新型二茂铁基1,2,4-三唑Mannich碱的合成及其Cdc25B抑制活性  

Synthesis and Inhibitory Activity of Novel Ferrocenyl 1,2,4-Triazole Mannich Bases

作　　者：张成路[1] 王雪[1] 国阳[1] 吴一非[1] 高丽娜[1] 孙丽杰[1] 柴金华[1] 朱长安[1] 

机构地区：[1]辽宁省生物与制药重点实验室辽宁师范大学化学化工学院,大连116029

出　　处：《有机化学》2014年第11期2331-2337,共7页Chinese Journal of Organic Chemistry

基　　金：辽宁省教育厅科学技术(No.2009A426)资助项目~~

摘　　要：以5种二茂铁基三唑席夫碱为原料,分别与吗啉、哌嗪和N-甲基哌嗪等进行曼尼希反应,首次设计合成了15个新型3-二茂铁基-1,2,4-均三唑曼尼希碱(3a^3e、4a^4e和5a^5e).通过IR、1H NMR和HRMS等测试方法对目标化合物结构进行了表征,并对代表目标化合物3b进行X-ray单晶衍射测试.研究了目标产物对Cdc25B的抑制活性,结果发现,13个目标化合物表现出良好的抑制活性,其中3c、4a、5b、5c和5e等5个化合物的IC50值小于阳性参照物正矾酸钠(1.86±0.24μg·m L-1),分别为0.91±0.18、0.62±0.13、1.10±0.33、0.44±0.04和0.67±0.13μg·m L-1,对比PTP1B抑制活性筛选结果,目标化合物对Cdc25B有选择性的抑制作用,可以作为潜在的Cdc25B抑制剂.15 novel 3-ferrocenyl-1,2,4-triazole Mannich bases （3a^3e, 4a^4e and 5a^5e） were designed and synthesized for the first time by Mannich reaction from five 3-ferrocenyl-1,2,4-triazole Schiff bases, which reacted with morpholine, 1-methylpiperazine and piperazine, respectively. The structures of 3, 4 and 5 were characterized by IR, 1H NMR and HRMS. The X-ray single crystal diffraction of 3b was obtained. The results showed that the target compounds were successfully syn-thesized. The target products were evaluated for their Cdc25B inhibitory activities. The test results indicated that 13 of 15 Mannich bases exhibited good inhibitory activity, wherein IC50 values of 3c, 4a, 5b, 5c and 5e were lower than the positive control compound Na3VO4 （1.86±0.24 μg·mL-1） with 0.91±0.18, 0.62±0.13, 1.10±0.33, 0.44±0.04 and 0.67±0.13μg·mL-1, respectively. Compared with PTP1B inhibition activity results, the target products have a selective inhibitory effect on Cdc25B.

关 键 词：二茂铁 1 2 4-三唑 曼尼希碱 Cdc25B抑制剂 

分 类 号：O627.81[理学—有机化学]