SIOC English
有机化学
高级检索

有机化学 >

2020 , Vol. 40 >Issue 8: 2402 - 2410

DOI: https://doi.org/10.6023/cjoc202003009

研究论文

1,2,4-三唑-3-硫醚衍生物的合成、晶体结构与神经氨酸酶抑制活性

  • 何梅 ,
  • 贺超凡 ,
  • 刘玲 ,
  • 叶姣 ,
  • 胡艾希 ,
  • 陈云 ,
  • 许律捷 ,
  • 刘艾林
展开
  • a 湖南大学化学化工学院 长沙 410082;
    b 中国医学科学院北京协和医学院药物研究所 北京 100050

收稿日期: 2020-03-05

  修回日期: 2020-05-21

  网络出版日期: 2020-05-29

基金资助

湖南省自然科学基金（No.2019JJ40030）资助项目.

收起

Synthesis, Crystal Structure and Neuraminidase Inhibitory Activity of 1,2,4-Triazole-3-sulfide Derivatives

  • He Mei ,
  • He Chaofan ,
  • Liu Ling ,
  • Ye Jiao ,
  • Hu Aixi ,
  • Chen Yun ,
  • Xu Lujie ,
  • Liu Ailin
Expand
  • a College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082;
    b Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050

Received date: 2020-03-05

  Revised date: 2020-05-21

  Online published: 2020-05-29

Supported by

Project supported by the Natural Science Foundation of Hunan Province (No. 2019JJ40030).

Fold

摘要

设计并合成了一系列1，2，4-三唑-3-硫醚衍生物，目标化合物的化学结构经1H NMR、13C NMR、质谱和元素分析确证；采用单晶X射线衍射法测定了（E）-4-（4-羟基-3-甲氧基苯基亚甲氨基）-5-乙基-4H-1，2，4-三唑-3-丙硫醚（1c）的晶体结构.目标化合物体外神经氨酸酶（Neuraminidase，NA，H1N1）抑制活性测试结果表明，大部分化合物1具有较好的NA抑制活性，其中（E）-4-（4-羟基-3-甲氧基苯基亚甲氨基）-5-乙基-4H-1，2，4-三唑-3-乙硫醚（1b）和1c的NA抑制活性最佳，其IC50值分别为（6.86±2.08）和（9.1±1.56）μg/mL.

关键词： 1,2,4-三唑-3-硫醚衍生物; 合成; 晶体结构; 神经氨酸酶抑制活性

本文引用格式

何梅 , 贺超凡 , 刘玲 , 叶姣 , 胡艾希 , 陈云 , 许律捷 , 刘艾林 . 1,2,4-三唑-3-硫醚衍生物的合成、晶体结构与神经氨酸酶抑制活性[J]. 有机化学, 2020 , 40(8) : 2402 -2410 . DOI: 10.6023/cjoc202003009

Abstract

A series of 1,2,4-triazole-3-sulfide derivatives were designed and synthesized. Their chemical structures were confirmed by 1H NMR, 13C NMR, MS and elemental analysis. The crystal structure of (E)-4-(4-hydroxy-3-methoxyphenyl-methyleneamino)-5-ethyl-4H-1,2,4-triazole-3-propylsulfide (1c) was determined by X-ray diffraction analysis. The preliminary assay of neuraminidase (NA, H1N1) inhibitory activity in vitro showed that most of compound 1 has more potent NA inhibitory activity. Among them, compounds (E)-4-(4-hydroxy-3-methoxyphenyl-methyleneamino)-5-ethyl-4H-1,2,4-triazole-3-ethylsulfide (1b) and 1c showed the best inhibitory activity with IC50 values of (6.86±2.08) and (9.1±1.56) μg/mL, respectively.

Key words： 1,2,4-triazole-3-sulfide derivative; synthesis; crystal structure; neuraminidase inhibitory activity

参考文献

[1] Williams, S.; Fitzner, J.; Merianos, A. Bull. W. H. O. 2014, 92, 60.
[2] Kobasa, D.; Jones, S. M.; Shinya, K. Nature 2016, 445, 319.
[3] Wang, P. C; Fang, J. M.; Tsai, K. C. J. Med. Chem. 2016, 59, 5297.
[4] Kakuta, M.; Kubo, S.; Tanaka, M. Antiviral Res. 2013, 100, 190.
[5] Leang, S. K.; Kwok, S.; Sullivan, S. G. Influenza Other Respir. Viruses 2014, 8, 135.
[6] Harrington, P. J.; Brown, J. D.; Foderaro, T. Org. Process Res. Dev. 2003, 8, 86.
[7] Zhao, X.; Jie, Y.; Rosenberg, M. Antiviral Res. 2012, 96, 91.
[8] LackenAy, A.; Aesselaar, T. G.; Daniels, R. S. Antiviral Res. 2018, 157, 38.
[9] Air, G. M. Influenza Other Respir. Viruses 2012, 6, 245.
[10] Tong, S.; Li, Y.; Rivailler, P.; Conrardy, C.; Alvarez Castillo, D. A.; Chen, L. M.; Recuenco, S.; Ellison, J. A.; Davis, C. T.; York, I. A.; Turmelle, A. S.; Moran, D.; Rogers, S.; Shi, M.; Tao, Y.; Weil, M. R.; Tang, K.; Rowe, L. A.; Sammons, S.; Xu, X.; Frace, M.; Lindblade, K. A.; Cox, N. J.; Anderson, L. J.; Rupprecht, C. E.; Donis, R. O. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 4269.
[11] Wang, K.; Fei, Y.; Wang, L. Eur. J. Med. Chem. 2017, 141, 648.
[12] Pires, C. D. M.; Drusano, G. L.; Adams, J. R. Eur. J. Pharm. Sci. 2018, 111, 443.
[13] Dai, X. Q.; Zhu, Y. B.; Wang, Z. Y.; Weng, J. Q. Chin. J. Org. Chem. 2017, 37, 1924(in Chinese). (戴小强, 朱亚波, 汪洲洋, 翁建全, 有机化学, 2017, 37, 1924.)
[14] Shen, Z. H.; Sun, Z. H.; Becnel, J. J.; Estep, A.; Wedge, D. E.; Tan, C. X.; Weng, J. Q.; Han, L.; Liu, X. H. Lett. Drug Des. Discovery 2018, 15, 951.
[15] Chen, L.; Shen, Z. H.; Xu, T. M.; Tan, C. X.; Weng, J. Q.; Han, L.; Peng. W. L.; Liu, X. H. J. Heterocycl. Chem. 2018, 55, 946.
[16] Zhai, Z. W.; Wang, Q.; Shen, Z. H.; Tan, C. X.; Weng, J. Q.; Liu, X. H. Chin. J. Org. Chem. 2017, 37, 232(in Chinese). (翟志文, 汪乔, 沈钟华, 谭成侠, 翁建全, 刘幸海, 有机化学, 2017, 37, 232.)
[17] Liu, X. H.; Zhao, W.; Shen, Z. H.; Xing, J. H.; Xu, T. M.; Peng, W. L. Eur. J. Med. Chem. 2017, 125, 881.
[18] Li, Q. M.; Pang, K. S.; Zhao, J. P.; Liu, X. H.; Weng, J. Q. Chin. J. Org. Chem. 2017, 37, 1009(in Chinese). (李倩梅, 庞凯胜, 赵建平, 刘幸海, 翁建全, 有机化学, 2017, 37, 1009.)
[19] Shi, J. J.; Ren, G. H.; Dai, Z. M.; Wu, N, J.; Weng, J. Q.; Xu, T. M.; Liu, X. H.; Tan, C. X. Lett. Drug Des. Discovery 2018, 15, 15.
[20] Wang, Y. R.; Zheng, D. D.; Wang, Y.; Ye, H.; Yao, W.; Ding, Y. Chin. J. Org. Chem. 2019, 39, 2053(in Chinese). (王誉蓉, 郑丹丹, 王杨, 叶浩, 姚炜, 丁颖, 有机化学, 2019, 39, 2053.)
[21] Ezabadia, I. R.; Camoutsisa, C.; Zoumpoulakisb, P.; Geronikakic, A.; Sokovićd, M.; Glamočilijad, J.; Ćirićd, A. Bioorg. Med. Chem. 2008, 16, 1150.
[22] Pardeshi, S.; Bobade, V. D. Bioorg. Med. Chem. Lett. 2011, 21, 6559.
[23] Upmanyu, N.; Gupta, J. K.; Shah, K. J. Pharm. BioAllied Sci. 2011.
[24] Liu, X. H.; Pan, L.; Weng, J. Q. Mol. Diversity 2012, 16, 251.
[25] Abou-Seri, S. M. Eur. J. Med. Chem. 2010, 45, 4113.
[26] Sharma, V.; Mehta, D. K.; Das, R.; Kaur, P. K. Int. J. Pharm. Pharm. Sci. 2016, 8, 28.
[27] Liu, X.; Clercq, E. D.; Aalzarini, J. Lett. Drug Des. Discovery 2013, 10, 27.
[28] Kamel, M. M.; Megally, N. Y. Eur. J. Med. Chem. 2014, 86, 75.
[29] El-Husseiny, W. M.; El-Sayed, M. A.-A.; Abdel-Aziz, N. I.; El-Azab, A. S.; Asirig, Y. A. Eur. J. Med. Chem. 2018, 158, 134.
[30] Liu, L.; Ye, J.; Xiao, M. W.; Yuan, K. Y; He, M.; Hu, A. X. J. Heterocycl. Chem. 2019, 56, 2192.
[31] Yang, Q. C.; Sun, X. H.; Liu, Y. F. Chin. J. Struct. Chem. 2015, 34, 197.
[32] Sheldrick, G. M. SADABS, Program for Empirical Absorption Correction of Area Detector Data, University of Gotingen, Germany, 1996.
[33] Sheldrick, G. M. SHELXTL V5.1, Software Reference Manual, Brucker AXS, Inc., Madision, Wisconsin, USA, 1997.
[34] Wang, X. F. M.S. Thesis, Nankai University, Tianjin, 2014 (in Chinese). (王晓芳, 硕士论文, 南开大学, 天津, 2014.)
Options
文章导航

/

〈 〉