Design, synthesis and biological activity of novel substituted pyrazole amide derivatives targeting EcR/USP receptor

引用本文: Xi-Le Deng, Jin Xie, Yong-Qiang Li, De-Kai Yuan, Xue-Ping Hu, Li Zhang, Qing-Min Wang, Ming Chi, Xin-Ling Yang. Design, synthesis and biological activity of novel substituted pyrazole amide derivatives targeting EcR/USP receptor[J]. Chinese Chemical Letters, 2016, 27(4): 566-570. shu

Citation: Xi-Le Deng, Jin Xie, Yong-Qiang Li, De-Kai Yuan, Xue-Ping Hu, Li Zhang, Qing-Min Wang, Ming Chi, Xin-Ling Yang. Design, synthesis and biological activity of novel substituted pyrazole amide derivatives targeting EcR/USP receptor[J]. Chinese Chemical Letters, 2016, 27(4): 566-570. shu

Design, synthesis and biological activity of novel substituted pyrazole amide derivatives targeting EcR/USP receptor

a Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China;
b State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
基金项目:
This work was supported by the National Natural Science Foundation of China (No. 21272265) and the National High Technology Research and Development Program of China (No. 2011AA10A204).

摘要: In order to discover highly active ecdysone analogs, a series of new substituted pyrazole amide derivatives were obtained using structure-guided optimization method and further screened for their insecticidal activities, in the basis of the core structures of the two active compounds N-(3-methoxyphenyl)-3-(tert-butyl)-1-phenyl-1H-pyrazole-5-carboxamide (6e) and N-(4-(tert-butyl)phenyl)-3-(tert-butyl)-1-phenyl-1H-pyrazole-5-carboxamide (6i), previously presented by us. The chemical structures of the title compounds were identified by spectral analyses. The preliminary bioassay results indicated that one among the synthesized pyrazole derivatives, compound 34, endowed with good activity against Mythimna Separata at 10 mg/L, which was equal to that displayed by the positive control tebufenozide. In addition, examples of molecular docking and molecular dynamics studies demonstrated that 34 may be the potential inhibitor to EcR and its docking conformation was similar to that of tebufenozide. In addition, increasing the hydrophobic effect and considering the suitable bulk effect on pyrazole ring are beneficial to the inhibiting activity to EcR and activity in vivo.

关键词:

English

Design, synthesis and biological activity of novel substituted pyrazole amide derivatives targeting EcR/USP receptor

a Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China;
b State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
Received Date: 25 December 2015
Revised Date: 23 January 2016
Available Online: 02 March 2016
Fund Project:
This work was supported by the National Natural Science Foundation of China (No. 21272265) and the National High Technology Research and Development Program of China (No. 2011AA10A204).

Abstract: In order to discover highly active ecdysone analogs, a series of new substituted pyrazole amide derivatives were obtained using structure-guided optimization method and further screened for their insecticidal activities, in the basis of the core structures of the two active compounds N-(3-methoxyphenyl)-3-(tert-butyl)-1-phenyl-1H-pyrazole-5-carboxamide (6e) and N-(4-(tert-butyl)phenyl)-3-(tert-butyl)-1-phenyl-1H-pyrazole-5-carboxamide (6i), previously presented by us. The chemical structures of the title compounds were identified by spectral analyses. The preliminary bioassay results indicated that one among the synthesized pyrazole derivatives, compound 34, endowed with good activity against Mythimna Separata at 10 mg/L, which was equal to that displayed by the positive control tebufenozide. In addition, examples of molecular docking and molecular dynamics studies demonstrated that 34 may be the potential inhibitor to EcR and its docking conformation was similar to that of tebufenozide. In addition, increasing the hydrophobic effect and considering the suitable bulk effect on pyrazole ring are beneficial to the inhibiting activity to EcR and activity in vivo.

Key words:

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Design, synthesis and biological activity of novel substituted pyrazole amide derivatives targeting EcR/USP receptor

English

Design, synthesis and biological activity of novel substituted pyrazole amide derivatives targeting EcR/USP receptor

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Design, synthesis and biological activity of novel substituted pyrazole amide derivatives targeting EcR/USP receptor

English

Design, synthesis and biological activity of novel substituted pyrazole amide derivatives targeting EcR/USP receptor

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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