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

It is important to develop new insecticides with a new mode of action because of increasing pesticide resistance. In this study, a series of novel aryl isoxazoline derivatives containing the pyrazole-5-carboxamide motif were designed and synthesized. Their structures were confirmed by 1H NMR, 13C NMR, and HRMS. Bioassays indicated that the 24 compounds synthesized possessed excellent insecticidal activity against Mythimna separate and no activity against Aphis craccivora and Tetranychus cinnabarinus. Among these aryl isoxazoline derivatives, 3-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydrozol-3-yl)-N-(4-fluorophenyl)-1-methyl-1H-pyrazole-5-carboxamide (IA-8) had the best insecticidal activity against M. separate, which is comparable with the positive control fluralaner. The molecular docking results of compound IA-8 and fluralaner with the GABA model demonstrated the same docking mode between compound IA-8 and positive control fluralaner in the active site of GABA. Molecular structure comparisons and ADMET analysis can potentially be used to design more active compounds. The structure-activity relationships are also discussed. This work provided an excellent insecticide for further optimization.

• Publication year

  2023

• Venue

  Journal of Agricultural and Food Chemistry

• Publication date

  2023-10-02

• Fields of study

  Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.1021/acs.jafc.3c01608PMID 37782011
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Potential Fungicide Candidates: A Dual Action Mode Study of Novel Pyrazole-4-carboxamides against Gibberella zeae.

  2023cited by this paper
• Discovery of Novel Isoxazoline Compounds that Incorporate a para-Diamide Moiety as Potential Insecticidal Agents against Fall Armyworm (Spodoptera frugiperda).

  2023cited by this paper
• Design, Synthesis, and Insecticidal and Fungicidal Activities of Ether/Oxime-ether Containing Isoxazoline Derivatives.

  2023cited by this paper
• Multi-centre discriminating concentration determination of broflanilide and potential for cross-resistance to other public health insecticides in Anopheles vector populations

  2022cited by this paper
• High frequency of ryanodine receptor and cytochrome P450 CYP9A186 mutations in insecticide-resistant field populations of Spodoptera exigua from China.

  2022cited by this paper
• Novel Dioxolane Ring Compounds for the Management of Phytopathogen Diseases as Ergosterol Biosynthesis Inhibitors: Synthesis, Biological Activities, and Molecular Docking.

  2022cited by this paper
• Design, Synthesis, and Insecticidal and Fungicidal Activities of Quaternary Ammonium Salt Derivatives of a Triazolyphenyl Isoxazoline Insecticide.

  2022cited by this paper
• Discovery of N-Methoxy-(biphenyl-ethyl)-pyrazole-carboxamides as Novel Succinate Dehydrogenase Inhibitors.

  2022cited by this paper
• Novel Pyrazole Carboxamide Containing a Diarylamine Scaffold Potentially Targeting Fungal Succinate Dehydrogenase: Antifungal Activity and Mechanism of Action.

  2022cited by this paper
• Activity, selection response and molecular mode of action of the isoxazoline afoxolaner in Tetranychus urticae.

  2022cited by this paper
• Synthesis, crystal structure, herbicidal activity and mode of action of new cyclopropane-1,1-dicarboxylic acid analogues.

  2022cited by this paper
• The mode of action of isocycloseram: A novel isoxazoline insecticide.

  2022cited by this paper
• Design, Synthesis, and Pesticidal Activities of Pyrimidin-4-amine Derivatives Bearing a 5-(Trifluoromethyl)-1,2,4-oxadiazole Moiety.

  2021cited by this paper
• Synthesis, insecticidal activities and DFT study of pyrimidin-4-amine derivatives containing the 1,2,4-oxadiazole motif

  2021cited by this paper
• Enantioselective Detection, Bioactivity and Metabolism of the Novel Chiral Insecticide Fluralaner.

  2020cited by this paper
• Synthesis and Herbicidal Activity of Novel Pyrazole Aromatic Ketone Analogs as HPPD Inhibitor.

  2019cited by this paper
• Novel 4-pyrazole carboxamide derivatives containing flexible chain motif: design, synthesis and antifungal activity.

  2019cited by this paper
• Neurotoxicity and mode of action of fluralaner on honeybee Apis mellifera L.

  2019cited by this paper
• Lethal and sublethal effects of fluralaner on the two-spotted spider mites, Tetranychus urticae Koch (Acari: Tetranychidae).

  2019cited by this paper
• Synthesis, Crystal Structure, Antifungal Activity, and Docking Study of Difluoromethyl Pyrazole Derivatives

  2019cited by this paper
• Fluxametamide: A novel isoxazoline insecticide that acts via distinctive antagonism of insect ligand-gated chloride channels.

  2018cited by this paper
• Insecticidal spectrum of fluralaner to agricultural and sanitary pests

  2017cited by this paper
• Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner

  2017cited by this paper
• Lotilaner - a novel systemic tick and flea control product for dogs

  2017cited by this paper
• Mechanisms of Action, Resistance and Toxicity of Insecticides Targeting GABA Receptors.

  2017cited by this paper
• Synthesis, nematocidal activity and SAR study of novel difluoromethylpyrazole carboxamide derivatives containing flexible alkyl chain moieties.

  2017cited by this paper
• Synthesis and in vivo nematocidal evaluation of novel 3-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives

  2017cited by this paper
• Design and synthesis of sarolaner, a novel, once-a-month, oral isoxazoline for the control of fleas and ticks on dogs.

  2016cited by this paper
• Synthesis, nematocidal activity and docking study of novel chiral 1-(3-chloropyridin-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives.

  2016cited by this paper
• Broflanilide: A meta-diamide insecticide with a novel mode of action.

  2016cited by this paper
• The novel isoxazoline ectoparasiticide fluralaner: selective inhibition of arthropod γ-aminobutyric acid- and L-glutamate-gated chloride channels and insecticidal/acaricidal activity.

  2014cited by this paper
• The Calculation of Molecular Structural Similarity: Principles and Practice

  2014cited by this paper
• New GABA/glutamate receptor target for [³H]isoxazoline insecticide.

  2013cited by this paper

• Synthesis, Biological Activity and in silico Study of Pyrimidine-triazole Hybrids

  2026cites this paper
• Electrochemical Acceptorless Dehydrogenation of N-Heterocycles: Sustainable Synthesis of Aromatic Compounds with Hydrogen Release.

  2025cites this paper
• Comprehensive Overview of Pyrazole Amide Derivatives as Novel Pesticides for Crop Protection and Pest Management.

  2025cites this paper
• Computer‐aided design of novel anthranilic diamides containing fluorinated alkoxy groups as potential ryanodine receptor insecticides

  2025cites this paper
• Pyrazole derivatives: Recent advances in discovery and development of pesticides

  2025cites this paper
• Novel 5-(Trifluoromethyl)-1,2,4-oxadiazole-Based Pyrimidin-4-ether Histone Deacetylase Inhibitors for Controlling Rust Disease: Design, Synthesis, Activity, and Structure-Activity Relationship.

  2025cites this paper
• Synthetic aspects, structural insights and pharmacological potential of pyrazole derivatives: an overview

  2025cites this paper
• Isoxazoline: An Emerging Scaffold in Pesticide Discovery.

  2025cites this paper
• Prevention strategies for organophosphate and pyrethroid pesticide poisoning: case studies of flucythrinate and dichlorvos

  2025cites this paper
• Design, synthesis, herbicidal activity, and the molecular docking study of novel phenylpyrazole derivatives with strobilurin moieties

  2025cites this paper
• Isoxazoline: A Privileged Scaffold for Agrochemical Discovery.

  2025cites this paper
• Selectivity of chirality isoxazoline insecticides upon GABARs among on‐target and non‐target species via molecular model

  2025cites this paper
• Design, synthesis, and mechanism study of novel isoquinoline derivatives containing an oxime moiety as antifungal agents.

  2025cites this paper
• Novel 5‐(Trifluoromethyl)‐1,2,4‐Oxadiazole Substituted Benzamide Derivatives Containing 5‐(Trifluoromethyl)‐1,2,4‐Oxadiazole Moiety: Design, Synthesis, Anti‐Rust and In Silico Study

  2025cites this paper
• Efficient synthesis of trifluoromethyl-containing vicinal chlorohydrins and dichlorides via Mn-mediated chlorohydroxylation and dichlorination of α-(trifluoromethyl)styrenes.

  2025cites this paper
• Pyrazole Amide Scaffolds in Agricultural Chemistry: From Molecular Design to Applications.

  2025cites this paper
• Design, Synthesis, and Anti-Oomycete and Antifungal Activities of Novel Paeonol Derivatives Containing a Pyrazole Ring.

  2025cites this paper
• Design, Synthesis of Novel Pyrimidine Derivatives Containing Alkenyl Moieties With Herbicidal Activities

  2024cites this paper
• Novel Pyrazole Acyl(thio)urea Derivatives Containing a Biphenyl Scaffold as Potential Succinate Dehydrogenase Inhibitors: Design, Synthesis, Fungicidal Activity, and SAR.

  2024cites this paper
• Synthesis and Biological Activities of Novel Pyrazole Carboxamides Containing an Aryloxypyridyl Ethylamine Module.

  2024cites this paper
• (NH4)2S2O8 promoted tandem radical cyclization of quinazolin-4(3H)-ones with oxamic acids for the construction of fused quinazolinones under metal-free conditions.

  2024cites this paper
• Novel Insecticidal Butenolide‐Containing Methylxanthine Derivatives: Synthesis, Crystal Structure, Biological Activity Evaluation, DFT Calculation and Molecular Docking

  2024cites this paper
• Novel Uracilphenyl sulfonamide-based inhibitors of protoporphyrinogen oxidase: Design, synthesis, and herbicidal activity

  2024cites this paper
• Visible-light-induced Cascade Radical Cyclization for the Synthesis of Amide-functionalized Fused Quinazolinones

  2024cites this paper
• Comparative Biological Half-Life of Penthiopyrad and Tebufenpyrad in Angelica Leaves and Establishment of Pre-Harvest Residue Limits (PHRLs)

  2024cites this paper
• Design, Synthesis, Antifungal and Antibacterial Activities of Novel Difluoromethyl Pyrazole Derivatives

  2024cites this paper
• Recent Research Progress in Oxime Insecticides and Perspectives for the Future.

  2024cites this paper
• Design, Synthesis, and Acaricidal/Insecticidal Activities of New Phenylpyrazole Derivatives Comprising an Imide Moiety.

  2024cites this paper
• Synthesis, Crystal Structure, Hirshfeld Surface Analysis, Energy Frameworks, Molecular Docking and DFT Calculation of New Pyrazole-4-carboxamide Compound as Antifungal Agent

  2024cites this paper
• Discovery of the Chlorinated and Ammoniated Derivatives of Vanillin as Potential Insecticidal Candidates Targeting V-ATPase: Structure-Based Virtual Screening, Synthesis, and Bioassay.

  2024cites this paper
• Synthesis, antifungal activity, and 3d-QSAR study of L-carvone-based pyrazole-oxime ester compounds

  2024cites this paper
• N‐Methoxy Pyrazole‐4‐Carboxamide Derivatives: Synthesis, Spectral Analyses, Antifungal Activity, In Silico Molecular Docking, ADMET, and DFT Studies

  2024cites this paper
• Studies on the synthesis, crystal structures, biological activities and molecular docking of novel natural methylxanthine derivatives containing piperazine moiety

  2024cites this paper
• Synthesis and Insecticidal Activity of Novel Trifluoromethylbenzimidazole Linked N-Phenylamide Compounds

  2023cites this paper
• Discovery of Highly Efficient Novel Antifungal Lead Compounds Targeting Succinate Dehydrogenase: Pyrazole-4-carboxamide Derivatives with an N-Phenyl Substituted Amide Fragment.

  2023cites this paper
• Novel Nitrophenyl Substituted Anthranilic Diamide Derivatives: Design, Synthesis, Selectivity, and Antiresistance.

  2023cites this paper
• Synthesis, Herbicidal Activity, Mode of Action, and In Silico Analysis of Novel Pyrido[2,3-d]pyrimidine Compounds

  2023influential citation