Design, Synthesis, Insecticidal Activity, and SAR of Aryl Isoxazoline Derivatives Containing Pyrazole-5-carboxamide...

Area of Science:

• Organic Chemistry
• Insecticide Development
• Molecular Biology

Background:

• Increasing pesticide resistance necessitates novel insecticides with new modes of action.
• Pyrazole-5-carboxamide and aryl isoxazoline motifs are explored for insecticidal properties.

Purpose of the Study:

• Design and synthesize novel aryl isoxazoline derivatives with a pyrazole-5-carboxamide core.
• Evaluate the insecticidal activity of synthesized compounds against key agricultural pests.
• Investigate the mode of action and structure-activity relationships of potent compounds.

Main Methods:

• Synthesis of novel aryl isoxazoline derivatives.
• Structural confirmation using 1H NMR, 13C NMR, and HRMS.
• Bioassays against Mythimna separate, Aphis craccivora, and Tetranychus cinnabarinus.
• Molecular docking studies with the GABA receptor model.

Main Results:

• Twenty-four novel compounds were synthesized and characterized.
• Compounds showed excellent insecticidal activity against Mythimna separate but no activity against Aphis craccivora and Tetranychus cinnabarinus.
• Compound IA-8 exhibited the highest insecticidal efficacy against Mythimna separate, comparable to fluralaner.
• Molecular docking revealed a similar binding mode of IA-8 and fluralaner to the GABA receptor.

Conclusions:

• Novel aryl isoxazoline derivatives containing the pyrazole-5-carboxamide motif are effective insecticides against Mythimna separate.
• Compound IA-8 represents a promising lead for developing new insecticides to combat pesticide resistance.
• Structure-activity relationship and ADMET analysis can guide future optimization efforts.