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

doi:10.6023/cjoc201811030

Chin. J. Org. Chem. ›› 2019, Vol. 39 ›› Issue (4): 1029-1036.DOI: 10.6023/cjoc201811030 Previous Articles Next Articles

Articles

含1H-苯并[d]咪唑或1H-苯并[d][1,2,3]三唑结构的新型查尔酮衍生物的合成及PTP1B抑制活性研究

付洋^a,b, 盛丽^c, 高立信^c, 李佳^c, 孙良鹏^a

a 延边大学医学院延吉 133002;
b 中国科学院长春应用化学研究所长春 130000;
c 中国科学院上海药物研究所国家新药筛选中心上海 201203

收稿日期:2018-11-26 修回日期:2018-12-21 发布日期:2019-01-10
通讯作者: 李佳, 孙良鹏 E-mail:lpsun@ybu.edu.cn;jli@simm.ac.cn
基金资助:
国家自然科学基金（Nos.81460524，81773779）和吉林省教育厅"十二五"科学技术研究项目（No.2015-50）资助项目.

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

Received:2018-11-26 Revised:2018-12-21 Published:2019-01-10
Contact: 10.6023/cjoc201811030 E-mail:lpsun@ybu.edu.cn;jli@simm.ac.cn
Supported by:
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).

1. Synthesis and PTP1B Inhibitory Activity of Novel Chalcone Derivatives Bearing 1^H-Benzo[d]imidazol or 1H-Benzo[d][1,2,3]triazol Moieties.PDF(6557KB)

Abstract

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.

Key words: PTP1B inhibitor, 1H-benzo[d]imidazol, 1H-benzo[d] [1,2,3]triazol, chalcone

Cite this article

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]. Chin. J. Org. Chem., 2019, 39(4): 1029-1036.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[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] (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] (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] 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.
[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.
[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.
[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.
[8] Du, Y.; Ling, H.; Zhang, M.; Shen, J.; Li, Q. Bioorg. Med. Chem. 2015, 23, 4891.
[9] Liu, P.; Du, Y.; Song, L.; Shen, J.; Li, Q. Eur. J. Med. Chem. 2016, 118, 27.
[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.
[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).(孙良鹏, 姜哲, 高立信, 李英哲, 孙立云, 李佳, 朴虎日, 有机化学, 2012, 32, 2108.)
[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).(孙良鹏, 姜哲, 高立信, 刘晓芳, 全迎春, 郑光浩, 李佳, 朴虎日, 有机化学, 2013, 33, 1496.)
[13] Chen, Z. H.; Zheng, C. J.; Sun, L. P.; Piao, H. R. Eur. J. Med. Chem. 2010, 45, 5739.
[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.
[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] (a) Kus, 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] (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] (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] (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] 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.
[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.
[22] http://www.rcsb.org.

含1H-苯并[d]咪唑或1H-苯并[d][1,2,3]三唑结构的新型查尔酮衍生物的合成及PTP1B抑制活性研究

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

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Ran Zhou, Chunmei Yuan, Tao Zhang, Piao Mao, Yi Liu, Kaini Meng, Hui Xin, Wei Xue. Design, Synthesis and Bioactivity of Chalcone Derivative Containing Quinazolinone [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3196-3209.
[2]	Duoduo Tang, Danfeng Huang, Kehu Wang, Hu Ma, Yang Feng, Yuanyuan Ren, Junjiao Wang, Yulai Hu. Tin Powder-Promoted Synthesis of 1,3-Disubstituted 1,3-Dihydroisobenzofuran Compounds [J]. Chinese Journal of Organic Chemistry, 2023, 43(12): 4227-4238.
[3]	Yingjun Li, Ledi Lin, Jihong Liu, Lixin Gao, Li Sheng, Kun Jin, Xuejie Liu, Hongjing Yang, Jia Li. Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel N-Acylhydrazone Derivatives Containing Carbazole and Aromatic Ring/Aromatic Fused Heterocycle [J]. Chinese Journal of Organic Chemistry, 2021, 41(9): 3593-3607.
[4]	Xin Liu, Runmei Xu, Lin Wang, Yaxue Liu, Zhihao Chen, Wei Qin, Yushun Tian. Synthesis and Evaluation in vitro of Dihydrothiophenopyridine-Chalcone Derivatives as Anticancer Activity Agents [J]. Chinese Journal of Organic Chemistry, 2021, 41(9): 3550-3559.
[5]	Xiao Tingting, Cheng Wei, Qian Weifeng, Zhang Tingting, Lu Tong, Gao Yang, Tang Xiaorong. Synthesis of Chalcone Derivatives and Studies on Their Inhibitory Activity and Molecular Docking [J]. Chinese Journal of Organic Chemistry, 2020, 40(6): 1704-1715.
[6]	Li Sha, Xu Jiayu, Luo Xian, Yang Wenhan, Yao Changsheng. Efficient N-Heterocyclic Carbene-Catalyzed Cascade Synthesis of Functionalized Naphthopyranone [J]. Chinese Journal of Organic Chemistry, 2020, 40(2): 470-477.
[7]	Li Yingjun, Liu Xuejie, Liu Jihong, Gao Lixin, Jin Kun, Sheng Li, Yang Hongjing, Lin Ledi, Li Jia. Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel Carbazole-Based Carbohydrazone Derivatives [J]. Chinese Journal of Organic Chemistry, 2020, 40(2): 478-488.
[8]	Fu Lin, Sun Bingxia, Zhai Jiadai, Li Yuanyuan, Liu Xinqiang, Song Ru, Shi Guanqun, Li Jiaona, Song Yuanxia, Sang Feng. Synthesis and Antibacterial Activity Study of Natural 5'-Hydroxyisoprenyl Chalcones [J]. Chinese Journal of Organic Chemistry, 2020, 40(1): 201-208.
[9]	Li Yingjun, Yang Kaidong, Jin Kun, Gao Lixin, Sheng Li, Liu Xuejie, Yang Hongjing, Lin Ledi, Li Jia. Synthesis and Cdc25B/PTP1B Inhibitory Activity Evaluation of Novel Carbazole-Based Mono-/Bis-thiocarbohydrazone Derivatives [J]. Chinese Journal of Organic Chemistry, 2020, 40(1): 162-174.
[10]	Li Yongkun, Tang Yanling, Li Minxin, Yang Xiaobi, Gao Hui, Mao Zewei. Synthesis and Antibacterial Activity of Thienyl Chalcone Derivatives Bearing Piperazine Moiety [J]. Chinese Journal of Organic Chemistry, 2020, 40(1): 108-114.
[11]	Li Yingjun, Zhao Yue, Jin Kun, Gao Lixin, Sheng Li, Liu Xuejie, Yang Hongjing, Lin Ledi, Li Jia. Synthesis and PTP1B/TCPTP Inhibitory Activity Evaluation of Novel 2,5-Disubstituted-1,3,4-thiadiazolamide Derivatives Containing Carbazole/Benzimidazole Moity [J]. Chin. J. Org. Chem., 2019, 39(9): 2599-2608.
[12]	Zhu Li, Yang Yanqiu, Gao Peipei, An Xue, Sun Yingying, Sun Xiaowen, Hou Yue, Shan Lihong. Synthesis and Anti-inflammatory Activity Evaluation of 2-Dehydroepiandrosterone Benzene Methyl Derivatives [J]. Chin. J. Org. Chem., 2019, 39(9): 2625-2631.
[13]	Gu Yingchun, Huang You. Tributylphosphine Catalyzed Cross Rauhut-Currier Reaction of Chalcones and Acrylates [J]. Chin. J. Org. Chem., 2019, 39(8): 2251-2256.
[14]	Shi shuzhi, Liang zhipeng, Sun jiangyong, Shi Yujun. Novel Ester Derivatives of Lithocolic Acid-3-oxime and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B [J]. Chin. J. Org. Chem., 2019, 39(7): 2106-2116.
[15]	Sheng Qiwei, Zhao Wanqiu, Zeng Ming, Xie Zhongpao, Xia Yaping, Cui Dongmei. Synthesis and Evaluation of Chalcone Derivatives as Novel Anticancer Agents [J]. Chin. J. Org. Chem., 2019, 39(3): 703-708.