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

Based on the similarities in the conformation of VS008 (N-(4-methylphenyI)-3-(tert-butyl)-1(phenylmethyl)-1H-pyrazole-5-carboxamide) and BYI06830 (N'-(3,5-dimethylbenzoyl)-N'-tert-butyl5-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, H-1 NMR, C-13 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 Helicoveipa 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. (C) 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.