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

作　　者：Xi-Le Deng Jin Xie Yong-Qiang Li De-Kai Yuan Xue-Ping Hu Li Zhang Qing-Min Wang Ming Chi Xin-Ling Yang 

机构地区：[1]Department of Applied Chemistry, College of Science, China Agricultural University [2]State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University

出　　处：《Chinese Chemical Letters》2016年第4期566-570,共5页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China (No. 21272265);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 Ec R 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 Ec R and activity in vivo.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 Ec R 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 Ec R and activity in vivo.

关 键 词：Moulting hormone Pyrazole amide Bioactivity Molecular docking Molecular dynamics simulation INSECT growth regulators 

分 类 号：O626[理学—有机化学] TQ453[理学—化学]