Synthesis and Bioactivity Evaluation of Novel 1, 3, 5-Triazine-1H-pyrazole-triazol-ethiadiazole Derivatives

doi:10.6023/cjoc201704028

Chin. J. Org. Chem. ›› 2018, Vol. 38 ›› Issue (5): 1223-1232.DOI: 10.6023/cjoc201704028 Previous Articles Next Articles

Articles

新型1,3,5-三嗪-1H-吡唑-三唑并噻二唑衍生物的合成及活性评价

张成路, 李传银, 顾耀东, 孙晓娜, 唐杰, 王静, 李益政, 王华玉

辽宁师范大学化学化工学院大连 116029

收稿日期:2017-04-17 修回日期:2017-06-28 发布日期:2018-01-03
通讯作者: 张成路,E-mail:zhangchenglu@lnnu.edu.cn E-mail:zhangchenglu@lnnu.edu.cn
基金资助:
辽宁省教育厅科学技术研究（No.2009A426）资助项目.

Synthesis and Bioactivity Evaluation of Novel 1, 3, 5-Triazine-1H-pyrazole-triazol-ethiadiazole Derivatives

Zhang Chenglu, Li Chuanyin, Gu Yaodong, Sun Xiaona, Tang Jie, Wang Jing, Li Yizheng, Wang Huayu

College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029

Received:2017-04-17 Revised:2017-06-28 Published:2018-01-03
Contact: 10.6023/cjoc201704028 E-mail:zhangchenglu@lnnu.edu.cn
Supported by:
Project supported by the Science and Technology Research Program of Liaoning Provincial Department of Education (No. 2009A426).

1. Synthesis and Bioactivity Evaluation of Novel 1, 3, 5-Triazine-1H-pyrazole-triazol-ethiadiazole Derivatives.PDF(10414KB)

Abstract

Twenty-one novel 1, 3, 5-triazine-1H-pyrazole-triazolethiadiazole derivatives are designed and synthesized, in which the excellent pharmacological activitive pyrazole is used as key skeleton by connecting 1, 3, 5-triazine and introducing triazolothiadiazole. The structures of 21 target compounds are characterized by IR, ¹H NMR and HRMS. The inhibitory activities of 21 novel target products against Cdc25B and PTP1B are evaluated. As a result, most of the target compounds exhibit excellent inhibitory activities. In the Cdc25B inhibitory activity test, 14 target compounds have higher inhibitory activities than the positive reference sodium orthovanadate, and they are expected to be potential of Cdc25B inhibitors. In the PTP1B inhibitory activity test, 9 target compounds have better inhibitory activities than the control oleanolic acid, and they are expected to be potential of PTP1B inhibitors.

Key words: pyrazole, 1, 3, 5-triazine, triazolothiadiazole, Cdc25B inhibitor, PTP1B inhibitor

Cite this article

Zhang Chenglu, Li Chuanyin, Gu Yaodong, Sun Xiaona, Tang Jie, Wang Jing, Li Yizheng, Wang Huayu. Synthesis and Bioactivity Evaluation of Novel 1, 3, 5-Triazine-1H-pyrazole-triazol-ethiadiazole Derivatives[J]. Chin. J. Org. Chem., 2018, 38(5): 1223-1232.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] Salahuddin; Shaharyar, M.; Mazumder, A.; Ahsan, M. J. Arabian J. Chem. 2014, 7, 418.
[2] Yang, L.; Yan, J.-F.; Fan, L.; Chen, X.; Shangguan, R.-Y.; Wang, L.-F.; Yang, D.-C. Chin. J. Org. Chem. 2012, 32, 1908(in Chinese). (杨龙, 晏菊芳, 范莉, 陈欣, 上官瑞燕, 汪林发, 杨大成, 有机化学, 2012, 32, 1908.)
[3] (a) Neel, B. G.; Tonks, N. K. Curr. Opin. Cell Biol. 1997, 9, 193.
(b) Hunter, T. Cell 2000, 100, 113.
(c) Tonks, N. K.; Neel, B. G. Curr. Opin. Cell Biol. 2001, 13, 182.
[4] Lavecchia, A.; Giovanni, C. D.; Pesapane, A.; Montuori, N.; Ragno, P.; Martucci, N. M.; Masullo, M.; Vendittis, E. D.; Novellino, E. J. Med. Chem. 2012, 55, 4142.
[5] Zhang, Z.-Y. Annu. Rev. Pharmacol. Toxicol. 2002, 42, 209.
[6] 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.
[7] Li, Y.; Yu, Y.; Jin, K.; Gao, L.; Luo, T.; Sheng, L.; Shao, X.; Li, J. Bioorg. Med. Chem. Lett. 2014, 24, 4125.
[8] Owen, C.; Czopek, A.; Agouni, A.; Grant, L.; Judson, R.; Lees, E. K.; McIlroy, G. D.; Goransson, O.; Welch, A.; Bence, K. K.; Kahn, B. B.; Neel, B. G.; Mody, N.; Delibegovic, M. PloS One 2012, 7, 32693.
[9] Farag, A. M.; Mayhoub, A. S.; Barakat, S. E.; Bayomi, A. H. Bioorg. Med. Chem. 2008, 16, 881.
[10] Xia, Y.; Fan, C.-D.; Zhao, B.-X.; Zhao, J.; Shin, D.-S.; Miao, J.-Y. Eur. J. Med. Chem. 2008, 43, 2347.
[11] Xia, Y.; Dong, Z.-W.; Zhao, B.-X.; Ge, X.; Meng, N.; Shin, D.-S.; Miao, J.-Y. Bioorg. Med. Chem. 2007, 15, 6893.
[12] Rao, K. S.; Ramesh, P.; Trivedi, R.; Kantam, M. L. Tetrahedron Lett. 2016, 57, 1227.
[13] Silvestri, R.; Cascio, M. G.; Regina, G. L.; Piscitelli, F.; Lavecchia, A.; Brizzi, A.; Pasquini, S.; Botta, M.; Novellino, E.; Marzo, V. D.; Corelli, F. J. Med. Chem. 2008, 51, 1560.
[14] Wittman, M. D.; Carboni, J. M.; Yang, Z.; Lee, F. Y.; Antman, M.; Attar, R.; Balimane, P.; Chang, C.; Chen, C.; Discenza, L.; Frennesson, D.; Gottardis, M. M.; Greer, A.; Hurlburt, W.; Johnson, W.; Langley, D. R.; Li, A.; Li, J.; Liu, P.; Mastalerz, H.; Mathur, A.; Menard, K.; Patel, K.; Sack, J.; Sang, X.; Saulnier, M.; Smith, D.; Stefanski, K.; Trainor, G.; Velaparthi, U.; Zhang, G.; Zimmermann, K.; Vyas, D. M. J. Med. Chem. 2009, 52, 7360.
[15] (a) Kuo, G.-H.; DeAngelis, A.; Emanuel, S.; Wang, A.-H.; Zhang, Y.; Connolly, P. J.; Chen, X.; Gruninger, R. H.; Rugg, C.; Fuentes-Pesquera, A.; Middleton, S. A.; Jolliffe, L.; Murray, W. V. J. Med. Chem. 2005, 48, 4535.
(b) Robert, J.; Jarry, C. J. Med. Chem. 2003, 46, 4805.
[16] Misra, R. N.; Xiao, H.-Y.; Williams, D. K.; Kim, K. S.; Lu, S.; Keller, K. A.; Mulheron, J. G.; Batorsky, R.; Tokarski, J. S.; Sack, J. S.; Kimball, S. D.; Lee, F. Y.; Webster, K. R. Bioorg. Med. Chem. Lett. 2004, 14, 2973.
[17] Badr, S. M. I.; Barwa, R. M. Bioorg. Med. Chem. 2011, 19, 4506.
[18] Guzeldemirci, N. U.; Kucukbasmaci, O. Eur. J. Med. Chem. 2010, 45, 63.
[19] Taori, K.; Paul V. J.; Luesch, H. J. Am. Chem. Soc. 2008, 130, 1806.
[20] Pettit, G. R.; Singh, S. B.; Niven, M. L.; Hamel, E.; Schmidt, J. M. J. Nat. Prod. 1987, 50, 119.
[21] Pettit, G. R.; Singh, S. B.; Hamel, E.; Lin, C. M.; Alberts, D. S.; Garcia-Kendall, D. Experientia 1989, 45, 209.
[22] Romagnoli, R.; Baraldi, P. G.; Kimatrai, S. M.; Preti, D.; Aghazadeh, T. M.; Bassetto, M.; Brancale, A.; Hamel, E.; Castagliuolo, I.; Bortolozzi, R.; Basso, G.; Viola, G. J. Med. Chem. 2013, 56, 2606.
[23] Chaudhary, V.; Venghateri, J. B.; Dhaked, H. P.; Bhoyar, A. S.; Guchhait, S. K.; Panda, D. J. Med. Chem. 2016, 59, 3439.
[24] Madadi, N. R.; Penthala, N. R.; Howk, K.; Ketkar, A.; Eoff, R. L.; Borrelli, M. J.; Crooks, P. A. Eur. J. Med. Chem. 2015, 103, 123.
[25] Qin, Y.-J.; Li, Y. J.; Jiang, A.-Q.; Yang, M.-R.; Zhu, Q.-Z.; Dong, H.; Zhu, H. L. Eur. J. Med. Chem. 2015, 94, 447.
[26] Zhang, Q.; Peng, Y.; Wang, X.-I.; Keenan, S. M.; Arora, S.; Welsh, W. J. J. Med. Chem. 2007, 50, 749.
[27] Kamel, M. M.; Megally Abdo, N. Y. Eur. J. Med. Chem. 2014, 86, 75.
[28] Matsuno, T.; Kato, M.; Tsuchida, Y.; Takahashi, M.; Yaguchi, S.; Terada, S. Chem. Pharm. Bull. 1997, 45, 291.
[29] Zhu, W.; Liu, Y.; Zhao, Y.; Wang, H.; Tan, L.; Fan, W.; Gong, P. Arch. Pharm. 2012, 345, 812.
[30] Zhang, C.-L.; Sun, X.-N.; Li, C.-Y.; Cai, J.-Y.; Wang, J.; Li, Y.-Z.; Wang, H.-Y. Chem. J. Chin. Univ. 2017, 38, 1764(in Chinese). (张成路, 孙晓娜, 李传银, 蔡继颖, 王静, 李益政, 王华玉, 高等学校化学学报, 2017, 38, 1764.)
[31] Zhang, C.-L.; Tang, J.; Yin, L.-Y. Xi, H. Guo, Y.; Sun, L.-J. Chin. J. Org. Chem. 2016, 36, 358(in Chinese). (张成路, 唐杰, 殷立莹, 袭焕, 国阳, 孙丽杰, 有机化学, 2016, 36, 358.)
[32] Bijul, L. A.; Gupta, R. L. Indian J. Chem. 2010, 49B, 1235.
[33] Wang, X. M.S. Thesis, Liaoning Normal University, Dalian, 2015 (in Chinese). (王雪, 硕士论文, 辽宁师范大学, 大连, 2015.)
[34] Park, H.; Bahn, Y. J.; Jung, S-K.; Jeong, D.G.; Lee, S-H.; Seo, I.; Yoon, T-S.; Kim, S. J.; Ryu, S. E. J. Med. Chem. 2008, 51, 5533.
[35] Baskaran, S. K.; Goswami, N.; Selvaraj, S.; Muthusamy, V. S.; Lakshmi, B. S. J. Chem. Inf. Model. 2012, 52, 2004.

新型1,3,5-三嗪-1H-吡唑-三唑并噻二唑衍生物的合成及活性评价

Synthesis and Bioactivity Evaluation of Novel 1, 3, 5-Triazine-1H-pyrazole-triazol-ethiadiazole Derivatives

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Hu Ma, Danfeng Huang, Kehu Wang, Duoduo Tang, Yang Feng, Yuanyuan Reng, Junjiao Wang, Yulai Hu. Synthesis of 3-Trifluoromethylpyrazole Derivatives [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3257-3267.
[2]	Rongchao Lei, Wenjie Lan, Mengzhu Li, Bin Fu. A Convenient Approach to Benzosultam-Linked Pyrazole Compounds [J]. Chinese Journal of Organic Chemistry, 2023, 43(7): 2553-2560.
[3]	Yang Sun, Yang Wang, Zichan Zhang, Ye Qian, Guicheng Luo, Beibei Zhou, Lisha Miao, Yudie Chen, Hong Dai, Baolin Xu, Zhengguang Wu. Synthesis and Bioactivities of Novel Pyrazole Oxime Derivatives Containing 1,3,4-Oxadiazole Group [J]. Chinese Journal of Organic Chemistry, 2023, 43(4): 1584-1590.
[4]	Zichan Zhang, Yang Sun, Sheng Hua, Baolin Xu, Min Zhang, Qin Zhao, Dandan Zheng, Yang Wang, Jianfeng Ju, Yujun Shi, Hong Dai. Synthesis and Insecticidal Activity of Novel Pyrazole Amides Containing an Isoxazole Moiety [J]. Chinese Journal of Organic Chemistry, 2023, 43(4): 1435-1443.
[5]	Haojie Ma, Fengyuan Zhou, Jinlei Liu, Bo Han, Hua Yang, Yuqi Zhang, Jijiang Wang. Construction of Substituted N-Phenylpyrazoles via a Catalyst- Free and Additive-Free Intermolecular Cyclization Process [J]. Chinese Journal of Organic Chemistry, 2022, 42(6): 1843-1848.
[6]	Changkai Wang, Tengda Sun, Xuebo Zhang, Xinling Yang, Xingxing Lu, Huan Xu, Fasheng Shi, Li Zhang, Yun Ling. Design, Synthesis and Bioactivity of Novel Fluoropyrazole Hydrazides [J]. Chinese Journal of Organic Chemistry, 2022, 42(5): 1527-1536.
[7]	Wei Wang, Furan Wu, Yidan Ma, Dan Xu, Gong Xu. Study on Synthesis and Antifungal Activity of Novel Benzamides Containing Substituted Pyrazole Unit [J]. Chinese Journal of Organic Chemistry, 2022, 42(2): 607-618.
[8]	Siyu Mu, Hongxia Li, Zhilin Wu, Junmei Peng, Jinyang Chen, Weimin He. Electrocatalytic Three-Component Synthesis of 4-Bromopyrazoles from Acetylacetone, Hydrazine and Diethyl Bromomalonate [J]. Chinese Journal of Organic Chemistry, 2022, 42(12): 4292-4299.
[9]	Yunshu Liu, Guodong Zhao, Wenju Wu, Yunze Wang, Yanchao Yu, Jun You, Bo Liu. Study on Asymmetric Conjugate Cyanation of 3,5-Dimethyl-N-α,β-unsaturated Acylpyrazole Catalyzed by Magnesium-Bisoxazoline Complex [J]. Chinese Journal of Organic Chemistry, 2022, 42(1): 208-217.
[10]	Haojie Ma, Xiaoqiang Zhou, Bo Han, Ran Li, Xueyan Hou, Xingyue Ji, Yuqi Zhang, Guosheng Huang, Jijiang Wang. A Catalyst-Free One-Pot Protocol for the Construction of Substituted Sulfonyl Pyrazoles [J]. Chinese Journal of Organic Chemistry, 2021, 41(9): 3710-3716.
[11]	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.
[12]	Jiaoli Ma, Penghu Guo, Jing Li, Xincheng Liao, Huicheng Cheng. Synthesis and Antitumor Activity of Amide Derivatives Containing 1,3,4-Thiadiazole and Pyrazole Moieties [J]. Chinese Journal of Organic Chemistry, 2021, 41(8): 3214-3222.
[13]	Guanglei Li, Haifeng Huang, Jun Yang, Hongzhen Duan. Progress in the Synthesis of Energetic Salts Based on Pyrazole [J]. Chinese Journal of Organic Chemistry, 2021, 41(4): 1466-1488.
[14]	Wenqing Zhu, Tingyi Xu, Wenyong Han. Recent Progress in the Application of Difluoromethyl Diazomethane as Fluorine-Containing Building Block [J]. Chinese Journal of Organic Chemistry, 2021, 41(4): 1275-1287.
[15]	Haojie Ma, Zhou Sun, Jinlei Liu, Xia Zhang, Huali Cui, Yuqi Zhang, Jijiang Wang. CBr₄-Mediated Intermolecular Cyclization Reaction: Efficient Synthesis of Substituted N-Acylpyrazoles [J]. Chinese Journal of Organic Chemistry, 2021, 41(11): 4353-4360.