Citation: Li Jiali, Hu Tao, Zhang Hongjian, Gong Guohua, Quan Zhe-Shan. Synthesis and Anticonvulsant Activity Evaluation of 6-Substituted-pyrido[3, 2-e] [1, 2, 4]triazolo[4, 3-a]pyrazine Derivatives[J]. Chinese Journal of Organic Chemistry, ;2018, 38(7): 1673-1679. doi: 10.6023/cjoc201712026 shu

Synthesis and Anticonvulsant Activity Evaluation of 6-Substituted-pyrido[3, 2-e] [1, 2, 4]triazolo[4, 3-a]pyrazine Derivatives

Li Jiali ^a ,
Hu Tao ^a ,
Zhang Hongjian ^a ,
Gong Guohua ^b,c,, ,
Quan Zhe-Shan ^a,,

a.
College of Pharmacy, Yanbian University, Yanji 133002
b.
Inner Mongolia Autonomous Region Key laboratory of Mongolian Medicine Pharmacology for Cardio-cerebral Vascular System, Tongliao 028000
c.
Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao 028000

Corresponding author: Gong Guohua, gongguohua0211@163.com Quan Zhe-Shan, zsquan@ybu.edu.cn
Received Date: 18 December 2017
Revised Date: 2 February 2018
Available Online: 12 July 2018
Fund Project: the National Natural Scicence Foundation of China 21662036the National Natural Scicence Foundation of China 81660837Project supported by the National Natural Scicence Foundation of China (Nos. 21662036, 81660837)

Figures(2)

In this paper, a series of 6-substituted-pyrido[3, 2-e] [1, 2, 4]triazolo[4, 3-a]pyrazine derivatives have been synthesized. Their anticonvulsant activity and neurotoxicity in mice were evaluated by maximal electroshock (MES) and rotarod test, respectively. The structures were confirmed by ¹H NMR, ¹³C NMR, MS and HRMS. The experimental results show that 6-phenoxypyrido[3, 2-e] [1, 2, 4]triazolo[4, 3-a]pyrazine (5g) was safer than the reference drug, carbamazepine, with ED₅₀value of 93.9 mg·kg^-1and protective index (PI) value of 24.3, which was a potential anti-epilepsy candidate compound.
- pyrido[2, 3-b]pyrazine,
- triazole,
- synthesis,
- anticonvulsant,
- the maximal electroshock
1. [1]
  Sirven, J. I.; Noe, K.; Hoerth, M.; Drazkowski, J. Mayo Clin. Proc. 2012, 87, 879. doi: 10.1016/j.mayocp.2012.05.019
2. [2]
  Wang, P.; Ren, R. N. Int. J. Intern. Med. 2007, 34(2), 91 (in Chinese).
3. [3]
  Genc, M.; Karagoz, G. Z.; Tekin, S.; Sandal, S.; Sirajuddin, M.; Hadda, T. B.; Sekerci, M. Acta Chim. Slov. 2016, 63(4), 726.
4. [4]
  Milošev, M. Z.; Jakovljević, K.; Joksović, M. D.; Stanojković, T.; Matić, I. Z.; Perović, M.; Tešić, V.; Kanazir, S.; Mladenović, M.; Rodić, M. V.; Leovac, V. M.; Trifunović, S.; Marković, V. Chem. Biol. Drug Des. 2017, 89(6), 943. doi: 10.1111/cbdd.2017.89.issue-6
5. [5]
  Mekheimer, R. A.; Sayed, A. A.; Ahmed, E. A.; Sadek, K. U. Arch. Pharm. (Weinheim) 2015, 348(9), 650. doi: 10.1002/ardp.v348.9
6. [6]
  El-Sayed, N. N.; Abdelaziz, M. A.; Wardakhan, W. W. Mohareb, R. M. Steroids 2016, 107, 98. doi: 10.1016/j.steroids.2015.12.023
7. [7]
  Wittine, K.; Stipković, B. M.; Makuc, D.; Plavec, J.; Kraljević, P. S.; Sedić, M.; Pavelić, K.; Leyssen, P.; Neyts, J.; Balzarini, J.; Mintas, M. Bioorg. Med. Chem. 2012, 20(11), 3675. doi: 10.1016/j.bmc.2012.01.054
8. [8]
  Benci, K.; Suhina, T.; Mandić, L.; Pavelić, S. K.; Paravić, A. T.; Pavelić, K.; Balzarini, J.; Wittine, K.; Mintas, M. Antivir. Chem. Chemother. 2011, 21(6), 221. doi: 10.3851/IMP1762
9. [9]
  Akbari, D. K.; Nasuhi, P. F.; Hatami, N. M. Iran. J. Pharm. Res. 2015, 14(3), 693.
10. [10]
  Xiao, H.; Li, P.; Hu, J.; Li, R.; Wu, L.; Guo, D. Appl. Biochem. Biotechnol. 2014, 172(4), 2188. doi: 10.1007/s12010-013-0657-5
11. [11]
  Flieger, J.; Kowalska, A.; Pizoń, M.; Plech, T.; Łuszczki, J. J. Sep. Sci. 2015, 38(12), 2149. doi: 10.1002/jssc.v38.12
12. [12]
  Plech, T.; Kaproń, B.; Luszczki, J. J.; Paneth, A.; Siwek, A.; Kołaczkowski, M.; Żołnierek, M.; Nowak, G. Eur. J. Med. Chem. 2014, 86, 690. doi: 10.1016/j.ejmech.2014.09.034
13. [13]
  Chen, J.; Sun, X. Y.; Chai, K. Y.; Lee, J. S.; Song, M. S.; Quan, Z. S. Bioorg. Med. Chem. 2007, 15(21), 6775. doi: 10.1016/j.bmc.2007.08.004
14. [14]
  Zhang, H. J.; Jin, P.; Wang, S. B.; Li, F. N.; Guan, L. P.; Quan, Z. S. Arch. Pharm. (Weinheim) 2015, 348(8), 564. doi: 10.1002/ardp.v348.8
15. [15]
  Bian, M.; Deng, X. Q.; Gong, G. H.; Wei, C. X.; Quan, Z. S. J. Enzyme Inhib. Med. Chem. 2013, 28(4), 792. doi: 10.3109/14756366.2012.684052
16. [16]
  Xie, D.; Lu, J.; Xie, J.; Cui, J.; Li, T. F.; Wang, Y. C.; Chen, Y.; Gong, N.; Li, X. Y.; Fu, L.; Wang, Y. X. Eur. J. Med. Chem. 2016, 117, 19. doi: 10.1016/j.ejmech.2016.04.017
17. [17]
  Han, Z.; Hao, X.; Ma, B.; Zhu, C. Eur. J. Med. Chem. 2016, 121, 308. doi: 10.1016/j.ejmech.2016.05.036
18. [18]
  Unciti-Broceta, A.; Pineda de las Infantas, M. J.; Gallo, M. A.; Espinosa, A. Chemistry 2007, 13(6), 1754. doi: 10.1002/(ISSN)1521-3765
19. [19]
  Zhang, H. M.; Zhang, H. J.; Tian, Y. S.; Quan, Z. S. Chin. J. Org. Chem. 2017, 37(9), 2322 (in Chinese).
20. [20]
  Liu, Q. L.; Fang, P. J.; Zhao, Z. L.; Zhang, H. Z.; Zhou, C. H. J. Org. Chem. 2017, 12, 3146 (in Chinese).
21. [21]
  Güngör, T.; Chen, Y.; Golla, R.; Ma, Z.; Corte, J. R.; Northrop, J. P.; Bin, B.; Dickson, J. K.; Stouch, T.; Zhou, R.; Johnson, S. E.; Seethala, R.; Feyen, J. H. J. Med. Chem. 2006, 49, 2440. doi: 10.1021/jm0509389
22. [22]
  Alagarsamy, V.; Dhanabal, K.; Parthiban, P.; Anjana, G.; Deepa, G.; Murugesan, B.; Rajkumar, S.; Beevi, A. J. J. Pharm. Pharmacol. 2007, 59, 669. doi: 10.1211/jpp.59.5.0007
23. [23]
  Krall, R. L.; Penry, J. K.; White, B. G. Epilepsia 1978, 19, 409. doi: 10.1111/epi.1978.19.issue-4
24. [24]
  Porter, R. J.; Cereghino, J. J.; Gladding, G. D. Cleveland Clin. Q. 1984, 51, 293. doi: 10.3949/ccjm.51.2.293
1. [1]
  Jing WU , Puzhen HUI , Huilin ZHENG , Pingchuan YUAN , Chunfei WANG , Hui WANG , Xiaoxia GU . Synthesis, crystal structures, and antitumor activities of transition metal complexes incorporating a naphthol-aldehyde Schiff base ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2422-2428. doi: 10.11862/CJIC.20240278
2. [2]
  Xinting XIONG , Zhiqiang XIONG , Panlei XIAO , Xuliang NIE , Xiuying SONG , Xiuguang YI . Synthesis, crystal structures, Hirshfeld surface analysis, and antifungal activity of two complexes Na(Ⅰ)/Cd(Ⅱ) assembled by 5-bromo-2-hydroxybenzoic acid ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1661-1670. doi: 10.11862/CJIC.20240145
3. [3]
  Jiaming Xu , Yu Xiang , Weisheng Lin , Zhiwei Miao . Research Progress in the Synthesis of Cyclic Organic Compounds Using Bimetallic Relay Catalytic Strategies. University Chemistry, 2024, 39(3): 239-257. doi: 10.3866/PKU.DXHX202309093
4. [4]
  Aidang Lu , Yunting Liu , Yanjun Jiang . Comprehensive Organic Chemistry Experiment: Synthesis and Characterization of Triazolopyrimidine Compounds. University Chemistry, 2024, 39(8): 241-246. doi: 10.3866/PKU.DXHX202401029
5. [5]
  Tianlong Zhang , Rongling Zhang , Hongsheng Tang , Yan Li , Hua Li . Online Monitoring and Mechanistic Analysis of 3,5-diamino-1,2,4-triazole (DAT) Synthesis via Raman Spectroscopy: A Recommendation for a Comprehensive Instrumental Analysis Experiment. University Chemistry, 2024, 39(6): 303-311. doi: 10.3866/PKU.DXHX202312006
6. [6]
  Yonghui ZHOU , Rujun HUANG , Dongchao YAO , Aiwei ZHANG , Yuhang SUN , Zhujun CHEN , Baisong ZHU , Youxuan ZHENG . Synthesis and photoelectric properties of fluorescence materials with electron donor-acceptor structures based on quinoxaline and pyridinopyrazine, carbazole, and diphenylamine derivatives. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 701-712. doi: 10.11862/CJIC.20230373
7. [7]
  Yahui HAN , Jinjin ZHAO , Ning REN , Jianjun ZHANG . Synthesis, crystal structure, thermal decomposition mechanism, and fluorescence properties of benzoic acid and 4-hydroxy-2, 2′: 6′, 2″-terpyridine lanthanide complexes. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 969-982. doi: 10.11862/CJIC.20240395
8. [8]
  Yihao Zhao , Jitian Rao , Jie Han . Synthesis and Photochromic Properties of 3,3-Diphenyl-3H-Naphthopyran: Design and Teaching Practice of a Comprehensive Organic Experiment. University Chemistry, 2024, 39(10): 149-155. doi: 10.3866/PKU.DXHX202402050
9. [9]
  Qilu DU , Li ZHAO , Peng NIE , Bo XU . Synthesis and characterization of osmium-germyl complexes stabilized by triphenyl ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1088-1094. doi: 10.11862/CJIC.20240006
10. [10]
  Wanmin Cheng , Juan Du , Peiwen Liu , Yiyun Jiang , Hong Jiang . Photoinitiated Grignard Reagent Synthesis and Experimental Improvement in Triphenylmethanol Preparation. University Chemistry, 2024, 39(5): 238-242. doi: 10.3866/PKU.DXHX202311066
11. [11]
  Weikang Wang , Yadong Wu , Jianjun Zhang , Kai Meng , Jinhe Li , Lele Wang , Qinqin Liu . 三聚氰胺泡沫支撑的S型硫铟锌镉/硫掺杂氮化碳异质结的绿色H₂O₂合成：协同界面电荷转移调控与局域光热效应. Acta Physico-Chimica Sinica, 2025, 41(8): 100093-. doi: 10.1016/j.actphy.2025.100093
12. [12]
  Caixia Lin , Zhaojiang Shi , Yi Yu , Jianfeng Yan , Keyin Ye , Yaofeng Yuan . Ideological and Political Design for the Electrochemical Synthesis of Benzoxathiazine Dioxide Experiment. University Chemistry, 2024, 39(2): 61-66. doi: 10.3866/PKU.DXHX202309005
13. [13]
  Jiaojiao Yu , Bo Sun , Na Li , Cong Wen , Wei Li . Improvement of Classical Organic Experiment Based on the “Reverse-Step Optimization Method”: Taking Synthesis of Ethyl Acetate as an Example. University Chemistry, 2025, 40(3): 333-341. doi: 10.12461/PKU.DXHX202405177
14. [14]
  Yuan Zheng , Quan Lan , Zhenggen Zha , Lingling Li , Jun Jiang , Pingping Zhu . Teaching Reform of Organic Synthesis Experiments by Introducing Reverse Thinking and Design Concepts: Taking the Synthesis of Cinnamic Acid Based on Retrosynthetic Analysis as an Example. University Chemistry, 2024, 39(6): 207-213. doi: 10.3866/PKU.DXHX202310065
15. [15]
  Yufang GAO , Nan HOU , Yaning LIANG , Ning LI , Yanting ZHANG , Zelong LI , Xiaofeng LI . Nano-thin layer MCM-22 zeolite: Synthesis and catalytic properties of trimethylbenzene isomerization reaction. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1079-1087. doi: 10.11862/CJIC.20240036
16. [16]
  Jian Jin , Jing Cheng , Xueping Yang . Integration Practice of Organic Chemistry Experiment and Safety Education: Taking the Synthesis of Triphenylmethanol as an Example. University Chemistry, 2024, 39(3): 345-350. doi: 10.3866/PKU.DXHX202309010
17. [17]
  Renxiao Liang , Zhe Zhong , Zhangling Jin , Lijuan Shi , Yixia Jia . A Palladium/Chiral Phosphoric Acid Relay Catalysis for the One-Pot Three-Step Synthesis of Chiral Tetrahydroquinoline. University Chemistry, 2024, 39(5): 209-217. doi: 10.3866/PKU.DXHX202311024
18. [18]
  Jinghua Wang , Yanxin Yu , Yanbiao Ren , Yesheng Wang . Integration of Science and Education: Investigation of Tributyl Citrate Synthesis under the Promotion of Hydrate Molten Salts for Research and Innovation Training. University Chemistry, 2024, 39(11): 232-240. doi: 10.3866/PKU.DXHX202402057
19. [19]
  Bingliang Li , Yuying Han , Dianyang Li , Dandan Liu , Wenbin Shang . One-Step Synthesis of Benorilate Guided by Green Chemistry Principles and in vivo Dynamic Evaluation. University Chemistry, 2024, 39(6): 342-349. doi: 10.3866/PKU.DXHX202311070
20. [20]
  Zhuo Wang , Xue Bai , Kexin Zhang , Hongzhi Wang , Jiabao Dong , Yuan Gao , Bin Zhao . MOF模板法合成氮掺杂碳材料用于增强电化学钠离子储存和去除. Acta Physico-Chimica Sinica, 2025, 41(3): 2405002-. doi: 10.3866/PKU.WHXB202405002

Get Citation

PDF

XML

Metrics

PDF Downloads(9)
Abstract views(794)
HTML views(103)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142