Citation: Li Yingjun, Li Jiyang, Peng Lin, Gao Lixin, Jin Kun, Sheng Li, Zhang Nan, Wang Siyuan, Li Jia. Synthesis and Cell Division Cycle 25B Phosphatase and Protein Ty-rosine Phosphatase 1B Inhibitory Activity Evaluation of Novel 3, 6-Disubstituted Triazolothiadiazole Derivatives[J]. Chinese Journal of Organic Chemistry, ;2017, 37(2): 485-495. doi: 10.6023/cjoc201607030 shu

Synthesis and Cell Division Cycle 25B Phosphatase and Protein Ty-rosine Phosphatase 1B Inhibitory Activity Evaluation of Novel 3, 6-Disubstituted Triazolothiadiazole Derivatives

Li Yingjun ^a,*,, ,
Li Jiyang ^a ,
Peng Lin ^a ,
Gao Lixin ^b ,
Jin Kun ^c ,
Sheng Li ^b ,
Zhang Nan ^a ,
Wang Siyuan ^a ,
Li Jia ^b,*,,

a.
College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029
b.
State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203
c.
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012

Corresponding author: Li Yingjun, chemlab.lnnu@163.com Li Jia, chemlab.lnnu@163.com
Received Date: 20 July 2016
Revised Date: 30 August 2016

Fund Project: the Natural Science Foundation of Liaoning Province 20102126

Figures(1)

A series of new 3, 6-disubstituted triazolothiadiazole derivatives 7a~7y containing benzimidazole and arylsulfonyl moities have been synthesized by o-phenylenediamine and chloroacetic acid as starting materials via multistep reactions.The structures of the intermediates 3, 4, 6 and the target compounds 7 were characterized by ¹H NMR, IR spectra and elemental analysis.All synthesized target compounds were screened for their inhibitory activity against cell division cycle 25B phosphatase (Cdc25B) and protein tyrosine phosphatase 1B (PTP1B).The results show that some of them display significant inhibitory activities against Cdc25B and PTP1B.Among them, compound 7d exhibits the highest inhibitory activity against Cdc25B [IC₅₀=(7.72±0.73)μg/mL]and 7u exhibits the highest inhibitory activity against PTP1B[IC₅₀=(3.31±0.57)μg/mL].It is noteworthy that compounds 7b, 7d, 7l, 7t and 7u show higher inhibitory activities against Cdc25B and PTP1B.They can be considered as potential Cdc25B and PTP1B inhibitors, and have great application prospects in the treatment of cancers and diabetes.
- triazolothiadiazole,
- benzimidazole,
- arylsulfonyl,
- synthesis,
- Cdc25B and PTP1B inhibitors
1. [1]
  Ramaprasad, G. C.; Kalluraya, B.; Sunil, K. B. Med. Chem. Res. 2014, 23, 3644. doi: 10.1007/s00044-014-0944-x
2. [2]
  Kamel, M. M.; Abdo, N. Y. M. Eur. J. Med. Chem. 2014, 86, 75. doi: 10.1016/j.ejmech.2014.08.047
3. [3]
  Ramaprasada, G. C.; Kalluraya, B.; Kumar, B. S.; Mallya, S. Pharma Chem. 2012, 49, 1026.
4. [4]
  Sunil, D.; Isloor, A. M.; Shetty, P.; Satyamoorthy, K.; Prasad, A. S. B. Med. Chem. Res. 2011, 20, 1074. doi: 10.1007/s00044-010-9436-9
5. [5]
  Badr, S. M. I.; Barwa, R. M. Bioorg. Med. Chem. 2011, 19, 4506. doi: 10.1016/j.bmc.2011.06.024
6. [6]
  Kotaiah, Y.; Nagaraju, K.; Harikrishna, N.; Rao, C. V.; Yamini, L.; Vijjulatha, M. Eur. J. Med. Chem. 2014, 75, 195. doi: 10.1016/j.ejmech.2014.01.006
7. [7]
  Hunashal, R. D.; Satyanarayana, D. Int. J. Pharma Bio. Sci. 2012, 3, 183.
8. [8]
  Prasad, D. J.; Ashok, M.; Karegoudar, P.; Poojary, B.; Holla, B. S. Kumari, N. S. Eur. J. Med. Chem. 2009, 44, 551. doi: 10.1016/j.ejmech.2008.03.025
9. [9]
  Akhter, M. W.; Hassan, M. Z.; Amir, M. Arabian J. Chem. 2014, 7, 955. doi: 10.1016/j.arabjc.2014.05.036
10. [10]
  Malladi, S.; Isloor, A. M.; Shetty, P.; Fun, H. K.; Telkar, S.; Mahmood, R.; Isloor, N. Med. Chem. Res. 2012, 21, 3272. doi: 10.1007/s00044-011-9865-0
11. [11]
  Husain, A.; Naseer, M. A. Med. Chem. Res. 2011, 20, 47. doi: 10.1007/s00044-009-9281-x
12. [12]
  Sujith, K. V.; Kalluraya, B.; Adhikari, A.; Vijayanarayana, K. Med. Chem. Res. 2012, 21, 543. doi: 10.1007/s00044-011-9569-5
13. [13]
  Khan, I.; Ibrar, A.; Zaib, S.; Ahmad, S.; Furtmann, N.; Hameed, S.; Simpson, J.; Bajorath, J.; Iqbal, J. Bioorg. Med. Chem. 2014, 22, 6163. doi: 10.1016/j.bmc.2014.08.026
14. [14]
  Khan, I.; Ibrar, A.; Abbas, N. Eur. J. Med. Chem. 2013, 63, 854. doi: 10.1016/j.ejmech.2013.01.060
15. [15]
  Yadav, G.; Ganguly, S. Eur. J. Med. Chem. 2015, 97, 419. doi: 10.1016/j.ejmech.2014.11.053
16. [16]
  Ranjith, P. K.; Rajeesh, P.; Haridas, K. R.; Susanta, N. K.; Row, T. N. G.; Rishikesan, R.; Kumari, N. S. Bioorg. Med. Chem. Lett. 2013, 23, 5228. doi: 10.1016/j.bmcl.2013.06.072
17. [17]
  Gupta, S. K.; Pancholi, S. S. Pharma Chem. 2011, 3, 274.
18. [18]
  Al-Mohammed, N. N.; Alias, Y.; Abdullah, Z.; Shakir, R. M.; Taha, E. M.; Hamid, A. A. Molecules 2013, 18, 11978. doi: 10.3390/molecules181011978
19. [19]
  Gijsen, H. J. M.; Cleyn, M. A. J. D.; Surkyn, M.; Van Lommen, G. R. E.; Verbist, B. M. P. Bioorg. Med. Chem. Lett. 2012, 22, 547. doi: 10.1016/j.bmcl.2011.10.091
20. [20]
  Travins, J. M.; Bernotas, R. C.; Kaufman, D. H.; Quinet, E.; Nambi, P.; Feingold, I.; Huselton, C.; Wilhelmsson, A.; Goos-Nilsson, A.; Wrobel, J. Bioorg. Med. Chem. Lett. 2010, 20, 526. doi: 10.1016/j.bmcl.2009.11.099
21. [21]
  Zhao, F.; Wang, J.; Ding, X.; Shu, S.-J.; Liu, H. Chin. J. Org. Chem. 2016, 36, 490 (in Chinese). doi: 10.6023/cjoc201510006
22. [22]
  Mei, W.-W.; Guo, Y.-W.; Li, J.; Cai, M.-Y.; Ma, W.-Q.; Gong, J.-X.; Wang, X.-D. Chin. J. Org. Chem. 2016, 36, 533 (in Chinese). doi: 10.6023/cjoc201509024
23. [23]
  Li, Y.-J.; Shi, X.-L.; Gao, L.-X.; Jin, K.; Sheng, L.; Wu, J.-H.; Peng L-N; Li, J. Chin. J. Org. Chem. 2015, 35, 191 (in Chinese). doi: 10.6023/cjoc201405032
24. [24]
  Li, Y.-J.; Yu, Y.; Jin, K.; Gao, L.-X.; Luo, T.-C.; Sheng, L.; Sao. X.; Li, J. Chin. J. Org. Chem. 2015, 35, 129 (in Chinese). doi: 10.6023/cjoc201405020
25. [25]
  Li, Y. J.; Yu, Y.; Jin, K.; Gao, L. X.; Luo, T. C.; Sheng, L.; Shao, X.; Li, J. Bioorg. Med. Chem. Lett. 2014, 24, 4125. doi: 10.1016/j.bmcl.2014.07.055
26. [26]
  Srinicas, K.; Dubey, P. K. Chem. Sci. Trans. 2014, 3, 375.
27. [27]
  Srinivas, K.; Dubey, P. K. Synth. Commun. 2011, 41, 1584. doi: 10.1080/00397911.2010.488310
28. [28]
  Dubey, P. K.; Reddy, P. V. V.; Srinivas, K. J. Heterocycl. Chem. 2010, 47, 1317. doi: 10.1002/jhet.v47:6
29. [29]
  Liu, S. L.; Dong, X. Y.; Wei, F.; Wang, X.; Lv, X.; Zhong, J.; Wu, L.; Quek, S. Y.; Chen, H. Ultrason. Sonochem. 2015, 23, 100. doi: 10.1016/j.ultsonch.2014.10.015
30. [30]
  Srinivas, K.; Dubey, P. K. Adv. Appl. Sci. Res. 2014, 5, 336.
31. [31]
  Darehkordi, A.; Ghazi, S. Arabian J. Chem. 2015, DOI: 10.1016/j.arabjc.2015.01.010. doi: 10.1016/j.arabjc.2015.01.010
32. [32]
  Li, Y.-J.; Liu, L.-J.; Jin, K.; Sun, S.-Q.; Xu, Y.-T. Acta Chim. Sinica 2010, 68, 1577 (in Chinese).
33. [33]
  Raban, M.; Chang, H.; Craine, L.; Hortelano, E. J. Org. Chem. 1985, 50, 2205. doi: 10.1021/jo00213a001
34. [34]
  Huang, W. G.; Jiang, Y. Y.; Li, Q.; Li, J.; Li, J. Y.; Lu, W.; Cai, J. C. Tetrahedron 2005, 61, 1863. doi: 10.1016/j.tet.2004.12.033
35. [35]
  Sun, L. P.; Shen, Q.; Piao, H. H.; Ma, W. P.; Gao, L. X.; Zhang, W.; Nan, F. J.; Li, J.; Piao, H. R. Eur. J. Med. Chem. 2011, 46, 3630. doi: 10.1016/j.ejmech.2011.05.027
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