Application of cyclopropanamide substituted benzamide derivative in prevention and treatment of animal parasites

Abstract

The invention belongs to the technical field of animal parasite prevention and treatment, and particularly relates to a benzamide derivative substituted by cyclobenzamide as shown in a formula (I). The compound as shown in the formula (I) shows good activity on various animal parasites. Moreover, the compounds can obtain a good prevention and treatment effect at a very low dosage, so that the compounds can be used for preventing and treating animal parasites.

Description

Technical Field

[0001] This invention belongs to the field of animal parasite control technology, specifically relating to the application of a cyclopropamide-substituted benzamide derivative in the control of animal parasites. Background Technology

[0002] Controlling animal parasites is crucial for protecting animal health. However, due to the long-term use of many commercially available insecticides, harmful parasites have gradually developed resistance to these agents, leading to unsatisfactory control effects. Therefore, developing new agents that can more effectively control animal parasites is an urgent need.

[0003] Patent CN118063349A discloses cyclopropamide-substituted benzamides as insecticides and acaricides, which can therefore be used to control agricultural plant pests. Although veterinary uses are briefly mentioned, none of them have been verified. Summary of the Invention

[0004] To address the aforementioned technical problems, the present invention provides a method for protecting animals from parasites, the method comprising administering to the animal an insecticidally effective amount of a compound of formula (I), its stereoisomers, racemates, tautomers, isotopic markers, nitrogen oxides, solvates, polymorphs, esters, or pharmaceutically acceptable salts thereof.

[0005]

[0006] R1, R2, R3, R4, R5, R 11 R 12 R 13 R 14 They may be the same or different, and are independently selected from H, F, Cl, Br, I, CN, NH2, NO2, SF5, C1-C4 alkyl, C3-C6 cycloalkyl, C2-C4 alkenyl, C2-C4 alkoxy, halo-C1-C4 alkyl, halo-C1-C4 alkoxy, C1-C4 alkyl thio, C1-C4 alkyl-SO-, C1-C4 alkyl-SO2- or halo-C1-C4 alkyl-SO2-;

[0007] R6 and R7 may be the same or different, and are independently selected from H, F, Cl, Br, I or C1-C4 alkyl groups;

[0008] R8 and R9 may be the same or different, and are independently selected from H or C1-C4 alkyl groups;

[0009] R 10Selected from H, C1-C4 alkyl, halogenated C1-C4 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl C1-C4 alkyl-, C1-C4 alkyl-CO-, C3-C6 cycloalkyl-CO- or C1-C4 alkoxy-C1-C4 alkyl-CO-;

[0010] R 15 Selected from -C1-C4 alkyl-cyano, -C1-C4 alkyl-CF3 or -C1-C4 alkyl-CHF2;

[0011] R 16 Selected from -C1-C4 alkyl-cyano, unsubstituted or optionally substituted by one, two or more Rs: C3-C6 cycloalkyl or -C1-C4 alkyl-C3-C6 cycloalkyl; Rs are selected from halogens, C1-C4 alkyl or halo-C1-C4 alkyl;

[0012] Q1 and Q2 may be the same or different, and are selected independently from O or S.

[0013] According to an embodiment of the present invention: in formula (I),

[0014] R1, R2, R3, R4, R5, R 11 R 12 R 13 R 14 They may be the same or different, and are independently selected from H, F, Cl, Br, CN, SF5, methyl, ethyl, cyclopropyl, methoxy, difluoromethyl, trifluoromethyl, or trifluoromethoxy;

[0015] R6 and R7 may be the same or different, and are independently selected from H, F, Cl or Br;

[0016] R8 and R9 may be the same or different, and are independently selected from H or methyl groups;

[0017] R 10 Selected from H, C1-C4 alkyl, halogenated C1-C4 alkyl, C3-C6 cycloalkyl or C3-C6 cycloalkyl-C1-C4 alkyl-.

[0018] According to an embodiment of the present invention: in formula (I),

[0019] R1, R5, R8, R9, R 11 and R 12 H is the highest value; Q1 and Q2 are both O.

[0020] R2 is a halo-C1-C3 alkyl group, F, Cl, Br, or CN;

[0021] R3 can be H, F, Cl, or Br;

[0022] R4 is a halogenated C1-C3 alkyl group, F, Cl, Br, or methyl group;

[0023] R6 and R7 are F, Cl, and Br, respectively.

[0024] R 10 H, methyl or methylcyclopropyl

[0025] R 13 For example, H, F, Cl, Br;

[0026] R 14 For example, H, F, Cl, Br;

[0027] R 15 Selected from -C1-C4 alkyl-cyano groups;

[0028] R 16 Selected from C3-C6 cycloalkyl groups.

[0029] According to an embodiment of the present invention: in formula (I),

[0030] R1, R5, R8, R9, R 11 and R 12 H is the highest value; Q1 and Q2 are both O.

[0031] R2 is trifluoromethyl, Cl, or CN;

[0032] R3 is H, F, or Cl;

[0033] R4 is trifluoromethyl, Cl, F or methyl;

[0034] R6 and R7 are Cl;

[0035] R 10 H, methyl or methylcyclopropyl

[0036] R 13 It is H or Cl;

[0037] R 14 For H or F;

[0038] R 15 Selected from -C1-C4 alkyl-cyano groups;

[0039] R 16 It is selected from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0040] In some implementations, R 15 When it is a -C1-C4 alkyl-cyano group, R 16The substitution may be a substituted or unsubstituted -C1-C4 alkyl-C3-C6 cycloalkyl group, or a substituted or unsubstituted -C3-C6 cycloalkyl group; the substitution may be, for example, substitution by one, two or more of the following groups: F, Cl, methyl, ethyl, cyclopropyl, methoxy, difluoromethyl, trifluoromethyl or trifluoromethoxy; the substitution is preferably on the C3-C6 cycloalkyl group of the -C1-C4 alkyl-C3-C6 cycloalkyl group;

[0041] In some implementations, R 15 R 16 Not simultaneously -C1-C4 alkyl-cyano;

[0042] In some implementations, R 15 When R is -C1-C4 alkyl-CF3, 16 The substitution may be a substituted or unsubstituted -C3-C6 cycloalkyl or -C1-C4 alkyl-cyano group; the substitution may be, for example, by one, two or more of the following groups: F, Cl, methoxy, difluoromethyl, trifluoromethyl or trifluoromethoxy.

[0043] In some implementations, R 15 When R is -C1-C4 alkyl-CHF2, 16 The substituted or unsubstituted -C3-C6 cycloalkyl group; the substitution may be, for example, by one, two or more of the following groups: F, Cl, methoxy, difluoromethyl, trifluoromethyl or trifluoromethoxy.

[0044] In some implementations, R 15 The compounds are cyanomethyl, cyanoethyl, cyanopropyl, trifluoroethyl, difluoroethyl, trifluoropropyl, and difluoropropyl.

[0045] In some implementations, R 16 The compounds are cyanomethyl, cyanoethyl, cyclopropyl, cyclopropylmethyl, dichlorocyclopropyl, difluorocyclopropyl, fluorochlorocyclopropyl, methylcyclopropyl, and trifluoromethylcyclopropyl.

[0046] In some implementations, R 15 R 16 Together with the N atoms they are attached to, they form the following groups:

[0047]

[0048] In some implementations, Q1 and Q2 are selected from O.

[0049] According to an embodiment of the present invention: in formula (I),

[0050] R1, R2, R3, R4, and R5 may be the same or different, and are independently selected from H, F, Br, methyl, trifluoromethyl, CHF2, or Cl;

[0051] R6 and R7 are selected from Cl or Br;

[0052] R8 is selected from H;

[0053] R9 is selected from H;

[0054] R 10 Selected from H, methyl, ethyl, trifluoroethyl, cyclopropyl, or cyclopropylmethyl;

[0055] R 11 R 12 They are either the same or different, and are selected independently from H;

[0056] R 13 R 14 They are independently selected from H, F, Br, Cl, or CF3;

[0057] R 15 R 16 Together with the N atoms they are attached to, they form the following groups:

[0058]

[0059] Q1 and Q2 are selected from O.

[0060] According to an embodiment of the present invention: in formula (I),

[0061] R1, R2, R3, R4, and R5 may be the same or different, and are independently selected from H, F, Br, methyl, trifluoromethyl, CHF2, or Cl;

[0062] R6 and R7 are selected from Cl or Br;

[0063] R8 is selected from H;

[0064] R9 is selected from H;

[0065] R 10 Selected from H, methyl, ethyl, trifluoroethyl, cyclopropyl, or cyclopropylmethyl;

[0066] R 11 R 12 They are either the same or different, and are selected independently from H;

[0067] R 13 R 14 They are independently selected from H, F, Br, Cl, or CF3;

[0068] R 15 R16 Together with the N atoms they are attached to, they form the following groups:

[0069]

[0070] Q1 and Q2 are selected from O.

[0071] As an example, the compound of formula (I) is selected from the following compounds:

[0072]

[0073] Where R1 = H, R5 = H, R8 = H, R9 = H, R 11 =H,R 12 =H, Q 1＝ O, Q2 = O

[0074] Table 1

[0075]

[0076]

[0077]

[0078]

[0079]

[0080]

[0081]

[0082]

[0083]

[0084]

[0085]

[0086]

[0087]

[0088]

[0089]

[0090]

[0091]

[0092]

[0093]

[0094]

[0095]

[0096]

[0097]

[0098]

[0099]

[0100]

[0101]

[0102]

[0103]

[0104]

[0105]

[0106]

[0107]

[0108]

[0109]

[0110]

[0111]

[0112]

[0113]

[0114]

[0115]

[0116]

[0117]

[0118]

[0119]

[0120]

[0121]

[0122]

[0123]

[0124]

[0125]

[0126]

[0127]

[0128]

[0129]

[0130]

[0131] Where R6 = Cl, R7 = Cl, R8 = H, R9 = H, Q 1＝ O, Q2 = O

[0132] Table 2

[0133]

[0134]

[0135]

[0136]

[0137]

[0138]

[0139]

[0140] According to an embodiment of the present invention, the method is a non-therapeutic method.

[0141] According to an embodiment of the present invention, the method involves contacting the parasite or its environment with an insecticidally effective amount of the compound represented by formula (I), its stereoisomers, racemates, tautomers, isotopic markers, nitrogen oxides, solvates, polymorphs, esters, or pharmaceutically acceptable salts thereof.

[0142] The present invention also provides a non-treatment method for preventing parasitic infestation, the method comprising contacting the parasite or its environment with an insecticidally effective amount of a compound of formula (I), its stereoisomers, racemates, tautomers, isotopic markers, nitrogen oxides, solvates, polymorphs, esters, or pharmaceutically acceptable salts thereof.

[0143] The present invention also provides the use of the compound of formula (I), its stereoisomers, racemates, tautomers, isotope labels, nitrogen oxides, solvates, polymorphs, esters or pharmaceutically acceptable salts thereof in the preparation of medicaments for the prevention and treatment of animal parasites.

[0144] The present invention also relates to such methods, wherein the parasite or its environment is contacted with a composition and at least one additional component, the composition comprising a biologically effective amount of a compound of formula (I), its stereoisomers, racemates, tautomers, isotopic labels, nitrogen oxides, solvates, polymorphs, esters or pharmaceutically acceptable salts thereof, the additional component being selected from surfactants, solid diluents and liquid diluents, and the composition optionally further comprising a biologically effective amount of at least one additional biological compound or reagent.

[0145] The present invention also provides methods for treating, preventing, inhibiting, and / or killing external and / or internal parasites, said methods comprising applying to animals and / or to animals an insecticidally effective amount of a compound of formula (I), its stereoisomers, racemates, tautomers, isotope-labeled compounds, nitrogen oxides, solvates, polymorphs, esters, or pharmaceutically acceptable salts thereof (e.g., the compositions described herein). The present invention also relates to such methods in which an insecticidally effective amount of a compound of formula (I), its stereoisomers, racemates, tautomers, isotope-labeled compounds, nitrogen oxides, solvates, polymorphs, esters, or pharmaceutically acceptable salts thereof (e.g., the compositions described herein) is applied to the environment in which the animal inhabits (e.g., a pen or blanket).

[0146] [Application route]

[0147] According to an embodiment of the present invention, the route of administration is local administration (such as dripping, pouring, spraying), oral administration, or gastrointestinal administration.

[0148] According to an embodiment of the present invention, the route of administration is parenteral, such as injection.

[0149] According to an embodiment of the present invention, the animal is a vertebrate.

[0150] According to an embodiment of the present invention, the animal is a mammal, bird, or fish.

[0151] According to an embodiment of the present invention, the mammal is a human.

[0152] According to an embodiment of the invention, the mammal is livestock, such as a ruminant, especially a domestic cattle.

[0153] According to an embodiment of the invention, the mammal is a companion animal, particularly a canine or feline, especially a dog or cat.

[0154] According to an embodiment of the present invention, the parasite is an ectoparasite.

[0155] According to an embodiment of the present invention, the parasite is an endoparasite.

[0156] According to an embodiment of the present invention, the parasite is an invertebrate parasite.

[0157] According to an embodiment of the present invention, the parasite is a worm.

[0158] According to an embodiment of the present invention, the parasite is an arthropod.

[0159] According to an embodiment of the invention, the parasite is a Hemiptera (stomach bug); preferably a Reduvius.

[0160] According to an embodiment of the invention, the parasite is a Diptera; preferably a fly or mosquito; more preferably a Culex spp. (mosquito), such as Culex, or preferably a Sarcophagus superfamily, such as Culicoides.

[0161] According to an embodiment of the invention, the parasite is a mite, preferably a Demodex mite, such as Demodex folliculorum.

[0162] According to an embodiment of the present invention, the parasite is a lice (Phthiraptera) (sucking louse), preferably a species of the genus Phthiraptera, and more preferably a tick or louse, such as bed bug, cattle lice, pig lice, sheep lice, or cat lice.

[0163] According to an embodiment of the present invention, the parasite is a flea, preferably a cat flea or a dog flea.

[0164] According to an embodiment of the invention, the parasite is a bed bug or a tick, preferably a hard tick or a soft tick, such as the soft tick (O. moubata) or the blood-headed fan tick (R. sanguineus).

[0165] According to an embodiment of the invention, the parasite is a maggot, such as the spiral fly maggot (Cochliomyiahominivorax).

[0166] According to embodiments of the present invention, the parasites are cat fleas, dog fleas, blood-headed fan ticks, soft ticks, bed bugs, hair follicle mites, blowflies, Culex mosquitoes, spiral fly larvae, and assassin bugs.

[0167] According to embodiments of the present invention, the method can cause a mortality rate of at least 45% for animal parasites, preferably at least 70%, and more preferably at least 80%; in particular, it can cause a mortality rate of at least 80% for cat fleas, dog fleas, blood-headed ticks, soft ticks, bed bugs, blowflies, Culex mosquitoes, spiral fly larvae, and assassin bugs.

[0168] According to an embodiment of the present invention, the method of application is oral application twice a year.

[0169] According to an embodiment of the present invention, the method of application is oral application once a month.

[0170] According to an embodiment of the present invention, the method of application is oral application twice a month.

[0171] The embodiments of the present invention can be combined in any of the above ways.

[0172] [Compositions and Applications]

[0173] The present invention also provides a composition for protecting animals from parasites, the composition comprising one, two or more of the following as active ingredients: a compound of formula (I) as described in any of the preceding claims, its stereoisomers, racemates, tautomers, isotopic labels, nitrogen oxides, solvates, polymorphs, esters or pharmaceutically acceptable salts thereof.

[0174] According to embodiments of the present invention, the composition further includes at least one additional ingredient selected from surfactants, solid diluents, and liquid diluents. Optionally, the composition also includes at least one additional biologically active compound or reagent, for example, the composition may also include at least one other active compound for controlling invertebrate parasites.

[0175] According to embodiments of the present invention, the composition is a topical composition, an oral composition, or an injectable composition.

[0176] The present invention includes a method for preparing a composition for protecting animals from invertebrate parasites, the method comprising mixing one, two or more of the following: a compound of formula (I), a stereoisomer thereof, a racemic mixture, a tautomer thereof, an isotope label thereof, a nitrogen oxide thereof, a solvate thereof, a polymorph thereof, an ester thereof, or a pharmaceutically acceptable salt thereof, with at least one pharmaceutically or veterinary acceptable carrier.

[0177] Those skilled in the art will recognize that, because the salts of compounds are in equilibrium with their corresponding non-salt forms under environmental and physiological conditions, the salts and non-salt forms have common biological uses. Various salts of compounds of formula (I) can be used to control invertebrate pests and animal parasites. Salts of compounds of formula (I) include acid addition salts with inorganic or organic acids such as hydrobromic acid, hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, acetic acid, butyric acid, fumaric acid, lactic acid, maleic acid, malonic acid, oxalic acid, propionic acid, salicylic acid, tartaric acid, 4-methylbenzenesulfonic acid, or valeric acid.

[0178] According to embodiments of the invention, the composition of the compound of formula (I) further comprises adjuvants and additives known to those skilled in the art as formulation auxiliaries (some of which are solid diluents, liquid diluents, or surfactants). Such formulation auxiliaries and additives can control: pH (buffers), foaming during processing (defoamers, such as polysiloxanes), sedimentation of the active ingredient (suspending agents), viscosity (thixotropic thickeners), microbial growth (antimicrobial agents), product freezing (antifreeze agents), color (dye / pigment dispersions), elution (film-forming agents or binders), evaporation (anti-evaporation agents), and other formulation properties. Film-forming agents include, for example, polyvinyl acetate, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymers, polyvinyl alcohol, polyvinyl alcohol copolymers, and waxes.

[0179] The present invention also provides a method for using a compound of formula (I) in combination with at least one other invertebrate-controlling active ingredient. This method involves using the other invertebrate-controlling active ingredient to have a different site of action than the compound of formula (I). In some cases, combination with at least one other invertebrate-controlling active ingredient having a similar range of control but a different site of action will be advantageous for resistance management. Therefore, compositions consisting of compounds of formula (I) that can be used in the methods of the present invention further comprise a biologically effective amount of at least one additional invertebrate-controlling active ingredient having a similar range of control but a different site of action.

[0180] According to embodiments of the invention, the application method involves spraying an aqueous dispersion or refined oil solution of the compound of formula (I). Combining the compound with spray oil, spray oil concentrate, thickener, adjuvants, other solvents, and synergists such as piperonyl butyl ether enhances its efficacy. Such sprays can be applied from a spray container, such as a canister, bottle, or other container, via a pump or by releasing them from a pressurized container, such as a pressurized aerosol spray can. Such spray compositions can take various forms, such as sprays, mists, foams, smoke, or dust. Such spray compositions may also contain propellants, foaming agents, etc. The spray composition contains a biologically effective amount of the compound or composition of formula (I) and a carrier. Representative propellants include, but are not limited to, methane, ethane, propane, butane, isobutane, butene, pentane, isopentane, neopentane, pentene, hydrofluorocarbons, chlorofluorocarbons, dimethyl ethers, and mixtures thereof. A spray composition for controlling at least one invertebrate parasite, wherein the invertebrate parasite is selected from mosquitoes, black mosquitoes, horseflies, wasps, hornets, giant hornets, ticks, spiders, ants, etc., including various of the above-mentioned pests or combinations thereof.

[0181] [Parasitates and animals awaiting treatment]

[0182] According to embodiments of the present invention, the control of animal parasites includes the control of ectoparasites that parasitize the surface of a host animal's body (e.g., shoulders, armpits, abdomen, inner thighs) and endoparasites that parasitize the interior of the host animal's body (e.g., stomach, intestines, lungs, veins, subcutaneous tissue, lymphatic tissue). Ectoparasitic or disease-transmitting pests include, for example, chiggers, ticks, lice, mosquitoes, flies, mites, and fleas. Endoparasites include canine filarial worms, hookworms, and worms. Compounds and compositions of formula (I) are particularly suitable for combating ectoparasites. Compounds and compositions of formula (I) are suitable for systemic and / or non-systemic control of infiltration or infection caused by parasites in animals.

[0183] The compounds and compositions of formula (I) are suitable for combating invertebrate parasites that parasitize animals, including wild animals, livestock, and agricultural draft animals. The term livestock, as used, refers to domesticated animals raised in agricultural environments to produce, for example, food or fiber, or for their labor; livestock includes cattle, sheep, goats, horses, pigs, donkeys, camels, buffalo, rabbits, hens, turkeys, ducks, and geese. Combating parasites reduces mortality and mitigates reduced yields.

[0184] Compounds and compositions of formula (I) are particularly suitable for combating invertebrate parasites that parasitize companion animals and pets (e.g., dogs, cats, pet birds and ornamental fish), research and laboratory animals (e.g., hamsters, guinea pigs, rats and mice), and animals kept in zoos, wild habitats and / or circuses.

[0185] In embodiments of the invention, the animal is preferably a vertebrate, and more preferably a mammal, bird, or fish. In a particular embodiment, the animal is a mammal (including great apes, such as humans). Other mammals include primates (e.g., monkeys), bovids (e.g., cattle or dairy cows), suidae (e.g., domestic pigs or wild boars), sheep (e.g., goats or sheep), equines (e.g., horses), canids (e.g., dogs), felines (e.g., house cats), camels, deer, donkeys, buffalo, antelopes, rabbits, and rodents (e.g., guinea pigs, squirrels, rats, mice, gerbils, and hamsters). Birds include anatidae (swans, ducks, and geese), columbidae (e.g., doves and pigeons), pheasants (e.g., partridges, grouse, and turkeys), gallinae (e.g., chickens), parrots (e.g., parrots, macaws, and parrots), birds of prey, and ostriches.

[0186] For the purposes of this invention, the term "fish" includes bony fish, i.e., cephalopods. The orders Salmoniformes (including Salmonidae) and Perciformes (including Acanthodiana) are both included in the category of bony fish. Possible examples of fish include Salmonidae, Pleuronectiidae, Cichlididae, and Acanthodiana.

[0187] The method of the present invention also includes marsupial mammals (e.g., kangaroos), reptiles (e.g., farmed turtles), and other economically important livestock for which the method of the present invention can safely and effectively treat or prevent parasitic infection or contamination.

[0188] Examples of invertebrate parasites controlled by applying an effective amount of an insecticidal compound of formula (I) to the protected animal include ectoparasites (arthropods, mites, etc.) and endoparasites (worms, such as nematodes, flukes, tapeworms, acanthocephalans, etc.).

[0189] Helminthiasis is generally described as a disease or class of diseases caused by parasitic infections in animal hosts called worms. The term "helminth" is intended to include nematodes, flukes, tapeworms, and acanthocephalans. Helminthiasis is a problem associated with domesticated animals such as pigs, sheep, horses, cattle, goats, dogs, cats, and poultry.

[0190] Among worms, a class of worms described as nematodes can cause widespread and serious infections in a variety of animal types. The nematodes treated by the compounds and methods of this invention include the following genera: *Echinopsula*, *Strongyloides felis*, *Ahrodontia*, *Strongyloides angiostrongylus*, *Ascaris lumbricoides*, *Ascaris*, *Brugia*, *Odontostomum*, *Capillaria*, *Churchis*, *C. chaetotrichum*, *C. cubitus*, *C. angiostrongylus*, *C. dilatatum*, *C. bulgaricus*, *C. chaetotrichum*, *C. chaetotrichum*, *C. chaetotrichum*, *C. chaetotrichum*, *C. chaetotrichum*, *C. chaetotrichum*, *C. pinworm*, *C. chaetotrichum*, *Haemaphysalis*, *Heterostigma*, and rabbits. The genera *Ascaris*, *Loa*, *Mansonia*, *Müller*, *Cytomala*, *Ceratophyllum*, *Ceratophyllum*, *Nodularia*, *Gastrocera*, *Ceratophyllum*, *Parasiticus*, *Parasiticus*, *Pterygotylla*, *Protostrophus*, *Brachiodera*, *Zygotylla*, *Euphorbia*, *Strongyloides*, *Strongyloides*, *Strongyloides*, *Sucking Nematodes*, *Toxocara*, *Toxocara*, *Tricholoma*, *Tricholoma*, *Tricholoma*, *Tricholoma*, *Tricholoma*, *Tricholoma*, *Tricholoma*, *Tricholoma*, *Tricholoma*, *Tricholoma*, *Tricholoma*, *Tricholoma*, *Tricholoma*, and *Hookworm*.

[0191] The most common nematode genera that can infect the aforementioned animals are *Haemaphysalis*, *Trichodina*, *Gastroceras*, *Nematoda*, *Cuppella*, *Ascaris*, *Odontospira*, *Nodularia*, *Chaetomium*, *Strongyloides*, *Trichuris*, *Trichodina*, *Trichodina*, *Trichodina*, *Trichodina*, *Dictamnus*, *Capillaria*, *Heterostigma*, *Toxocara*, *Gastroceras*, *Gastroceras*, *Caulis Ascaris*, *Acanthocephala*, *Hooktospira*, *Hookworm*, *Toxocara*, and *Parascaris*. Some of these, such as *Trichodina*, *Cuppella*, and *Nodularia*, primarily attack the intestines, while others, such as *Haemaphysalis* and *Gastroceras*, are more prevalent in the stomach, and still others, such as *Dictamnus*, are found in the lungs. Other parasites are also found in other tissues, such as the heart and blood vessels, subcutaneous tissue, and lymphatic tissue.

[0192] The trematodes treated by the compounds and methods of this invention include the following genera: *Schistosome*, *Diplophora*, *Trichoderma*, and *Taenia*.

[0193] The most common genera of parasites in the human gastrointestinal tract are *Ahletodon*, *Isodon*, *Ascaris*, *Strongyloides*, *Trichodina*, *Capillaria*, *Trichuris*, and *Pinus*. Other medically important genera of parasites found in the blood or in other tissues and organs outside the gastrointestinal tract include filarial worms such as *Wuce*, *Brugia*, *Caulis Cyclostrum*, and *Loa*, as well as *Draconis*, and other intestinal ascarids such as *Strongyloides* and *Capillaria*.

[0194] The compound of formula (I) is effective against a variety of animal ectoparasites (such as arthropod ectoparasites of mammals and birds).

[0195] Insects and ticks / mites include biting insects such as flies and mosquitoes, mites, ticks, lice, fleas, stink bugs, parasitic maggots, etc.

[0196] Adult flies include, for example, hornflies or bloodflies, horseflies or horseflies, stable flies or stable jiushiying, black flies or black flies, deer flies or spotted flies, lice flies or planthoppers, and tsetse flies or tsetse flies. Parasitic fly larvae include, for example, skin flies (stomach flies and mad flies), blowflies or green bottle flies, voles or blowfly larvae, cow flies or footflies, wool flies larvae, and horse stomach flies larvae. Mosquitoes include, for example, Culex, Anopheles, and Aedes.

[0197] Mites include mites in the suborder Mesophora, such as Mesophora spp. like avian mites and chicken spp.; scabies mites or itch mites, such as the Sarcoptidae family, such as human scabies mites; animal itch mites, such as the Oitchidae family, including bovine foot mites and sheep itch mites; chiggers, such as the Chiggeridae family, such as North American chiggers and Aspergillus chutneyus; and ticks, such as Demodex mites, including Demodex folliculorum.

[0198] Ticks include, for example, soft-bodied ticks, which include types of the family Cryptorchididae, such as those of the genera *Ixodes* and *Ixodes*; and hard-bodied ticks, including those of the family Ixodes, such as *Hemiberlesia serratifolia*, *Tectus variegata*, *Tectus angustifolia*, *Tectus anamensis*, *Tectus anamensis*, *Tectus anamensis*, and other types of the genus *Tectus* (including the previously mentioned *Tectus*).

[0199] Lice include, for example, blood-sucking lice such as those of the genera *Brief louse* and *Brief louse*; biting lice such as those of the genera *Hydroceta*, *Gnaphalium*, and *Vibrio*.

[0200] Fleas include, for example, species of the genus *Ctenopharynx* such as canine fleas (*Ctenopharynx canis*) and felid fleas (*Ctenopharynx felis*); species of the genus *Xenopsylla cheopis* such as oriental fleas (*Xenopsylla cheopis*); and species of the genus *Pulex irritans* such as human fleas.

[0201] Stink bugs include, for example, stink bugs of the genus *Cimexlectularius* or common stink bugs; subfamily Assassinoidea, including assassin bugs also known as assassin bugs; for example, long-red assassin bugs and trident bugs.

[0202] Flies, fleas, lice, mosquitoes, mites, ticks, and worms cause enormous damage to livestock and companion animals. Arthropod parasites also cause problems for humans and can be carriers of pathogenic organisms in both humans and animals.

[0203] Many other invertebrate parasitic pests are known in the art and can also be treated with compounds of formula (I).

[0204] Specifically, compounds of formula (I) are particularly effective against ectoparasites, including stable flies; ticks such as those of the genera *Ixodes*, *Ixodes*, *Ixodes*, *Ixodes*, *Ixodes*, *Ixodes*, *Ixodes*, and *Ixodes*; and fleas such as cat fleas (*C. cephalides felis*) and dog fleas (*C. cephalides canis*).

[0205] Compounds of formula (I) are also effective against ectoparasites, including: flies such as Haematobiairritans, Simulium type (black flies), Glossina type (tsetse flies), Hydrotaeairritans (big-headed flies), Musca autumnalis (autumn housefly), Musca domestica (housefly), Morellia simplex (simple black fly), Tabanus type (horsew fly), Bovine bark fly, striped bark fly, silky green fly, Lucilia acuminata (copper green fly), Culicoides type (blooming fly), Newland bark fly type, Oestrus ovis (sheep fly), Culicoides type (midge), horse fly, horse stomach fly, red horse stomach fly and horse nose stomach fly; lice such as cattle lice (livestock lice), horse lice, donkey blood lice, cat bird lice, dog lice, spiny-jaw lice and dog biting lice; sheep tick flies such as sheep tick; and mites such as itch mite type, scabies mite type, scabies mite, cattle foot mite, horse worm mite, chelicerate mite type, cat ear mite, chigger mite type and Otodectescyanotis (ear mite).

[0206] [Combined Treatment]

[0207] In the methods and compositions of this invention, compounds of formula (I) may be applied simultaneously or separately from other biologically active compounds or reagents. As described below, such biologically active compounds may be included in compositions of formula (I). Such biologically active compounds used in this invention include organophosphate insecticides, carbamate insecticides, biopesticides, and other miscellaneous insecticides. These insecticides have a very broad range of activities as insecticides and, in some cases, insecticidal activity.

[0208] Organophosphate insecticides include, for example, chlorpyrifos, terbufos, dimethoate, phoxim, ethion, trichlorfon, phosmet, chlorpyrifos, malathion, acephate, methamidophos, methamidophos, ethyl parathion, methyl parathion, methamidophos, phorate, phorate, trichlorfon, and fenthion; carbamate insecticides include, for example, abamectin, chlorfenapyr, aldicarb, quizalofop-p-ethyl, ethoxysulfuron, and chlorfenapyr; biological insecticides include repellents and pyrethroids. (and its synthetic variants, such as propyrene, pyrethrum, pyrethrum, tetrabromopyrethrin) and nicotine, which is commonly used as an acaricide; other miscellaneous insecticides include: Bacillus thuringiensis, chlorobenzene, formamidin (e.g., amitraz), copper compounds (e.g., copper hydroxide and copper oxychloride), cypermethrin, deltamethrin, trichlorfon, endosulfan, cis-cypermethrin, cypermethrin, deltamethrin, methoxydimethylamine, and sulfur.

[0209] Alternatively, the biologically active compounds or reagents used in this invention may be selected from anthelmintics known in the art, such as fenbendazoles (e.g., ivermectin, moxibustion, milbemycin), benzimidazoles (e.g., albendazole, triclobenzazole), N-salicylic acid aniline (e.g., chlorsenoyl, hydroxychlorozadamide), substituted phenols (e.g., nitrohydroxyiodine), pyrimidines (e.g., pyrimidine), imidazoles (e.g., levamisole), and praziquantel.

[0210] Alternatively, other biologically active compounds or reagents used in this invention may be selected from insect growth regulators (IGRs) and juvenile hormone analogs (JHAs), such as diflubenzuron, chlorfenapyr, fluzoflubenzuron, cyprodinil, and methoxyprotein, thereby providing initial and sustained control of parasites to the animal and its environment (at all stages of insect growth, including eggs).

[0211] Alternatively, other biologically active compounds or reagents used in this invention may be selected from pyrenoidin-based antiparasitic compounds. Pyrenoidin-based compounds include potent antiparasitic agents known to be effective against a broad spectrum of mammalian internal and external parasites.

[0212] Ivermectin is a preferred compound that can be used within the scope of this invention. Ivermectin is a semi-synthetic derivative of chlorpyrifos and is generally prepared to contain at least 80% 22,23-dihydrochlorpyrifos B. 1a and less than 20% 22,23-dihydropyridine B 1b A mixture.

[0213] [Dosage Form]

[0214] The present invention can be administered by conventional methods, such as external administration in the form of tablets, capsules, decoctions, infusions, granules, pastes, pills, via feeding or suppositories; or by non-enteric administration, such as by injection (including intramuscular, subcutaneous, intravenous, and intraperitoneal injection) or implantation; or by nasal administration.

[0215] Compounds of formula (I) can be administered in a controlled release form, such as a slow-release formulation administered subcutaneously or orally.

[0216] Typically, the antiparasitic compositions described in this invention comprise a compound of formula (I), its nitrogen oxide or salt, and a mixture of one or more pharmaceutically or veterinarily acceptable carriers, said carriers comprising excipients and adjuvants selected according to the intended route of administration (e.g., oral or parenteral administration, such as injection) and according to standard operating procedures. Furthermore, suitable carriers are selected based on compatibility with one or more active ingredients in the composition, including, for example, considerations of relative stability with pH and water content. Therefore, compositions for protecting animals from invertebrate parasites, comprising an effective amount of a compound of formula (I) and at least one carrier, are of particular interest.

[0217] For parenteral administration (including intravenous, intramuscular, and subcutaneous injection), compounds of formula (I) can be formulated into suspensions, solutions, or emulsions in oily or aqueous carriers and may contain adjuvants such as suspending agents, stabilizers, and / or dispersants. Compounds of formula (I) can also be formulated for bolus injection or continuous infusion. Injectable pharmaceutical compositions comprise an aqueous solution of the active ingredient (e.g., a salt of the active compound), preferably in a physiologically compatible buffer containing other excipients or adjuvants as known in the pharmaceutical formulation field. Furthermore, suspensions of the active compound can be prepared in lipophilic carriers. Suitable lipophilic carriers include fatty oils such as sesame oil, synthetic fatty acid esters such as ethyl oleate and triglycerides, or substances such as liposomes. Aqueous injectable suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Formulations for injection may be in a single dosage form, such as an ampoule or a multi-dose container. Alternatively, the active ingredient may be in powder form and combined with a suitable carrier, such as pyrogen-free sterile water, before use.

[0218] In addition to the formulations described above, compounds of formula (I) can also be formulated into long-acting formulations. Such long-acting formulations can be administered by inoculation (e.g., subcutaneous or intramuscular) or by intramuscular or subcutaneous injection. For this route of administration, compounds of formula (I) can be formulated with a suitable polymeric or hydrophobic material (e.g., in an emulsion containing a pharmaceutically acceptable oil) and an ion exchange resin, or the compounds can be formulated into slightly soluble derivatives such as, but not limited to, slightly soluble salts.

[0219] For administration by inhalation, the compound of formula (I) can be delivered in aerosol spray form using pressurized packaging or nebulizers and suitable propellants such as (unrestricted) dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, or carbon dioxide. With pressurized aerosols, the dosage unit can be controlled by providing a valve to deliver a measured amount. Gelatin capsules and cartridges for inhalers or nebulizers can be formulated to contain a powder mixture of the compound and a suitable powder base such as lactose or starch.

[0220] The compound of formula (I) surprisingly possesses favorable pharmacokinetic and pharmacodynamic properties, providing systemic availability through oral administration and ingestion. Therefore, after ingestion by the animal to be protected, the parasitic effective concentration of the compound of formula (I) in the blood can protect the treated animal from blood-sucking pests such as fleas, ticks, and lice. It is therefore noteworthy that the composition in its oral form (i.e., in addition to a parasitic effective amount of the compound of formula (I), also comprises one or more carriers selected from binders and fillers suitable for oral administration and concentrated feed carriers) is intended to protect animals from invertebrate parasites.

[0221] For oral administration in the form of solutions (the most readily available absorbed form), emulsions, suspensions, pastes, gels, capsules, tablets, granules, powders, granules, rumen retentions, and food / water / lick bricks, compounds of formula (I) may be formulated with binders / fillers known in the art suitable for oral compositions, such as sugars and sugar derivatives (e.g., lactose, sucrose, mannitol, sorbitol), starches (e.g., corn starch, wheat starch, rice starch, potato starch), cellulose and derivatives (e.g., methylcellulose, carboxymethylcellulose, ethyl hydroxycellulose), protein derivatives (e.g., corn gluten, gels), and synthetic polymers (e.g., polyvinyl alcohol, polyvinylpyrrolidone). Lubricants (e.g., magnesium stearate), disintegrants (e.g., cross-linked polyvinylpyrrolidone, agar, alginate), and dyes or pigments may be added if desired. Pastes and gels typically also contain binders (e.g., acacia, alginate, bentonite, cellulose, xanthan gum, colloidal magnesium aluminum silicate) to help maintain the composition in contact with the oral cavity and prevent it from being expelled.

[0222] A preferred embodiment is the method composition of the present invention formulated into a chewable and / or edible product (e.g., a chewable processed product or an edible tablet). Such products would ideally have a taste, texture, and / or aroma that is desirable to the protected animal for oral administration of a compound with a thyme (I) structure.

[0223] If the antiparasitic composition is in the form of a concentrated feed, the carrier is typically selected from high-performance feeds, feed cereals, or concentrated protein. In addition to the antiparasitic active ingredient, such compositions containing concentrated feed also contain additives that can promote animal health or growth, improve the meat quality from slaughtered animals, or are suitable for livestock farming. These additives include, for example, vitamins, antibiotics, chemotherapeutic agents, antibacterial agents, antifungal agents, anticoccidial drugs, and hormones.

[0224] Compounds of formula (I) can also be formulated into rectal administration compositions, such as suppositories or retention enemas, using conventional suppository bases such as coconut oil or other glycerides.

[0225] Formulations used in the methods of this invention may contain antioxidants, such as BHT (butylated hydroxytoluene). The content of said antioxidant is generally 0.1% to 5% (weight / volume). Some formulations require solubilizers such as oleic acid to dissolve the active agent, especially when spinosad is contained. Common spreading agents used in these pouring formulations include isopropyl myristate, isopropyl palmitate, and saturated C... 12 -C 18 Fatty alcohols, including caprylic / capric acid esters, oleic acid esters, ethyl oleate, triglycerides, silicone oil, and dipropylene glycol methyl ether. The casting formulation for use in the method of this invention can be prepared according to known techniques. When the casting formulation is a solution, the "parasitic agent" / insecticide is mixed with a carrier or medium by heating and stirring (if necessary). Additives or supplementary ingredients can be added to the mixture of the active agent and the carrier, or they can be mixed with the active agent before adding the carrier. Casting formulations in emulsion or suspension form can be prepared similarly using known techniques.

[0226] Other delivery systems for more hydrophobic drug compounds can be used. Liposomes and emulsions are well-known examples of delivery media or carriers for hydrophobic drugs. Additionally, organic solvents such as dimethyl sulfoxide can be used if desired.

[0227] The amount of insecticide required for effective control of invertebrate parasites (i.e., the "effective insecticide dose") will depend on factors such as the species of invertebrate to be controlled, the life cycle and stage of the pest, its size, location, time of year, host crop or animal, feeding behavior, mating behavior, environmental moisture, temperature, etc. Those skilled in the art can readily determine the effective insecticide dose required to achieve the desired level of invertebrate control. Generally, in veterinary applications, the effective insecticide dose is applied to animals, especially warm-blooded animals, to be protected from invertebrate parasites. The effective insecticide dose is the amount of active ingredient required to achieve the observed reduction in the incidence or activity of the target invertebrate. Those skilled in the art will recognize that the effective insecticide dose can vary depending on the compound and composition used in the method of the present invention, the desired insecticidal effect and duration, the target invertebrate species, the animal to be protected, the mode of application, etc., and the amount required to achieve a specific effect can be determined through simple experiments.

[0228] For oral or enteral administration to animals, the dosage of the compounds of the present invention administered at appropriate intervals is generally in the range of about 0.01 mg / kg to about 100 mg / kg, and preferably in the range of about 0.01 mg / kg to about 30 mg / kg of animal body weight. The appropriate dosing interval for the compounds of the present invention to animals is in the range of about once daily to about once a year. Dosing intervals in the range of about once weekly to about once every 6 months are noteworthy. A monthly dosing interval (i.e., administering the compound to the animal once a month) is particularly noteworthy.

[0229] Beneficial effects

[0230] The compounds shown in Formula I exhibit excellent activity against a variety of animal parasites. Furthermore, these compounds achieve good control effects at very low doses, and therefore can be used for the control of animal parasites.

[0231] Terminology Definitions and Explanations

[0232] Unless otherwise defined, all technical terms in this document have the same meanings as commonly understood by one of ordinary skill in the art to which the subject matter of the claims pertains. Unless otherwise stated, all patents, patent applications, and publications cited in this document are incorporated herein by reference in their entirety. If multiple definitions exist for terms in this document, the definitions in this chapter shall prevail.

[0233] Some groups in this application (e.g.) )middle The location indicates the connection point.

[0234] In this application, "more than" means three or more.

[0235] It should be understood that references (including Carey and Sundberg, "Advanced Organic Chemistry 4") may be included. TH ED."Vols.A(2000)and B(2001),Plenum Press,New Definitions of standard chemical terms can be found in the York ( ). Unless otherwise stated, conventional methods within the scope of the art, such as mass spectrometry, NMR, and pharmacological methods, are used. Unless specifically defined, the terms used herein in the relevant descriptions of analytical chemistry, organic synthetic chemistry, and pharmaceutical and medicinal chemistry are known in the art. Standard techniques can be used in chemical synthesis, chemical analysis, drug preparation, formulation and delivery, and in the treatment of patients. For example, reactions and purifications can be carried out using the manufacturer's instructions for use of kits, or in accordance with methods known in the art or the descriptions of this application. The techniques and methods described herein are generally carried out according to conventional methods well known in the art, based on the descriptions in several summary and more specific documents cited and discussed in this specification. In this specification, groups and their substituents can be selected by those skilled in the art to provide stable structural moieties and compounds. When a substituent is described by a conventional chemical formula written from left to right, the substituent also includes chemically equivalent substituents obtained when the structural formula is written from right to left, provided that they conform to the valence bond rules. For example, CH2O is equivalent to OCH2 and can be attached to the substitution position by an oxygen atom or a carbon atom of a methylene group.

[0236] The term "halogen" refers to fluorine, chlorine, bromine, or iodine.

[0237] The term “C1-C4 alkyl” should be understood to mean a straight-chain or branched saturated monovalent hydrocarbon group having 1 to 4 carbon atoms, such as methyl, ethyl, propyl, butyl, isopropyl, isobutyl, sec-butyl, and tert-butyl.

[0238] The term “C1-C6 alkyl” should be understood to mean a straight-chain or branched saturated monovalent hydrocarbon group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, butyl, isopropyl, isobutyl, sec-butyl, and tert-butyl.

[0239] The above definition of the term "alkyl" also applies to other terms containing "C1-C4 alkyl", such as "C1-C4 alkoxy (C1-C4 alkyloxy)," "halogenated C1-C4 alkyl," "halogenated C1-C4 alkoxy," "C1-C4 alkyl thio," "(C1-C4) alkyl-SO-," "(C1-C4) alkyl-SO2-," "(C1-C4) haloalkyl sulfone-SO2-," etc.

[0240] The term "C3-C6 cycloalkyl" should be understood to refer to a saturated monovalent monocyclic or bicyclic hydrocarbon ring having 3 to 6 carbon atoms. In particular, the group has 3, 4, 5, or 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0241] Term "C" 2- "C4 alkenyl" should be understood to refer to a straight-chain or branched monovalent hydrocarbon group containing one or more double bonds and having 2 to 4 carbon atoms. It should be understood that when the alkenyl group contains more than one double bond, the double bonds may be separable or conjugated.

[0242] Term "C" 2- "C4 alkynyl" should be understood as representing a straight-chain or branched monovalent hydrocarbon group that contains one or more triple bonds and has 2 to 4 carbon atoms.

[0243] As used herein, the term "pharmaceutically acceptable salt" refers to a salt that retains the bioavailability of the free acid and free base of the specified compound and has no adverse effects in biological or other respects. The compounds in this application also include pharmaceutically acceptable salts, such as nitrates, hydrochlorides, sulfates, phosphates, acetates, trifluoroacetates, malates, or citrates, and other salts generally usable in the agricultural and horticultural fields. A pharmaceutically acceptable salt refers to a salt form obtained by converting a base group in a parent compound into a salt form. Pharmaceutically acceptable salts include, but are not limited to, inorganic or organic acid salts with base groups such as amine (amino) groups. The pharmaceutically acceptable salts of this application can be synthesized from the parent compound by reacting a basic group in the parent compound with 1-4 equivalents of an acid in a solvent system. Suitable salts are listed in Remingtong's Pharmaceutical Sciences, 17. th See, for example, hydrochloride, in Mack Publishing Company, Easton, Pa., 1985, p. 1418 and Journal of Pharmaceutical Science, 66, 2 (1977).

[0244] As used herein, “stereoisomers” refers to isomers resulting from different spatial arrangements of atoms in a molecule. Compounds of Formula (I) contain asymmetric or chiral centers, and therefore, different stereoisomers exist. All stereostructures and mixtures of Formula (I), including racemic mixtures, are included as part of this application. Diastereomeric mixtures can be separated into individual diastereomers based on their different physicochemical properties using well-known methods, such as the resolution of enantiomers by reacting them with a suitable optically active substance (e.g., a chiral alcohol or Mosher's chloride) to convert them to diastereomers, separating and converting them (e.g., hydrolysis) to the corresponding single isomer. Some compounds in Formula (I) may be transisomers (e.g., substituted aryl groups), which are also part of this application. Enantiomers can also be separated using chiral chromatographic columns. Compounds of Formula (I) may exist in different tautomeric forms, all of which are included within the scope of this application. For example, compounds in the keto-enol and imine-enamine forms.

[0245] Compounds of formula (I) may exist in one or more stereoisomers. These stereoisomers include enantiomers, diastereomers, and transisomers. Those skilled in the art will appreciate that a stereoisomer may be more active and / or may exhibit beneficial effects when enriched relative to other stereoisomers or when isolated from them. Furthermore, those skilled in the art know how to isolate, enrich, and / or selectively prepare said stereoisomers. Compounds of formula (I) may exist as mixtures of stereoisomers, individual stereoisomers, or as optically active forms.

[0246] As used in this article, "tautomer" refers to structural isomers with different energies that can interconvert through a low energy barrier. If tautomerism is possible (e.g., in solution), chemical equilibrium can be achieved for the tautomers. For example, proton tautomers (also known as prototro pictautomers) involve interconversions via proton migration, such as keto-enol isomerization and imine-enamine isomerization. Valence tautomers involve interconversions via the rearrangement of some bonding electrons. A specific example of a keto-enol tautomer is the interconversion between pentane-2,4-dione and 4-hydroxypent-3-en-2-one. Another example of tautomerism is phenol-keto tautomerism. A specific example of a phenol-keto tautomer is the interconversion between pyridine-4-ol and pyridine-4(1H)-keto. Unless otherwise stated, all tautomer forms of the compounds of this invention are within the scope of this invention.

[0247] As used herein, "solvent" refers to an association formed by one or more solvent molecules with the compounds of this invention. Solvents that form solvates include, but are not limited to, water, isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, and aminoethanol. The term "hydrate" refers to an association formed when the solvent molecules are water.

[0248] As used herein, "ester" refers to an ester that is hydrolyzable in vivo, formed from compounds containing a hydroxyl or carboxyl group. Such esters are, for example, pharmaceutically acceptable esters that, upon hydrolysis in humans or animals, produce a parent alcohol or acid. The compounds of formula (I) of this invention contain a carboxyl group and can form hydrolyzable esters in vivo with suitable groups, including, but not limited to, alkyl, arylalkyl, etc.

[0249] As used herein, “nitrogen oxide” refers to a compound containing several amine functional groups, in which one or more nitrogen atoms can be oxidized to form an N-oxide. Specific examples of N-oxides are N-oxides of tertiary amines or N-oxides of nitrogen-containing heterocyclic nitrogen atoms. The corresponding amines can be treated with oxidizing agents such as hydrogen peroxide or peracids (e.g., peroxycarboxylic acids) to form N-oxides (see Advanced Organic Chemistry, Wiley Interscience, 4th ed., Jerry March, pages). In particular, N-oxides can be prepared using the LWDeady method (Syn. Comm. 1977, 7, 509-514), in which the amine compound is reacted with m-chloroperoxybenzoic acid (MCPBA), for example, in an inert solvent such as dichloromethane.

[0250] The term "isotope labeling" as used herein includes, but is not limited to, compounds of the present invention labeled with isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine, sulfur, and chlorine (e.g., 2H, 3H, 13C, 14C, 15N, 18O, 17O, 18F, 35S, and 36Cl). Isotope-labeled compounds of the present invention can be used for the determination of the tissue distribution of the compounds, their prodrugs, and metabolites; preferred isotopes for such determinations include 3H and 14C. Furthermore, in some cases, substitution with a heavier isotope (e.g., deuterium (2H or D)) can provide increased metabolic stability, which offers therapeutic advantages, such as increased in vivo half-life or reduced dose requirements. The isotope-labeled compounds of the present invention can generally be prepared according to the methods described herein by replacing non-isotope-labeled reagents with isotope-labeled reagents.

[0251] The terms "pests," "invertebrate pests," and "invertebrate parasites" used in this article include arthropods, gastropods, and nematodes that are economically important pests. The term "arthropods" includes insects, mites, spiders, scorpions, centipedes, millipedes, solitary worms, and other synodontids. The term "gastropods" includes snails and other stalked-eye animals. The term "nematodes" includes all worms, such as roundworms, canine filariasis, trematodes (trematodes), acanthocephalans, and tapeworms (taenia).

[0252] "Prevention and control of invertebrate pests" refers to inhibiting the growth of invertebrate pests and can be defined in a similar way.

[0253] Parasitic "infection" refers to the presence of a large number of parasites that are dangerous to an animal. The infection may be present in the environment (e.g., the animal's housing, bedding, and surrounding property or structures) or on the animal's skin or fur. When the infection is present inside the animal (e.g., in the blood or other internal tissues), it is used according to the general understanding of the term "infection" in the art, unless otherwise specified. The term "infection" is also synonymous with the term "infection." Detailed Implementation

[0254] The technical solution of the present invention will be further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanatory of the present invention, and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0255] The following tests confirmed the control efficacy of compounds of formula (I) against specific pests. "Control efficacy" refers to the ability to inhibit the development of invertebrate parasites and lead to a significant reduction in feeding (including mortality). However, the pest control protection provided by the compounds is not limited to these species.

[0256] Table 3

[0257]

[0258]

[0259]

[0260]

[0261]

[0262]

[0263]

[0264]

[0265]

[0266]

[0267]

[0268]

[0269]

[0270]

[0271]

[0272]

[0273]

[0274]

[0275]

[0276]

[0277]

[0278]

[0279]

[0280] The preparation methods for the compounds in Table 3 are disclosed in patent CN118063349A. Where a method for preparing compound (I) is required, this patent publication is incorporated herein by reference.

[0281] Bioactivity Assay Examples

[0282] Test Example 1: To evaluate the control effect against cat fleas (Ctenocephalides felis), mice were orally administered the test compound dissolved in propylene glycol / cyclomethylene glycerol ether (60:40) at a dose of 10 mg / kg. Two hours after oral administration of the test compound, approximately 8 to 16 adult cat fleas were applied to each mouse. The mortality rate of the cat fleas was then evaluated 48 hours after the mice were treated.

[0283] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138, 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 22 6, 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306, 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542, 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 6 08, 611, 614, 620, 623, 624, 626, 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681, 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730, 731, 735, 740, 742, 745 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789, 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813, 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0284] Test Example 2: To evaluate the control effect against cat fleas (Ctenocephalides felis), mice were orally administered the test compound dissolved in propylene glycol / cyclomethylene glycerol ether (60:40) at a dose of 10 mg / kg. Twenty-four hours after oral administration of the test compound, approximately 8 to 16 adult cat fleas were applied to each mouse. The mortality rate of the cat fleas was then evaluated 48 hours after the application.

[0285] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138, 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 22 6, 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306, 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542, 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 6 08, 611, 614, 620, 623, 624, 626, 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681, 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730, 731, 735, 740, 742, 745 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789, 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813, 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0286] Test Example 3: To evaluate the control effect against canine fleas (Ctenocephalides canis), mice were subcutaneously injected with the test compound dissolved in propylene glycol / cyclomethylene glycerol ether (60:40) at a dose of 10 mg / kg. Two hours after the subcutaneous injection of the test compound, approximately 8 to 16 adult canine fleas were applied to each mouse. Then, 48 hours after the application of canine fleas to the mice, the mortality rate of the canine fleas was evaluated.

[0287] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138, 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 22 6, 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306, 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542, 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 6 08, 611, 614, 620, 623, 624, 626, 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681, 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730, 731, 735, 740, 742, 745 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789, 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813, 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0288] Test Example 4: To evaluate the control efficacy against canine fleas (Ctenocephalides canis), the test compound was dissolved in propylene glycol / cyclomethylene glycerol ether (60:40), and then diluted in bovine blood to a final test concentration of 30 ppm. The treated blood was placed in tubes, and the bottom of the tubes was covered with a film. Approximately 10 adult canine fleas were allowed to feed on the treated blood through the film. The mortality rate of the adult canine fleas was then evaluated after 72 hours.

[0289] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138, 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 22 6, 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306, 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542, 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 6 08, 611, 614, 620, 623, 624, 626, 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681, 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730, 731, 735, 740, 742, 745 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789, 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813, 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0290] Test Example 5: To evaluate the control efficacy against *Rhizoctonia sanguineus*, beagle dogs were orally administered the test compound dissolved in propylene glycol / cyclomethylene glycerol ether (60:40) at a dose of 10 mg / kg. Two hours after oral administration of the test compound, 20 *Rhizoctonia sanguineus* ticks were applied to each beagle dog for infection. Forty-eight hours after the application of *Rhizoctonia sanguineus* ticks, the tick count was performed to evaluate the mortality rate.

[0291] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138. 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 226 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 608, 611, 614, 620, 623, 624, 626 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730 731, 735, 740, 742, 745, 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789

[0299] 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813, 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0300] Test Example 6: To evaluate the control efficacy against *Rhizoctonia sanguineus*, beagle dogs were subcutaneously injected with the test compound dissolved in propylene glycol / cyclomethylene glycerol ether (60:40) at a dose of 10 mg / kg. Two hours after the subcutaneous injection, 20 *Rhizoctonia sanguineus* ticks were applied to each beagle dog for infection. Forty-eight hours after the application of *Rhizoctonia sanguineus*, the tick counts were performed to evaluate the mortality rate.

[0301] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138. 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 226 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 608, 611, 614, 620, 623, 624, 626 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730 731, 735, 740, 742, 745, 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789

[0309] 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813, 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0310] Test Example 7: To evaluate the control efficacy against soft ticks (O. moubata), the test compound was dissolved in propylene glycol / cyclomethylene glycerol ether.

[0311] In (60:40), six guinea pigs were treated with a compound administered orally at a dose of 10 mg / kg body weight. All guinea pigs were locally infected with juvenile soft ticks (O. moubata) prior to treatment. Twenty hours after infection, 10 satiated ticks were collected to assess the percentage of individuals killed, thus evaluating the soft tick mortality rate.

[0312] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138. 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 226 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 608, 611, 614, 620, 623, 624, 626 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730 731, 735, 740, 742, 745, 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789

[0320] 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813, 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0321] Test Example 8: To evaluate the control efficacy against soft ticks (O. moubata), the test compound was dissolved in propylene glycol / cyclomethylene glycerol ether.

[0322] In (60:40), six guinea pigs were treated subcutaneously with a compound at a dose of 10 mg / kg body weight. All guinea pigs were locally infected with juvenile soft ticks prior to treatment. Twenty hours after infection, 10 satiated ticks were collected to assess the percentage of individuals killed, thus evaluating the soft tick mortality rate.

[0323] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138. 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 226 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 608, 611, 614, 620, 623, 624, 626 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730 731, 735, 740, 742, 745, 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789

[0331] 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813, 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0332] Test Example 9: To evaluate the control efficacy against soft ticks (O. moubata), the test compound was dissolved in propylene glycol / cyclomethylene glycerol ether.

[0333] In (60:40), six guinea pigs were treated with a compound administered intraperitoneally at a dose of 10 mg / kg body weight. All guinea pigs were locally infected with juvenile soft ticks prior to treatment. Twenty hours after infection, 10 satiated ticks were collected to assess the percentage of individuals killed, thus evaluating the soft tick mortality rate.

[0334] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138, 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 22 6, 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306, 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542, 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 6 08, 611, 614, 620, 623, 624, 626, 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681, 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730, 731, 735, 740, 742, 745 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789, 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813, 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0335] Test Example 10: To evaluate the control efficacy against bed bugs (C. lectularius), the test compound was dissolved in propylene glycol / cyclomethylene glycerol ether (60:40), and six guinea pigs were treated with an oral dose of 10 mg / kg body weight. All guinea pigs were locally infected with bed bugs before treatment. Twenty hours after infection, ten satiated bed bugs of each species were collected to assess the percentage of killed individuals. The mortality rate of the bed bugs was evaluated.

[0336] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138, 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 22 6, 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306, 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542, 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 6 08, 611, 614, 620, 623, 624, 626, 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681, 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730, 731, 735, 740, 742, 745 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789, 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813, 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0337] Test Example 11: To evaluate the control efficacy against bed bugs (C. lectularius), the test compound was dissolved in propylene glycol / cyclomethylene glycerol ether (60:40), and six guinea pigs were treated subcutaneously with 10 mg / kg body weight of the compound. All guinea pigs were locally infected with bed bugs before treatment. Twenty hours after infection, ten satiated bed bugs of each species were collected to assess the percentage of individuals killed. The mortality rate of the bed bugs was evaluated.

[0338] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138, 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 22 6, 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306, 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542, 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 6 08, 611, 614, 620, 623, 624, 626, 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681, 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730, 731, 735, 740, 742, 745 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789, 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813, 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0339] Test Example 12: To evaluate the control efficacy against bed bugs (C. lectularius), the test compound was dissolved in propylene glycol / cyclomethylene glycerol ether (60:40), and six guinea pigs were treated with an intraperitoneal administration of 10 mg / kg body weight of the compound. All guinea pigs were locally infected with bed bugs before treatment. Twenty hours after infection, ten satiated bed bugs of each species were collected to assess the percentage of individuals killed. The mortality rate of the bed bugs was evaluated.

[0340] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138, 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 226, 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272 276, 287, 301, 302, 304, 306, 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542, 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 608, 611, 614, 620, 623, 624, 626, 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730 731, 735, 740, 742, 745, 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789

[0343] 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813,

[0344] 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0345] Test Example 13: To evaluate the control efficacy against *Culicoides*, beagle dogs were orally administered a test compound dissolved in propylene glycol / cyclomethylene glycerol ether (60:40) at a dose of 10 mg / kg. Two hours after oral administration of the test compound, approximately 20 *Culicoides* flies were applied to each beagle dog. Then, 48 hours after the application of *Culicoides* flies to the beagle dogs, the fly counts were performed to evaluate the fly mortality rate.

[0346] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138. 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 226 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 608, 611, 614, 620, 623, 624, 626 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730 731, 735, 740, 742, 745, 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789

[0354] 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813,

[0355] 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0356] Test Example 14: To evaluate the control efficacy against *Culicoides*, beagle dogs were subcutaneously injected with the test compound dissolved in propylene glycol / cyclomethylene glycerol ether (60:40) at a dose of 10 mg / kg. Two hours after the subcutaneous injection, approximately 20 *Culicoides* flies were applied to each beagle dog. Then, 48 hours after the application of *Culicoides* flies to the beagle dogs, the fly counts were performed to evaluate the mortality rate.

[0357] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138. 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 226 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 608, 611, 614, 620, 623, 624, 626 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730 731, 735, 740, 742, 745, 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789

[0365] 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813,

[0366] 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0367] Test Example 15: To evaluate the control efficacy against Culex mosquitoes, cats were orally administered a test compound dissolved in propylene glycol / cyclomethylene glycerol ether (60:40) at a dose of 10 mg / kg. Two hours after oral administration of the test compound, 30 Culex mosquitoes were applied to each cat. The mosquitoes were then counted and the mortality rate was evaluated 48 hours after the application.

[0368] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138. 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 226 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 608, 611, 614, 620, 623, 624, 626 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730 731, 735, 740, 742, 745, 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789

[0376] 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813,

[0377] 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0378] Test Example 16: To evaluate the control efficacy against Culex mosquitoes, cats were subcutaneously injected with a test compound dissolved in propylene glycol / cyclomethylene glycerol ether (60:40) at a dose of 10 mg / kg. Two hours after the subcutaneous injection, 30 Culex mosquitoes were applied to each cat. Forty-eight hours after the application, the mosquitoes were counted, and the mortality rate was evaluated.

[0379] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138. 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 226 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 608, 611, 614, 620, 623, 624, 626 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730 731, 735, 740, 742, 745, 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789

[0387] 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813,

[0388] 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0389] Test Example 17: To evaluate the control effect against Cochliomyia hominivorax larvae, cats were orally administered the test compound dissolved in propylene glycol / cyclomethylene glycerol ether (60:40) at a dose of 10 mg / kg. Two hours after oral administration of the test compound, 20 Cochliomyia hominivorax larvae were applied to each cat. Then, 48 hours after the cats were treated with the Cochliomyia hominivorax larvae, the larvae were counted, and the mortality rate of the Cochliomyia hominivorax larvae was evaluated.

[0390] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138. 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 226 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 608, 611, 614, 620, 623, 624, 626 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730 731, 735, 740, 742, 745, 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789

[0398] 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813,

[0399] 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0400] Test Example 18: To evaluate the control effect against Cochliomyia hominivorax larvae, cats were subcutaneously injected with the test compound dissolved in propylene glycol / cyclomethylene glycerol ether (60:40) at a dose of 10 mg / kg. Two hours after the subcutaneous injection of the test compound, 20 Cochliomyia hominivorax larvae were applied to each cat. Then, 48 hours after the application of the Cochliomyia hominivorax larvae to the cats, the larvae were counted, and the mortality rate of the Cochliomyia hominivorax larvae was evaluated.

[0401] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138. 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 226 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 608, 611, 614, 620, 623, 624, 626 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730 731, 735, 740, 742, 745, 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789

[0409] 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813,

[0410] 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0411] Test Example 19: To evaluate the control effect against assassin bugs, cats were orally administered the test compound dissolved in propylene glycol / cyclomethylene glycerol ether (60:40) at a dose of 10 mg / kg. Two hours after oral administration of the test compound, approximately 30 assassin bugs were applied to each cat. Then, 48 hours after the cats were treated with the assassin bugs, the number of bugs was counted, and the mortality rate of the assassin bugs was evaluated.

[0412] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138. 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 226 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 608, 611, 614, 620, 623, 624, 626 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730 731, 735, 740, 742, 745, 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789

[0420] 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813,

[0421] 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0422] Test Example 20: To evaluate the control effect against assassin bugs, cats were subcutaneously injected with a solution of propylene glycol / cyclomethylene glycerol ether at a dose of 10 mg / kg.

[0423] The test compound was in (60:40). Two hours after subcutaneous injection of the test compound, approximately 30 assassin bugs were administered to each cat. The assassin bugs were then counted and the mortality rate was assessed 48 hours after administration.

[0424] Of the compounds tested, the following compounds caused at least 80% mortality: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138, 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 22 6, 227, 231, 241, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306, 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542, 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 6 08, 611, 614, 620, 623, 624, 626, 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681, 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730, 731, 735, 740, 742, 745 746, 748, 753, 758, 760, 763, 770, 771, 775, 776, 780, 781, 789, 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813, 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0425] Test Example 21: To evaluate the efficacy against Demodex folliculorum, beagle dogs were orally administered a solution of propylene glycol / cyclomethylene glycerol ether at a dose of 10 mg / kg.

[0426] The test compound was in (60:40). Two hours after oral administration of the test compound, 30 Demodex mites were administered to each beagle dog. Then, 48 hours after administration of the Demodex mites, the mites were counted and the mortality rate was evaluated.

[0427] Among the tested compounds, the following compounds are listed: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138, 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 226, 227, 231, 2 41, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306, 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542, 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 608, 611, 614, 620, 623, 624, 626, 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681, 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730, 731, 735, 740, 742, 745, 746, 748, 753 The following numbers did not exceed 45% mortality rate: 758, 760, 763, 770, 771, 775, 776, 780, 781, 789, 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813, 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0428] Test Example 22: To evaluate the control efficacy against Demodex folliculorum, beagle dogs were subcutaneously injected with the test compound dissolved in propylene glycol / cyclomethylene glycerol ether (60:40) at a dose of 10 mg / kg. Two hours after the subcutaneous injection of the test compound, 30 Demodex mites were applied to each beagle dog. Then, 48 hours after the application of the Demodex mites to the beagle dogs, the Demodex mites were counted, and the mortality rate of the Demodex mites was evaluated.

[0429] Among the tested compounds, the following compounds are listed: 1, 2, 3, 4, 6, 7, 17, 32, 36, 47, 61, 62, 63, 64, 66, 67, 77, 81, 91, 92, 93, 96, 106, 107, 121, 122, 124, 126, 136, 137, 138, 139, 152, 157, 167, 181, 182, 183, 184, 186, 187, 196, 197, 201, 211, 212, 213, 214, 226, 227, 231, 2 41, 242, 243, 244, 246, 257, 258, 261, 271, 272, 276, 287, 301, 302, 304, 306, 361, 362, 363, 366, 377, 422, 423, 424, 426, 481, 482, 484, 486, 497, 501, 512, 516, 542, 543, 544, 546, 547, 557, 558, 561, 602, 603, 604, 605, 608, 611, 614, 620, 623, 624, 626, 629, 632, 638, 640, 645, 652, 653, 656, 663, 665, 666, 670, 672, 674, 676, 677, 679, 681, 686, 688, 691, 692, 694, 698, 699, 704, 706, 709, 710, 712, 717, 722, 724, 727, 728, 730, 731, 735, 740, 742, 745, 746, 748, 753 The following numbers did not exceed 45% mortality rate: 758, 760, 763, 770, 771, 775, 776, 780, 781, 789, 800, 806, 811-1, 812-1, 814-1, 815-1, 817-1, 818-1, 820-1, 821-1, 823-1, 824-1, 811, 813, 814, 815, 816, 818, 819, 821, 823, 832, 841, 853, 863, 868, 871, 878, 881, 882.

[0430] The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiments. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for protecting an animal from invertebrate parasites, the method comprising administering to the animal an insecticidally effective amount of a compound of formula (I), its stereoisomers, racemates, tautomers, isotopic markers, nitrogen oxides, solvates, polymorphs, esters, or pharmaceutically acceptable salts thereof. R1, R2, R3, R4, R5, R 11 R 12 R 13 R 14 They may be the same or different, and are independently selected from H, F, Cl, Br, I, CN, NH2, NO2, SF5, C1-C4 alkyl, C3-C6 cycloalkyl, C2-C4 alkenyl, C2-C4 alkoxy, halo-C1-C4 alkyl, halo-C1-C4 alkoxy, C1-C4 alkyl thio, C1-C4 alkyl-SO-, C1-C4 alkyl-SO2- or halo-C1-C4 alkyl-SO2-; R6 and R7 may be the same or different, and are independently selected from H, F, Cl, Br, I or C1-C4 alkyl groups; R8 and R9 may be the same or different, and are independently selected from H or C1-C4 alkyl groups; R 10 Selected from H, C1-C4 alkyl, halogenated C1-C4 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl C1-C4 alkyl-, C1-C4 alkyl-CO-, C3-C6 cycloalkyl-CO- or C1-C4 alkoxy-C1-C4 alkyl-CO-; R 15 Selected from -C1-C4 alkyl-cyano, -C1-C4 alkyl-CF3 or -C1-C4 alkyl-CHF2; R 16 Selected from -C1-C4 alkyl-cyano, unsubstituted or optionally substituted by one, two or more Rs: C3-C6 cycloalkyl or -C1-C4 alkyl-C3-C6 cycloalkyl; Rs are selected from halogens, C1-C4 alkyl or halo-C1-C4 alkyl; Q1 and Q2 may be the same or different, and are selected independently from O or S.

2. The method according to claim 1, characterized in that, In equation (I), R1, R2, R3, R4, R5, R 11 R 12 R 13 R 14 They may be the same or different, and are independently selected from H, F, Cl, Br, CN, SF5, methyl, ethyl, cyclopropyl, methoxy, difluoromethyl, trifluoromethyl, or trifluoromethoxy; R6 and R7 may be the same or different, and are independently selected from H, F, Cl or Br; R8 and R9 may be the same or different, and are independently selected from H or methyl groups; R 10 Selected from H, C1-C4 alkyl, halo-C1-C4 alkyl, C3-C6 cycloalkyl or C3-C6 cycloalkyl-C1-C4 alkyl-; Preferably, in formula (I), R1, R5, R8, R9, R 11 and R 12 H is the highest value; Q1 and Q2 are both O. R2 is a halo-C1-C3 alkyl group, F, Cl, Br, or CN; R3 can be H, F, Cl, or Br; R4 is a halogenated C1-C3 alkyl group, F, Cl, Br, or methyl group; R6 and R7 are F, Cl, and Br, respectively. R 10 H, methyl or R 13 is H, F, Cl, Br; R 14 is H, F, Cl, Br; R 15 Selected from -C1-C4 alkyl-cyano groups; R 16 Selected from C3-C6 cycloalkyl groups; Preferably, in formula (I), R1, R5, R8, R9, R 11 and R 12 H is the highest value; Q1 and Q2 are both O. R2 is trifluoromethyl, Cl, or CN; R3 is H, F, or Cl; R4 is trifluoromethyl, Cl, F or methyl; R6 and R7 are Cl; R 10 H, methyl or methylcyclopropyl R 13 It is H or Cl; R 14 For H or F; R 15 Selected from -C1-C4 alkyl-cyano groups; R 16 It is selected from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

3. The method according to claim 1 or 2, characterized in that, In equation (I), R 15 When it is a -C1-C4 alkyl-cyano group, R 16 The substitution is a substituted or unsubstituted -C3-C6 cycloalkyl group, or a substituted or unsubstituted -C1-C4 alkyl-C3-C6 cycloalkyl group; the substitution is by one, two or more of the following groups: F, Cl, methyl, ethyl, cyclopropyl, methoxy, difluoromethyl, trifluoromethyl or trifluoromethoxy; the substitution is preferably on the C3-C6 cycloalkyl group of the -C1-C4 alkyl-C3-C6 cycloalkyl group; Preferably, R 15 When it is -C1-C4 alkyl-CF3, R 16 The substitution is a substituted or unsubstituted -C3-C6 cycloalkyl, -C1-C4 alkyl-cyano group; the substitution is by one, two or more of the following groups: F, Cl, methoxy, difluoromethyl, trifluoromethyl or trifluoromethoxy; Preferably, R 15 When R is -C1-C4 alkyl-CHF2, 16 The substituted or unsubstituted -C3-C6 cycloalkyl group; the substitution is by being substituted by one, two or more of the following groups: F, Cl, methoxy, difluoromethyl, trifluoromethyl or trifluoromethoxy.

4. The method according to any one of claims 1-3, characterized in that, In equation (I), R 15 The compounds are cyanomethyl, cyanoethyl, cyanopropyl, trifluoroethyl, difluoroethyl, trifluoropropyl, and difluoropropyl. R 16 The compounds are cyanomethyl, cyanoethyl, cyclopropyl, cyclopropylmethyl, dichlorocyclopropyl, difluorocyclopropyl, fluorochlorocyclopropyl, methylcyclopropyl, and trifluoromethylcyclopropyl.

5. The method according to any one of claims 1-4, characterized in that, In formula (I), R1, R2, R3, R4, and R5 may be the same or different, and are independently selected from H, F, Br, methyl, trifluoromethyl, CHF2, or Cl; R6 and R7 are selected from Cl or Br; R8 is selected from H; R9 is selected from H; R 10 Selected from H, methyl, ethyl, trifluoroethyl, cyclopropyl, or cyclopropylmethyl; R 11 R 12 They are either the same or different, and are selected independently from H; R 13 R 14 They are independently selected from H, F, Br, Cl, or CF3; R 15 R 16 Together with the N atoms they are attached to, they form the following groups: Q1 and Q2 are selected from O.

6. The method according to any one of claims 1-5, characterized in that, The compound of formula (I) is selected from the following compounds. Where R1 = H, R5 = H, R8 = H, R9 = H, R 11 =H,R 12 =H, Q 1＝ O, Q2 = O Or, the following compounds Where R6 = Cl, R7 = Cl, R8 = H, R9 = H, Q 1＝ O, Q2 = O Table 2 7. The method according to any one of claims 1-6, characterized in that, The method described is not a treatment method; Preferably, the method involves contacting the parasite or its environment with an insecticidally effective amount of the compound of formula (I), its stereoisomers, racemates, tautomers, isotopic markers, nitrogen oxides, solvates, polymorphs, esters, or pharmaceutically acceptable salts thereof.

8. The method according to any one of claims 1-7, characterized in that, The route of administration is oral, gastrointestinal, or injection.

9. The method according to any one of claims 1-8, wherein the parasite is an invertebrate parasite; Preferably, the parasite is an ectoparasite; Preferably, the parasite is an endoparasite; Preferably, the parasite is a worm; Preferably, the parasite is an arthropod; Preferably, the parasite is a Hemiptera (sting bug); more preferably, it is a Reduvius. Alternatively, the parasite may be of the order Diptera; preferably a fly or mosquito; more preferably a species of the genus Culex (mosquito), such as Culex, or preferably a species of the superfamily Sarcophagoidea, such as Culicoides; Alternatively, the parasite may be a mite, preferably a Demodex mite, such as Demodex folliculorum; Alternatively, the parasite may be a Phthiraptera (sucking louse), preferably a species of the Phthiraptera genus, and more preferably a tick or louse, such as bed bug, cattle lice, pig lice, sheep lice, or cat lice; Alternatively, the parasite may be a flea, preferably a cat flea or a dog flea; Alternatively, the parasite may be a bedbug or a tick, preferably a hard tick or a soft tick, such as the soft tick (O. moubata) or the blood-headed fan tick. (R. sanguineus); Alternatively, the parasite may be a maggot, such as the spiral fly maggot (Cochliomyia hominivorax). More preferably, the parasites are cat fleas, dog fleas, blood-headed fan ticks, soft ticks, bed bugs, hair follicle mites, blowflies, Culex mosquitoes, spiral fly larvae, and assassin bugs; preferably, the animals are vertebrates; Preferably, the animal is a mammal, bird, or fish; Preferably, the mammal is a human; Preferably, the mammal is a livestock; Preferably, the mammal is a canine; Preferably, the mammal is a feline.

10. A non-treatment method for preventing parasitic infestation, the method comprising contacting the parasite or its environment with an insecticidally effective amount of a compound of formula (I) of any one of claims 1-6, its stereoisomers, racemates, tautomers, isotopic labels, nitrogen oxides, solvates, polymorphs, esters, or pharmaceutically acceptable salts thereof.

11. Use of the compound of formula (I) as claimed in any one of claims 1-6, its stereoisomers, racemates, tautomers, isotopic labels, nitrogen oxides, solvates, polymorphs, esters or pharmaceutically acceptable salts thereof in the preparation of a medicament for the prevention and treatment of animal parasites.

12. A method for protecting an animal from invertebrate parasites, the method comprising administering to the animal an insecticidally effective amount of a composition, characterized in that, The composition comprises one, two or more of the following as active ingredients: a compound of formula (I) as claimed in any one of claims 1-6, a stereoisomer, a racemate, a tautomer, an isotope label, a nitrogen oxide, a solvate, a polymorph, an ester, or a pharmaceutically acceptable salt thereof.

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