Structural Derivatization And Biological Activities Of The Diamides

The diamide insecticides, targeting at insect ryanodine receptors (RyRs), are classified as group28insecticides by Insecticide Resistance Action Committee (IRAC). Due to unique chemical structures, novel modes of action, high potency and low ecotoxicity, the diamides are the key components of today’s integrated pest management (IPM). Focusing on the Flubendiamide and Chlorantraniliprole, four series of novel diamide derivatives were designed and synthesized, and their bioactivities were evaluated with a view of providing more guidance for further structural optimization.1)1,2,3-triazoles were introduced into the aliphatic amide moiety of Flubendiamide, and a series of novel phthalic diamide derivatives were synthesized by one-pot click reactions. The reaction conditions were optimized and the amount of Et3N was essential to synthesis of target compounds in high yields. Bioassays indicated that some of the compounds exhibited high insecticidal activities against armyworm (Mythimna separata) with50%mortality at a concentration of4mg L-1. The introduction of two methyl units onto the aliphatic amide chain markedly increased the insecticidal activities.2) On the basis of the atropisomerism, a series of novel anthranilic diamides containing1,5-benzodiazepine-2,4-dione core to fix the amide were synthesized using three-component reactions. The target compounds were screened for their insecticidal activities and cytotoxic activities. Most of the compounds had no insecticidal activities, but displayed moderate to good antitumor activities against five cancer cell lines. Exhilaratingly, the activity level of two compounds rivaled that of commercialized5-Fluorouracil (5-Fu) against MCF-7cell lines.3) Based on the structure of Chlorantraniliprole, a series of novel anthranilic diamides with benzyl sulfide scaffold were synthesized, in which N-pyridylpyrazole moiety generally regarded as key pharmacophore was abandoned. The preliminary bioassays indicated that most of the title compounds were endowed with good insecticidal activities against armyworm(Mythimna separata) at500mg L-1and one-third of compunds were also active against Tetranychus cinnabarinus at500mg L-1, which provided a novel lead to obtain active compounds.4) Through bioisosteric replacement of the amide group with1,2,3-triazoles, a series of novel anthranilic diamides with tricyclic scaffold were synthesized. Most compounds exhibited no insecticidal activities expect one which was active against armyworm (Mythimna separata) with50%mortality at500mg L-1. The alignment of Chlorantraniliprole and tricyclic amide compounds indicated that the introduction of tricyclic system caused a big gap in configuration, which might result in no activity.