7-氨基-6-硝基-[1,2,5]噁二唑并[3,4-b]吡啶-1-氧化物的胺化开环反应及产物的抗肿瘤活性
收稿日期: 2016-02-24
修回日期: 2016-04-15
网络出版日期: 2016-05-06
基金资助
国家自然科学基金（No.21102125）资助项目.
Convenient Aminative Ring-Opening Reaction of 7-Amino-6-nitro-[1,2,5]oxadiazolo[3,4-b]pyridine-1-oxide and Antitumor Activity of Corresponding Products
Received date: 2016-02-24
Revised date: 2016-04-15
Online published: 2016-05-06
Supported by
Project supported by the National Natural Science Foundation of China (No.21102125).
7-氨基-6-硝基-[1，2，5]噁二唑并[3，4-b]吡啶-1-氧化物（1）与胺在温和条件下反应，氧化呋咱环开环，释放一分子次硝酸，得到了蓝绿色的开环产物2-胺取代的-3-亚硝基-4-氨基-5-硝基吡啶5a~5f.发现化合物1中的6-位硝基对其氧化呋咱开环起到关键作用.利用1H NMR，13C NMR和HRMS对目标化合物进行了结构表征.用四甲基偶氮唑盐（MTT）法测试了目标化合物体外抑制人肺癌细胞株（H522）和脑胶质瘤细胞株（U87）两种肿瘤细胞的增殖活性.测试结果显示，所有目标化合物均表现较强的体外肿瘤细胞抑制活性.
李泽民 , 黄道锐 , 马丛明 , 许晓娟 , 刘祖亮 , 姚其正 . 7-氨基-6-硝基-[1,2,5]噁二唑并[3,4-b]吡啶-1-氧化物的胺化开环反应及产物的抗肿瘤活性[J]. 有机化学, 2016 , 36(9) : 2236 -2241 . DOI: 10.6023/cjoc201602023
Reaction of 7-amino-6-nitro[1,2,5]oxadiazolo[3,4-b]pyridine-1-oxide (1, namely pyridofuroxan) with ammonia or/and amines under mild conditions let to the corresponding 5-nitro-3-nitroso-2,4-diaminopyridine 5a~5f. It is shown that the ring-opening reactivity of pyridofuroxan 1 was significantly affected by the 6-nitro substituent. The structures of all target compounds were identified by 1H NMR, 13C NMR and HRMS. The biological evaluation was performed on human lung cancer cell line (H522) and glioma cell line (U87) by 3-(4,5-dimethylthigal-2-yl)-2,5-(diphenyltetragalium) bromide (MTT) assay. The results suggested that all of the target compounds exhibited potent anti-tumor activities in vitro.
[1] Cerecetto, H.; González, M. Benzofuroxan and Furoxan. Chemistry and Biology, Bioactive Heterocycles IV, Springer Berlin Heidelberg, 2007, p. 265.
[2] Sartini, S.; Cosconati, S.; Marinelli, L.; Barresi, E.; Di Maro, S.; Simorini, F.; Taliani, S.; Salerno, S.; Marini, A. M.; Da Settimo, F.; Novellino, E.; La Motta, C. J. Med. Chem. 2012, 55(23), 10523.
[3] Deng, Y. J.; Shi, J. B.; Jiang, L. X.; Gao, J.; Yao, Q. Z. Acta Chim. Sinica 2006, 64(18), 1911(in Chinese). (邓艳君, 石静波, 姜力勋, 高静, 姚其正, 化学学报, 2006, 64(18), 1911.)
[4] Ma, C.; Wang, Y.; Hou, K.; Liu, Z.; Yao, Q. Z. Chin. J. Org. Chem. 2013, 31(10), 1299.
[5] Tannant, G.; Wallace, G. M. J. Chem. Soc., Chem. Commun. 1982, 4), 267.
[6] Arris, C. E.; Boyle, F. T.; Calvert, A. H.; Curtin, N. J.; Endicott, J. A.; Garman, E. F.; Gibson, A. E.; Golding, B. T.; Grant, S.; Griffin, R. J. J. Med. Chem. 2000, 43(15), 2797.
[7] Sayle, K. L.; Bentley, J.; Boyle, F. T.; Calvert, A. H.; Cheng, Y.; Curtin, N. J.; Endicott, J. A.; Golding, B. T.; Hardcastle, I. R.; Jewsbury, P.; Mesguiche, V.; Newell, D. R.; Noble, M. E. M.; Parsons, R. J.; Pratt, D. J.; Wang, L. Z.; Griffin, R. J. Bioorg. Med. Chem. Lett. 2003, 13(18), 3079.
[8] Lowe-Ma, C. K., Nissan, R. A., Wilson, W. S. J. Org. Chem. 1990, 55(12), 3755.
[9] Cmoch, P.; Kamieński, B.; Kamieńska-Trela, K.; Stefaniak, L.; Webb G. A. J. Phys. Org. Chem. 2000, 13(8), 480.
/
| 〈 |
|
〉 |
