含噻唑联哌啶烟酰胺类化合物的合成与生物活性研究
收稿日期: 2018-12-14
修回日期: 2019-02-18
网络出版日期: 2019-03-08
基金资助
浙江省绿色农药2011协同创新中心开放基金资助项目.
Synthesis and Biological Activity of Thiazolidine Piperidine Nicotinamide Compounds
Received date: 2018-12-14
Revised date: 2019-02-18
Online published: 2019-03-08
Supported by
Project supported by the Collaborative Innovation Center of Zhejiang Province Green Pesticide.
噻唑联哌啶结构能够影响生物体内胆固醇类化合物的代谢活动，是氟噻唑吡乙酮抑制病原菌的氧胆固醇结合蛋白（OSBP）的关键药效基团.为了寻找具有生物活性的新型含噻唑联哌啶结构的化合物，设计并合成了14个未见文献报道的新颖含噻唑联哌啶烟酰胺类化生物，其结构经1H NMR、13C NMR和HRMS确证，生测结果显示：在100 μg/mL浓度下，目标化合物普遍具有抑菌活性，其中1个化合物对小麦赤霉病的抑菌活性为60%；3个化合物对黄瓜灰霉病的抑菌活性为60%；6个化合物对苹果褐斑病的抑菌效果为70%；（4-（5-（2，3-二氯苯基）-4-甲基噻唑-2-基）哌啶-1-基）（5，6-二氯吡啶-3-基）甲酮（6k）对马铃薯晚疫病的抑菌活性为75%.
丁成荣 , 潘亚运 , 殷许 , 谭成侠 . 含噻唑联哌啶烟酰胺类化合物的合成与生物活性研究[J]. 有机化学, 2019 , 39(7) : 2099 -2105 . DOI: 10.6023/cjoc201812027
The structure of thiazolidine piperidine could affect the metabolic activitives of cholesterol compounds in vivo, and it is the key pharmacophore of oxythiazolidine to inhibit the oxygen cholesterol-binding protein (OSBP) of pathogenic bacteria. 14 novel thiazolidine piperidine nicotinamide derivatives were designed and synthesized in search of new bioactive compounds containing thiazolidine piperidine structure. The structures of target compounds were characterized by 1H NMR, 13C NMR and HRMS spectra. The preliminary bioassay showed that the target compounds generally had antibacterial activities. At the concentration of 100 μg/mL, the antibacterial activity of one compound against Fusarium graminearum was 60%, the antibacterial activities of three compounds against Botrytis cinerea were 60%, the bacteriostatical activities of six compounds aganist Diplocarpon mali were 70%, and the antibacterial activity of (4-(5-(2,3-dichlorophenyl)-4-methylthiazol-2- yl)piperidin-1-yl)(5,6-dichloropyridin-3-yl)methanone (6k) against Phytophthora infestans (Mont.) de Bary was 75%. There- fore it was worth for further research about structural optimization.
Key words： structure; thiazolidine piperidine; nicotinamide; antibacterial activity
[1] Huang, X. F.; Tang, J. F.; Ji, J. L. J. Organomet. Chem. 2012, 878, 1.
[2] Chavva, K.; Pillalamarri, S.; Banda, V. Bioorg. Med. Chem. Lett, 2014, 23, 5893.
[3] Dev, G. J.; Poornachandra, Y.; Reddy, K. R.; Kumar, R. N. Eur. J. Med. Chem. 2017, 130, 223.
[4] Liu, R. B.; Zheng, Y. Q.; Wang, Y. L. Agrochemicals 2018, 57, 326(in Chinese). (刘瑞宾, 郑怡倩, 汪焱鲁, 农药, 2018, 57, 326.)
[5] Cederbaum, F. WO 2014118142, 2014[Chem. Abstr. 2014, 161, 320959].
[6] Lamberth, C. WO 2014154530, 2014[Chem. Abstr. 2014, 161, 640429].
[7] Tomoki, T. US 20130296272, 2013[Chem. Abstr. 2014, 156, 337332].
[8] Gregory, V. WO 2009055514, 2009[Chem. Abstr. 2009, 150, 578441].
[9] Stefan, H. US 20160198713, 2016[Chem. Abstr. 2016, 162, 400022].
[10] Pierre, C. US 20110312999, 2011[Chem. Abstr. 2011, 155, 615369].
[11] Hanagan, M. A. WO 2009094407, 2009[Chem. Abstr. 2009, 151, 234956].
[12] Kamireddy, B. WO 2009094445, 2009[Chem. Abstr. 2009, 151, 173451].
[13] Pasteris, R. J. WO 2008013925, 2008[Chem. Abstr. 2008, 160, 302215].
[14] Hu, D. J.; Liu, S. F.; Huang, T. H. Molecules 2009, 14, 1288.
[15] Chen, L.; Zhu, Y. J.; Fan, Z. J. J. Agric. Food Chem. 2017, 65, 745.
[16] Sulzermosse, S.; Cederbaum, F.; Lamberth, C. Bioorg. Med. Chem. 2015, 23, 2129.
[17] Choi, W. S.; Nam, S. W.; Kim, I. D.; Kim, S. H.; Park, K. H.; Bae, I. K. J. Chem. 2015, 241793.
[18] Li, F. Y.; Zhu, Y. J.; Fan, Z. J.; Xu, J. H.; Guo X. F.; Zong, G. N.; Song, Y. Q.; Qian, X. L.; Ma, L. Y.; Wang, J. R. Chin. J. Struct. Chem. 2015, 34, 5659.
[19] Wang, K. B.; Pu, T.; Luo, Y. J. Yunnan Agric. Univ. 2018, 33, 218(in Chinese). (王凯博, 普特, 罗艳, 云南农业大学学报, 2018, 33, 218.)
[20] Ye, X. World Pestic. 2018, 40, 63(in Chinese). (叶萱. 世界农药, 2018, 40, 63.)
[21] Xu, J.; Ma, L.; Liu, X. B. Chin. J. Org. Chem. 2018, 38, 1680(in Chinese). (徐姣, 马玲, 刘秀波, 有机化学, 2018, 38, 1680.)
[22] Sun, N. B.; Shen, Z. H.; Zhai, Z. W. Chin. J. Org. Chem. 2017, 37, 2044(in Chinese). (孙娜波, 沈钟华, 翟志文, 有机化学, 2017, 37, 2044.)
[23] Dai, H.; Li, H.; Jin, Z. C. Chin. J. Org. Chem. 2016, 36, 185(in Chinese). (戴红, 李宏, 金智超, 有机化学, 2016, 36, 185.)
[24] Dai, H.; Chen, J.; Cao, X. F. Chin. J. Org. Chem. 2016, 36, 377(in Chinese). (戴红, 陈佳, 曹雄飞, 有机化学, 2016, 36, 377.)
[25] Li, Q. M.; Pang, K. S.; Zhao, J. P. Chin. J. Org. Chem. 2017, 37, 1009(in Chinese). (李倩梅, 庞凯胜, 赵建平, 有机化学, 2017, 37, 1009.)
[26] Li, L.; Chen, H.; Lin, Y. Synth. Commun. 2007, 37, 85.
[27] Groß, A.; Schneiders, N.; Daniel, K. Tetrahedron 2008, 64, 10882.
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