Citation: Zhang Haiming, Zhang Hongjian, Tian Yushun, Quan Zheshan. Synthesis and Anticonvulsant Activity Evaluation of Phthalazine and Heterocyclic Derivatives[J]. Chinese Journal of Organic Chemistry, ;2017, 37(9): 2322-2327. doi: 10.6023/cjoc201703019 shu

Synthesis and Anticonvulsant Activity Evaluation of Phthalazine and Heterocyclic Derivatives

College of Pharmacy, Yanbian University, Yanji 133002

Corresponding author: Tian Yushun, ld-l@163.com
Received Date: 2 March 2017
Revised Date: 30 March 2017
Available Online: 10 September 2017
Fund Project: Project supported by the National Natural Science Foundation of China (No. 21272005)National Natural Science Foundation of China 21272005

Figures(1)

Four series of derivatives, 6-substituted-1, 2, 4-triazolo[3, 4-a] phthalazine derivatives and 6-substituted tetrazolo[5, 1-a]phthalazine derivatives have been synthesized. The structures of compounds are confirmed by ¹H NMR, ¹³C NMR, IR and HRMS. The anticonvulsant effects of the compounds are evaluated with maximal electroshock test by intraperitoneally injected in mice. The experimental results show that N-(4-bromophenyl)tetrazolo[5, 1-a]phthalazin-6-amine (7a) was the most potent compound, with a median effective dose of 5.89 mg·kg^-1. Its anticonvulsant effect is better than the reference drug, carbamazepine.
- phthalazine,
- triazolo,
- tetrazolo,
- synthesis,
- anticonvulsant,
- the maximal electroshock
1. [1]
  Gasior, M.; Carter, R. B.; Goldberg, S. R.; Witkin, J. M.; Pharmacol, J. Exp. Ther. 1997, 282, 544.
2. [2]
  Mccormick, D. A.; Contreras, D. Annu. Rev. Physiol. 2001, 63, 815. doi: 10.1146/annurev.physiol.63.1.815
3. [3]
  Strine, T. W.; Kobau, R.; Chapman, D. P.; Thurman, D. J.; Price, P.; Balluz, L. S. Epilepsia 2005, 46, 1133. doi: 10.1111/epi.2005.46.issue-7
4. [4]
  Sirven, J. I.; Noe, K.; Hoerth, M.; Drazkowski, J. Mayo. Clin. Proc. 2012, 87, 879. doi: 10.1016/j.mayocp.2012.05.019
5. [5]
  Kwan, P.; Brodie, M. J. N. Engl. J. Med. 2000, 342, 315.
6. [6]
  Penovich, P. E.; Willmore, L. J. Epilepsia 2009, 50, 38. doi: 10.1111/epi.2009.50.issue-s12
7. [7]
  Bialer, M.; Johannessen, S. I.; Kupferberg, H. J.; Levy, R. H.; Perucca, E.; Tomson, T. Epilepsy Res. 2007, 73, 2.
8. [8]
  Bootsma, H. P.; Ricker, L.; Hekster, Y. A.; Hulsman, J.; Lambrechts, D.; Majoie, M.; Schellekens, A.; Krom, D. M.; Aldenkamp, A. P. Seizure 2009, 18, 328.
9. [9]
  Ramaiya, S.; Sundararaj, K. G.; Somasundaram, R.; Joseph, T. L. Eur. J. Med. Chem. 2002, 37, 793. doi: 10.1016/S0223-5234(02)01405-8
10. [10]
  Guo, L. J.; Wei, C. X.; Jia, J. H.; Zhao, L. M.; Quan, Z. S. Eur. J. Med. Chem. 2009, 44, 954. doi: 10.1016/j.ejmech.2008.07.010
11. [11]
  Sun, X. Y.; Wei, C. X.; Deng, X. Q.; Sun, Z. G.; Quan, Z. S. Pharmacol. Rep. 2010, 62, 273. doi: 10.1016/S1734-1140(10)70266-8
12. [12]
  Wang, S. B.; Deng, X. Q.; Zheng, Y.; Yuan, Y. P.; Quan, Z. S.; Guan, L. P. Eur. J. Med. Chem. 2012, 56, 139. doi: 10.1016/j.ejmech.2012.08.027
13. [13]
  Zhu, Z. S.; Wang, S. B.; Deng, X. Q.; Liu, D. C.; Quan, Z. S. Lett. Drug Des. Dis. 2014, 11, 628. doi: 10.2174/1570180810666131122003939
14. [14]
  Wang, S. B.; Deng, X. Q.; Liu, D. C.; Zhang, H. J.; Quan, Z. S. Med. Chem. Res. 2014, 23, 4619. doi: 10.1007/s00044-014-1030-0
15. [15]
  Tan, Y. D.; He, X. Y.; Rao, B. Q.; Cheng, B. B.; Song, M. X.; Deng, X. Q. Chin. J. Org. Chem. 2016, 36, 2449(in Chinese).
16. [16]
  Zhang, L.; Guan, L. P.; Sun, X. Y.; Wei, C. X.; Chai, K. Y.; Quan, Z. S. Chem. Biol. Drug Des. 2009, 73, 313. doi: 10.1111/jpp.2009.73.issue-3
17. [17]
  Deng, X. Q.; Wei, C. X.; Song, M. X.; Quan, Z. S. Arzneim. Forsch. 2010, 60, 587.
18. [18]
  Bian, M.; Deng, X. Q.; Gong, G. H.; Wei, C. X.; Quan, Z. S. J. Enzyme Inhib. Med. Chem. 2013, 28, 792. doi: 10.3109/14756366.2012.684052
19. [19]
  Street, L. J.; Sternfeld, F.; Jelley, R. A.; Reeve, A. J.; Carling, R. W.; Moore, K. W.; McKernan, R. M.; Sohal, B.; Cook, S.; Pike, A.; Dawson, G. R.; Bromidge, F. A.; Wafford, K. A.; Seabrook, G. R.; Thompson, S. A.; Marshall, G.; Pillai, G. V.; Castro, J. L.; Atack, J. R.; MacLeod, A. M. J. Med. Chem. 2004, 47, 3642. doi: 10.1021/jm0407613
20. [20]
  Wu, Y.; Sun, L. P.; Ma, L. X.; Che, J.; Song, M. X. Chem. Biol. Drug Des. 2013, 81, 591. doi: 10.1111/cbdd.2013.81.issue-5
21. [21]
  Wang, C. J.; Cao, Q. P.; Yang, H.; Song, P. P.; Xue, D. Q.; Cui, F.; Gu, Y. F.; Zhang, X. S.; Tian, Y. N.; Zhang, Q. R.; Liu, H. M. Chin. J. Org. Chem. 2016, 36, 16 27(in Chinese).
22. [22]
  Xue, D. Q.; Zhang, X. Y.; Wang, C. J.; Ma, L. Y.; Zhu, N.; He, P.; Shao, K. P.; Chen, P. J.; Gu, Y, F.; Zhang, X. S.; Wang, C. F.; Ji, C. H.; Zhang, Q. R.; Liu, H. M. Eur. J. Med. Chem. 2014, 85, 235. doi: 10.1016/j.ejmech.2014.07.031
23. [23]
  Bian, M.; Deng, X. Q.; Gong, G. H.; Wei, C. X.; Quan, Z. S. J. Enzyme Inhib. Med. Chem. 2013, 28, 792. doi: 10.3109/14756366.2012.684052
24. [24]
  Okada, R.; Negishi, N.; Nagaya, H. Brain Res. 1989, 480, 384.
25. [25]
  Liu, D. C.; Deng, X. Q.; Wang, S. B.; Quan, Z. S. Arch. Pharm. (Weinheim, Ger.) 2014, 347, 269.
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]
  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
7. [7]
  Shahua Huang , Xiaoming Guo , Lin Lin , Guangping Chang , Sheng Han , Zuxin Zhou . Application of “Integration of Industry and Education” in Engineering Chemistry: Improvement of the Pesticide Fipronil Production. University Chemistry, 2024, 39(3): 199-204. doi: 10.3866/PKU.DXHX202309064
8. [8]
  Yujia LI , Tianyu WANG , Fuxue WANG , Chongchen WANG . Direct Z-scheme MIL-100(Fe)/BiOBr heterojunctions: Construction and photo-Fenton degradation for sulfamethoxazole. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 481-495. doi: 10.11862/CJIC.20230314
9. [9]
  Zhiwen HU , Weixia DONG , Qifu BAO , Ping LI . Low-temperature synthesis of tetragonal BaTiO₃ for piezocatalysis. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 857-866. doi: 10.11862/CJIC.20230462
10. [10]
  Rui Gao , Ying Zhou , Yifan Hu , Siyuan Chen , Shouhong Xu , Qianfu Luo , Wenqing Zhang . Design, Synthesis and Performance Experiment of Novel Photoswitchable Hybrid Tetraarylethenes. University Chemistry, 2024, 39(5): 125-133. doi: 10.3866/PKU.DXHX202310050
11. [11]
  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
12. [12]
  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
13. [13]
  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
14. [14]
  Shuhui Li , Rongxiuyuan Huang , Yingming Pan . Electrochemical Synthesis of 2,5-Diphenyl-1,3,4-Oxadiazole: A Recommended Comprehensive Organic Chemistry Experiment. University Chemistry, 2025, 40(5): 357-365. doi: 10.12461/PKU.DXHX202407028
15. [15]
  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
16. [16]
  Kaihui Huang , Dejun Chen , Xin Zhang , Rongchen Shen , Peng Zhang , Difa Xu , Xin Li . Constructing Covalent Triazine Frameworks/N-Doped Carbon-Coated Cu₂O S-Scheme Heterojunctions for Boosting Photocatalytic Hydrogen Production. Acta Physico-Chimica Sinica, 2024, 40(12): 2407020-. doi: 10.3866/PKU.WHXB202407020
17. [17]
  Xiaofeng Xia , Jielian Zhu . Innovative Comprehensive Experimental Design: Synthesis of 6-Fluoro-N-benzoyl Tetrahydroquinoline. University Chemistry, 2024, 39(10): 344-352. doi: 10.12461/PKU.DXHX202405063
18. [18]
  Xiao SANG , Qi LIU , Jianping LANG . Synthesis, structure, and fluorescence properties of Zn(Ⅱ) coordination polymers containing tetra-alkenylpyridine ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(11): 2124-2132. doi: 10.11862/CJIC.20240158
19. [19]
  Yifeng TAN , Ping CAO , Kai MA , Jingtong LI , Yuheng WANG . Synthesis of pentaerythritol tetra(2-ethylthylhexoate) catalyzed by h-MoO₃/SiO₂. Chinese Journal of Inorganic Chemistry, 2024, 40(11): 2155-2162. doi: 10.11862/CJIC.20240147
20. [20]
  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

Get Citation

PDF

XML

Metrics

PDF Downloads(5)
Abstract views(870)
HTML views(82)

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