Skip to content
2000
image of Research Progress of Isoxazoline Insecticides

Abstract

Isoxazoline insecticides constitute a class of compounds featuring the isoxazoline structure, which primarily exert their effects by inhibiting the γ-aminobutyric acid (GABA)-gated chloride channel in insects. GABA serves as the primary inhibitory neurotransmitter in invertebrates, with its receptor composed of subunits encoded by the gene. By selectively inhibiting the GABA-Cl receptor subunit in invertebrates, isoxazolines block inhibitory neurotransmission, ultimately resulting in insect mortality. This unique mechanism of action endows isoxazolines with a high degree of selective toxicity toward insects while maintaining relative safety for mammals. Recently, isoxazoline insecticides have garnered considerable attention due to their broad-spectrum efficacy, high potency, and environmentally friendly profile. These compounds have emerged as promising solutions in crop protection and animal health management, offering innovative means to combat insect pests and parasites. Their development represents a significant advancement in pesticides, offering farmers and veterinarians effective and sustainable options for managing agricultural and animal health challenges. This review mainly introduces the current commercialized and under-development isoxazoline insecticides, the research progress on the mechanism of action of isoxazoline insecticides, the study of synthetic methods, as well as the research progress in structural derivation and structure-activity relationship.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cos/10.2174/0115701794353877241213051959
2024-12-26
2025-10-03

  • From This Site

    /content/journals/cos/10.2174/0115701794353877241213051959
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Ventura-Hernández K.I. Delgado-Alvarado E. Pawar T.J. Olivares-Romero J.L. Chirality in insecticide design and efficacy. J. Agric. Food Chem. 2024 72 38 20722 20737 10.1021/acs.jafc.4c05363 39255417
    [Google Scholar]
  2. Shah H.K. Srinivasan V. Venkatesan S. Balakrishnan V. Candasamy S. Mathew N. Kumar A. Kuttiatt V.S. Evaluation of the mosquitocidal efficacy of fluralaner, a potential candidate for drug based vector control. Sci. Rep. 2024 14 1 5628 10.1038/s41598‑024‑56053‑x 38454095
    [Google Scholar]
  3. Gao Y.C. Song X. Jia T. Zhao C. Yao G. Xu H. Discovery of new N-Phenylamide Isoxazoline derivatives with high insecticidal activity and reduced honeybee toxicity. Pestic. Biochem. Physiol. 2024 200 105843 10.1016/j.pestbp.2024.105843 38582603
    [Google Scholar]
  4. Song X. Wang H. Gao Y. Xu K. Sun Z. Zhao C. Yao G. Xu H. Design, synthesis, and evaluation of novel isoxazoline derivatives containing 2-phenyloxazoline moieties as potential insecticides. Pestic. Biochem. Physiol. 2024 204 106109 10.1016/j.pestbp.2024.106109 39277414
    [Google Scholar]
  5. Jiang B. Feng D. Shi J. Wu W. Dong Y. Ren H. Design, synthesis, and insecticidal activity of isoxazoline derivatives incorporating an acylhydrazine moiety. J. Agric. Food Chem. 2024 72 38 20974 20980 10.1021/acs.jafc.4c04005 39283195
    [Google Scholar]
  6. Liu X. Liu F. Tang T. Wang J. Wang Y. Huang Q. Wang Q. Zhao C. Comparative Insecticidal Activity and Mechanism of Isocycloseram versus Other GABAergic Insecticides against the Fall Armyworm. J. Agric. Food Chem. 2024 72 34 18816 18823 10.1021/acs.jafc.4c02866 39143896
    [Google Scholar]
  7. do Vale T.L. Costa A.R. Miranda L.M. Silva G.F. Silva N.C.S. Lima T.B. Chaves D.P. Sager H. Lasmar P.V.F. Costa-Junior L.M. Efficacy of lotilaner against myiasis caused by Cochliomyia hominivorax (Diptera: Calliphoridae) in naturally infested dogs. Parasit. Vectors 2023 16 1 86 10.1186/s13071‑023‑05661‑z 36879347
    [Google Scholar]
  8. Duncan K. Barrett A.W. Little S.E. Sundstrom K.D. Guerino F. Fluralaner (Bravecto®) treatment kills Aedes aegypti after feeding on Dirofilaria immitis-infected dogs. Parasit. Vectors 2023 16 1 208 10.1186/s13071‑023‑05819‑9 37340454
    [Google Scholar]
  9. Lawson B.E. McDermott E.G. Topical, contact, and oral susceptibility of adult Culicoides biting midges (Diptera: Ceratopogonidae) to fluralaner. Parasit. Vectors 2023 16 1 281 10.1186/s13071‑023‑05899‑7 37580834
    [Google Scholar]
  10. Li B.J. Wang K.K. Yu Y. Wei J.Q. Zhu J. Wang J.L. Lin F. Xu H.H. PxRdl2 dsRNA increased the insecticidal activities of GABAR-targeting compounds against Plutella xylostella. Pestic. Biochem. Physiol. 2023 195 105548 10.1016/j.pestbp.2023.105548 37666591
    [Google Scholar]
  11. Geurden T. Chapin S. McCall J.W. Mansour A. Mahabir S.P. Kryda K. McTier T. Insecticidal activity of Simparica and Simparica Trio against Aedes aegypti in dogs. Parasit. Vectors 2023 16 1 95 10.1186/s13071‑023‑05699‑z 36894954
    [Google Scholar]
  12. Reif K.E. Kollasch T.M. Neilson J.C. Herrin B.H. Ryan W.G. Bell M.C. Beltz M.S. Dryden M.W. Jesudoss Chelladurai J.R.J. Miller K.R. Sutherland C.J. Comparative speed of kill provided by lotilaner (Credelio™), sarolaner (Simparica Trio™), and afoxolaner (NexGard™) to control Amblyomma americanum infestations on dogs. Parasit. Vectors 2024 17 1 313 10.1186/s13071‑024‑06363‑w 39030610
    [Google Scholar]
  13. Reckziegel G.H. de Freitas M.G. Tutija J.F. Rodrigues V.D. Borges D.G.L. de Freitas M.D.B. Gallina T. Lopes W.D.Z. de Castro Rodrigues D. de Oliveira Arriero Amaral H. Strydom T. Torres S. de Almeida Borges F. Efficiency of fluralaner pour-on in different strategic control protocols against Rhipicephalus microplus on Brangus cattle in a tropical area. Parasit. Vectors 2024 17 1 110 10.1186/s13071‑024‑06199‑4 38449052
    [Google Scholar]
  14. Zapa D.M.B. de Aquino L.M. Couto L.F.M. Heller L.M. de Morais I.M.L. Salvador V.F. Leal L.L.L.L. Trindade A.S.N. de Freitas Paula W.V. de Lima N.J. Ferreira L.L. de Castro Rodrigues D. Strydom T. Torres S. Soares V.E. de Oliveira Monteiro C.M. da Silva Krawczak F. Lopes W.D.Z. Enzootic stability of tick fever in Holstein calves grazing in a tropical region, subjected to strategic cattle tick control with fluralaner. Parasit. Vectors 2024 17 1 120 10.1186/s13071‑024‑06212‑w 38461304
    [Google Scholar]
  15. Gallina T. dos Santos Lagranha C. Bilo G. Malavolta C. Ferreira L.L. de Almeida Borges F. de Castro Rodrigues D. Strydom T. Torres S. Arnhold E. Lopes W.D.Z. Control of Rhipicephalus microplus on taurine cattle with fluralaner in a subtropical region. Parasit. Vectors 2024 17 1 101 10.1186/s13071‑024‑06200‑0 38429835
    [Google Scholar]
  16. de Aquino L.M. Zapa D.M.B. de Castro Rodrigues D. Strydom T. Torres S. Ferreira L.L. Barufi F. de Amaral H.O.A. de Borges F.A. Gallina T. de Mendonça R.P. Soares V.E. Monteiro C.M.O. Lopes W.D.Z. Two protocols using fluralaner for Rhipicephalus microplus strategic control on taurine cattle in a tropical region. Parasit. Vectors 2024 17 1 15 10.1186/s13071‑023‑06107‑2 38191412
    [Google Scholar]
  17. Xu J. Dou Z. Zuo S. Lv M. Wang Y. Hao M. Chen L. Xu H. Semi-preparation and X-ray single-crystal structures of sophocarpine-based isoxazoline derivatives and their pesticidal effects and toxicology study. J. Agric. Food Chem. 2024 72 44 24198 24206 10.1021/acs.jafc.3c08101 39460697
    [Google Scholar]
  18. Raulf M.K. Raue K. Schwarz A. Petersen I. Zschiesche E. Heinau L. Strube C. A single treatment with a fluralaner injectable suspension (Bravecto® injectable) provides 1-year efficacy against Rhipicephalus sanguineus sensu lato and Ctenocephalides felis in dogs. Parasit. Vectors 2024 17 1 438 10.1186/s13071‑024‑06535‑8 39462404
    [Google Scholar]
  19. Gastaldi M.S. Felsztyna I. Miguel V. Sánchez-Borzone M.E. García D.A. Theoretical and experimental study of molecular interactions of fluralaner with lipid membranes. J. Agric. Food Chem. 2023 71 4 2134 2142 10.1021/acs.jafc.2c06811 36688903
    [Google Scholar]
  20. Mermans C. Dermauw W. Geibel S. Van Leeuwen T. Activity, selection response and molecular mode of action of the isoxazoline afoxolaner in Tetranychus urticae. Pest Manag. Sci. 2023 79 1 183 193 10.1002/ps.7187 36116012
    [Google Scholar]
  21. Huang Q. Jia Z. Wu S. Liu F. Wang Y. Song G. Chang X. Zhao C. The acute toxicity, mechanism, bioconcentration and elimination of fluxametamide on zebrafish (Danio rerio). Environ. Pollut. 2023 317 120808 10.1016/j.envpol.2022.120808 36464115
    [Google Scholar]
  22. El Mahmoudi A. Fegrouche R. Tachallait H. Lumaret J.P. Arshad S. Karrouchi K. Bougrin K. Green synthesis, characterization, and biochemical impacts of new bioactive isoxazoline‐sulfonamides as potential insecticidal agents against the Sphodroxia maroccana Ley. Pest Manag. Sci. 2023 79 12 4847 4857 10.1002/ps.7686 37500586
    [Google Scholar]
  23. Mihalca A.D. Deak G. Panait L.C. Rabei Ș. Beugnet F. Efficacy of afoxolaner (NexGard®) against natural infestations with Trichodectes canis in dogs under field conditions. Parasit. Vectors 2022 15 1 317 10.1186/s13071‑022‑05428‑y 36071527
    [Google Scholar]
  24. Tielemans E. Rautenbach C. Besselaar J.F. Beugnet F. Efficacy of a topical product combining esafoxolaner, eprinomectin and praziquantel against bedbug ( Cimex lectularius ) experimental infestations in cats. Parasite 2022 29 59 10.1051/parasite/2022060 36562440
    [Google Scholar]
  25. Selzer P.M. Epe C. Antiparasitics in Animal Health: Quo Vadis? Trends Parasitol. 2021 37 1 77 89 10.1016/j.pt.2020.09.004 33039282
    [Google Scholar]
  26. Ai D.P. Ju X.L. Liu G.Y. Isoxazoline parasiticides acted on ionotropic GABA receptors. Chem. Bull. 2020 83 986 996
    [Google Scholar]
  27. Mueller R.S. Rosenkrantz W. Bensignor E. Karaś-Tęcza J. Paterson T. Shipstone M.A. Diagnosis and treatment of demodicosis in dogs and cats. Vet. Dermatol. 2020 31 1 4 10.1111/vde.12806 31957202
    [Google Scholar]
  28. Rowe M.L. Whiteley P.L. Carver S. The treatment of sarcoptic mange in wildlife: A systematic review. Parasit. Vectors 2019 12 1 99 10.1186/s13071‑019‑3340‑z 30867019
    [Google Scholar]
  29. Wismer T. Means C. Toxicology of newer insecticides in small animals. Vet. Clin. N. Vet. Clin. North Am. Small Anim. Pract. 2018 48 6 1013 1026 10.1016/j.cvsm.2018.06.005 30149970
    [Google Scholar]
  30. Buckingham S.D. Ihara M. Sattelle D.B. Matsuda K. Mechanisms of action, resistance and toxicity of insecticides targeting GABA receptors. Curr. Med. Chem. 2017 24 27 2935 2945 28606041
    [Google Scholar]
  31. Wells J. Jones A.K. Variations in the insect GABA receptor, RDL, and their impact on receptor pharmacology. ACS Symposium Ser. 2017 2017 1 21 10.1021/bk‑2017‑1265.ch001
    [Google Scholar]
  32. Packianathan R. Colgan S. Hodge A. Davis K. Six R.H. Maeder S.E. Efficacy and safety of sarolaner (Simparica) in the treatment and control of naturally occurring flea infestations in dogs presented as veterinary patients in Australia Parasit. Vectors 2017 10 387/1 387/9
    [Google Scholar]
  33. Weber T. Selzer P.M. Isoxazolines: A novel chemotype highly effective on ectoparasites. ChemMedChem 2016 11 3 270 276 10.1002/cmdc.201500516 26733048
    [Google Scholar]
  34. Zhao C.Q. Han Z.J. Tang T. Research progress on bioeffect and toxicology of insecticide fluralaner and its derivatives. Chin. J. Pestic. Sci. 2015 17 251 256
    [Google Scholar]
  35. Casida J.E. Golden age of RyR and GABA-R diamide and isoxazoline insecticides: Common genesis, serendipity, surprises, selectivity, and safety. Chem. Res. Toxicol. 2015 28 4 560 566 10.1021/tx500520w 25688713
    [Google Scholar]
  36. Ozoe Y. Ozoe F. Kita T. Rahman M.M. Liu G.Y. Hisano K. Takashima M. Nakata Y. Multiple sites of insecticidal action in ionotropic GABA receptors. ACS Symposium Ser. 2015 2015 431 446 10.1021/bk‑2015‑1204.ch030
    [Google Scholar]
  37. Kumar K.A. Govindaraju M. Renuka N. Kumar G.V. Isoxazolines: An insight to their synthesis and diverse applications. J. Chem. Pharm. Res. 2015 7 250 257
    [Google Scholar]
  38. Wang Y. Wang C. Tian Q. Li Y. Recent research progress in oxime insecticides and perspectives for the future. J. Agric. Food Chem. 2024 72 27 15077 15091 10.1021/acs.jafc.4c02096 38920088
    [Google Scholar]
  39. Gonçalves I.L. Machado das Neves G. Porto Kagami L. Eifler-Lima V.L. Merlo A.A. Discovery, development, chemical diversity and design of isoxazoline-based insecticides. Bioorg. Med. Chem. 2021 30 115934 10.1016/j.bmc.2020.115934 33360575
    [Google Scholar]
  40. Zhou X. Hohman A. Hsu W.H. Review of extralabel use of isoxazolines for treatment of demodicosis in dogs and cats. J. Am. Vet. Med. Assoc. 2020 256 12 1342 1346 10.2460/javma.256.12.1342 32459587
    [Google Scholar]
  41. Zhou X. Hohman A.E. Hsu W.H. Current review of isoxazoline ectoparasiticides used in veterinary medicine. J. Vet. Pharmacol. Ther. 2022 45 1 1 15 10.1111/jvp.12959 33733534
    [Google Scholar]
  42. Sheng C.W. Jia Z.Q. Liu D. Wu H-Z. Luo X-M. Song P-P. Xu L. Peng Y-C. Han Z-J. Zhao C-Q. Insecticidal spectrum of fluralaner to agricultural and sanitary pests. J. Asia Pac. Entomol. 2017 20 4 1213 1218 10.1016/j.aspen.2017.08.021
    [Google Scholar]
  43. Morita T. Momota Y. Mori A. Oda H. Ike K. Sako T. Successful treatment of refractory demodicosis and transient papules with a single dose of fluralaner in a dog with uncontrolled severe endocrine disease. J. Vet. Med. Sci. 2018 80 4 672 675 10.1292/jvms.17‑0274 29515061
    [Google Scholar]
  44. Long J. K. Selby T. P. Xu M. Preparation of naphthalenylisoxazoline compounds for control of invertebrate pests. W.O. Patent 2009045999 2009
  45. Sioutas G. Papadopoulos E. Madder M. Beugnet F. Tielemans E. Efficacy of afoxolaner or the combination of afoxolaner with milbemycin oxime against Otodectes cynotis in naturally infested dogs. Vet. Parasitol. 2024 326 110108 10.1016/j.vetpar.2023.110108 38154391
    [Google Scholar]
  46. Shoop W.L. Hartline E.J. Gould B.R. Waddell M.E. McDowell R.G. Kinney J.B. Lahm G.P. Long J.K. Xu M. Wagerle T. Jones G.S. Dietrich R.F. Cordova D. Schroeder M.E. Rhoades D.F. Benner E.A. Confalone P.N. Discovery and mode of action of afoxolaner, a new isoxazoline parasiticide for dogs. Vet. Parasitol. 2014 201 3-4 179 189 10.1016/j.vetpar.2014.02.020 24631502
    [Google Scholar]
  47. Mita T. Kikuchi T. Mizukoshi T. Yaosaka M. Komoda M. Preparation of isoxazoline-substituted benzamide derivatives as insecticides, acaricides, and parasiticides. W.O. Patent 2005085216 2005
  48. McTier T.L. Chubb N. Curtis M.P. Hedges L. Inskeep G.A. Knauer C.S. Menon S. Mills B. Pullins A. Zinser E. Woods D.J. Meeus P. Discovery of sarolaner: A novel, orally administered, broad-spectrum, isoxazoline ectoparasiticide for dogs. Vet. Parasitol. 2016 222 3 11 10.1016/j.vetpar.2016.02.019 26961590
    [Google Scholar]
  49. Rufener L. Danelli V. Bertrand D. Sager H. The novel isoxazoline ectoparasiticide lotilaner (Credelio™): A non-competitive antagonist specific to invertebrates γ-aminobutyric acid-gated chloride channels (GABACls). Parasit. Vectors 2017 10 1 530 10.1186/s13071‑017‑2470‑4 29089046
    [Google Scholar]
  50. Little S.E. Lotilaner - a novel systemic tick and flea control product for dogs. Parasit. Vectors 2017 10 1 539 10.1186/s13071‑017‑2471‑3 29089062
    [Google Scholar]
  51. Wright I. Lotilaner - a novel formulation for cats provides systemic tick and flea control. Parasit. Vectors 2018 11 1 407 10.1186/s13071‑018‑2970‑x 30001733
    [Google Scholar]
  52. Mita T. Furukawa Y. Toyama K. I. Yaosaka M. Ikeda E. Masuzawa Y. Komoda M. Preparation of isoxazoline-substituted benzamide compounds as pesticides. W.O. Patent 2007026965 2007
  53. Long A. Isoxazolines: Preeminent ectoparasiticides of the early twenty‐first century. Gener. Rev. 2018 8 319 351 10.1002/9783527802883.ch16
    [Google Scholar]
  54. Mita T. Creation of a novel isoxazoline class of insecticide, fluxametamide. Fain Kemikaru 2019 48 19 28
    [Google Scholar]
  55. Cassayre J. Smejkal T. Blythe J. Hoegger P. Renold P. Pitterna T. Prasanna C.S. Smits H. Godineau E. Luksch T. Berthon G. Rawal G. Patre R. Lal M. Boussemghoune M. Masala S. Barreteau F. Flaeschel M. Vogt J. Qacemi M.E. Recent highlights in the discovery and optimization of crop protection products. Elsevier 2021
    [Google Scholar]
  56. Roe S. Houillon F. Mason B. Stuart C. Isocycloseram formulation. W.O. Patent 2022128912 2022
  57. Luo J. Bian C. Rao L. Zhou W. Li Y. Li B. Determination of the residue behavior of isocycloseram in Brassica oleracea and soil using the QuEChERS method coupled with HPLC. Food Chem. 2022 367 130734 10.1016/j.foodchem.2021.130734 34359003
    [Google Scholar]
  58. An Z. Y. Chen L. Chen S. H. Defauw J. M. Holmstrom S. D. Hu P. Tang C. Z. White W. H. Wu W. T. Zhang Y. D. Dihydroisoxazole compounds, their preparation, parasiticidal uses in plants and animals, and formulations thereof. W.O. Patent 2012155676 2012
  59. Yang C.H. Le Hir De Fallois L.P. Meng C.Q. Long A. Gorter De Vries R.J. Lafont S. Gay De Saint Michel M. Kozlovic S. A process for the preparation of (S)-afoxolaner and isoxazoline derivatives. W.O. Patent. 2017 2017176948 A1
    [Google Scholar]
  60. http://sitem.herts.ac.uk/aeru/ppdb/en/Reports/3813.htm
  61. Sine S.M. Engel A.G. Recent advances in Cys-loop receptor structure and function. Nature 2006 440 7083 448 455 10.1038/nature04708 16554804
    [Google Scholar]
  62. Lynagh T. Lynch J.W. Molecular mechanisms of Cys-loop ion channel receptor modulation by ivermectin. Front. Mol. Neurosci. 2012 5 60 10.3389/fnmol.2012.00060 22586367
    [Google Scholar]
  63. Ozoe Y. Asahi M. Ozoe F. Nakahira K. Mita T. The antiparasitic isoxazoline A1443 is a potent blocker of insect ligand-gated chloride channels. Biochem. Biophys. Res. Commun. 2010 391 1 744 749 10.1016/j.bbrc.2009.11.131 19944072
    [Google Scholar]
  64. Gassel M. Wolf C. Noack S. Williams H. Ilg T. The novel isoxazoline ectoparasiticide fluralaner: Selective inhibition of arthropod γ-aminobutyric acid- and l-glutamate-gated chloride channels and insecticidal/acaricidal activity. Insect Biochem. Mol. Biol. 2014 45 111 124 10.1016/j.ibmb.2013.11.009 24365472
    [Google Scholar]
  65. Zhao C. Casida J.E. Insect γ-aminobutyric acid receptors and isoxazoline insecticides: Toxicological profiles relative to the binding sites of [³H]fluralaner, [³H]-4′-ethynyl-4-n-propylbicycloorthobenzoate, and [³H]avermectin. J. Agric. Food Chem. 2014 62 5 1019 1024 10.1021/jf4050809 24404981
    [Google Scholar]
  66. Nakata Y. Fuse T. Yamato K. Asahi M. Nakahira K. Ozoe F. Ozoe Y. A Single amino acid substitution in the third transmembrane region has opposite impacts on the selectivity of the parasiticides fluralaner and ivermectin for ligand-gated chloride channels. Mol. Pharmacol. 2017 92 5 546 555 10.1124/mol.117.109413 28887352
    [Google Scholar]
  67. Yamato K. Nakata Y. Takashima M. Ozoe F. Asahi M. Kobayashi M. Ozoe Y. Effects of intersubunit amino acid substitutions on GABA receptor sensitivity to the ectoparasiticide fluralaner. Pestic. Biochem. Physiol. 2020 163 123 129 10.1016/j.pestbp.2019.11.001 31973848
    [Google Scholar]
  68. Kono M. Ozoe F. Asahi M. Ozoe Y. State-dependent inhibition of GABA receptor channels by the ectoparasiticide fluralaner. Pestic. Biochem. Physiol. 2022 181 105008 10.1016/j.pestbp.2021.105008 35082031
    [Google Scholar]
  69. Asahi M. Yamato K. Ozoe F. Ozoe Y. External amino acid residues of insect GABA receptor channels dictate the action of the isoxazoline ectoparasiticide fluralaner. Pest Manag. Sci. 2023 79 10 4078 4082 10.1002/ps.7606 37288963
    [Google Scholar]
  70. Blythe J. Earley F.G.P. Piekarska-Hack K. Firth L. Bristow J. Hirst E.A. Goodchild J.A. Hillesheim E. Crossthwaite A.J. The mode of action of isocycloseram: A novel isoxazoline insecticide. Pestic. Biochem. Physiol. 2022 187 105217 10.1016/j.pestbp.2022.105217 36127059
    [Google Scholar]
  71. Zhang Y. Huang Q. Sheng C. Liu G. Zhang K. Jia Z. Tang T. Mao X. Jones A.K. Han Z. Zhao C. G3’MTMD3 in the insect GABA receptor subunit, RDL, confers resistance to broflanilide and fluralaner. PLoS Genet. 2023 19 6 e1010814 10.1371/journal.pgen.1010814 37384781
    [Google Scholar]
  72. Annis G. D. Method for preparing 3-trifluoromethyl chalcones. W.O. Patent 2009126668A2 2009
  73. Zhu B. Yue H. L. Li H. J. Sun Q. H. Xu X. Q. Preparation of fluralaner. C. N. Patent 118047728 A 2024
  74. Billen D. Chubb N. A. L. Curtis M. Greenwood S. D. W. Menon S. Stuk T. Vaillancourt V. A. Spirocyclic isoxazoline derivatives as antiparasitic agents. W.O. Patent 2012120399 2012
  75. Li B. B. Jiang Q. Zhu J. L. Preparation method of oxazoline insecticide. C.N. Patent 109879826 2019
  76. Guo C.X. Chang X.H. Xu J.B. Song Y.Q. Sun N.N. Wu H.F. The Synthesis and insecticidal activity of isocycloseram. Nong Yao 2021 60 9 12
    [Google Scholar]
  77. An Z.Y. Chen L. Chen S.H. Defauw J.M. Holmstrom S.D. Hu P. Tang C.Z. White W.H. Wu W.T. Zhang Y. Preparation of parasiticidal dihydroisoxazole compounds. W.O. Patent. 2012 2012158396 A1
    [Google Scholar]
  78. Lamberth C. Oxazole and isoxazole chemistry in crop protection. J. Heterocycl. Chem. 2018 55 9 2035 2045 10.1002/jhet.3252
    [Google Scholar]
  79. Mita T. Toyama K. Furukawa Y. Komoda M. Preparation of substituted isoxazoline or enone oxime compounds as pest control agents. W.O. Patent 2009005015A1 2009
  80. Pitterna T. El Qacemi M. Bobosik V. Renold P. Cassayre J. Y. Jung P. J. M. Insecticidal compounds. C.N. Patent 102131789A 2011
  81. Renold P. Zambach W. Maienfisch P. Muehlebach M. Isoxazole-thietane derivatives as insecticides and their preparation and use in the combat or control of insects, acarines, nematodes and molluscs. W.O. Patent 2009080250A2 2009
  82. Kaiser F. Koerber K. Von D. W. Deshmukh P. Narine A. Dickhaut J. Bandur N. G. Langewald J. Culbertson D. L. Anspaugh D. D. Preparation of azoline substituted isoxazoline benzamide compounds for combating animal pests. W.O. Patent 2012007426 2012
  83. Yves C. J. Peter R. Thomas P. Myriem E. Q. Process for the preparation of thietane derivatives. W.O. Patent 2013026930A1 2013
  84. Mihara J. Murata T. Yamazaki D. Yoneta Y. Shibuya K. Shimojo E. Preparation of diarylisoxazolines as insecticides and animal parasiticides. W.O. Patent 2008019760 2008
  85. Mita T. Furukawa H. Masuzawa S. Komoda M. Preparation of isoxazoline compounds as pesticides. J.P. Patent 2007016017 2007
  86. Mita T. Maeda K. Yamada Y. Ikeda E. Toyama K.-I. Komoda M. Preparation of substituted isoxazoline compounds as pesticides. W.O. Patent 2009035004 2009
  87. Iwata J. Kawaguchi M. Preparation of nitrogen-containing heterocyclic compounds as pesticides. W.O. Patent 2010032437 2010
  88. Cassayre J. Y. El Qacemi M. Insecticidal compounds based on arylthioacetamide derivatives. W.O. Patent 2014079935 2014
  89. Ihara H. Kumamoto K. Preparation of azolyl aryl hydrazides as pesticides. W.O. Patent 2010090344 2010
  90. Kowata A. Ujihara K. Hydrazide compound having dihydroisoxazole ring, and use thereof for controlling harmful arthropods. W.O. Patent 2015005408 2015
  91. Huang S. Zhu B. Wang K. Yu M. Wang Z. Li Y. Liu Y. Zhang P. Li S. Li Y. Liu A. Wang Q. Design, synthesis, and insecticidal and fungicidal activities of quaternary ammonium salt derivatives of a triazolyphenyl isoxazoline insecticide. Pest Manag. Sci. 2022 78 5 2011 2021 10.1002/ps.6824 35118797
    [Google Scholar]
  92. Huang S. Ma H. Wang Z. Zhang P. Li S. Li Y. Liu A. Li Y. Liu Y. Wang Q. Design, synthesis, and insecticidal and fungicidal activities of ether/oxime-ether containing isoxazoline derivatives. J. Agric. Food Chem. 2023 71 13 5107 5116 10.1021/acs.jafc.2c08161 36947168
    [Google Scholar]
  93. Zhang C. Yuan H. Hu Y. Li X. Gao Y. Ma Z. Lei P. Structural diversity design, synthesis, and insecticidal activity analysis of ester-containing isoxazoline derivatives acting on the GABA Receptor. J. Agric. Food Chem. 2023 71 7 3184 3191 10.1021/acs.jafc.2c07910 36757129
    [Google Scholar]
  94. Jiang B. Feng D. Li F. Luo Y. He S. Dong Y. Hu D. Design, synthesis, and insecticidal activity of novel isoxazoline compounds that contain meta-diamides against fall armyworm (Spodoptera frugiperda). J. Agric. Food Chem. 2023 71 2 1091 1099 10.1021/acs.jafc.2c07035 36599080
    [Google Scholar]
  95. Jiang B. Li F. Feng D. Wei W. Luo Y. He S. Dong Y. Hu D. Discovery of novel isoxazoline compounds that incorporate a para-diamide moiety as potential insecticidal agents against fall armyworm (Spodoptera frugiperda). J. Agric. Food Chem. 2023 71 14 5516 5524 10.1021/acs.jafc.3c00351 37000156
    [Google Scholar]
  96. Feng D. Wu S. Jiang B. He S. Luo Y. Li F. Song B. Song R. Discovery of novel isoxazoline derivatives containing diaryl ether against fall armyworms. J. Agric. Food Chem. 2023 71 18 6859 6870 10.1021/acs.jafc.3c00824 37126004
    [Google Scholar]
  97. Li Y. Zhang W. Wu Z. Song B. Song R. Design, synthesis, and insecticidal activity of novel isoxazoline diacylhydrazine compounds as GABA receptor inhibitors. J. Agric. Food Chem. 2023 71 17 6561 6569 10.1021/acs.jafc.2c08880 37075263
    [Google Scholar]
  98. Li F. Jiang B. Luo Y. He S. Feng D. Hu D. Song R. Discovery of a novel class of acylthiourea-containing isoxazoline insecticides against Plutella xylostella. Molecules 2023 28 8 3300 10.3390/molecules28083300 37110534
    [Google Scholar]
  99. Yang S. Tang J. Li B. Yao G. Peng H. Pu C. Zhao C. Xu H. Rational design of insecticidal isoxazolines containing sulfonamide or sulfinamide structure as antagonists of GABA receptors with reduced toxicities to honeybee and zebrafish. J. Agric. Food Chem. 2023 71 39 14211 14220 10.1021/acs.jafc.3c03459 37737111
    [Google Scholar]
  100. Li Y. Li S. Yin X. Liu S. Design, synthesis and insecticidal activity of novel Isoxazoline Acylhydrazone compounds. Pest Manag. Sci. 2023 80 3 ps.7897 10.1002/ps.7897 37985394
    [Google Scholar]
  101. Lahm G. P. Shoop W. L. Xu M. Preparation of isoxazolines for controlling invertebrate pests. W.O. Patent 2007079162 2007
  102. Lahm G. P. Wagerle T. Xu M. Isoxazolines for controlling invertebrate pests. W.O. Patent 2008154528 2008
  103. Renold P. Cassayre J. Y. Pabba J. El Qacemi M. Pitterna T. Preparation of phenyldihydroisoxazolylbenzothiadiazolecarboxamide derivatives and analogs for use as insecticides. W.O. Patent 2010084067 2010
  104. Iwata J. Kawaguchi M. Preparation of isoxazoline compounds as pest control agents. W.O. Patent 2009022746 2009
  105. Bindschaedler P. Datta G.K. Von Deyn W. Braun F.J. Preparation of azoline compounds substituted by a carbocyclic condensed ring system useful for controlling invertebrate pests. W.O. Patent 2016102488 2016
  106. Zhong L.K. Sun X.P. Han L. Tan C.X. Weng J.Q. Xu T.M. Shi J.J. Liu X.H. Design, synthesis, insecticidal activity, and SAR of aryl isoxazoline derivatives containing pyrazole-5-carboxamide motif. J. Agric. Food Chem. 2023 71 40 14458 14470 10.1021/acs.jafc.3c01608 37782011
    [Google Scholar]
  107. Huwyler N. Koerber K. Schwengers S. A. Preparation of N-(3-(aminomethyl)phenyl)-5-(4-phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-amine derivatives and similar compounds as pesticides. W.O. Patent 2024061665 2024
/content/journals/cos/10.2174/0115701794353877241213051959
Loading
Research Progress of Isoxazoline Insecticides
Bentham Science Publishers ; https://doi.org/10.2174/0115701794353877241213051959
/content/journals/cos/10.2174/0115701794353877241213051959
/content/journals/cos/10.2174/0115701794353877241213051959
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: Structure-activity relationship ; Synthetic methods ; Isoxazoline insecticides ; Mechanism of action ; Commercialized and under-development products ; Structural derivation

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test