Synthesis And Bioactivities Of Pyrazole-Heterocyclic Diamide

The long-term use of some high-toxic pesticides caused some problems like ecological environment changes and pesticide resistance. So it had been attracted wide concern to develop novel pesticides which were high-effective, wide-spectrum, less-poisonous and safe.Fipronil and chlorantraniliprole are two high-effective insecticides with special insecticidal mechanism. In this thesis, based on the structural features of these two molecules, 16 novel pyrazole-heterocyclic diamides 3a~3p were designed and synthesized according to the principle of combination of bioactive substructures and the structures were shown in the figure below. All chemicals were characterized by IR, 1H NMR and HRMS. The crystal structure of 3h was determined by X-ray diffraction analysis. Bioassay for all novel compounds were carried out, the preliminary results showed that some compounds exhibited lethal activities against mythimna sepatara and aphis medicaginis at the dosage of 500mg/L, the lethal rate of mythimna sepatara treated with 3f was 80%, the lethal rate of aphis medicaginis treated with 3n was 80%; most compounds had anti-feeding effect against the larvae of ectropis oblique hypulina wehrli at the dosage of 100mg/L, the feeding area was 9% ( CK was 100%) after being treated with 3e and the lethal rate was 60% in 48h and increased to 80% after 72h.In order to discover high-active compounds more efficiently, the computer aided molecular design software, Discovery Studio 2.5, was used to estimate the activities and conduct molecular design.Based on 21 ryanodine receptor activators and their LC50 data, qualitative and quantitative pharmacophore models were created and optimized respectively. 3D-QSAR of those synthetic target compounds was researched. It directed further molecular structure optimization that insecticidal activities may increase remarkably by introducing hydrogen bond acceptor to the pyrazole ring on the 4th position. Hydrogen bond acceptor may be those functional groups containing N, O, S etc.In conclusion, the novel synthetic pyrazole-heterocyclic diamides showed high insecticidal activities and 3D-QSAR research provided assistance to further optimization of this kind of compounds.