Design, Synthesis, and Biological Evaluation of Pyrido [1,2-α] Pyrimidinone Mesoionic Derivatives Bearing Propenylbenzene as the Vector Control Insecticide.

A series of novel pyrido [1,2-α] pyrimidinone mesoionic derivatives bearing a propenylbenzene group at the 1-position were synthesized on the basis of the structure of mesoionic insecticides triflumezopyrim and dicloromezotiaz via a rationally conceived pharmacophore model and evaluated for their insecticidal activities against three insect vectors. The bioassay results showed that some compounds exerted remarkable insecticidal activities against M. domestica , Ae. albopictus , and B. germanica . Particularly, compound 26l displayed outstanding insecticidal activity against Ae. Albopictus , with an LC 50 value of 0.45 μg/mL, far superior to that of imidacloprid (LC 50 = 1.82 μg/mL) and equivalent to that of triflumezopyrim (0.35 μg/mL). Meanwhile, compound 34l presented a broad insecticidal spectrum, with LC 50 values of 1.51 μg/g sugar, 0.52 μg/mL and 0.14 μg/adult, which were about 2.88, 3.50, and 1.50 times better than that of imidacloprid (LC 50 = 4.35 μg/g sugar, 1.82 μg/mL and 0.21 μg/adult against M. domestica , Ae. albopictus , and B. germanica , respectively) and equivalent to that of triflumezopyrim against M. domestica (1.13 μg/g sugar) and Ae. albopictus (0.35 μg/mL) but lower than the potency against B. germanica (0.06 μg/g sugar). The molecular docking study by energy minimizations revealed that introducing propenylbenzene at the 1-position of compounds 26l and 34l could embed into the binding pocket of nicotinic acetylcholine receptors and form pi-alkyl interaction with LEU306. These results demonstrated that compounds 26l and 34l could be promising candidates for vector control insecticides, which deserved further investigation.