一锅法合成3-取代-1-吗啉基-1,2,4-均三唑Mannich碱及其活性评价
收稿日期: 2015-07-24
修回日期: 2015-10-08
网络出版日期: 2015-10-23
基金资助
辽宁省教育厅科学技术研究(No. 2009A426)资助项目
One Pot Synthesis of 3-Substituted-1-morpholino-1,2,4-triazole Mannich Bases and Their Activity Evaluation
Received date: 2015-07-24
Revised date: 2015-10-08
Online published: 2015-10-23
Supported by
Project supported by the Science and Technology Research Program of Liaoning Provincial Department of Education (No. 2009A426).
将3-对氯苯基、3-对甲氧基苯基和3-正十一烷基-1,2,4-均三唑分别与5个芳香醛反应合成了15个Schiff碱, 然后将Schiff碱、甲醛和吗啉进行多组分一锅反应, 合成14个新型Mannich碱(PCTABM、PMTABM和PUTABM). 为了对比探究3-取代基对分子生物活性的影响, 以3-二茂铁基-1,2,4-均三唑为原料, 利用相似的方法合成了4个3-二茂铁基-1,2,4-均三唑Mannich碱(FcTABM). 应用IR, 1H NMR和HRMS等对15种新物质进行了结构表征. 评价了目标分子对植物生长调节活性、除草活性和抑制Cdc25B活性. 结果发现, 目标化合物在植物生长调节和除草活性中均表现出优良的活性, 14个目标分子对Cdc25B表现出优良的抑制活性, 其中7c、8e、9e、10b～10e的IC50值低于参照物Na3VO4, 有望成为Cdc25B抑制剂.
张成路 , 唐杰 , 殷立莹 , 袭焕 , 国阳 , 孙丽杰 . 一锅法合成3-取代-1-吗啉基-1,2,4-均三唑Mannich碱及其活性评价[J]. 有机化学, 2016 , 36(2) : 358 -362 . DOI: 10.6023/cjoc201507029
15 Schiff bases were synthesized by the reactions of 3-p-chlorophenyl, 3-p-methoxyphenyl and 3-n-pentyl-1,2,4-triazole with five different aromatic aldehydes, respectively. Then 14 novel Mannich bases (PCTABM, PMTABM and PETABM) were first afforded by the reactions of Schiff bases with formaldehyde and morpholine through multi-component one-pot reaction. In order to explore the effect of different 3-substituted groups on biological activities, four Mannich bases FcTABM of 3-ferrocenyl-1,2,4-triazole were also synthesized starting from 3-ferrocenyl-1,2,4-triazole by the similar method. IR, 1H NMR and HRMS were used to characterize the structure of the target molecules. The biological activities of the target molecules were evaluated. As a result, the target compounds exhibited excellent activities in plant growth regulators and herbicidal activity. There are 14 target compounds exhibited excellent inhibitory activity against Cdc25B, in which the IC50 values of 7c, 8e, 9e, 10b～10e IC50 were all smaller than the reference Na3VO4, which were expected to be Cdc25B inhibitors.
[1] Ashok, M.; Holla, B. S.; Poojary, B. Eur. J. Med. Chem. 2007, 42, 1095.
[2] Roman, G. Eur. J. Med. Chem. 2015, 89, 743.
[3] Li, G. H.; Yang, H. Chin. J. Org. Chem. 2008, 28, 1918 (in Chinese). (李国华, 杨红, 有机化学, 2008, 28, 1918.)
[4] Navidpour, L.; Shafaroodi, H.; Abdi, K.; Amini, M.; Ghahremani, H. M.; Dehpour, A. R.; Shafiee, A. Bioorg. Med. Chem. 2006, 14, 2507.
[5] Holla, B. S.; Veerendra, B.; Shivananda, M. K.; Poojary, B. Eur. J. Med. Chem. 2003, 38, 759.
[6] Wang, B. L.; Shi, Y. X.; Ma, Y.; Liu, X. H.; Li, Y. H.; Song, H. B.; Li, B. J.; Li, Z. M. J Agric Food Chem. 2010, 58, 5515.
[7] Deng, X. M.; Wang, J. H.; Zhang, J. M.; Sim, T.; Kim, N. D.; Sasaki, T.; Luther, W.; George, R. E.; Janne, P. A.; Gray, N. S. Med. Chem. Lett. 2011, 2, 379.
[8] Kunj, B. M.; Vinod, K. T. J. Org. Chem. 2014, 79, 5752.
[9] Burbuliene, M. M.; Jakubkiene, V.; Mekuskiene, G.; Udrenaitea, E.; Smiciusa, R.; Vainilaviciusa, P. Farmaco 2004, 59, 767.
[10] Koparir, M.; Orek, C.; Parlak, A. E.; Söylemez, A.; Koparir, P.; Karatepe, M.; Dastan, S. D. Eur. J. Med. Chem. 2013, 63, 340.
[11] Jakubkiene, V.; Burbuliene, M. M.; Mekuskiene, G.; Emilija, U.; Gaidelis, P.; Vainilavi?ius, P. Farmaco 2003, 58, 323.
[12] Ashok, M.; Holla, B. S.; Poojary, B. Eur. J. Med. Chem. 2007, 42, 1095.
[13] Holla, B. S.; Rao, B. S.; Shridhara, K.; Akberali, P. M. Farmaco 2000, 55, 338.
[14] Hu, G. Q.; Wang, G. Q.; Duan, N. N.; Wen, X. Y.; Cao, T.Y.; Xie, S. Q.; Huang, W. L. Acta Pharm. Sin. B 2012, 2, 312.
[15] Kaminski, K.; Obniska, J.; Chlebek, I.; Wiklik, B.; Rzepka, S. Bioorg. Med. Chem. 2013, 21, 6821.
[16] Arafa, W. A. A; Mohamed, A. S. Chin. J. Chem. 2011, 29, 1661.
[17] Mohamed, R. A. Molecules 2014, 19, 18897.
[18] Mostafa, A. H.; Refaat, M. S.; Mohammed, A. A.; Mohammed, F. M. Arch. Pharm. Res. 2011, 34, 1239.
[19] Tsuchiya, A.; Hirai, G.; Koyama, Y.; Oonuma, K.; Otani, Y.; Osada, H.; Sodeoka, M. Med. Chem. Lett. 2012, 3, 294.
[20] Li, Q. H.; Wang, M. M. Chem. Res. Appl. 2010, 22, 186 (in Chinese). (李清寒, 王苗苗, 化学研究与应用, 2010, 22, 186.)
[21] Zhu, C. A.; Wu, F. Y.; Wang, X.; Gao, L. N.; Weng, Q. F.; Shi, L.; Zhang, C. L. Chin. J. Appl. Chem. 2014, 31, 455 (in Chinese). (朱长安, 武飞宇, 王雪, 高丽娜, 翁前锋, 石丽, 张成路, 应用化学, 2014, 31, 455.)
[22] Lavecchia, A.; Giovanni, C. D.; Pesapane, A.; Montuori, N.; Ragno, P.; Martucci, N. M.; Masullo, M.; Vendittis, E. D. J. Med. Chem. 2012, 55, 4142.
[23] Sahoo, P. K.; Sharma, R.; Pattanayak, P. Med. Chem. Res. 2010, 19, 127.
[24] George, T.; Mehta, D. V.; Tahilramani, R.; David, J.; Talwalker, P. K. J. Med. Chem. 1971, 14, 335.
[25] Zhang, C. L.; Wang, X.; Guo, Y. Wu, Y. F.; Gao, L. N.; Sun, L. J.; Chai, J. H.; Zhu, C. A. Chin. J. Org. Chem. 2014, 34, 2331 (in Chinese). (张成路, 王雪, 国阳, 吴一非, 高丽娜, 孙丽杰, 柴金华, 朱长安, 有机化学, 2014, 34, 2331.)
[26] Gupta, A, K.; Prachand, S.; Patel, A.; Jain, S. Int. J. Pharm. Life Sci. 2012, 3, 1848.
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