,5-二羟基邻苯二甲酰亚胺和邻苯二甲酰亚胺类化合物的结构设计合成了一系列N-取代-3,5-二甲氧基邻苯二甲酰亚胺及N-取代-3,5-二羟基邻苯二甲酰亚胺类衍生物,其结构经1H NMR,13C NMR和MS分析确证. 选取人肺腺癌细胞A549及人脐静脉血管内皮细胞HUEVC为测试细胞株,评价了所合成化合物的体外抗肿瘤及抗血管生成活性,结果表明,部分化合物表现出一定的活性.

关键词: 脱皮马勃, 邻苯二甲酰亚胺, N-取代, 沙利度胺, 抗肿瘤

Abstract:

One novel compound 3,5-dimethoxy phthalimide had been isolated from Lasiosphaera fenzlii Reich. The compound exhibited definite antioxidant activity. Meanwhile it was reported that many compounds with the skeleton of phthalimide displayed many bioactivities such as anti-angiogenesis, anti-inflammatory, immune regulation and anti-tumor and so on. On the comprehensive review of above evidences, a series of N-substituted-3,5-dimethoxy phthalimide derivatives and N-substituted-3,5-dihydroxy phthalimide derivatives were designed and synthesized. Those compounds were synthesized by the multi-step reaction, 3,5-dimethoxybenzoic acid was used as a starting material, and sequentially generates the phthalic anhydride and phthalimide, then reacted with a series of halogenated hydrocarbons, and stripped of methyl to obtain the target compounds. Thirty-one new compounds were synthesized, and the structures were characterized by 1H NMR, 13C NMR and MS techniques. Their anti-tumor and anti-angiogenesis activities against A549 and HUVEC cell line in vitro were tested. Some compounds showed a certain activity.

Key words: Lasiosphaera fenzlii Reich., Phthalimide, N-Substituted, Thalidomide, Anti-tumor

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