Target-based design, synthesis and biological activity of new pyrazole amide derivatives

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• 作者：Xi-Le Deng^a ; Li Zhang^a ; ^{zhang_li@cau.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Xue-Ping Hu^a ; Bin Yin^a ; Pei Liang^b ; Xin-Ling Yang^a ; ^{yangxl@cau.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Molting hormone ; Pyrazole amide ; Rational design ; Bioactivity ; Molecular docking
• 刊名：Chinese Chemical Letters
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：27
• 期：2
• 页码：251-255
• 全文大小：555 K

文摘

Based on the similarities in the conformation of VS008 (N-(4-methylphenyl)-3-(tert-butyl)-1-(phenylmethyl)-1H-pyrazole-5-carboxamide) and BYIO6830 (N′-(3,5-Dimethylbenzoyl)-N′-tert-butyl-5-methyl-2,3-dihydro-1,4-benzodioxine-6-carbohydrazide) bound to the active site of the EcR subunit of the ecdysone receptor (EcR)-ultraspiracle protein (USP) heterodimeric receptor, a series of new pyrazole amide derivatives were designed and synthesized. Their structures were confirmed by IR, ¹H NMR, ¹³C NMR and elemental analysis. Results from a preliminary bioassay revealed that two of the pyrazole derivatives exhibited promising insecticidal activity. Specifically, compounds 6e and 6i exhibited good activity against Helicoverpa armigera (cotton bollworm) at low concentration. Symptoms displayed by tebufenozide-treated H. armigera were identical with those displayed by its treated counterpart. 6i showed the same poisoning symptoms as those of tebufenozide. In addition, results from molecular docking result indicated that the binding modes of 6e and 6i at the active site of the EcR subunit of the heterodimeric receptor were similar to that of the bound tebufenozide.