含三氮唑结构的1,5-苯并硫氮杂䓬的合成及抑菌活性
收稿日期: 2020-12-27
修回日期: 2021-02-09
网络出版日期: 2021-03-12
基金资助
河北省自然科学基金(B2017205100); 河北师范大学研究生创新基金(CXZZSS2021052)
Synthesis and Antimicrobial Activity of 1,5-Benzothiazepines Incorporated with Triazole Moiety
Received date: 2020-12-27
Revised date: 2021-02-09
Online published: 2021-03-12
Supported by
Natural Science Foundation of Hebei Province(B2017205100); Graduate Student Innovation Fundation of Hebei Normal University(CXZZSS2021052)
设计合成了4类含三氮唑结构的1,5-苯并硫氮杂?化合物: 2,3/2,5-二氢-3-(1H-1,2,4-三氮唑甲基)-4-芳基-1,5-苯并硫氮杂?(9a~9f和10a~10f)和2,3/2,5-二氢-3-(2H-1,2,3-三氮唑甲基)-4-芳基-1,5-苯并硫氮杂?(17a~17f和18a~18f).合成中发现15a~15f在转化为目标产物的过程中发生了三氮唑环的异构化. 分离出两个新化合物19a和20a, 提出了它们生成的可能历程. 目标产物的抑菌活性测试表明: 9a~9d和10a~10d对真菌有中到高度的抑制作用, 其中9b、9c和10b对新生隐球菌的抑制作用高于对照药物氟康唑, 可用于抗真菌药物研发的进一步研究.
孙雨佳 , 王紫薇 , 王岩 , 许同绣 , 田克情 , 张萍 . 含三氮唑结构的1,5-苯并硫氮杂䓬的合成及抑菌活性[J]. 有机化学, 2021 , 41(6) : 2361 -2373 . DOI: 10.6023/cjoc202012044
Four kinds of 1,5-benzothiazepines incorporated with triazole moiety: 2,3/2,5-dihydro-3-[(1H-1,2,4-triazol-1-yl) methyl]-4-aryl-1,5-benzothiazepines (9a~9f,10a~10f) and 2,3/2,5-dihydro-3-[(2H-1,2,3-triazol-2-yl)methyl]-4-aryl-1,5- benzothiazepines (17a~17f, 18a~18f) were designed and synthesized. It was found that the isomerization of triazole occurred during the conversion of 15a~15f to the target compounds. Two new compounds 19a and 20a were isolated and their possible formation mechanism was proposed. The antimicrobial activity test of the target products showed that compounds 9a~9d and 10a~10d had moderate to high inhibitory effect on fungi, and compounds 9b, 9c, and 10b showed higher inhibition on C. neoformans than that of fluconazole, which can be used for further investigation for the development of antifungal drugs.
Key words： triazole; 1; 5-benzothiazepine; antimicrobial activity
| [1] | Herranz, R. Med. Res. Rev. 2003, 23,559. |
| [2] | Schwarz, M. K.; Tumelty, D.; Gallop, M. A. J. Org. Chem. 1999, 64,2219. |
| [3] | Liao, Y.; Venhuis, B. J.; Rodenhuis, N.; Timmerman, W.; Wikstrom, H.; Meier, E.; Bartoszyk, G. D.; Bottcher, H.; Seyfried, C. A.; Sundell, S. J. Med. Chem. 1999, 42,2235. |
| [4] | Gudisela, M. R.; Srinivasu, N.; Mulakayala, C.; Bommu, P.; Rao, M. V. B.; Mulakayala, N. Bioorg. Med. Chem. Lett. 2017, 27,4140. |
| [5] | Di, Santo, R.; Costi, R. Farmaco 2005, 60,385. |
| [6] | Kim, H.-Y.; Kong, S.; Oh, S.; Yang, J.; Jo, E.; Ko, Y.; Kim, S.-H.; Hwang, J. Y.; Song, R.; Windisch, M. P. Antiviral Res. 2016, 129,39. |
| [7] | Shimotori, Y.; Hoshi, M.; Murata, M.; Ogawa, N.; Miyakoshi, T.; Kanamoto, T. Heterocycl. Commun. 2018, 24,219. |
| [8] | Patil, M.; Poyil, A. N.; Joshi, S. D.; Patil, S. A.; Patil, S. A.; Bugarin, A. Bioorg. Chem. 2019, 92.103217. |
| [9] | Chaffman, M.; Brogden, R. N. Drugs 1985, 29,387. |
| [10] | Kawakita, S.; Kinoshita, M.; Ishikawa, H.; Kagoshima, T.; Katori, R.; Ishikawa, K.; Hirota, Y. Clin. Cardiol. 1991, 14,53. |
| [11] | Yadav, A.; Awasthi, A.; Rao, N. K. Eur. J. Med. Chem. 2009, 44,1. |
| [12] | Dreyfuss, J.; Cohen, A. I.; Hess, S. M. J. Pharm. Sci. 1968, 57,1505. |
| [13] | Feng, Z. Y.; Wang, Z. G. J. Psychiatry 2010, 23,475(in Chinese). |
| [13] | (冯志颖, 王中刚, 精神医学杂志, 2010, 23,475.) |
| [14] | Bariwal, J. B.; Upadhyay, K. D.; Manvar, A. T.; Trivedi, J. C.; Singh, J. S.; Jain, K. S.; Shah, A. K. Eur. J. Med. Chem. 2008, 43,2279. |
| [15] | Del, Arco, J.; Galindo, J.; Javier Clemente-Suarez, V.; Corrales, A.; Fernandez-Lucas, J. Biochim. Biophys. Acta, Proteins Proteom. 2020, 1868 140251. |
| [16] | Bhatt, J. D.; Chudasama, C. J.; Patel, K. D. Arch. Pharm. 2016, 349,791. |
| [17] | Cao, X.; Wang, W.; Wang, S.; Bao, L. Eur. J. Med. Chem. 2017, 139,718. |
| [18] | Xu, Z.; Zhao, S.-J.; Liu, Y. Eur. J. Med. Chem. 2019, 183.111700. |
| [19] | Kritsanida, M.; Mouroutsou, A.; Marakos, P.; Pouli, N.; Papakonstantinou-Garoufalias, S.; Pannecouque, C.; Witvrouw, M.. De Clercq, E. Farmaco 2002, 57,253. |
| [20] | Chu, X.-M.; Wang, C.; Wang, W.-L.; Liang, L.-L.; Liu, W.; Gong, K.-K.; Sun, K.-L. Eur. J. Med. Chem. 2019, 166,206. |
| [21] | Najafi, Z.; Mahdavi, M.; Saeedi, M.; Karimpour-Razkenari, E.; Edraki, N.; Sharifzadeh, M.; Khanavi, M.; Akbarzadeh, T. Bioorg. Chem. 2019, 83,303. |
| [22] | Aggarwal, R.; Sumran, G. Eur. J. Med. Chem. 2020, 205,112652. |
| [23] | Xu, Z. Eur. J. Med. Chem. 2020, 206,112686. |
| [24] | Wang, Y.; Kong, L.; Wang, R.; Tian, K.; Zhang, P. Chin. J. Org. Chem. 2019, 39,2663(in Chinese). |
| [24] | (王岩, 孔令满, 王冉冉, 田克情, 张萍, 有机化学, 2019, 39,2663.) |
| [25] | Wang, R.; Wang, Y.; Bian, Y.; Zhang, P. Chin. J. Org. Chem. 2020, 40,398(in Chinese). |
| [25] | (王冉冉, 王岩, 边彦青, 张萍, 有机化学, 2020, 40,398.) |
| [26] | Kumar, L.; Sarswat, A.; Lal, N.; Jain, A.; Kumar, S.; Kumar, S. T. V. S. K.; Maikhuri, J. P.; Pandey, A. K.; Shukla, P. K.; Gupta, G.; Sharma, V. L. Bioorg. Med. Chem. Lett. 2011, 21,176. |
| [27] | Xu, L.; Zhang, S.; Gao, H.; Jiao, K. Chem. Res. Chin. Univ. 2003, 19,437. |
| [28] | Ogata, M.; Matsumoto, H.; Kida, S.; Shimizu, S.; Tawara, K.; Kawamura, Y. J. Med. Chem. 1987, 30,149. |
| [29] | Xing, Q. Y.; Pei, W. W.; Xu, R. Q.; Pei, J. Basic Organic Chemistry (І), Peking University Press, Beijing, 2016, p.641(in Chinese). |
| [29] | (邢其毅, 裴伟伟, 徐瑞秋, 裴坚, 基础有机化学上, 北京大学出版社, 北京, 2016, p. 641.) |
| [30] | Wang, L. Z.; Zhang, P.; Zhang, X. M.; Zhang, Y. H.; Li, Y.; Wang, Y. X. Eur. J. Med. Chem. 2009, 44,2815. |
| [31] | Lass-Florl, C.; Speth, C.; Kofler, G.; Dierch, M. P.; Gunsilius, E.; Wurzner, R. Int. J. Antimicrob. Agents 2003, 21,229. |
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