Design, Synthesis and Antifungal Activity of Novel Pyrazole-Thiophene Carboxamide Derivatives

doi:10.6023/cjoc202004013

Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (9): 2836-2844.DOI: 10.6023/cjoc202004013 Previous Articles Next Articles

新型吡唑联噻吩甲酰胺类衍生物的设计、合成及其抑菌活性研究

李安邦, 李中珊, 赵洋, 姚停停, 程敬丽, 赵金浩

浙江大学农药与环境毒理研究所杭州 310058

收稿日期:2020-04-09 修回日期:2020-05-16 发布日期:2020-06-28
通讯作者: 程敬丽, 赵金浩 E-mail:chengjingli@zju.edu.cn;jinhaozhao@zju.edu.cn
基金资助:
浙江省自然科学基金（No.LY19C140006）、国家重点研发计划（No.2017YFD0200505）和国家自然科学基金（No.31872022）资助项目.

Design, Synthesis and Antifungal Activity of Novel Pyrazole-Thiophene Carboxamide Derivatives

Li Anbang, Li Zhongshan, Zhao Yang, Yao Tingting, Cheng Jingli, Zhao Jinhao

Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou 310058

Received:2020-04-09 Revised:2020-05-16 Published:2020-06-28
Supported by:
Project supported by the Natural Science Foundation of Zhejiang Province (No. LY19C140006), the National Key Research & Development Program of China (No. 2017YFD0200505) and the National Natural Science Foundation of China (No. 31872022).

1. cjoc202004013辅助材料.pdf(9536KB)

Abstract

Succinate dehydrogenase inhibitor is a low-toxic and high active fungicide. In order to develop novel and broad-spectrum succinate dehydrogenase inhibitor (SDHI) fungicides, thiophene was introduced into the structure of pyrazole carboxamide fungicides. Twenty four pyrazole-thiophene carboxamides were designed, synthesized and characterized by ¹H NMR, ¹³C NMR and HRMS. The crystal structure of N-(4-methoxyphenyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7i) was determined by X-ray diffraction. The antifungal activity of all the synthesized compounds was determined against six plant pathogenic fungi, and preliminary bioassays suggested that some compounds exhibited good antifungal activity against Rhizoctonia solani, Fusarium graminearum and Botrytis cinerea. Among them, N-(4-fluorophenethyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7c) exhibited the best antifungal activities against R. solani in vitro with EC₅₀ value of 11.6 μmol/L, and N-(2-fluorophenyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7j) against F. graminearum with EC₅₀ value of 28.9 μmol/L. And N-(4-chlorophenyl)-4-(1-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide (7h) showed similar inhibition abilities with thifluzamide against B. cinerea with EC₅₀ value of 21.3 μmol/L. The molecular docking results showed that the high antifungal activitie compounds form stronger interactions with important amino acid residues of succinate dehydrogenase.

Key words: succinate dehydrogenase inhibitor, pyrazole-furan carboxamide, antifungal activity, molecular docking

Cite this article

Li Anbang, Li Zhongshan, Zhao Yang, Yao Tingting, Cheng Jingli, Zhao Jinhao. Design, Synthesis and Antifungal Activity of Novel Pyrazole-Thiophene Carboxamide Derivatives[J]. Chinese Journal of Organic Chemistry, 2020, 40(9): 2836-2844.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] Walter, H. In Bioactive Carboxylic Compound Classes, Wiley-VCH Verlag GmbH & Co. KgaA, Weinheim, 2016, pp. 405~425.
[2] Oyedotun, K. S.; Lemire, B. D. J. Biol. Chem. 2004, 279, 9424.
[3] Fungicide Resistance Action Committee FRAC Code List 2020:Fungal Control Agents Sorted by Cross Resistance Pattern and Mode of Action, Basel, 2020, pp. 1~16.
[4] Avenot, H. F.; Michailides, T. J. Crop Prot. 2010, 29, 643.
[5] Xiong, L.; Shen, Y.-Q.; Jiang, L.-N.; Zhu, X.-L.; Yang, W.-C.; Huang, W.; Yang, G.-F. In Discovery and Synthesis of Crop Protection Products, ACS Publications, Washington, 2015, pp. 175~194.
[6] Yu, F.-Q.; Guan, A.-Y.; Sun, X.-F.; Li, H.-C.; Li, X.-W. Chin. J. Org. Chem. 2019, 39, 397(in Chinese). (于福强, 关爱莹, 孙旭峰, 李慧超, 李小武, 有机化学, 2019, 39, 397.)
[7] Liu, X. H.; Qiao, L.; Zhai, Z. W.; Cai, P. P.; Cantrell, C. L.; Tan, C. X.; Weng, J. Q.; Han, L.; Wu, H. K. Pest Manage. Sci. 2019, 75, 2892.
[8] Xiao, T.-T.; Cheng, W.; Qian, W.-F.; Zhang, T.-T.; Lu, T.; Gao, Y.; Tang, X.-R. Chin. J. Org. Chem. 2020, 40, 1704(in Chinese). (肖婷婷, 程玮, 钱伟烽, 张婷婷, 陆童, 高扬, 唐孝荣, 有机化学, 2020, 40, 1704.)
[9] Xiong, L.; Li, H.; Jiang, L.-N.; Ge, J.-M.; Yang, W.-C.; Zhu, X. L.; Yang, G.-F. J. Agric. Food Chem. 2017, 65, 1021.
[10] Guo, X. F.; Zhao, B.; Fan, Z. J.; Yang, D. Y.; Zhang, N. L.; Wu, Q. F.; Yu, B.; Zhou, S.; Kalinina, T. A.; Belskaya, N. P. J. Agric. Food Chem. 2019, 67, 1647.
[11] Wu, Y.-Y.; Shao, W.-B.; Zhu, J.-J.; Long, Z.-Q.; Liu, L.-W.; Wang, P.-Y.; Li, Z.; Yang, S. J. Agric. Food Chem. 2019, 67, 13892.
[12] Du, S. J.; Lu, H. Z.; Yang, D. Y.; Li, H.; Gu, X. L.; Wan, C.; Jia, C. M.; Wang, M.; Li, X. Y.; Qin, Z. H. Molecules 2015, 20, 4071.
[13] Li, H. X.; Nuckols, T. A.; Harris, D.; Stevenson, K. L.; Brewer, M. T. Pest Manage. Sci. 2019, 75, 3093.
[14] Hou, Y.-P.; Mao, X.-W.; Wang, J.-X.; Zhan, S.-W.; Zhou, M. G. Crop Prot. 2017, 96, 237.
[15] Zhang, A. G.; Zhou, J. Y.; Tao, K.; Hou, T. P.; Jin, H. Bioorg. Med. Chem. Lett. 2018, 28, 3042.
[16] Yan, W.; Wang, X.; Li, K.; Li, T. X.; Wang, J. J.; Yao, K. C.; Cao, L.-L.; Zhao, S.-S.; Ye, Y.-H. Pestic. Biochem. Phys. 2019, 156, 160.
[17] Xue, H. S.; Liu, A. P.; Liu, W. D.; Li, J. M.; Ren, Y. G.; Huang, L.; He, L.; Ou, X. M.; Ye, J.; Huang, M. Z. Chem. Res. Chin. Univ. 2016, 32, 781.
[18] Yao, T.-T.; Xiao, D.-X.; Li, Z.-S.; Cheng, J.-L.; Fang, S.-W.; Du, Y.-J.; Zhao, J.-H.; Dong, X.-W.; Zhu, G.-N. J. Agric. Food Chem. 2017, 65, 5397.
[19] Yao, T. T.; Fang, S. W.; Li, Z. S.; Xiao, D. X.; Cheng, J. L.; Ying, H. Z.; Du, Y. J.; Zhao, J. H. J. Agric. Food Chem. 2017, 65, 3204.
[20] Zhang, L.-J.; Yang, M.-Y.; Sun, Z.-H.; Tan, C.-X.; Weng, J.-Q.; Wu, H.-K.; Liu, X.-H. Lett. Drug. Des. Discovery 2014, 11, 1107.
[21] Ye, Y.-H.; Ma, L.; Dai, Z.-C.; Xiao, Y.; Zhang, Y.-Y.; Li, D.-D.; Wang, J.-X.; Zhu, H.-L. J. Agric. Food Chem. 2014, 62, 4063.
[22] Lv, X. H.; Ren, Z.-L.; Liu, P.; Li, B. X.; Li, Q. S.; Chu, M. J.; Cao, H. Q. Pest Manage. Sci. 2017, 73, 1585.
[23] Huang, L.-S.; Sun, G.; Cobessi, D.; Wang, A. C.; Shen, J. T.; Tung, E. Y.; Anderson, V. E.; Berry, E. A. J. Biol. Chem. 2006, 281, 5965.

新型吡唑联噻吩甲酰胺类衍生物的设计、合成及其抑菌活性研究

Design, Synthesis and Antifungal Activity of Novel Pyrazole-Thiophene Carboxamide Derivatives

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Simin Wu, Jiaxin Tang, Yujia Zhou, Xuetao Xu, Haoxing Zhang, Shaohua Wang. α-Glucosidase Inhibition Research of Derivatives Based on 2β-Acetoxyferruginol Scaffold Excluding Acetic Acid Group [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 613-621.
[2]	Feng Wang, Yu Chen, Hongyan Pei, Jing Zhang, Lixin Zhang. Design, Synthesis and Antifungal Activities of Novel 1,2,4-Oxadiazole Derivatives Containing Piperidine [J]. Chinese Journal of Organic Chemistry, 2023, 43(8): 2826-2836.
[3]	Min Liu, Dongyan Yang, Yumei Xiao, Wangcang Su, Fenghai Zhao, Qin Zhaohai .. Synthesis and Bioactivities of 5-Nitroimino-[1,4-2H]-1,2,4-triazolines as Olefin-Imidacloprid Mimics [J]. Chinese Journal of Organic Chemistry, 2023, 43(8): 2790-2799.
[4]	Huan Xu, Hongfei Wu, Xiaoming Zhang, Xingxing Lu, Tengda Sun, Yue Qi, Yufan Lin, Xinling Yang, Li Zhang, Yun Ling. Design, Synthesis and Bioactivity of Sulfonyl Hydrazides and Hydrazides Containing Fragment 1,2,3,4-Tetrahydroisoquinoline [J]. Chinese Journal of Organic Chemistry, 2023, 43(2): 725-733.
[5]	Meng Li, Dongguo Xia, Yunxiao Wang, Xiang Cheng, Jiexiu Gong, Yao Chen, Xianhai Lü. Design, Synthesis and Antifungal Bioactivity Evaluation of Thiazole Benzoate Derivatives [J]. Chinese Journal of Organic Chemistry, 2023, 43(2): 686-696.
[6]	Changxing Sun, Fuhao Zhang, Huan Zhang, Penghui Li, Lin Jiang. Design, Synthesis, Fungicidal Activity and Molecular Docking Study of Novel 2-(1-Methyl-1H-pyrazol-4-yl)pyrimidine-4-carboxamides [J]. Chinese Journal of Organic Chemistry, 2023, 43(1): 229-235.
[7]	Wei Chen, Simin Lei, Yuxin Lan, Haojian Xu, Pingbin Yu, Rui Zhang, Run Wu, Yang Chen. Design, Synthesis and Antifungal Activities of Novel Quinazolinone Derivatives [J]. Chinese Journal of Organic Chemistry, 2022, 42(7): 2164-2171.
[8]	Changkai Wang, Tengda Sun, Xuebo Zhang, Xinling Yang, Xingxing Lu, Huan Xu, Fasheng Shi, Li Zhang, Yun Ling. Design, Synthesis and Bioactivity of Novel Fluoropyrazole Hydrazides [J]. Chinese Journal of Organic Chemistry, 2022, 42(5): 1527-1536.
[9]	Xiu Wang, Wengui Duan, Guishan Lin, Baoyu Li, Wenjing Zhang, Fuhou Lei. Synthesis, Antifungal Activity, Three-Dimensional Quantitative Structure-Activity Relationship and Molecular Docking Study of 4-Acyl-3-amino-1,2,4-triazole-thioether Derivatives Containing Natural Pinene Structure [J]. Chinese Journal of Organic Chemistry, 2022, 42(3): 871-883.
[10]	Yuanfang Kong, Bin Yang, Yan Zhuang, Jingyu Zhang, Demei Sun, Chunhong Dong. Research Progress on the Synthesis and Structure-Activity Relationship of Five Hypoglycemic Active Heterocycles Based on Dipeptidyl Peptidase 4 (DPP-4) Target Design [J]. Chinese Journal of Organic Chemistry, 2022, 42(3): 770-784.
[11]	Wei Wang, Furan Wu, Yidan Ma, Dan Xu, Gong Xu. Study on Synthesis and Antifungal Activity of Novel Benzamides Containing Substituted Pyrazole Unit [J]. Chinese Journal of Organic Chemistry, 2022, 42(2): 607-618.
[12]	Yucheng Cui, Meihua Chen, Guishan Lin, Wengui Duan, Qingmin Li, Renxuan Zou, Bo Cen. Synthesis, Antifungal Activity and Molecular Docking Study of 1,3,4-Thiadiazole-Urea Compounds Containing gem-Dimethylcyclopropane Ring Structure [J]. Chinese Journal of Organic Chemistry, 2022, 42(11): 3784-3797.
[13]	Yingjun Li, Ledi Lin, Jihong Liu, Lixin Gao, Li Sheng, Kun Jin, Xuejie Liu, Hongjing Yang, Jia Li. Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel N-Acylhydrazone Derivatives Containing Carbazole and Aromatic Ring/Aromatic Fused Heterocycle [J]. Chinese Journal of Organic Chemistry, 2021, 41(9): 3593-3607.
[14]	Yingjun Li, Ledi Lin, Kun Jin, Lixin Gao, Li Sheng, Jihong Liu, Jia Li. Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel Arylaminoacetylhydrazone Derivatives Containing Carbazole Moiety [J]. Chinese Journal of Organic Chemistry, 2021, 41(8): 3157-3170.
[15]	Weiwei Wang, Yu Zhao, Xinlei Liu, Jiazhen Jiang, Ming'an Wang. Synthesis and Antifungal Activity of 3-Aryl-7-methyl- 7-hydroxy-2-octen-6-olide [J]. Chinese Journal of Organic Chemistry, 2021, 41(6): 2343-2353.