Design, Synthesis, and Bioactivities of Novel 4-(Trifluoromethyl)nicotinamide Derivatives for Use as Insecticides.

Abstract

Hemiptera pests damage crops and transmit viruses through piercing-sucking mouthparts, causing enormous economic losses and inducing resistance to insecticides. Novel insecticides are critical to combat rising resistance. Nicotinamidase, a newly validated target present in the insect chordotonal organ, has attracted attention. A series of novel sulfonyl, carbonyl, and amide group-based 4-(trifluoromethyl)nicotinamide derivatives was designed using the prodrug strategy and an intermediate derivatization method. Bioactivity assays indicated that most compounds possessed enhanced insecticidal activity. B-38 exhibited outstanding lethality against Sitobion avenae (LC50 = 0.710 mg/L), outperforming that of flonicamid (LC50 = 13.7 mg/L). The 3D-QSAR model revealed that the introduction of electron-withdrawing groups at the R3 position and electron-donating groups at the R4 positions, respectively, enhanced insecticidal potency. DFT calculations suggested that propargyl and imide groups may be essential for bioactivity. This study provides fundamental insights for developing green and efficient insecticides.