Novel Insecticidal Benzo[4,5]imidazo[1,2‐b]pyrazole Derivatives Identified through Ring‐Closure Scaffold Hopping on Fipronil

Abstract A series of innovative benzo[4,5]imidazo[1,2‐ b ]pyrazole scaffold containing compounds were rationally designed through a ring‐closure scaffold hopping strategy and synthetized with an intermediate derivatization approach. Physicochemical properties analysis indicated the potential pesticide‐likeness of the target compounds. The optimal target compound A14 showed relatively good insecticidal activity against P. xylostella , with an LC 50 value of 37.58 mg/L, and demonstrated lower acute fish toxicity compared to fipronil. Docking binding mode analysis demonstrated that compound A14 bound to GABAR through a H‐bond between the amide group and the residue of 6’Thr. The differences in binding modes between benzo[4,5]imidazo[1,2‐ b ]pyrazole target compounds and fipronil may be a key factor for the reduced insecticidal activities. The elucidated binding mode and SAR profile lay a foundation for the further structural optimization of insecticidal benzo[4,5]imidazo[1,2‐ b ]pyrazole derivatives.