Synthesis,insecticidal activities,and molecular docking studies of 1,5‐disubstituted‐1,3,5‐hexahydrotriazine‐2‐(N‐nitro)imines

A series of novel neonicotinoids analogs were designed by modifying the pharmacophore of imidacloprid to 1,3,5‐hexahydrotriazine conjugated to nitroimine (?NNO₂) and introducing the phenyl or arylmethyl at the 5‐position, and their insecticidal activities were evaluated. Introducing a heterocyclic methyl at 5‐position increased the insecticidal activities, whereas other phenyl, phenylmethyl or phenylethyl substituents were unfavorable to activities. Molecular docking study was also performed to clarify the interactions of the most potent analog 1‐((6‐chloropyridin‐3‐yl)methyl)‐5‐(3‐pyridylmethyl)‐1,3,5‐hexahydrotriazine‐2‐(N‐nitro) imine ( 7s ) with the target nicotinic acetylcholine receptor, which explained the structure‐activity relationships observed in vitro, and revealed further possibilities for insecticide development. J. Heterocyclic Chem., (2011).