SIOC English
有机化学
高级检索

有机化学 >

2012 , Vol. 32 >Issue 11: 2187 - 2192

DOI: https://doi.org/10.6023/cjoc201206006

研究简报

四氢吡啶并[4,3-d]二氢嘧啶酮衍生物的合成及其初步抗癌活性测定

  • 王晶 ,
  • 丁丽 ,
  • 肖笛 ,
  • 薛思佳
展开
  • 上海师范大学生命与环境科学学院化学系 上海 200234

收稿日期: 2012-06-06

  修回日期: 2012-06-27

  网络出版日期: 2012-07-04

基金资助

“十二五”国家科技支撑计划(No. 2011BAE06B01-17)、国家自然科学基金(Nos. 21042010, 21102092, 30870560)资助项目.

收起

Synthesis and Preliminary Anticancer Activity Evaluation of Tetrahydropyrido[4,3-d]dihydropyrimidine-2-one Derivatives

  • Wang Jing ,
  • Ding Li ,
  • Xiao Di ,
  • Xue Sijia
Expand
  • College of Life and Environment Sciences, Shanghai Normal University, Shanghai 200234

Received date: 2012-06-06

  Revised date: 2012-06-27

  Online published: 2012-07-04

Supported by

Project supported by the Key Scientific “Twelfth Five-Year” National Technology Support Program (No. 2011BAE06B01-17), and the National Natural Science Foundation of China (Nos. 21042010, 21102092, 30870560).

Fold

摘要

为寻找新型抗癌药物的先导化合物, 设计合成了16种未见文献报道的四氢吡啶并[4,3-d]二氢嘧啶酮衍生物2a～2p, 结构经1H NMR, IR, MS, 元素分析确证. 初步的生物活性测试结果表明, 在100 μg/mL浓度下, 目标化合物对白血病K562细胞的增殖表现出显著的抑制活性, 对卵巢癌HO-8910和肝癌SMMC-7721细胞系的增殖也表现出一定的抑制活性.

关键词： 四氢吡啶并[4,3-d]二氢嘧啶酮; 衍生物; 合成; 白血病K562; 抗癌活性

本文引用格式

王晶 , 丁丽 , 肖笛 , 薛思佳 . 四氢吡啶并[4,3-d]二氢嘧啶酮衍生物的合成及其初步抗癌活性测定[J]. 有机化学, 2012 , 32(11) : 2187 -2192 . DOI: 10.6023/cjoc201206006

Abstract

In search of more effective anticancer agents, sixteen novel tetrahydropyrido[4,3-d]dihydropyrimidine-2-one derivatives 2a～2p were synthesized by reacting N-(4-substituted benzyl)-3,5-bisbenzylidene-4-piperidone with urea in EtONa/EtOH under reflux condition. The structures were confirmed by 1H NMR, IR, MS and elemental analysis. The preliminary bioassay indicated that some title compounds exhibited good antiproliferative activities against K562 cells, certain antiproliferative activities against ovarian cancer HO-8910 cells and liver cancer SMMC-7721 cells.

Key words： tetrahydropyrido[4,3-d]dihydropyrimidine-2-one; derivative; synthesis; leukemic K562 cells; anticancer activities

参考文献

[1] Zhou, Y.-Y.; Guo, Q.-H.; Gu, X.-X. Chin. J. Chem. Educ. 2004, (5), 10 (in Chinese).
(周勇义, 郭启华, 古学新, 化学教育, 2004, (5), 10.)
[2] Jamieson, C. H.; Ailles, L. E.; Dylla, S. J.; Muijtjens, M.; Jones, C.; Zehnder, J. L.; Gotlib, J.; Li, K.; Manz, M. G.; Keating, A.; Sawyers, C. L.; Weissman, I. L. N. Engl. J. Med. 2004, 351(7), 657.
[3] Szakacs, G.; Paterson, J. K.; Ludwig, J. A.; Booth-Genthe, C.; Gottesman, M. M. Nat. Rev. Drug Discovery 2006, 5, 219.
[4] O'Connor, R. Curr. Cancer Drug Targets 2009, 9, 273
[5] Wang, J.; Meng, W.; Ni, Z. J.; Xue, S. J. Chin. J. Chem. 2011, 29, 2421.
[6] Perez-Rebolledo, A.; Ayala, J. D.; de Lima, G. M.; Marchini, N.; Bombieri, G.; Zani, C. L.; Souza-Fagundes, E. M.; Beraldo, H. Eur. J. Med. Chem. 2005, 40, 467.
[7] Liu, X.; Go, M.-L. Bioorg. Med. Chem. 2006, 14, 153.
[8] Huang, S. L.; Lin, R. H.; Yu, Y.; Lu, Y. H.; Peter, J. C.; George, C.; Li, S. J.; Stuart, L. E.; Steven, A. M. Bioorg. Med. Chem. Lett. 2007, 17, 1243.
[9] Bazgira, A.; Khanaposhtani, M. M.; Soorki, A. A. Bioorg. Med. Chem. Lett. 2008, 18, 5800.
[10] Nair, V.; Chi, G.; Shu, Q.; Julander, J.; Smee, D. F. Bioorg. Med. Chem. Lett. 2009, 19, 1425.
[11] Fang, Z. K.; Xue. S. J.; Chen, L.; Xu, Y. Yin, A. Q.; Li, C. Y. Chin. J. Chem. 2009, 27, 397.
[12] Tu, S. J.; Han, Z. G.; Miao, C. B.; Shi, F.; Ma, N.; Zhang, G. J. Comb. Chem. 2010, 12, 16.
[13] EI-Subbagh, H. I.; Abu-Zaid, S. M.; Mahran, M. A.; Badria, F. A.; Al-Obaid, A. M. J. Med. Chem. 2000, 43, 2915.
[14] Al-Omar, M. A.; Youssef, K. M.; El-Sherbeny, M. A.; Awadalla, S. A. A.; El-Subbagh, H. I. Arch. Pharm. Chem. Life Sci. 2005, 338, 175.
[15] Hansen, M. B.; Nielsen, S. E.; Berg, K. J. Immunol. Methods 1989, 119, 203
Options
文章导航

/

〈 〉