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

doi:10.6023/cjoc201607030

Chin. J. Org. Chem. ›› 2017, Vol. 37 ›› Issue (2): 485-495.DOI: 10.6023/cjoc201607030 Previous Articles Next Articles

ARTICLE

新型3,6-二取代三唑并噻二唑衍生物的合成及细胞分裂周期25B磷酸酶和蛋白酪氨酸磷酸酶1B抑制活性研究

李英俊^a, 李继阳^a, 彭立娜^a, 高立信^b, 靳焜^c, 盛丽^b, 张楠^a, 王思远^a, 李佳^b

a 辽宁师范大学化学化工学院大连 116029;
b 中国科学院上海药物研究所国家新药筛选中心药物研究国家重点实验室上海 201203;
c 大连理工大学精细化工国家重点实验室大连 116012

收稿日期:2016-07-20 修回日期:2016-08-30 发布日期:2016-10-08
通讯作者: 李英俊, 李佳 E-mail:chemlab.lnnu@163.com
基金资助:
辽宁省自然科学基金（No.20102126）资助项目.

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

Received:2016-07-20 Revised:2016-08-30 Published:2016-10-08
Supported by:
Project supported by the Natural Science Foundation of Liaoning Province (No. 20102126).

1. Synthesis and Cell Division Cycle 25B Phosphatase and Protein Ty-rosine Phosphatase 1B Inhibitory Activity Evaluation of Novel 3,6-Disubstituted Triazolothiadiazole Derivatives.PDF(12266KB)

Abstract

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.

Key words: triazolothiadiazole, benzimidazole, arylsulfonyl, synthesis, Cdc25B and PTP1B inhibitors

Cite this article

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]. Chin. J. Org. Chem., 2017, 37(2): 485-495.

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[1] Ramaprasad, G. C.; Kalluraya, B.; Sunil, K. B. Med. Chem. Res. 2014, 23, 3644.
[2] Kamel, M. M.; Abdo, N. Y. M. Eur. J. Med. Chem. 2014, 86, 75.
[3] Ramaprasada, G. C.; Kalluraya, B.; Kumar, B. S.; Mallya, S. Pharma Chem. 2012, 49, 1026.
[4] Sunil, D.; Isloor, A. M.; Shetty, P.; Satyamoorthy, K.; Prasad, A. S. B. Med. Chem. Res. 2011, 20, 1074.
[5] Badr, S. M. I.; Barwa, R. M. Bioorg. Med. Chem. 2011, 19, 4506.
[6] Kotaiah, Y.; Nagaraju, K.; Harikrishna, N.; Rao, C. V.; Yamini, L.; Vijjulatha, M. Eur. J. Med. Chem. 2014, 75, 195.
[7] Hunashal, R. D.; Satyanarayana, D. Int. J. Pharma Bio. Sci. 2012, 3, 183.
[8] Prasad, D. J.; Ashok, M.; Karegoudar, P.; Poojary, B.; Holla, B. S. Kumari, N. S. Eur. J. Med. Chem. 2009, 44, 551.
[9] Akhter, M. W.; Hassan, M. Z.; Amir, M. Arabian J. Chem. 2014, 7, 955.
[10] Malladi, S.; Isloor, A. M.; Shetty, P.; Fun, H. K.; Telkar, S.; Mahmood, R.; Isloor, N. Med. Chem. Res. 2012, 21, 3272.
[11] Husain, A.; Naseer, M. A. Med. Chem. Res. 2011, 20, 47.
[12] Sujith, K. V.; Kalluraya, B.; Adhikari, A.; Vijayanarayana, K. Med. Chem. Res. 2012, 21, 543.
[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.
[14] Khan, I.; Ibrar, A.; Abbas, N. Eur. J. Med. Chem. 2013, 63, 854.
[15] Yadav, G.; Ganguly, S. Eur. J. Med. Chem. 2015, 97, 419.
[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.
[17] Gupta, S. K.; Pancholi, S. S. Pharma Chem. 2011, 3, 274.
[18] Al-Mohammed, N. N.; Alias, Y.; Abdullah, Z.; Shakir, R. M.; Taha, E. M.; Hamid, A. A. Molecules 2013, 18, 11978.
[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.
[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.
[21] Zhao, F.; Wang, J.; Ding, X.; Shu, S.-J.; Liu, H. Chin. J. Org. Chem. 2016, 36, 490 (in Chinese).(赵飞, 王江, 丁晓, 舒双杰, 柳红, 有机化学, 2016, 36, 490.)
[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).(梅雯雯, 郭跃伟, 李佳, 蔡妹艺, 马文泉, 龚景旭, 王学东, 有机化学, 2016, 36, 533.)
[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).(李英俊, 史相玲, 高立信, 靳焜, 盛丽, 吴疆红, 彭丽娜, 李佳, 有机化学, 2015, 35, 191.)
[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).(李英俊, 于洋, 靳焜, 高立信, 罗潼川, 盛丽, 邵昕, 李佳, 有机化学, 2015, 35, 129.)
[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.
[26] Srinicas, K.; Dubey, P. K. Chem. Sci. Trans. 2014, 3, 375.
[27] Srinivas, K.; Dubey, P. K. Synth. Commun. 2011, 41, 1584.
[28] Dubey, P. K.; Reddy, P. V. V.; Srinivas, K. J. Heterocycl. Chem. 2010, 47, 1317.
[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.
[30] Srinivas, K.; Dubey, P. K. Adv. Appl. Sci. Res. 2014, 5, 336.
[31] Darehkordi, A.; Ghazi, S. Arabian J. Chem. 2015, DOI: 10.1016/j.arabjc.2015.01.010.
[32] Li, Y.-J.; Liu, L.-J.; Jin, K.; Sun, S.-Q.; Xu, Y.-T. Acta Chim. Sinica 2010, 68, 1577 (in Chinese).(李英俊, 刘丽军, 靳焜, 孙淑琴, 许永廷, 化学学报, 2010, 68, 1577.)
[33] Raban, M.; Chang, H.; Craine, L.; Hortelano, E. J. Org. Chem. 1985, 50, 2205.
[34] Huang, W. G.; Jiang, Y. Y.; Li, Q.; Li, J.; Li, J. Y.; Lu, W.; Cai, J. C. Tetrahedron 2005, 61, 1863.
[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.

新型3,6-二取代三唑并噻二唑衍生物的合成及细胞分裂周期25B磷酸酶和蛋白酪氨酸磷酸酶1B抑制活性研究

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

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