Molecular Design Of Flexible Amide Bond Containing Cis Nitenpyram Analogues, Synthesis, Insecticidal Activity And Molecular Docking Studies

With the increase of usage and frequency of utilization of neonicotinoidsinsecticide, its resistance has become more and more serious. In order to search forleading compounds of neonicotinoid insecticides with novel structural features,unique mechanism of action, high activity, favorable safety and broad insecticidalspectra. Based on the strategies of donor/receptor structure-guided neonicotinoiddesign and obeying the principle of bioisosteric, two novel series of cis-nitenpyramanalogues IVand Vwith an amides linkage anchored on the tetrahydropyrimidine irngwere designed and synthesized. The structural formulas of compounds IVand V are asfollows respectively: All th’ese target compounds structures were confirmed by!H NMR, IR，elementary analysis, and LC-MS. Besides, their physic-chemical properties, spectrumproperties, reaction conditions and synthetic methods were discussed as well.The preliminary biological activities tests of target compounds IV and V werefinished in Zhejiang Chemical Industry Research Institute. Preliminary bioassaysagainst Nilaparvata lugens and Myzus persicae indicated that all the analogues had100%mortality at100mg/L, while the target compounds had higher insecticidalactivities against Nilaparvata lugens than Myzus persicae at a lower dose. Amongthese analogues, IV15、IV25and V3showed the best activity, which had100%mortality at4mg/L against Nilaparvata lugens, the LC50values of the analogues IV15、IV25and V3were0.128,0.123and0.122mg/L, respectively. And the analogue V3showed the best activity, which had100%(LC5o=0.122rrig/L) mortality at4mg/Lagainst Nilaparvata lugens, and which was lower than nitenpyram (IC50=0,123mg/L).Compounds IV3、IV15、IV25、VV V?and V12with high activity was studiedfor their binding activity into the nicotinic acetylcholine receptors (nAChRs) by(Gaussian03，Gaussian View, Accelrys DS visualizer2.5and AutoDock4.0)molecular docking simulations. The results clearly indicated that the active analogues exhibited significant H-bonding interactions with the amino acid residues of insectnAChRs, especially the amides linkage played an important role in the interactions.