Citation: Zhang Xiujun, Wang Lanzhi, Yan Jingyi, Gao Chen. Synthesis, Antibacterial Activity and Structure-Activity Relationship of 1H-2, 5-Dihydro-1, 5-benzodiazepine with Ester Group and the Aromatic Heterocyclic Ring[J]. Chinese Journal of Organic Chemistry, ;2017, 37(2): 462-473. doi: 10.6023/cjoc201604059 shu

Synthesis, Antibacterial Activity and Structure-Activity Relationship of 1H-2, 5-Dihydro-1, 5-benzodiazepine with Ester Group and the Aromatic Heterocyclic Ring

Zhang Xiujun ^a ,
Wang Lanzhi ^a,*,, ,
Yan Jingyi ^b ,
Gao Chen ^b

a.
College of Chemistry & Material Science, Hebei Normal University, Shijiazhuang 050024
b.
College of Life Sciences, Hebei Normal University, Shijiazhuang 050024

Corresponding author: Wang Lanzhi, wanglanzhi@126.com
Received Date: 29 April 2016
Revised Date: 23 May 2016

Fund Project: the Natural Science Foundation of Hebei Province B2016205165the National Natural Science Foundation of China 21276064

Figures(4)

Using (ethyl 4-methyl-2-(thiazol-2-yl)-1H-2, 5-dihydro-1, 5-benzodiazepine-3-carboxylate) (A) as a model compound, thirty 1H-2, 5-dihydro-1, 5-benzodiazepine derivatives 2~6 were synthesized by nucleophilic addition reaction, elimination reaction and cyclization reaction. The structures of these new compounds were characterized by ¹H NMR, ¹³C NMR, IR, MS and elemental analysis. The antibacterial activities of those compounds were screened using the disk diffusion method against C. neoformans, C. neoformans clinical isolates, C. albicans, E. coli and S. aureus. The bioactive assay results revealed that most of the 1H-2, 5-dihydro-1, 5-benzodiazepine derivatives exhibited considerable potency against all of the tested strains. In particular, some compounds exhibited excellent antimicrobial activities against the test microorganism MS except E. coli, and exhibited better antimicrobial activity against fungi than against bacteria. Furthermore, ethyl 4-ethyl-8-methyl-2-(thiazol-2-yl)-2, 5-dihydro-1, 5-benzodiazepine-3-carboxylate (4b) and ethyl 4-ethyl-8-fluoro-2-(thiazol-2-yl)-2, 5-dihydro-1, 5-benzo-diazepine-3-carboxylate (4c), which had good antibacterial activities, were subjected to further pharmacological evaluation, including minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC) and minimum bactericidal concentration (MBC) against C. neoformans, C. albicans, and S. aureus. The results showed that the MIC and MFC against C. albicans values for above compounds were much lower than those of fluconazole. A further study of the structure-activity rela-tionship revealed that the thiazole ring at C-2, the methyl, ethyl at C-4 and the methyl at C-8 are essential for antibacterial activity.
- 1H-2, 5-dihydro-1, 5-benzodiazepine,
- synthesis,
- characterization,
- antibacterial activity,
- structure-activity relationship
1. [1]
  Francisco, L. M.; Cecilio, Á.; Pilar, G. G. J. Anxiety Disord. 2011, 25, 554. doi: 10.1016/j.janxdis.2011.01.002
2. [2]
  Konda, S. G.; Shaikh, B. M.; Chavan, S. A.; Dawane, B. S. Chin. Chem. Lett. 2011, 22, 65. doi: 10.1016/j.cclet.2010.09.012
3. [3]
  Ganzella, M.; Faraco, R. B.; Almeida, R. F.; Fernandes, V. F.; Souza, D. O. Pharmacol. Biochem. Behav. 2011, 100, 271. doi: 10.1016/j.pbb.2011.09.001
4. [4]
  Zhou, X.; Zhang, M. Y.; Gao, S. T.; M, J. J.; W, C.; Liu, C. Chin. Chem. Lett. 2009, 20, 905. doi: 10.1016/j.cclet.2009.03.033
5. [5]
  Holbrook, A. M.; Crowther, R.; Lotter, A.; Cheng, C.; King, D. Can. Med. Assoc. J. 2000, 162, 225.
6. [6]
  Guzen, K. P.; Cella, R.; Stefani, H. A. Tetrahedron Lett. 2006, 47, 8133. doi: 10.1016/j.tetlet.2006.09.043
7. [7]
  Corral, C.; Lissavetzky, J.; Valdeolmillos, A. M. J. Heterocycl. Chem. 1985, 22, 1349. doi: 10.1002/jhet.v22:5
8. [8]
  Babu, M.; Pitchumani, K.; Ramesh, P. Med. Chem. Res. 2014, 23, 2070. doi: 10.1007/s00044-013-0694-1
9. [9]
  Ilango, S. S.; Remya, P. U.; Ponnuswamy, S. Indian J. Chem. 2013, 52B, 136.
10. [10]
  Wang, L. Z.; Li, X. Q.; An, Y. S. Org. Biomol. Chem. 2015, 13, 5497. doi: 10.1039/C5OB00655D
11. [11]
  Xiao, L. W.; Zhang, M.; Sun, W. H. Chem. Res. Chin. Univ. 2011, 27, 228.
12. [12]
  Binay, B.; Sessionsc, R. B.; Karagüler, N. G. Enzyme Microb. Technol. 2013, 52, 393. doi: 10.1016/j.enzmictec.2013.01.009
13. [13]
  Kantevari, S.; Vuppalapati, S. V. N.; Biradar, D. O.; Nagarapu, L. J. Mol. Catal. A: Chem. 2007, 266, 109. doi: 10.1016/j.molcata.2006.10.048
14. [14]
  Li, X. Q.; Wang, L. Z. Chin. Chem. Lett. 2014, 25, 327. doi: 10.1016/j.cclet.2013.11.035
15. [15]
  Pasquale, G. A.; Ruiz, D. M.; Jios, J. L.; Autino, J. C.; Romanelli, G. P. Tetrahedron Lett. 2013, 54, 6574. doi: 10.1016/j.tetlet.2013.09.101
16. [16]
  Arshad, A.; Osman, H.; Bagley, M. C.; Lam, C. K.; Mohamad, S.; Zahariluddin, A. S. M. Eur. J. Med. Chem. 2011, 46, 3788. doi: 10.1016/j.ejmech.2011.05.044
17. [17]
  Sidoryk, K.; Jaromin, A.; Edward, J. A.; Switalska, M.; Stefanska, J.; Cmoch, P.; Zagrodzka, J.; Szczepek, W.; Czoch, W. P.; Wietrzyk, J.; Kozubek, A.; Zarnowski, R.; Andes, D. R.; Kaczmarek, L. Eur. J. Med. Chem. 2014, 78, 304. doi: 10.1016/j.ejmech.2014.03.060
1. [1]
  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
2. [2]
  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
3. [3]
  Xuejie Wang , Guoqing Cui , Congkai Wang , Yang Yang , Guiyuan Jiang , Chunming Xu . 碳基催化剂催化有机液体氢载体脱氢研究进展. Acta Physico-Chimica Sinica, 2025, 41(5): 100044-. doi: 10.1016/j.actphy.2024.100044
4. [4]
  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
5. [5]
  Linjie ZHU , Xufeng LIU . Synthesis, characterization and electrocatalytic hydrogen evolution of two di-iron complexes containing a phosphine ligand with a pendant amine. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 939-947. doi: 10.11862/CJIC.20240416
6. [6]
  Xiaoyang Li , Xiaowei Huang , Yimeng Zhang , Huan Liu , Shao Jin , Junpeng Zhuang . Comprehensive Chemical Experiments on the Synthesis of 1,3-Dibromo-5,5-Dimethylhydantoin and Its Application as a Brominating Reagent. University Chemistry, 2025, 40(7): 286-293. doi: 10.12461/PKU.DXHX202408035
7. [7]
  Fei Liu , Dong-Yang Zhao , Kai Sun , Ting-Ting Yu , Xin Wang . Comprehensive Experimental Design for Photochemical Synthesis, Analysis, and Characterization of Seleno-Containing Medium-Sized N-Heterocycles. University Chemistry, 2024, 39(3): 369-375. doi: 10.3866/PKU.DXHX202309047
8. [8]
  Tingting Yu , Si Chen , Lianglong Sun , Tongtong Shi , Kai Sun , Xin Wang . Comprehensive Experimental Design for the Photochemical Synthesis, Analysis, and Characterization of Difluoropyrroles. University Chemistry, 2024, 39(11): 196-203. doi: 10.3866/PKU.DXHX202401022
9. [9]
  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
10. [10]
  Xiaoling LUO , Pintian ZOU , Xiaoyan WANG , Zheng LIU , Xiangfei KONG , Qun TANG , Sheng WANG . Synthesis, crystal structures, and properties of lanthanide metal-organic frameworks based on 2, 5-dibromoterephthalic acid ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1143-1150. doi: 10.11862/CJIC.20230271
11. [11]
  Jia JI , Zhaoyang GUO , Wenni LEI , Jiawei ZHENG , Haorong QIN , Jiahong YAN , Yinling HOU , Xiaoyan XIN , Wenmin WANG . Two dinuclear Gd(Ⅲ)-based complexes constructed by a multidentate diacylhydrazone ligand: Crystal structure, magnetocaloric effect, and biological activity. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 761-772. doi: 10.11862/CJIC.20240344
12. [12]
  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
13. [13]
  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
14. [14]
  Jingjing QING , Fan HE , Zhihui LIU , Shuaipeng HOU , Ya LIU , Yifan JIANG , Mengting TAN , Lifang HE , Fuxing ZHANG , Xiaoming ZHU . Synthesis, structure, and anticancer activity of two complexes of dimethylglyoxime organotin. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1301-1308. doi: 10.11862/CJIC.20240003
15. [15]
  Yukai Jiang , Yihan Wang , Yunkai Zhang , Yunping Wei , Ying Ma , Na Du . Characterization and Phase Diagram of Surfactant Lyotropic Liquid Crystal. University Chemistry, 2024, 39(4): 114-118. doi: 10.3866/PKU.DXHX202309033
16. [16]
  Hong RAO , Yang HU , Yicong MA , Chunxin LÜ , Wei ZHONG , Lihua DU . Synthesis and in vitro anticancer activity of phenanthroline-functionalized nitrogen heterocyclic carbene homo- and heterobimetallic silver/gold complexes. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2429-2437. doi: 10.11862/CJIC.20240275
17. [17]
  Liyang ZHANG , Dongdong YANG , Ning LI , Yuanyu YANG , Qi MA . Crystal structures, luminescent properties and Hirshfeld surface analyses of three cadmium(Ⅱ) complexes based on 2-(3-(pyridin-2-yl)-1H-pyrazol-1-yl)benzoate. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1943-1952. doi: 10.11862/CJIC.20240079
18. [18]
  Jiapei Zou , Junyang Zhang , Xuming Wu , Cong Wei , Simin Fang , Yuxi Wang . A Comprehensive Experiment Based on Electrocatalytic Nitrate Reduction into Ammonia: Synthesis, Characterization, Performance Exploration, and Applicable Design of Copper-based Catalysts. University Chemistry, 2024, 39(6): 373-382. doi: 10.3866/PKU.DXHX202312081
19. [19]
  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
20. [20]
  Yuanyuan Ping , Wangqing Kong . 光催化碳氢键官能团化合成1-苯基-1,2-乙二醇. University Chemistry, 2025, 40(6): 238-247. doi: 10.12461/PKU.DXHX202408092

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(1310)
HTML views(146)

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