研究简报

2,4-二氨基喹唑啉和2,4-二氨基吡啶并[2,3-d]嘧啶衍生物的合成

  • 邓兰青 ,
  • 钟宏 ,
  • 王帅
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  • a 中南大学化学化工学院 长沙 410083;
    b 岳阳职业技术学院 岳阳市中草药综合利用重点实验室 岳阳 414000;
    c 有色金属资源化学教育部重点实验室中南大学 长沙 410083

收稿日期: 2013-07-18

  修回日期: 2013-10-09

  网络出版日期: 2013-10-16

基金资助

国家高技术研究发展计划(863计划,No.2013AA064102)和湖南省科技厅(No.2010FJ4112)资助项目.

Synthesis of 2,4-Diaminoquinazoline and 2,4-Diaminopyrido- [2,3-d]pyrimidine Derivatives

  • Deng Lanqing ,
  • Zhong Hong ,
  • Wang Shuai
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  • a College of Chemistry and Chemical Engineering, Central South University, Changsha 410083;
    b Key Laboratory of Yueyang Chinese Herbal Utilization, Yueyang Vocational Technical College, Yueyang 414000;
    c Key Laboratory of Resourse Chemistry of Nonferrous Metals, Ministry of Education Central South University, Changsha 410083

Received date: 2013-07-18

  Revised date: 2013-10-09

  Online published: 2013-10-16

Supported by

Project supported by the National High Technology Research and Development Program of China (863 Program, No. 2013AA064102) and the Project of Science and Technology of Hunan Province (No. 2010FJ4112).

摘要

以6-氯-5-氰基烟酸、3-氰基-4-氟苯甲酸、4-氰基-3-氟苯甲酸和6-氯-5氰基-2-吡啶甲酸为原料,经过酰胺化和关环两步反应合成了2,4-二氨基喹唑啉和2,4-二氨基吡啶并[2,3-d]嘧啶衍生物,该方法操作简便,除6-氯-5-氰基-2-吡啶甲酸外,其它三种酸的反应收率可达65%以上. 采用氢核磁(1H NMR)、碳核磁(13C NMR)和高效液质联用(LC-MS)分析对目标产物进行了表征. 采用四甲基偶氮唑盐(MTT)法考察所合成化合物的体外抗肿瘤活性测性,结果表明部分化合物对所选肿瘤细胞的增殖有一定的抑制活性,化合物4c4d4e4f对人白血病细胞(K562)和人肝癌细胞(HepG2)的抑制活性强于阳性对照药5-氟尿嘧啶(5-Fu).

本文引用格式

邓兰青 , 钟宏 , 王帅 . 2,4-二氨基喹唑啉和2,4-二氨基吡啶并[2,3-d]嘧啶衍生物的合成[J]. 有机化学, 2014 , 34(2) : 414 -418 . DOI: 10.6023/cjoc201307028

Abstract

In this work, several 2,4-diaminoquinazoline and 2,4-diaminopyrido[2,3-d]pyrimidine derivatives were designed and synthesized by acylation reaction and ring-closure reaction, using 6-chloro-5-cyanonicotinic acid, 3-cyano-4-fluoroben- zoic acid, 4-cyano-3-fluorobenzoic acid and 6-chloro-5-cyanopicolinic acid as starting materials. This method is simple and efficient. For the used acids but 6-chloro-5-cyanopicolinic acid, the reaction yields are above 65%. The structures of terminational compounds were determined by 1H NMR, 13C NMR and LC-MS. The antitumor activities of the nitrogen mustard-linked chalcones were evaluated by an MTT assay. The results reveal that some of the title compounds exhibit potent anti-proliferative activities against selected tumor cells. Among which, compounds 4c, 4d, 4e and 4f against K562 and HepG2 were better than 5-fluorouracil.

参考文献

[1] Liu, C.-E; Yu, Q.-Y.; Tang, J.-H.; Li, J.-R. Chin. J. Org. Chem. 2012, 32(3), 537 (in Chinese).



(刘长娥, 于琪瑶, 唐健红, 李加荣, 有机化学, 2012, 32(3), 537.)



[2] Deng, L.-Q.; Xu, Z.-H.; Shang Y.-F.; Dai, W.-J.; Hu, H.-M.; Deng, S.-P.; Ouyang, J.-M. Chin. J. Org. Chem. 2012, 32(6), 1141 (in Chinese).



(邓兰青, 徐中海, 尚云峰, 戴文静, 胡辉敏, 邓穗平, 欧阳健明, 有机化学, 2012, 32(6), 1141.)



[3] Liu, H.-B.; Xu, H.-J.; Lv, P.; Pan, N.-N.; Li, S.-Q. Acta Chim. Sinica 2012, 32(5), 674 (in Chinese).



(刘海彬, 徐惠娟, 吕萍, 潘宁宁, 李双奇, 化学学报, 2012, 32(5), 674.)



[4] Ren, Q.-Y.; Wang, T.; Liu, J.-C.; He, H.-W. Chin. J. Org. Chem. 2005, 25(12), 1530 (in Chinese).



(任青云, 王涛, 刘建超, 贺红武, 有机化学, 2005, 25(12), 1530.)



[5] Liu, J.-H.; Liu, Y.; Jian, J.-Y.; Bao, X.-P. Chin. J. Org. Chem. 2013, 33(12), 370 (in Chinese).



(刘军虎, 刘勇, 蹇军友, 鲍小平, 有机化学, 2013, 33(12), 370.)



[6] Wang, Y.-K. M. S. Thesis, Dalian University of Technology, Dalian, 2012 (in Chinese).



(王永康, 硕士论文, 大连理工大学, 大连, 2012.)



[7] He, N.-Q.; Yan, S.-J.; Lin, J. Chemistry 2010, 314 (in Chinese).



(贺能琴, 严胜骄, 林军, 化学通报, 2010, 314.)



[8] Laddha, S.-S.; Bhatnagar, S.-P. Bioorg. Med. Chem. 2009, 17(9), 6796.



[9] Alafeefy, A.-M.; Kadi, A.-A.; Al-Deeb, O.-A. Eur. J. Med. Chem. 2010, 45(11), 4947.



[10] Mclaughlin, N.-P; Evans, P. J. Org. Chem. 2010, 75(2), 518.



[11] Manjula, S.-N.; Bharath, E.-N.; Divya, B. Int. J. Pharm. Biosci. 2011, 2(1), 780.



[12] Wang, Y.; Serradell, N.; Rosa, E. Drugs Future 2008, 33(6), 473.



[13] Selvam, T.-P.; Kumar, P.-V.; Kumar, A.-S. J. Pharm. Res. 2010, 3(7), 1637.



[14] Yang, S.-H; Khadka, D.-B.; Cho, S.-H. Bioorg. Med. Chem. 2011, 19(12), 968.



[15] Rusnak, D.-W.; Lackey, K.; Affleck, K. Mol. Cancer Ther. 2001, 1(2), 85.



[16] Graffner-Nordberg, M.; Kolmodin, K.; Aqvist, J.; Queener, F.-S.; Hallberg, A. Med. Chem. 2001, 44(15), 2391.



[17] Thurmond, J.; Butchbach, M.-E.-R.; Palomo, M.; Pease, B.; Rao, M.; Singh, J. J. Med. Chem. 2008, 51, 449.



[18] Zink, M.; Lanig, H.; Troschutz, R. Eur. J. Med. Chem. 2004, 39, 1079.



[19] Gangjee, A.; Adair, O.-O.; Pagley, M.; Queener, S.-F. J. Med. Chem. 2008, 51, 6195.



[20] Li, X.-M.; Hilgers, M.; Cunninghan, M.; Chen, Z.-Y.; Trzoss, M.; Zhang, J.-H.; Finn, J. Bioorg. Med. Lett. 2011, 21, 5171.



[21] Chao, B.; Tong, X.-K.; Tang, W.; Li, D.-W.; Garcia, J.-M.; Zuo, J.-P.; Hu, Y.-H. J. Med. Chem. 2012, 55, 3135.



[22] Gangjee, A.; Namjoshi, O.-A.; Raghavan, S.; Queener, S.-F.; Kisliuk, R.-L.; Cody, V. J. Med. Chem. 2013, 56, 4422.



[23] Mc Gowan, D.; Raboisson, P. J.-M. B.; Jonckers, T. H. M.; Last, S. J.; Embrechts, W.; Pieters, S. M. A. A. WO 2012/156498, 2012 [Chem. Abstr. 2012, 157, 734765].



[24] Yang, X.-B.; Liu, H.-X.; Fu, H.; Qiao, R.-Z.; Jiang, Y.-Y.; Zhao, Y.-F. Synlett 2010, 101.



[25] Khabnadideh, S.; Pez, D.; Musso, A.; Brun, R.; Perez, L.-M.-R.; Gilbert, H. Bioorg. Med. Chem. 2005, 13, 2637.

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