Citation: Fu Yang, Sheng Li, Gao Lixin, Li Jia, Sun Liangpeng. Synthesis and PTP1B Inhibitory Activity of Novel Chalcone Derivatives Bearing 1^H-Benzo[d]imidazol or 1H-Benzo[d][1,2,3]triazol Moieties[J]. Chinese Journal of Organic Chemistry, ;2019, 39(4): 1029-1036. doi: 10.6023/cjoc201811030 shu

Synthesis and PTP1B Inhibitory Activity of Novel Chalcone Derivatives Bearing 1^H-Benzo[d]imidazol or 1H-Benzo[d][1,2,3]triazol Moieties

Fu Yang ^a,b ,
Sheng Li ^c ,
Gao Lixin ^c ,
Li Jia ^c,, ,
Sun Liangpeng ^a,,

a.
Medical College, Yanbian University, Yanji 133002
b.
Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130000
c.
National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203

Corresponding author: Li Jia, jli@simm.ac.cn Sun Liangpeng, lpsun@ybu.edu.cn
Received Date: 26 November 2018
Revised Date: 21 December 2018
Available Online: 8 April 2019
Fund Project: Project supported by the National Natural Science Foundation of China (Nos. 81460524, 81773779) and the Scientific Research Fund Project of Education Department of Jilin Province (No. 2015-50)the National Natural Science Foundation of China 81460524the National Natural Science Foundation of China 81773779the Scientific Research Fund Project of Education Department of Jilin Province 2015-50

Figures(3)

Protein tyrosine phosphatase 1B (PTP1B) inhibitor has recently been identified as new candidate drug for type Ⅱ diabetes and obesity due to it is a negative regulator of the insulin and leptin-signaling pathway. In order to find new nonphosphonate-based pTyr mimetics, a series of novel chalcone derivatives bearing 1H-benzo[d]imidazol or 1H-benzo[d] [1,2,3]-triazol moieties were designed, synthesized, and evaluated for their PTP1B inhibitory activities. The results demonstrated that all compounds presented potent inhibitory activities against PTP1B, among which 2-(1H-benzo[d] [1,2,3]triazol-1-yl)-N'-(4-(3-(naphthalen-2-yl)-3-oxoprop-1-en-1-yl)benzylidene)acetohydrazide (10i) exhibited the best potency with IC₅₀ value of (2.98±0.04) μmol·L^-1. Importantly, 2-(1H-benzo[d] [1,2,3]triazol-1-yl)-N'-(4-(3-oxo-3-(p-tolyl)prop-1-en-1-yl)benzylidene)-acetohydrazide (10h) showed no significant inhibition on T-cell protein tyrosine phosphatase (TCPTP) at the concentration of 20 μg/mL, suggesting the highly selectivity of this agent toward PTP1B.
- PTP1B inhibitor,
- 1H-benzo[d]imidazol,
- 1H-benzo[d] [1, 2, 3]triazol,
- chalcone
1. [1]
  (a) Hunter, T. Cell 2000, 100, 113.
  (b) Zhang, Z. Y.; Lee, S. Y. Expert Opin. Invest. Drugs 2003, 12, 223.
  (c) Tonks, N. K. Cell 2005, 121, 667.
  (d) Zhang, Z. Y. Biochim. Biophys. Acta 2005, 1754, 100.
2. [2]
  (a) Bialy, L.; Waldmann, H. Angew. Chem., Int. Ed. 2005, 44, 3814.
  (b) Yip, S. C.; Saha, S.; Chernoff, J. Trends Biochem. Sci. 2010, 35, 442.
3. [3]
  (a) Lee, S.; Wang, Q. Med. Res. Rev. 2007, 27, 553.
  (b) Combs, A. P. J. Med. Chem. 2010, 53, 2333.
  (c) Barr, A. J. Future Med. Chem. 2010, 2, 1563.
  (d) Tamrakar, A. K.; Maurya, C. K.; Rai, A. K. Expert Opin. Ther. Pat. 2014, 24, 1.
4. [4]
  Combs, A. P.; Zhu, W.; Crawley, M. L.; Glass, B.; Polam, P.; Sparks, R. B.; Modi, D.; Takvorian, A.; McLaughlin, E.; Yue, E. W.; Wasserman, Z.; Bower, M.; Wei, M.; Rupar, M.; Ala, P. J.; Reid, B. M.; Ellis, D.; Gonneville, L.; Emm, T.; Taylor, N.; Yeleswaram, S.; Li, Y.; Wynn, R.; Burn, T. C.; Hollis, G.; Liu, P. C. C.; Metcalf, B. J. Med. Chem. 2006, 49, 3774. doi: 10.1021/jm0600904
5. [5]
  Sparks, R. B.; Polam, P.; Zhu, W.; Crawley, M. L.; Takvorian, A.; McLaughlin, E.; Wei, M.; Ala, P. J.; Gonneville, L.; Taylor, N.; Li, Y.; Wynn, R.; Burn, T. C.; Liu, P. C. C.; Combs, A. P. Bioorg. Med. Chem. Lett. 2007, 17, 736. doi: 10.1016/j.bmcl.2006.10.079
6. [6]
  Douty, B.; Wayland, B.; Ala, P. J.; Bower, M. J.; Pruitt, J.; Bostrom, L.; Wei, M.; Klabe, R.; Gonneville, L.; Wynn, R.; Burn, T. C.; Liu, P. C. C.; Combs, A. P.; Yue, E. W. Bioorg. Med. Chem. Lett. 2008, 18, 66. doi: 10.1016/j.bmcl.2007.11.012
7. [7]
  Black, E.; Breed, J.; Breeze, A. L.; Embrey, K.; Garcia, R.; Gero, T. W.; Godfrey, L.; Kenny, P. W.; Morley, A. D.; Minshull, C. A. Bioorg. Med. Chem. Lett. 2005, 15, 2503. doi: 10.1016/j.bmcl.2005.03.068
8. [8]
  Du, Y.; Ling, H.; Zhang, M.; Shen, J.; Li, Q. Bioorg. Med. Chem. 2015, 23, 4891. doi: 10.1016/j.bmc.2015.05.032
9. [9]
  Liu, P.; Du, Y.; Song, L.; Shen, J.; Li, Q. Eur. J. Med. Chem. 2016, 118, 27. doi: 10.1016/j.ejmech.2016.04.014
10. [10]
  Maccari, R.; Paoli, P.; Ottanà, R.; Jacomelli, M.; Ciurleo, R.; Manao, G.; Steindl, T.; Langer, T.; Vigorita, M. G.; Camici, G. Bioorg. Med. Chem. 2007, 15, 5137. doi: 10.1016/j.bmc.2007.05.027
11. [11]
  Sun, L. P.; Jiang, Z.; Gao, L. X.; Li, Y. Z.; Sun, L. Y.; Li, J.; Piao, H. R. Chin. J. Org. Chem. 2012, 32, 2108 (in Chinese).
12. [12]
  Sun, L. P.; Jiang, Z.; Gao, L. X.; Liu, X. F.; Quan, Y. C.; Zheng, G. H.; Li, J.; Piao, H. R. Chin. J. Org. Chem. 2013, 33, 1496 (in Chinese).
13. [13]
  Chen, Z. H.; Zheng, C. J.; Sun, L. P.; Piao, H. R. Eur. J. Med. Chem. 2010, 45, 5739. doi: 10.1016/j.ejmech.2010.09.031
14. [14]
  Jin, X.; Zheng, C. J.; Song, M. X.; Wu, Y.; Sun, L. P.; Li, Y. J.; Yu, L. J.; Piao, H. R. Eur. J. Med. Chem. 2012, 56, 203. doi: 10.1016/j.ejmech.2012.08.026
15. [15]
  (a) Yang, Y. H.; Cheng, M. S.; Wang, Q. H.; Nie, H.; Liao, N.; Wang, J.; Chen, H. Eur. J. Med. Chem. 2009, 44, 1808.
  (b) Rajasekaran, A.; Murugesan, S.; AnandaRajagopal, K. Arch. Pharm. Res. 2006, 29, 535.
  (c) Shingalapur, R. V.; Hosamani, K. M.; Keri, R. S.; Hugar, M. H. Eur. J. Med. Chem. 2010, 45, 1753.
  (d) Achar, K. C.; Hosamani, K. M.; Seetharamareddy, H. R. Eur. J. Med. Chem. 2010, 45, 2048.
16. [16]
  (a) Kuş, C.; Ayhan-Kilcigil, G.; Ozbey, S.; Kaynak, F. B.; Kaya, M.; Coban, T.; Can-Eke, B. Bioorg. Med. Chem. 2008, 16, 4294.
  (b) Mavrova; A. T.; Wesselinova, D.; Tsenov, Y. A.; Denkova, P. Eur. J. Med. Chem. 2009, 44, 63.
  (c) Kumar, H.; Javed, S. A.; Khan, S. A.; Amir, M. Eur. J. Med. Chem. 2008, 43, 2688.
  (d) Khan, I.; Ali, S.; Hameed, S.; Rama, N. H.; Hussain, M. T.; Wadood, A.; Uddin, R.; Ul-Haq, Z.; Khan, A.; Ali, S.; Choudhary, M. I. Eur. J. Med. Chem. 2010, 45, 5200.
17. [17]
  (a) Shi, L.; Yu, H. P.; Zhou, Y. Y.; Du, J. Q.; Shen, Q.; Li, J. Y.; Li, J. Acta Pharmacol. Sin. 2008, 29, 278.
  (b) Zhang, W.; Hong, D.; Zhou, Y. Y.; Zhang, Y. N.; Shen, Q.; Li, J. Y.; Hu, L. H.; Li, J. Biochim. Biophys. Acta 2006, 1760, 1505.
18. [18]
  (a) Qiu, W. W.; Shen, Q.; Yang, F.; Wang, B.; Zou, H.; Li, J. Y.; Li, J.; Tang, J. Bioorg. Med. Chem. Lett. 2009, 19, 6618.
  (b) Qian, S.; Li, H. J.; Chen, Y.; Zhang, W. Y.; Yang, S. Y.; Wu, Y.; J. Nat. Prod. 2010, 73, 1743.
19. [19]
  (a) Chung, Y. H.; Jang, S. C.; Kim, S. J.; Sung, N. D. J. Appl. Biol. Chem. 2007, 50, 52.
  (b) Lin, Z. H.; Zhang, Y.; Zhang, Y. N.; Shen, H.; Hu, L. H.; Jiang, H. L.; Shen, X. Biochem. Pharmacol. 2008, 76, 1251.
  (c) Zhang, Y. N.; Zhang, W.; Hong, D.; Shi, L.; Shen, Q.; Li, J. Y.; Li J.; Hu, L. H. Bioorg. Med. Chem. 2008, 16, 8697.
20. [20]
  Szczepankiewicz, B. G.; Liu, G.; Hajduk, P. J.; Abad-Zapatero, C.; Pei, Z. H.; Xin, Z. L.; Lubben, T. H.; Trevillyan, J. M.; Stashko, M. A.; Ballaron, S. J.; Liang, H.; Huang, F.; Hutchins, C. W.; Stephen, W. F.; Jirousek, M. R. J. Am. Chem. Soc. 2003, 125, 4087. doi: 10.1021/ja0296733
21. [21]
  Chen, J.; Gao, L. X.; Gong, J. X.; Jiang, C. S.; Yao, L. G.; Li, J. Y.; Li, J.; Xiao. W.; Guo, Y. W. Bioorg. Med. Chem. Lett. 2015, 25, 2211. doi: 10.1016/j.bmcl.2015.03.060
22. [22]
  http://www.rcsb.org.
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沈阳化工大学材料科学与工程学院沈阳 110142

Synthesis and PTP1B Inhibitory Activity of Novel Chalcone Derivatives Bearing 1H-Benzo[d]imidazol or 1H-Benzo[d][1,2,3]triazol Moieties

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通讯作者: 陈斌, bchen63@163.com

Synthesis and PTP1B Inhibitory Activity of Novel Chalcone Derivatives Bearing 1^H-Benzo[d]imidazol or 1H-Benzo[d][1,2,3]triazol Moieties