Novel phenylpyrazole insecticide compounds and compositions

Abstract

This disclosure is based on formula I: The present invention relates to novel and improved phenylpyrazole class insecticides, as shown in TIFF2026516139000045.tif31164. [wherein X, Y, Z, and Ar are as defined herein]. In particular, the Disclosure provides novel insecticidal compounds for use against a variety of insects (arthropods), such as in fields, crops, and other insecticidal applications, for the treatment or prevention of diseases or parasites in poultry and other livestock, horses, cats, dogs, and other companion animals. In specific embodiments, the Disclosure provides the use of the compounds for the treatment, control, suppression, or eradication of infections or parasites by insects (arthropods) (including, but not limited to, mites (Dermanyssus gallinae)), such as adults, insect eggs, insect larvae, insect nymphs, and / or insect pupae.

Description

[Technical Field]

[0001] Cross-reference of related applications This application is an international PCT application claiming priority to European application No. 23425020.7, filed on 9 May 2023, the contents of which are incorporated herein by reference in their entirety.

[0002] Field of the present invention This disclosure relates to novel and improved phenylpyrazole class insecticidal compounds. In particular, this disclosure provides novel insecticidal compounds for use against a variety of insects (arthropods), such as in field, crop, and other insecticidal applications, for the treatment or prevention of diseases or infestations in poultry and other livestock, horses, cats, dogs, and other companion animals. [Background technology]

[0003] Insecticides are chemical or biological agents used to control the proliferation of pests, primarily insects (arthropods), by killing them or by inhibiting key stages in their life cycle (e.g., egg, larva, nymph, pupa, and / or adult). Insecticides may exert their effects acutely (e.g., after a single exposure) or after chronic exposure. The methods by which insecticides can be applied vary depending on the nature of the pest. Thousands of the 5 to over 10 million known arthropod species, including over 1 million known true insect species, are considered pests or parasites. Some cause crop destruction, which accounts for the majority of commercial insecticide use. Other insects cause diseases in animals, including humans, pets (dogs, cats, horses, etc.), and livestock (e.g., poultry, cattle, pigs, sheep, goats).

[0004] Insecticides have various mechanisms of action, but they primarily act on the nervous system of insects and usually function as potent neurotoxins. For example, organochlorine insecticides (e.g., DDT) and pyrethroid insecticides promote the opening of sodium channels, organophosphate and carbamate insecticides inhibit acetylcholinesterase enzymes, neonicotinoid insecticides inhibit nicotinic acetylcholine receptors, and phenylpyrazole insecticides inhibit GABAergic chloride channels.

[0005] Phenylpyrazole insecticides are broad-spectrum insecticides and are among the most commonly used insecticides. Phenylpyrazole insecticides act on GABA (gamma-aminobutyric acid) receptors on insect neurons, blocking the conduction of chloride ions. Since the influx of chloride ions into neurons is inhibitory, disruption of GABA receptor opening leads to a state of hyperexcitability in the neurons. Fipronil was the first phenylpyrazole insecticide introduced in 1993. These agents were specifically developed to address the widespread resistance of insects to older classes of insecticides. In particular, fipronil has been used against insects resistant to pyrethroid, organophosphate, and carbamate insecticides, including cockroaches, beetles, ants, fleas, termites, mites, weevils, mole crickets, flies, mosquitoes, and moths. Other phenylpyrazole class insecticides include acetoprole, ethiprole, flufiprole, pyraclofos, pyrafluprole, pyriprole, pyrorane, and vaniliprole. These compounds share an N-phenylpyrazole ring, but are otherwise very structurally diverse. [ka]

[0006] Following their introduction, phenylpyrazole insecticides have played a significant role in pest control in crops, livestock, and pets. However, their widespread use has already led to the development of resistance. Furthermore, while phenylpyrazoles are generally relatively safe for mammals (due to structural differences between insect and mammalian GABA receptors), fipronil has recently been banned in many countries for certain uses due to its high toxicity to non-targeted beneficial organisms, including fish, aquatic invertebrates, and honeybees. See, for example, Li et al., Letters in Drug Design & Discovery, 2019, 16, 1175-1180; Guo et al., RSC Advances 2017, 7, 11796-11802; Leemans et al., Front. Endocrinol., 2019, 10: 743. Leemans et al. have characterized fipronil as a widespread environmental pollutant, found in soil, water, outdoor dust, and some foods. Fipronil is thought to be cytotoxic to epithelial cells, including intestinal epithelium. When ingested in sufficient quantities, fipronil can cause nausea, vomiting, abdominal pain, seizures, and toxic effects on the kidneys, liver, and thyroid.

[0007] Fipronil was associated with mass bee deaths in France during the 1990s and 2000s, resulting in its ban as a crop insecticide by the European Commission in 2014, as well as its use in food animals. While fipronil degrades slowly in the environment, it is rapidly metabolized in animals. Contributing to the risk of oral toxicity, the major metabolites of fipronil—sulfones, sulfides, and desulfinylated derivatives—are significantly more toxic, persistent, bioaccumulative, and less selective than the parent compound. See Leemans et al. [ka]

[0008] Fipronil has long been used to treat ectoparasites that infest poultry, such as fleas, lice, and ticks (especially mites (Dermanyssus gallinae)). However, in the EU, fipronil was banned from use on poultry for human consumption from 2013 to 2019. In 2017, a serious scandal shook the continent when fipronil was detected in eggs on the European market. This was the result of pesticide dealers illegally selling fipronil-containing products to unsuspecting farmers. As a result, millions of eggs were recalled from the market, millions of chickens were slaughtered, and the owners of the pesticide dealers faced prison sentences. Nevertheless, in 2018, the EU Court of Justice overturned part of the fipronil ban due to insufficient evidence, but calls for a complete ban on fipronil from the EU market remain.

[0009] Thus, efforts have been made to replace fipronil. Li et al. observed that molecular modeling predicted the existence of an intramolecular hydrogen bond between the amino group and the sulfoxide oxygen in fipronil, and thus devised a series of 1,4,6,7-tetrahydropyrazolo[3,4-d]oxazine derivatives. [ka]

[0010] Li et al. prepared and tested 25 compounds, but only four of them exhibited measurable insecticidal activity. These four compounds peaked at approximately 60% of the activity of fipronil against the beet armyworm (Plutella xylostella), and none possessed comparable insecticidal activity. The authors speculated that this disappointing result may be due to differences in physicochemical properties.

[0011] There is a continuing need for effective methods to control pests in crops, livestock, and pets, methods that do not carry the risk of drug accumulation in animals (e.g., animal-derived foods) and preferably avoid the formation of potentially hazardous metabolites.

Summary of the Invention

[0012] The present disclosure provides a novel N-phenyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile, which is effective as an insecticide for crops, livestock, humans, pets, and other insecticidal applications.

[0013] In a first aspect, the present disclosure provides a compound of formula I (Compound 1) in the form of a free body or a salt, having the following general structure:

Chemical formula

[0014] In a second embodiment, the Disclosure provides a pharmaceutical or insecticidal composition comprising a mixture of an effective amount of a compound of formula I, in the form of a free body or salt, and a pharmaceutically acceptable or insecticidal diluent or carrier. In some embodiments, the compositions described herein may or may be used to treat, control, suppress or eradicate infection or parasitism by insects (arthropods), such as adult insects, insect eggs, insect larvae, insect nymphs, and / or insect pupae, in animals or human patients, or in products or places where such infection or parasitism is required.

[0015] In another embodiment, the Disclosure provides a method (Method 1) for treating, controlling, suppressing or eradicating an infection or parasitism by insects (arthropods), such as adult insects, insect eggs, insect larvae, insect nymphs, and / or insect pupae, comprising administering or applying an effective amount of a compound of Formula I, in the form of a free form or a salt, or a composition comprising a compound of Formula I, in the form of a free form or a salt, to an animal or human patient in need, or to a product or place in need.

[0016] The general fields of application described herein are provided merely as examples and are not intended to limit the scope of this disclosure and the accompanying claims. Additional purposes and advantages relating to the compositions, methods, and processes of this disclosure will be understood by those skilled in the art in light of the claims, description, and examples. For example, various aspects and embodiments of the invention may be used in numerous combinations, all of which are expressly intended herein. These additional advantages, purposes, and embodiments are expressly included within the scope of this disclosure. Publications and other materials used herein to illustrate the background of the invention, and publications and other materials used in particular to provide additional details relating to the implementation, are incorporated by reference. Where applicable or unless specifically denied, any of the embodiments described herein are intended to be combined with one or more other embodiments, even if described under different aspects of this disclosure. [Modes for carrying out the invention]

[0017] Detailed explanation The following is a detailed description provided to assist those skilled in the art in carrying out the inventions disclosed herein. Those skilled in the art may modify and alter the embodiments described herein without departing from the spirit or scope of this disclosure. All publications, patent applications, patents, drawings, and other references referred herein are expressly incorporated by reference in their entirety.

[0018] This disclosure provides a novel N-phenyl-1H-pyrazolo[3,4-b]pyridine-3-carbonitride that is effective as an insecticide for crops, livestock, humans, pets, and other insecticidal applications.

[0019] In a first embodiment, the present disclosure provides a compound of formula I (compound 1) in the form of a free body or salt having the following general structure: [ka] Equation I [In the formula, X is -N- or -CR 1 -and; Y is either -N- or -CR 2 -and; Z is -CR 3 -and; R 1 , R 2 , and R 3 Each of these is independently H, halo, cyano, nitro, hydroxy, amino, and C. 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~6 Cycloalkoxy, C 3~6 Halocycloalkyl, NH(C) 1~6 Alkyl), N(C 1~6 Alkyl)(C 1~6 Selected from alkyl groups and 3- to 6-membered heterocycloalkyl groups, each of which may be appropriately substituted; Ar is a phenyl or 5- or 6-membered heteroaryl, which may be appropriately substituted with 1 to 5 R groups; R can be any of the following independently: halo, cyano, nitro, hydroxy, amino, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~6 Halocycloalkyl, NH(C) 1~6 Alkyl), N(C 1~6 Alkyl)(C 1~6 Selected from alkyl groups and 3- to 6-membered heterocycloalkyl groups, each of which may be substituted as appropriate.

[0020] In further embodiments of the first aspect, the disclosure provides: 1.1 Compound 1 where X is N; 1.2 X is -CR 1 - Compound 1; 1.3 Compound 1 or 1.2, R 1 However, H, halo (e.g., F, Cl), cyano, nitro, hydroxy, amino, C 1~6 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), C 1~6 Haloalkyl (e.g., trifluoromethyl), C 1~6 Alkoxy (e.g., methoxy, ethoxy), C 1~6 Haloalkoxys (e.g., trifluoromethoxy), C 3~6 Cycloalkoxy (e.g., cyclopropoxy), C 3~6 Halocycloalkyl (e.g., 2,2-difluorocyclopropyl), NH(C) 1~6 Alkyl) (e.g., N-methylamino), N(C 1~6 Alkyl)(C 1~6 Compound 1 or 1.2, selected from alkyl groups (e.g., N,N-dimethylamino) and 3- to 6-membered heterocycloalkyl groups (e.g., azilidinyl, azetidinyl, pyrrolidinyl), each of which may be appropriately substituted; 1.4 Compound 1.3, R 1 However, H, halo (e.g., F, Cl), cyano, nitro, hydroxy, amino, C 1~6 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), C 1~6 Haloalkyl (e.g., trifluoromethyl), C 1~6 Alkoxy (e.g., methoxy, ethoxy), C 1~6 Haloalkoxys (e.g., trifluoromethoxy), and C 3~6 Compound 1.3 is selected from cycloalkoxys (e.g., cyclopropoxy), each of which may be appropriately substituted; 1.5 Compound 1.4, R 1 However, H, halo (for example, F, Cl), cyano, nitro, C 1~6 Alkyl (e.g., methyl, ethyl), C 3~6Cycloalkyl (e.g., cyclopropyl), C 1~6 Haloalkyl (e.g., trifluoromethyl), C 1~6 Alkoxy (e.g., methoxy, ethoxy), and C 1~6 Haloalkoxy (e.g., trifluoromethoxy), each of which may be optionally substituted, Compound 1.4; 1.6 R 1 is halo (e.g., F, Cl), cyano, C 1~3 alkyl (e.g., methyl, ethyl), and C 1~3 haloalkyl (e.g., trifluoromethyl), each of which may be optionally substituted, Compound 1.5; 1.7 R 1 is halo (e.g., F, Cl), cyano, C 1~3 alkyl (e.g., methyl, ethyl), C 3~6 cycloalkyl (e.g., cyclopropyl), and C 1~3 haloalkyl (e.g., trifluoromethyl), each of which may be optionally substituted, Compound 1.5; 1.8 R 1 is C 1~3 alkyl (e.g., methyl, ethyl), C 3~6 cycloalkyl (e.g., cyclopropyl), and C 1~3 haloalkyl (e.g., trifluoromethyl), each of which may be optionally substituted, Compound 1.5; 1.9 R 1 [ is optionally substituted C 1~3 alkyl (e.g., methyl, ethyl), Compound 1.5; 1.10 R 1 is optionally substituted C 3~6 cycloalkyl (e.g., cyclopropyl), Compound 1.5; 1.11 R 1 is optionally substituted C1~3 Compound 1.5, which is a haloalkyl (e.g., trifluoromethyl); 1.12 R 1 Compound 1 or any of 1.2 to 1.11, wherein the alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkyl, or heterocycloalkyl is unsubstituted; 1.13 R 1 Compound 1 or any of 1.2 to 1.11, wherein the alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkyl, or heterocycloalkyl is substituted with one or more R a groups, where R a is selected from halo, hydroxy, cyano, nitro, hydroxy, amino, C 1~6 alkyl, C 3~6 cycloalkyl, C 1~6 haloalkyl, C 1~6 alkoxy, C 1~6 haloalkoxy, C 3~6 cycloalkoxy, C 3~6 halocycloalkyl, NH(C 1~6 alkyl), N(C 1~6 alkyl)(C 1~6 alkyl), and 3- to 6-membered heterocycloalkyl, and each of these may be further optionally substituted with one or more R b groups, where R b is selected from halo, hydroxy, cyano, nitro, hydroxy, amino, C 1~6 alkyl, C 3~6 cycloalkyl, C 1~6 haloalkyl, C 1~6 alkoxy, C 1~6 haloalkoxy, C 3~6 cycloalkoxy, C 3~6 halocycloalkyl, NH(C 1~6 alkyl), N(C 1~6 alkyl)(C 1~6 alkyl), and 3- to 6-membered heterocycloalkyl; 1.14 R 1 The compound selected from H, F, Cl, Br, I, cyano, nitro, hydroxy, amino, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, methoxy, ethoxy, propoxy, isopropoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, cyclopropoxy, cyclobutoxy, 2,2-difluorocyclopropyl, N-methylamino, N-ethylamino, N,N-dimethylamino, N,N-diethylamino, N-ethyl-N-methylamino, azilidinyl, azetidinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, morpholinol, piperidinyl, and piperazinyl is compound 1 or any of 1.2-1.13; 1.15 R 1 Compound 1.14, selected from H, F, Cl, Br, I, cyano, nitro, hydroxy, amino, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, cyclopropoxy, azilidinyl, azetidinyl, and oxetanyl; 1.16 R 1 Compound 1.15, selected from H, F, Cl, Br, I, cyano, methyl, ethyl, isopropyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, cyclopropoxy, azilidinyl, azetidinyl, and oxetanyl; 1.17 R 1 Compound 1.16, selected from H, F, Cl, Br, I, cyano, methyl, fluoromethyl, difluoromethyl, and trifluoromethyl; 1.18 Compound 1.17, R 1Compound 1.17, selected from fluoromethyl, difluoromethyl, and trifluoromethyl; 1.19 R 1 However, compound 1.18 is trifluoromethyl; 1.20 R 1 The compound is selected from methyl, ethyl, isopropyl, d3-methyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, chlorofluoromethyl, chlorodifluoromethyl, bromodifluoromethyl, and 1,1-difluoroethyl, either compound 1 or any of 1.2-1.13; 1.21 R 1 Compound 1.20, selected from methyl, isopropyl, d3-methyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, chlorofluoromethyl, chlorodifluoromethyl, bromodifluoromethyl, and 1,1-difluoroethyl; 1.22 R 1 Compound 1.20, selected from methyl, isopropyl, d3-methyl, and cyclopropyl; 1.23 R 1 Compound 1.20, selected from fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, chlorofluoromethyl, chlorodifluoromethyl, bromodifluoromethyl, and 1,1-difluoroethyl; 1.24 R 1 However, compound 1.20 is difluoromethyl; 1.25 Y is N, either compound 1 or one of compounds 1.1-1.24; 1.26 Y is -CR 2 - is either compound 1 or one of 1.1-1.24; 1.27 R 2 However, H, halo (e.g., F, Cl), cyano, nitro, hydroxy, amino, C 1~6 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), C 1~6 Haloalkyl (e.g., trifluoromethyl), C 1~6 Alkoxy (e.g., methoxy, ethoxy), C 1~6 Haloalkoxys (e.g., trifluoromethoxy), C 3~6 Cycloalkoxy (e.g., cyclopropoxy), C 3~6 Halocycloalkyl (e.g., 2,2-difluorocyclopropyl), NH(C) 1~6 Alkyl) (e.g., N-methylamino), N(C 1~6 Alkyl)(C 1~6 Compound 1 or 1.26 is selected from alkyl (e.g., N,N-dimethylamino) and 3- to 6-membered heterocycloalkyl (e.g., azilidinyl, azetidinyl, pyrrolidinyl), each of which may be appropriately substituted; 1.28 R 2 However, H, halo (e.g., F, Cl), cyano, hydroxy, amino, C 1~6 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), C 1~6 Haloalkyl (e.g., trifluoromethyl), C 1~6 Alkoxy (e.g., methoxy, ethoxy), C 1~6 Haloalkoxys (e.g., trifluoromethoxy), and C 3~6 Compound 1.27, selected from cycloalkoxys (e.g., cyclopropoxy), each of which may be appropriately substituted; 1.29 R 2 However, H, halo (e.g., F, Cl), cyano, hydroxy, C 1~3 Alkyl (e.g., methyl, ethyl), C 1~3 Haloalkyl (e.g., trifluoromethyl), C 1~3 Alkoxy (e.g., methoxy, ethoxy), and C1~3 Compound 1.28, selected from haloalkoxys (e.g., trifluoromethoxy), each of which may be substituted as appropriate; 1.30 R 2 However, H, halo (for example, F, Cl), cyano, C 1~3 Alkyl (e.g., methyl, ethyl), and C 1~3 Compound 1.29, selected from haloalkyl groups (e.g., trifluoromethyl), each of which may be appropriately substituted; 1.31 R 2 Compound 1.30, selected from H, halo (e.g., F, Cl), and cyano; 1.32 R 2 However, compound 1.31 is H; 1.33 R 2 Compound 1 or 1.27-1.30, wherein the alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkyl, or heterocycloalkyl is unsubstituted; 1.34 R 2 The alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkyl, or heterocycloalkyl is one or more R a It is substituted with the base, where R a However, halo, hydroxy, cyano, nitro, hydroxy, amino, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~6 Cycloalkoxy, C 3~6 Halocycloalkyl, NH(C) 1~6 Alkyl), N(C 1~6 Alkyl)(C 1~6 Selected from alkyls and 3- to 6-membered heterocycloalkyls, each of which has one or more R bThe group may be appropriately substituted with a group, and Rb may be halo, hydroxy, cyano, nitro, hydroxy, amino, or C. 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~6 Cycloalkoxy, C 3~6 Halocycloalkyl, NH(C) 1~6 Alkyl), N(C 1~6 Alkyl)(C 1~6 Compound 1 or 1.27-1.30, selected from alkyl and 3-6 membered heterocycloalkyl groups; 1.35 R 2 The compound selected from H, F, Cl, Br, I, cyano, nitro, hydroxy, amino, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, methoxy, ethoxy, propoxy, isopropoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, cyclopropoxy, cyclobutoxy, 2,2-difluorocyclopropyl, N-methylamino, N-ethylamino, N,N-dimethylamino, N,N-diethylamino, N-ethyl-N-methylamino, azilidinyl, azetidinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, morpholinol, piperidinyl, and piperazinyl is compound 1 or any of 1.27-1.34; 1.36 R 2 Compound 1.35, selected from H, F, Cl, Br, I, cyano, hydroxy, amino, methyl, ethyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, and methoxy; 1.37 R 2Compound 1.36, selected from H, F, Cl, Br, I, cyano, hydroxy, amino, methyl, fluoromethyl, difluoromethyl, and trifluoromethyl; 1.38 R 2 However, it is selected from H, F, Cl, Br, and cyano, R 2 Compound 1.37 may also contain H as appropriate; 1.39 R 3 However, H, halo (e.g., F, Cl), cyano, nitro, hydroxy, amino, C 1~6 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), C 1~6 Haloalkyl (e.g., trifluoromethyl), C 1~6 Alkoxy (e.g., methoxy, ethoxy), C 1~6 Haloalkoxys (e.g., trifluoromethoxy), C 3~6 Cycloalkoxy (e.g., cyclopropoxy), C 3~6 Halocycloalkyl (e.g., 2,2-difluorocyclopropyl), NH(C) 1~6 Alkyl) (e.g., N-methylamino), N(C 1~6 Alkyl)(C 1~6 Compound 1, or any of 1.1 to 1.38, selected from alkyl (e.g., N,N-dimethylamino) and 3- to 6-membered heterocycloalkyl (e.g., azilidinyl, azetidinyl, pyrrolidinyl), each of which may be appropriately substituted; 1.40 R 3 However, H, halo (e.g., F, Cl), cyano, nitro, hydroxy, amino, C 1~6 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), C 1~6 Haloalkyl (e.g., trifluoromethyl), C 1~6 Alkoxy (e.g., methoxy, ethoxy), NH(C) 1~6 Alkyl) (e.g., N-methylamino), N(C 1~6 Alkyl)(C 1~6Compound 1.39 is selected from alkyl groups (e.g., N,N-dimethylamino) and 3- to 6-membered heterocycloalkyl groups (e.g., azilidinyl, azetidinyl, pyrrolidinyl), each of which may be appropriately substituted; 1.41 R 3 However, hydroxy, amino, C 1~6 Alkyl (e.g., methyl, ethyl), NH(C) 1~6 Alkyl) (e.g., N-methylamino), N(C 1~6 Alkyl)(C 1~6 Compound 1.40 is selected from alkyl groups (e.g., N,N-dimethylamino) and 3- to 6-membered heterocycloalkyl groups (e.g., azilidinyl, azetidinyl, pyrrolidinyl), each of which may be appropriately substituted; 1.42 R 3 However, hydroxy, amino, and NH(C) 1~6 Compound 1.41, selected from alkyl (e.g., N-methylamino), each of which may be appropriately substituted; 1.43 R 3 Compound 1.42, selected from hydroxy, amino, and N-methylamino; 1.44 R 3 However, compound 1.43 is hydroxyl; 1.45 R 3 Compound 1 or 1.39-1.42, wherein the alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkyl, or heterocycloalkyl is unsubstituted; 1.46 R 3 The alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkyl, or heterocycloalkyl is one or more R a It is substituted with R a However, halo, hydroxy, cyano, nitro, hydroxy, amino, C 1~6Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~6 Cycloalkoxy, C 3~6 Halocycloalkyl, NH(C) 1~6 Alkyl), N(C 1~6 Alkyl)(C 1~6 Selected from alkyl groups and 3- to 6-membered heterocycloalkyl groups, each of which further comprises one or more R groups. b The base may be appropriately substituted, R b However, halo, hydroxy, cyano, nitro, hydroxy, amino, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~6 Cycloalkoxy, C 3~6 Halocycloalkyl, NH(C) 1~6 Alkyl), N(C 1~6 Alkyl)(C 1~6 Compound 1, or 1.1-1.42, selected from alkyl and 3-6 membered heterocycloalkyl groups; 1.47 R a or R b Compound 1.46, which is hydroxyl or amino; 1.48 R 3The compound is selected from H, F, Cl, Br, I, cyano, nitro, hydroxy, amino, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, methoxy, ethoxy, propoxy, isopropoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, cyclopropoxy, cyclobutoxy, 2,2-difluorocyclopropyl, N-methylamino, N-ethylamino, N,N-dimethylamino, N,N-diethylamino, N-ethyl-N-methylamino, azilidinyl, azetidinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, morpholinol, piperidinyl, and piperazinyl, either compound 1 or 1.1-1.42; 1.49 R 3 Compound 1.48, selected from H, F, Cl, Br, I, cyano, nitro, hydroxy, amino, methoxy, ethoxy, propoxy, isopropoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, cyclopropoxy, cyclobutoxy, N-methylamino, N-ethylamino, N,N-dimethylamino, N,N-diethylamino, N-ethyl-N-methylamino, azilidinyl, azetidinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, morpholino, piperidinyl, and piperazinyl; 1.50 R 3 Compound 1.49, selected from hydroxy, amino, methoxy, ethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, N-methylamino, N-ethylamino, azilidinyl, azetidinyl, and oxetanyl; 1.51 Compound 1, or any of 1.1 to 1.50, wherein Ar is a phenyl or 5- or 6-membered heteroaryl (e.g., thiophenyl, pyridyl) which may be appropriately substituted with 1 to 5 R groups; 1.52 Compound 1.51 in which Ar is a 5 or 6-membered heteroaryl (e.g., thiophenyl, pyridyl); 1.53 Ar is selected from thiophenyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isothiazolyl, and isoxazolyl, compound 1.52; 1.54 Ar is selected from pyridyl, pyrazinyl, pyridadinyl, and pyrimidinyl, compound 1.52; Compound 1.51, where 1.55 Ar is phenyl; 1.56 Ar is unsubstituted in either compound 1 or compound 1.51-1.55; 1.57 Compound 1, or any of 1.51-1.55, in which Ar is a six-membered ring substituted with 1, 2, 3, 4, or 5 R groups (e.g., phenyl or a six-membered heteroaryl); 1.58 Compound 1.57 in which Ar is a six-membered ring (e.g., phenyl or six-membered heteroaryl) substituted with one, two, or three R groups; Compound 1.59 is a phenyl compound substituted with 1, 2, or 3 R atoms; 1.60 Compound 1.59 in which Ar is a phenyl compound substituted with one R at the ortho, meta, or para position of the ring; 1.61 Compound 1.59 in which Ar is a phenyl compound substituted with two R groups, wherein the two R groups are located at two ortho positions on the ring, or at the ortho and para positions on the ring, or at two meta positions on the ring, or at the ortho and meta positions on the ring; 1.62 Compound 1.59 in which Ar is a phenyl compound substituted with three R groups, and each of the three R groups includes at least one group located in the para position of the ring; 1.63 Compound 1.62 in which the three R groups are located at the two ortho positions and the para position of the ring; 1.64 Each of the one or more R groups is independently a halo (e.g., F, Cl, Br, I), cyano, nitro, hydroxy, amino, or C group. 1~6 Alkyl (e.g., methyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), C 1~6 Haloalkyl (e.g., trifluoromethyl), C 1~6 Alkoxy (e.g., methoxy), C 1~6 Haloalkoxys (e.g., trifluoromethoxy), C 3~6 Halocycloalkyl (e.g., 2,2-difluorocyclopropyl), NH(C) 1~6 Alkyl) (e.g., N-methylamino), N(C 1~6 Alkyl)(C 1~6 Compound 1, or any of 1.57-1.63, selected from alkyl (e.g., N,N-dimethylamino) and 3-6 member heterocycloalkyl (e.g., azetidinyl, azilidinyl, oxetanyl), each of which may be appropriately substituted; 1.65 Each of the one or more R groups is independently a halo (e.g., F, Cl, Br, I), cyano, nitro, hydroxy, or C group. 1~6 Haloalkyl (e.g., trifluoromethyl), C 1~6 Haloalkoxys (e.g., trifluoromethoxy), and C 3~6 Compound 1.64 is selected from halocycloalkyl groups (e.g., 2,2-difluorocyclopropyl), each of which may be appropriately substituted; 1.66 Each of the one or more R groups is independently a halo (e.g., F, Cl, Br, I), cyano, nitro, or C 1~6 Haloalkyl (e.g., trifluoromethyl), and C 1~6 Compound 1.65, selected from haloalkoxys (e.g., trifluoromethoxy), each of which may be substituted as appropriate; 1.67 Each of the one or more R groups is independently a halo (e.g., F, Cl, Br, I), cyano, nitro, or C group. 1~3 Haloalkyl (e.g., trifluoromethyl), and C 1~3 Compound 1.66, selected from haloalkoxys (e.g., trifluoromethoxy), each of which may be substituted as appropriate; 1.68 Compound 1.67 in which one or more R groups are independently selected from F, Cl, Br, I, cyano, nitro, trifluoromethyl, and trifluoromethoxy; 1.69 Compound 1.68 in which one or more R groups are independently selected from F, Cl, Br, trifluoromethyl, and trifluoromethoxy; 1.70 Compound 1.69 in which one or more R groups are independently selected from Cl, Br, trifluoromethyl, and trifluoromethoxy; 1.71 Compound 1.70 in which one or more R groups are independently selected from Cl and trifluoromethyl; 1.72 Ar is 2,6-dichloro-4-trifluoromethylphenyl, 2,6-dichloro-4-trifluoromethoxyphenyl, 2,6-dichloro-4-bromophenyl, 2,6-dichloro-4-difluoromethylphenyl, 2,6-dichloro-4-difluoromethoxyphenyl, 2,6-dichloro-4-fluoromethylphenyl, 2,6-dichloro-4-methoxyphenyl, 2,6-dichloro-4-methylphenyl, 2,6-dichloro-4-methoxyphenyl, 2,4,6-trichloro Compound 1, or any of 1.57-1.71, selected from phenyl, 2-chloro-4-trifluoromethoxyphenyl, 2-chloro-4-bromophenyl, 2-chloro-4-difluoromethylphenyl, 2-chloro-4-difluoromethoxyphenyl, 2-chloro-4-fluoromethylphenyl, 2-chloro-4-methylphenyl, 2-chloro-4-methoxyphenyl, 2,4-dichlorophenyl, and 2-chloro-4-bromophenyl; 1.73 Compound 1.72 in which Ar is selected from 2,6-dichloro-4-trifluoromethylphenyl and 2,6-dichloro-4-trifluoromethoxyphenyl; 1.74 Ar is 2,6-dichloro-4-trifluoromethylphenyl, compound 1.73; 1.75 Compound of formula I, formula Ia: [ka] Compound 1, or any of 1.1-1.74, which is a compound of the above. [In the formula, X, Y, and R are as defined in any of the embodiments described above]; 1.76 Compound of formula I, formula Ib: [ka] Compound 1, or any of 1.1-1.74, which is a compound of the above. [In the formula, R 1 , R 2, and R are as defined in any of the embodiments described above]; 1.77 R 1 However, H, halo (for example, F, Cl), cyano, nitro, C 1~6 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), C 1~6 Haloalkyl (e.g., trifluoromethyl), C 1~6 Alkoxy (e.g., methoxy, ethoxy), and C 1~6 Selected from haloalkoxys (e.g., trifluoromethoxy), each of which may be substituted as appropriate as defined herein; R 2 However, H, halo (e.g., F, Cl), cyano, hydroxy, amino, C 1~6 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), C 1~6 Haloalkyl (e.g., trifluoromethyl), C 1~6 Alkoxy (e.g., methoxy, ethoxy), C 1~6 Haloalkoxys (e.g., trifluoromethoxy), and C 3~6 Compound 1.76, selected from cycloalkoxys (e.g., cyclopropoxy), each of which may be appropriately substituted; 1.78 R 1 However, halos (for example, F, Cl), cyanosides, and C 1~3 Alkyl (e.g., methyl, ethyl), and C 1~3 Selected from haloalkyls (e.g., trifluoromethyl), each of which may be appropriately substituted as defined herein, R 2 However, H, halo (e.g., F, Cl), cyano, hydroxy, C 1~3 Alkyl (e.g., methyl, ethyl), C 1~3 Haloalkyl (e.g., trifluoromethyl), C 1~3 Alkoxy (e.g., methoxy, ethoxy), and C 1~3Compound 1.76, selected from haloalkoxys (e.g., trifluoromethoxy), each of which may be substituted as appropriate; 1.79 R 1 However, halos (for example, F, Cl), cyanosides, and C 1~3 Alkyl (e.g., methyl, ethyl), and C 1~3 Selected from haloalkyls (e.g., trifluoromethyl), each of which may be appropriately substituted as defined herein, R 2 However, H, halo (for example, F, Cl), cyano, C 1~3 Alkyl (e.g., methyl, ethyl), and C 1~3 Compound 1.76, selected from haloalkyl groups (e.g., trifluoromethyl), each of which may be appropriately substituted; 1.80 R 1 However, R is selected from H, F, Cl, Br, I, cyano, methyl, ethyl, isopropyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, cyclopropoxy, azilidinyl, azetidinyl, and oxetanyl. 2 Compound 1.76, selected from H, F, Cl, Br, I, cyano, hydroxy, amino, methyl, fluoromethyl, difluoromethyl, and trifluoromethyl; 1.81 R 1 However, R is selected from H, F, Cl, Br, I, cyano, methyl, fluoromethyl, difluoromethyl, and trifluoromethyl. 2 Compound 1.76, selected from H, F, Cl, Br, and cyano; 1.82 R 1 However, C 1~3 It is a haloalkyl (e.g., trifluoromethyl), and R 2 Compound 1.76, selected from H, F, Cl, Br, and cyano; 1.83 R 1However, R is selected from fluoromethyl, difluoromethyl, and trifluoromethyl. 2 However, compound 1.76 is H; 1.84 R 1 However, halos (for example, F, Cl), cyanosides, and C 1~3 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), and C 1~3 Selected from haloalkyls (e.g., trifluoromethyl), each of which may be substituted as appropriate as defined herein; R 2 However, H, halo (e.g., F, Cl), cyano, hydroxy, amino, C 1~6 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), C 1~6 Haloalkyl (e.g., trifluoromethyl), C 1~6 Alkoxy (e.g., methoxy, ethoxy), C 1~6 Haloalkoxys (e.g., trifluoromethoxy), and C 3~6 Compound 1.76, selected from cycloalkoxys (e.g., cyclopropoxy), each of which may be appropriately substituted; 1.85 R 1 However, halos (for example, F, Cl), cyanosides, and C 1~3 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), and C 1~3 Selected from haloalkyls (e.g., trifluoromethyl), each of which may be substituted as appropriate as defined herein; R 2 However, H, halo (for example, F, Cl), cyano, C 1~6 Alkyl (e.g., methyl, ethyl), and C 1~6 Compound 1.76, selected from haloalkyl groups (e.g., trifluoromethyl), each of which may be appropriately substituted; 1.86 R 1 However, halos (for example, F, Cl), cyanosides, and C1~3 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), and C 1~3 Selected from haloalkyls (e.g., trifluoromethyl), each of which may be substituted as appropriate as defined herein; R 2 However, compound 1.76 is H; 1.87 R 1 However, C 1~3 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), and C 1~3 Selected from haloalkyls (e.g., trifluoromethyl), each of which may be substituted as appropriate as defined herein; R 2 However, compound 1.76 is H; 1.88 R 1 However, C 1~3 Alkyl (e.g., methyl, ethyl); R 2 However, compound 1.76 is H; 1.89 R 1 However, C 3~6 It is a cycloalkyl (e.g., cyclopropyl); R 2 However, compound 1.76 is H; 1.90 R 1 However, C 1~3 It is a haloalkyl (e.g., trifluoromethyl); R 2 However, compound 1.76 is H; 1.91 R 1 However, it is selected from methyl, ethyl, isopropyl, d3-methyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, chlorofluoromethyl, chlorodifluoromethyl, bromodifluoromethyl, and 1,1-difluoroethyl; R 2 However, compound 1.76 is H; 1.92 R 1However, it is selected from methyl, isopropyl, d3-methyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, chlorofluoromethyl, chlorodifluoromethyl, bromodifluoromethyl, and 1,1-difluoroethyl; R 2 However, compound 1.76 is H; 1.93 R 1 However, it is selected from methyl, isopropyl, d3-methyl, and cyclopropyl; R 2 However, compound 1.76 is H; 1.94 R 1 However, it is selected from fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, chlorofluoromethyl, chlorodifluoromethyl, bromodifluoromethyl, and 1,1-difluoroethyl; R 2 However, compound 1.76 is H; 1.95 R 1 However, it is difluoromethyl; R 2 However, compound 1.76 is H; 1.96 Compound of formula I, formula Ic: [ka] Compound 1, or any of 1.1-1.74, which is a compound of the above. [wherein R is as defined in any of the embodiments described above]; 1.97 There are 1, 2, or 3 R groups, each independently of the other, which are halo (e.g., F, Cl, Br, I), cyano, nitro, hydroxy, and C. 1~6 Haloalkyl (e.g., trifluoromethyl), C 1~6 Haloalkoxys (e.g., trifluoromethoxy), and C 3~6 Any of compounds 1.75 to 1.96 selected from halocycloalkyls (e.g., 2,2-difluorocyclopropyl); 1.98 There are 1, 2, or 3 R groups, each independently of a halo (e.g., F, Cl, Br, I), cyano, nitro, or C group. 1~6 Haloalkyl (e.g., trifluoromethyl), and C 1~6 Compounds 1.75–1.96 selected from haloalkoxys (e.g., trifluoromethoxy); 1.99 There are 1, 2, or 3 R groups, each independently of a halo (e.g., F, Cl, Br, I), cyano, nitro, or C group. 1~3 Haloalkyl (e.g., trifluoromethyl), and C 1~3 One of the compounds 1.75–1.96 selected from haloalkoxys (e.g., trifluoromethoxy); 1.100 Compound 1.75–1.96, which has one, two, or three R groups, each independently selected from F, Cl, Br, I, cyano, nitro, trifluoromethyl, and trifluoromethoxy; 1.101 One of compounds 1.75–1.96, each containing one, two, or three R groups, each independently selected from Cl, Br, trifluoromethyl, and trifluoromethoxy; 1.102 One of compounds 1.75–1.96 having one, two, or three R groups, each independently selected from F, Cl, and trifluoromethyl and trifluoromethoxy; 1.103 Compounds 1.75–1.96, each containing one, two, or three R groups, each independently selected from Cl and trifluoromethyl; 1.104 Any of compounds 1.97-1.103 that have two or three R groups; 1.105 One of compounds 1.97-1.103 that contains three R groups; 1.106 The compound of formula I has the following structure: [ka] Compound 1 or 1.1-1.105, either in free form or salt form; 1.107 Compound of formula I, formula Id: [ka] Compound 1, or any of 1.1-1.105, is a free form or salt of the compound. [In the formula, R 1 This is as defined in any of the embodiments described above, for example, R 1 H, halo, cyano, nitro, hydroxy, amino, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~6 Cycloalkoxy, C 3~6 Halocycloalkyl, NH(C) 1~6 Alkyl), N(C 1~6 Alkyl)(C 1~6 Selected from alkyl groups and 3- to 6-membered heterocycloalkyl groups, each of which may be appropriately substituted; 1.108 R 1 However, H, halo (for example, F, Cl), cyano, nitro, C 1~6 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), C 1~6 Haloalkyl (e.g., trifluoromethyl), C 1~6 Alkoxy (e.g., methoxy, ethoxy), and C 1~6 Compound 1.107, selected from haloalkoxys (e.g., trifluoromethoxy), each of which may be appropriately substituted as defined herein; 1.109 R 1 However, halos (for example, F, Cl), cyanosides, and C 1~3Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), and C 1~3 Compound 1.107, selected from haloalkyl groups (e.g., trifluoromethyl), each of which may be appropriately substituted as defined herein; 1.110 R 1 However, halos (for example, F, Cl), cyanosides, and C 1~3 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), and C 1~3 Compound 1.107, selected from haloalkyls (e.g., trifluoromethyl); 1.111 R 1 However, C 1~3 Alkyl (e.g., methyl, ethyl), C 3~6 Cycloalkyl (e.g., cyclopropyl), and C 1~3 Compound 1.107, selected from haloalkyls (e.g., trifluoromethyl); 1.112 R 1 However, C 1~3 Compound 1.107 is alkyl (e.g., methyl, ethyl); 1.113 R 1 However, C 3~6 Compound 1.107 is a cycloalkyl (e.g., cyclopropyl) compound; 1.114 R 1 However, C 1~3 Compound 1.107 is a haloalkyl (e.g., trifluoromethyl); 1.115 R 1 Compound 1.107, selected from methyl, ethyl, isopropyl, d3-methyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, chlorofluoromethyl, chlorodifluoromethyl, bromodifluoromethyl, and 1,1-difluoroethyl; 1.116 R 1 Compound 1.107, selected from methyl, isopropyl, d3-methyl, cyclopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, chlorofluoromethyl, chlorodifluoromethyl, bromodifluoromethyl, and 1,1-difluoroethyl; 1.117 R 1 Compound 1.107, selected from methyl, isopropyl, d3-methyl, and cyclopropyl; 1.118 R 1 Compound 1.107, selected from fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, chlorofluoromethyl, chlorodifluoromethyl, bromodifluoromethyl, and 1,1-difluoroethyl; 1.119 The compound of formula I has the following structure: [ka] Compound 1 or 1.1-1.118, either in the form of a free body or salt of the same compound; 1.120 The compound of formula I has the following structure: [ka] A compound selected from the group consisting of, each in the form of a free compound or salt, either compound 1 or compound 1.1-1.118; 1.121 Compound 1 or any of 1.1-1.120 in which the compound of formula I is in its free form (i.e., a free base); 1.122 Compound 1 or any of 1.1-1.121, wherein the compound of formula I is in the form of a salt, e.g., an acid addition salt or a base addition salt; 1.123 Compound 1.122 in which the form of the acid addition salt is selected from hydrochloride, hydrobromide, sulfate, phosphate, nitrate, acetate, propionate, benzoate, mesylate, besylate, tosylate, citrate, fumarate, glycolate, gluconate, tartrate, malate, maleate, succinate, or oxalate; 1.124 Compound 1.122 in which the base addition salt is selected from lithium salts, sodium salts, potassium salts, magnesium salts, calcium salts, or aluminum salts; 1.125 Any compound 1 or 1.1-1.124 intended for use in treating, controlling, or eradicating infection or parasitism caused by insects (arthropods) (e.g., adults, insect eggs, insect larvae, insect nymphs, and / or insect pupae); 1.126 The insect is selected from fleas, lice, ticks, mites, mosquitoes, grasshoppers, locusts, beetles (e.g., cane beetles, thrips, stink bugs, voxelder bugs, scarab beetles, jewel beetles), ants (e.g., carpenter ants, fire ants), cockroaches, termites, flies, aphids, moths, butterflies, and wasps, compound 1.125; 1.127 The insect is selected from one or more of the following compounds: 1.26: The order Acari includes ticks (e.g., Ixodes, Boophilus, e.g., Boophilus microplus, Amblyomma, Hyalomma, Rhipicephalus, e.g., Rhipicephalus appendiculatus, Haemaphysalis, Dermacentor, Ornithodorus, e.g., Ornithodorus moubata) and mites (e.g., Damalinia, Dermanyssus gallinae, Sarcoptes, e.g., Sarcoptes scabiei, Psoroptes, Chorioptes, Demodex, Eutrombicula, Tetranychus, Panonychus, and Bryobia (spider mites), Eriophyes (gall mites), and Polyphacotarsonemus); The class Chilopoda (centipedes) includes the order Scutigeromorpha (e.g., the genus Scutigera); The class Diplopoda (millipedes) includes Julida, such as the genus Blaniulus; The class Chilopoda (scolopendra) includes the genera Scutigerella, Symphylella, and Henseniella; They belong to the order Isopoda, which includes the genus Oniscus (woodlice); Diptera (including flies and mosquitoes), such as the genera Aedes, Anopheles, Culex, Musca, Hypoderma, Gasterophilus, Simulium, Hylemyia (seed flies), Atherigona and Chlorops (stem miners), Phytomyza (leaf miners), and Ceratitis (fruit flies); These are Hemiptera (true bugs), such as the genera Triatoma, Psylla, Bemisia, Trialeurodes, Aphis, Myzus, Megoura viciae, Phylloxera, Adelges, Phorodon humuli (honey aphid), Aeneolamia, Nephotettix (leafhoppers), Empoasca, Nilaparvata, Perkinsiella, Pyrilla, Aonidiella (red scale insects), Coccus, Pseucoccus, Helopeltis (mosquito bugs), Lygus, Dysdercus, Oxycarenus, and Nezara; They belong to the order Lice (locusts) (e.g., genera Damalinia, Linoqnathus); They belong to the order Fleas (fleas), such as the genera Ctenocephalides, Tunga, and Ceratophyllus; They belong to the order Blattodea (cockroaches), for example, the genera Periplaneta and Blatella; Hymenoptera (sawflies, wasps, and ants), such as the genera Athalia, Cephus (sawflies), Atta (leafcutter ants), Vespula, Dolichovespula, Vespa, Linepithema, Solenopsis, Anoplolepsis, Camponotus, Formica, Myrmica, and Monomorium, such as Monomorium pharaonis; Coleoptera (beetles) include genera such as Ephestia (moths), Anthrens (carpet beetles), Tribolium (grain weevils), Sitophilus (grain weevils), for example Hypothenemus hampei (coffee berry baller), Hylesinus (bark beetles), Anthonomus grandis (cotton weevil), Acalymma (cucumber beetles), Lema, Psylliodes, Leptinotarsa ​​decemlineata (colorado leaf beetle), Diabrotica (corn root worms), Gonocephalum (false horsehair worms), Agriotes (horsehair worms), Dermolepida and Heteronychus (scarabaeid larvae), and Phaedon This includes the genera cochleariae (mustard leaf beetle), Lissorhoptrus oryzophilus (rice water weevil), Melioethes (flower weevils), Ceutorhynchus, Rhynchophorus, and Cosmopolites (root weevils); Lepidoptera (including butterflies and moths, their larvae and caterpillars), for example, the genera Heliothis, e.g., Heliothis virescens (tobacco worm), Heliothis armioera and Heliothis zea; the genera Spodoptera, e.g., S. exempta, S. littoralis (Egyptian armyworm), S. eridania (Southern armyworm), Mamestra configurata (Barth's armyworm); the genera Earias, e.g., E. insulana (Egyptian cotton worm); the genera Pectinophora, e.g., Pectinophora gossypiella (peach nut worm); the genera Ostrinia, e.g., O. nubilalis (European corn borer); Trichoplusia These include the cabbage moth (ni), the genera Pieris (cabbage worms), Laphyqma (armyworms), Agrotis and Amathes (moths), Wiseana (polina moths), Chilo (grape leaf rollers), Tryporyza and Diatraea (sugarcane and rice leaf rollers), Sparuganothis pilleriana (grape leaf rollers), Cydia pomonella (codling moths), Archips (tortricans), and the genera Plutella, such as Plutella xylostella (diamondback moths); The order Thrips (thrips) includes, for example, genera Anaphothrips, Megalothrips, Scirtothrips, Sorgothrips, Frankiniella, and Thrips, such as Thrips tabaci; These are orthopterans, such as the genera Locusta and Schistocerca (grasshoppers), and crickets, such as the genera Gryllus and Acheta; They belong to the order Collembola (springtails), such as the genera Sminthurus and Onychiurus; Isoptera and Neoisoptera (termites), such as those of the genus Odontotermes, Reticulitermes, Heterotermes, Coptotermes; and Dermaptera (earwigs), such as those of the genus Forficula; 1.128 Compound 1.127, wherein the insect is Dermanyssus gallinae; 1.129 Compound 1.128, wherein the compound is administered to chickens or applied to chicken coops, chicken enclosures, chicken cages, other chicken enclosures, chicken farms, or chicken feed; 1.130 Compound 1 or any one of Compounds 1.1 to 1.129, which is intended to be used for treating, controlling, suppressing, or eradicating infection or infestation by insects (arthropods) (e.g., adults, insect eggs, insect larvae, insect nymphs, and / or insect pupae), and wherein the insects are selected from one or more of fleas, ticks, mites, lice, flies, termites, beetles, cockroaches, scale insects, thrips, cutworms, and weevils.

[0021] In a second aspect, the present disclosure also provides a pharmaceutical composition or an insecticidal composition (Composition 1) containing an effective amount of a compound of Formula I in free form or in the form of a salt, or any one of 1.1 to 1.130, and mixed with a pharmaceutically acceptable diluent or carrier, or an insecticide-acceptable diluent or carrier.

[0022] In a further embodiment of the second aspect, the present disclosure provides the following: 1.1 A pharmaceutical composition comprising a therapeutically effective amount of any one of Compounds 1.1 to 1.130 and at least one pharmaceutically acceptable diluent or carrier; 1.2 Composition 1.1, wherein the pharmaceutical composition is formulated for administration to a human patient; 1.3 The pharmaceutical composition is a composition 1.1 (e.g., a veterinary composition) formulated for administration to an animal patient; 1.4 Composition 1.3 in which the animal is a domestic animal, such as a chicken, turkey, goose, duck, pig, cow, goat, or sheep; 1.5 Composition 1.4 in which the compound does not bioaccumulate in livestock animals; 1.6 Composition 1.4 or 1.5 in which the compound does not accumulate in the food of livestock animals (e.g., meat such as beef, poultry, or pork, or eggs); 1.7 Composition 1.6 in which the food contains less than 5 ppm of the compound, for example, less than 4 ppm, or less than 3 ppm, or less than 2 ppm, or less than 1 ppm, or less than 0.5 ppm or less than 0.1 ppm; 1.8 Composition 1.3 in which the animal is a non-domesticated draft animal such as a horse, donkey, mule, cattle, llama, or camel; 1.9 Composition 1.3 in which the animal is a pet such as a dog, cat, rabbit, ferret, rat, or mouse; 1.10 Any of compositions 1.1 to 1.9, which are formulated for oral administration to humans or animals, for example, as tablets, capsules, liquids, oral gels, powders, oral sprays, feed additives, edible bait, saltlices, or nutritional supplements; 1.11 Any of compositions 1.1 to 1.9, wherein the composition is formulated for transdermal administration to humans or animals for systemic delivery, for example, as a liquid, gel, or patch; 1.12 Any of compositions 1.1 to 1.9, which are formulated for topical (non-systemic) delivery to humans or animals, for example, as a liquid, spray, gel (for example, for "spot-on" application), cream, ointment, shampoo, foam, bath, or dip; 1.13 Any of compositions 1.3 to 1.9, formulated for administration to an animal using a removable collar that is fitted around the animal's neck; 1.14 Any of compositions 1.1 to 1.9, which are formulated for administration to humans or animals as a rapid-acting injection (e.g., intravenous, subcutaneous, intramuscular, or intraperitoneal injection) to provide immediate release of the compound to the animal; 1.15 Any of compositions 1.1 to 1.9, formulated for administration to humans or animals as a long-acting injection (e.g., subcutaneous, intramuscular, or intraperitoneal injection) using a sustained-release or delayed-release vehicle (e.g., a polymer matrix) to provide a sustained-release or delayed-release of a therapeutically effective amount of the compound over a period of, for example, one week to one month, one month to three months, or three months to six months; 1.16 An insecticide composition comprising one of compounds 1.1 to 1.130 in an effective amount as an insecticide, and at least one insecticide-acceptable diluent or carrier; 1.17 Composition 1.16, which is formulated to be applied to plants or growing media (for example, to be applied to crops, farmland, orchards, vineyards, plantations, or soil for use in agriculture); 1.18 Composition 1.17 in which the plant or crop is selected from rice, corn, wheat, sugarcane, potato, rye, oat, barley, millet, soybean, cotton, vegetables (e.g., beans, lettuce, onion, tomato, bell pepper), fruits and nuts (e.g., grapes, apples, citrus fruits, bananas, kiwis, avocados, mangoes, olives, walnuts, peanuts), tea, coffee, tobacco, and cocoa; 1.19 Composition 1.16, which is formulated for application to ornamental plants such as greenhouses, gardens, or lawns for residential or commercial use; 1.20 Composition 1.16, which is formulated for residential or commercial use for application to, for example, houses, apartments, office buildings, manufacturing facilities, hotels, motels, parks, sports facilities (e.g., stadiums, golf courses), and other public spaces; 1.21 Composition 1.20, which is formulated for application to stored foods (e.g., grains, fruits, nuts, spices, tobacco), clothing, bedding, furniture, carpets, rugs, and other household items; 1.22 Any one of compositions 1.16 to 1.21, wherein the composition is formulated for application by aerosol spray, for example, as a suspension of solid or liquid particles with a size of less than 1 micron; 1.23 Any one of compositions 1.16 to 1.21, wherein the composition is formulated for application as a liquid spray (e.g., a mist of liquid droplets having a droplet size greater than 1 micron); 1.24 The composition is a dry formulation such as dust, wettable powder, granules, tablets, or water-dispersible granules, and is formulated to be applied, for example, by dusting (e.g., mist of solid particles having a particle size greater than 1 micron), sprinkling, spraying, or as a bulk liquid, fog, lacquer, paint, or smoke, any one of compositions 1.16 to 1.21; 1.25 Any of compositions 1 or 1.1 to 1.24, which are intended to be used to treat, control, suppress or eradicate infection or parasitism caused by insects (arthropods) (e.g., adult insects, insect eggs, insect larvae, insect nymphs, and / or insect pupae); 1.26 Composition 1.25 in which the insect is selected from one or more of the following: fleas, lice, ticks, mites, mosquitoes, grasshoppers, locusts, beetles (e.g., cane beetles, thrips, stink bugs, voxelder bugs, scarab beetles, jewel beetles), ants (e.g., carpenter ants, fire ants), cockroaches, termites, flies, aphids, moths, butterflies, and wasps; 1.27 The insect is selected from one or more of the following compositions 1.25, for example: Acariformes (e.g., ticks and mites; e.g., the superorders Parasitiformes and Acariformes, as well as the orders Ixodida, Mesostigmata, Sarcoptiformes, and Trombidiformes), which include ticks (e.g., Ixodes, Boophilus (e.g., Boophilus microplus), Amblyomma, Hyalomma, Rhipicephalus (e.g., Rhipicephalus appendiculatus), Haemaphysalis, Dermacentor, Ornithodorus (e.g., Ornithodorus moubata), and e.g., Dermanyssus (e.g., Dermanyssus gallinae), Ornithonyssus (e.g., Ornithonyssus This includes mites of the genera *Sylviarum*, *Gallinae*, *Sarcoptes* (e.g., *Sarcoptes scabiei*), *Psoroptes*, *Chorioptes*, *Demodex*, *Eutrombicula*, *Tetranychus*, *Panonychus*, and *Bryobia* (spider mites), *Eriophyes* (gall mites), *Polyphacotarsonemus*, and *Varroa* (e.g., *Varroa destructor*). Louses belong to the order Anoplura (e.g., genera Pediculus and Pthirus), Ischonocera (e.g., genera Bovicola, Damalinia, Felicola, Saemundssonia, and Trichodectes), and Amblycera (e.g., genera Holomenopon, Menopon, e.g., Menopon gallinae, Menecanthus, e.g., Menecanthus stramineus, Heterodoxus, e.g., Heterodoxus spiniger); The class Chilopoda (centipedes) includes the order Scutigeromorpha (e.g., the genus Scutigera); Diplopoda (millipedes), including Julida, e.g., the genus Blaniulus; Symphyla (symphylans), including the genera Scutigerella, Symphylella, and Henseniella; Isopoda, including the genus Oniscus (woodlice); Diptera (flies, including mosquitoes), e.g., the genera Aedes, Anopheles, Culex, Musca, Hypoderma, Gasterophilus, Simulium, Hylemyia (seed flies), Atherigona, and Chlorops (stem flies), Phytomyza (leaf miners), Ceratitis (fruit flies); Hemiptera (true bugs), e.g., the genera Triatoma, Psylla, Bemisia, Trialeurodes, Aphis, Myzus, Megoura viciae, Phylloxera, Adelges, Phorodon humuli (hop aphid), Aeneolamia, Nephotettix (green leafhoppers), Empoasca, Nilaparvata, Perkinsiella, Pyrilla, Aonidiella (scale insects), Coccus, Pseucoccus, Helopeltis (mosquito bugs), Lygus, Dysdercus, Oxycarenus, and Nezara; Phthiraptera (lice), e.g., the genera Damalinia, Linognathus; Siphonaptera (fleas), e.g., the genera Ctenocephalides, Tunga, Ceratophyllus; Blattodea (cockroaches), e.g., the genera Periplaneta, Blatella; Hymenoptera (sawflies, wasps, and ants), such as the genera Athalia, Cephus (sawflies), Atta (leafcutter ants), Vespula, Dolichovespula, Vespa, Linepithema, Solenopsis, Anoplolepsis, Camponotus, Formica, Myrmica, and Monomorium, such as Monomorium pharaonis; Coleoptera (beetles) include genera such as Ephestia (moths), Anthrens (carpet beetles), Tribolium (grain weevils), Sitophilus (grain weevils), for example Hypothenemus hampei (coffee berry baller), Hylesinus (bark beetles), Anthonomus grandis (cotton weevil), Acalymma (cucumber beetles), Lema, Psylliodes, Leptinotarsa ​​decemlineata (colorado leaf beetle), Diabrotica (corn root worms), Gonocephalum (false horsehair worms), Agriotes (horsehair worms), Dermolepida and Heteronychus (scarabaeid larvae), and Phaedon This includes the genera cochleariae (mustard leaf beetle), Lissorhoptrus oryzophilus (rice water weevil), Melioethes (flower weevils), Ceutorhynchus, Rhynchophorus, and Cosmopolites (root weevils); Lepidoptera (including butterflies and moths, their larvae and caterpillars), for example, the genera Heliothis, e.g., Heliothis virescens (tobacco worm), Heliothis armioera and Heliothis zea; the genera Spodoptera, e.g., S. exempta, S. littoralis (Egyptian armyworm), S. eridania (Southern armyworm), Mamestra configurata (Barth's armyworm); the genera Earias, e.g., E. insulana (Egyptian cotton worm); the genera Pectinophora, e.g., Pectinophora gossypiella (peach nut worm); the genera Ostrinia, e.g., O. nubilalis (European corn borer); Trichoplusia These include the cabbage moth (ni), the genera Pieris (cabbage worms), Laphyqma (armyworms), Agrotis and Amathes (noctuid moths), Wiseana (polina moths), Chilo (grape leaf rollers), Tryporyza and Diatraea (sugarcane and rice leaf rollers), Sparuganothis pilleriana (grape leaf rollers), Cydia pomonella (codling moths), Archips (tortricidal moths), and the genera Plutella, such as Plutella xylostella (diamondback moths); The order Thrips (thrips) includes, for example, genera Anaphothrips, Megalothrips, Scirtothrips, Sorgothrips, Frankiniella, and Thrips, such as Thrips tabaci; These are orthopterans, such as the genera Locusta and Schistocerca (grasshoppers), and crickets, such as the genera Gryllus and Acheta; They belong to the order Collembola (springtails), such as the genera Sminthurus and Onychiurus; The order Neoisoptera (termites), such as the genera Odontotermes, Reticulitermes, Heterotermes, and Coptotermes; They belong to the order Dermaptera (earwigs), for example, the genus Forficula; 1.28 Composition 1.25 in which the insect is a mite of the superorder Parasitiformes, for example, a mite of the suborder Mesostigmata, for example, a mite of the family Dermanyssidae or Macronyssidae, for example, a mite of the genus Dermanyssus (e.g., Dermanyssus gallinae) or Ornithonyssus (e.g., Ornithonyssus sylviarum), in particular a mite (Dermanyssus gallinae); 1.29 The composition further comprises one or more other insecticides, either composition 1 or any of compositions 1.1 to 1.28; 1.30 Composition 1.29 in which one or more other insecticides are selected from phenylpyrazoles, pyrethroids, neonicotinoids, organochlorine compounds, organophosphate esters, butenolides, carbamates, and diamides (reanoids); 1.31 The one or more other insecticides are fipronil, acetoprole, ethiprole, flufiprole, pyraclofos, pyrafluprole, pyriprole, pyrolane, and vaniliprole, allethrin, bifenthrin, cyfluthrin, cypermethrin, cyphenothrin, deltamethrin, dimefluthrin, esfenvalerate, etofenprox, fenpropatrin, fenvalerate, flucitrinate, flumethrin, imiprothrin, cyhalothrin (e.g., lambdacyhalothrin), metofluthrin, permethrin, phenothrin, prallethrin, resmethrin, silafluofen, fluvalinate (e.g., taufluvalinate), tefluthrin, tetramethrin Composition 1.29, selected from tralomethrin, transfluthrin, acetamiprid, clothiandin, dinotefuran, imidacloprid, nitenpyram, nithiazine, thiacloprid, thiamethoxam, aldrin, chlordane, dieldrin, endosulfan, endrin, heptachlor, azamethiphos, azinophosmethyl, chlorpyrifos, diazinon, dichlorvos, fenitrothion, malathion, parathion, parathionmethyl, phosmet, terbuphos, tetrachlorvinphos, flupyradiflon, aldicarb, benziocarb, carbofuran, carbaryl, etiocarb, phenobucarb, oxamyl, methomyl, and chlorantraniliprole; 1.32 The composition is an aqueous solution which may optionally contain an organic cosolvent (e.g., methanol, ethanol, isopropanol, methoxymethanol, ethoxyethanol, 2-butoxyethanol), either composition 1 or any of 1.1 to 1.31; 1.33 Composition 1.32, wherein the composition is an aqueous solution containing 2-butoxyethanol, ethanol, and water; 1.34 Composition 1.33 comprising 2-butoxyethanol, ethanol, and water in a ratio of 7:2:1 (v / v), for example, the composition comprising a compound of formula I dissolved, dispersed, or suspended in the solution comprising 2-butoxyethanol, ethanol, and water in a ratio of 7:2:1 (v / v); 1.35 Composition 1.32, wherein the composition is a solution containing ethanol and water; 1.36 The solution contains ethanol and water in a ratio of approximately 75:25 to 99:1 (v / v), for example, 75:25 to 95:5, or 75:25 to 90:10, or 75:25 to 85:15, or 75:25 to 80:20, or 80:20 to 99:1, or 80:20 to 95:5, or 80:20 to 90:10, or 80:20 to 85 Composition 1.35, containing in proportions of :15, or 85:15-99:1, or 85:15-95:5, or 85:15-90:10, or 90:10-99:1, or 90:10-95:5, or 95:5-99:1, or approximately 80:20, or approximately 85:15, or approximately 90:10, or approximately 95:5, or approximately 99:1 (v / v); 1.37 The composition is an aqueous suspension which may optionally contain an organic cosolvent (e.g., methanol, ethanol, isopropanol, methoxymethanol, ethoxyethanol, 2-butoxyethanol), either composition 1 or any of 1.1 to 1.31; 1.38 Composition 1.37, wherein the composition is a suspension containing 2-butoxyethanol, ethanol, and water; 1.39 The composition is a suspension comprising 2-butoxyethanol, ethanol, and water in a ratio of 7:2:1 (v / v), for example, the composition comprising a compound of formula I dissolved, dispersed, or suspended in a solution comprising 2-butoxyethanol, ethanol, and water in a ratio of 7:2:1 (v / v), composition 1.38; 1.40 Composition 1.37, wherein the composition is a suspension containing ethanol and water; 1.41 Composition 1.40, wherein the suspension contains ethanol and water in a ratio of approximately 1:99 to 75:25 (v / v), for example, 10:90 to 75:25, or 20:80 to 75:25, or 30:70 to 75:25, or 40:60 to 75:35, or 50:50 to 75:25, or 55:45 to 75:25, or 60:40 to 75:25, or 65:35 to 75:25, or 70:30 to 75:25 (v / v); 1.42 The composition contains the compound of formula I in an amount of 0.1 to 1.0%, for example, 0.1 to 0.5%, or 0.2 to 0.3%, or about 0.25% (w / v), either composition 1 or 1.1 to 1.41; 1.43 The composition is a concentrate containing the compound of formula I in an amount of 1 to 20%, for example, 1 to 15%, or 1 to 10%, or 1 to 5% (w / v), either composition 1 or any of compositions 1.1 to 1.41; 1.44 The composition is of the following formula: [ka] Compositions 1 or 1.1-1.43 comprising a compound of formula I, which is in the form of a free body or salt of; 1.45 The composition is formulated for delivery by spray (e.g., liquid spray or aerosol spray), either composition 1 or any of compositions 1.1 to 1.44; 1.46 Any composition 1 or 1.1 to 1.45 intended for use in treating, controlling, suppressing, or eradicating infection or parasitism by insects (arthropods) (e.g., adult insects, insect eggs, insect larvae, insect nymphs, and / or insect pupae, wherein the insect is Dermanyssus gallinae); 1.47 Any of compositions 1 or 1.1 to 1.46, wherein the composition is administered to chickens or applied to chicken coops, chicken enclosures, chicken cages, other chicken enclosures, poultry farms, or chicken feed; 1.48 Any composition 1 or 1.1 to 1.45 intended for use in treating, controlling, suppressing or eradicating infection or parasitism by insects (arthropods) (e.g., adult insects, insect eggs, insect larvae, insect nymphs, and / or insect pupae, wherein the insects are selected from one or more of the following: fleas, ticks, mites, lice, fire ants, termites, beetles, cockroaches, mole crickets, thrips, cutworms, and weevils).

[0023] In a third aspect, the Disclosure provides a method (Method 1) for treating, controlling, suppressing or eradicating infection or parasitism by insects (arthropods) (e.g., adult insects, insect eggs, insect larvae, insect nymphs, and / or insect pupae), the Method comprising administering or applying an effective amount of any compound of Formula I or 1.1-1.130, or any pharmaceutical composition 1 or 1.1-1.48, in the form of a free body or salt, to an animal or human patient in need, or applying any compound of Formula I or 1.1-1.130, or any insecticide composition 1 or 1.1-1.48, to a product or location in need of application.

[0024] In a further embodiment of the third aspect, the Disclosure provides: 1.1 A method for treating, controlling, suppressing or eradicating infection or parasitism caused by insects (arthropods) (e.g., adult insects, insect eggs, insect larvae, insect nymphs, and / or insect pupae), comprising administering or applying an effective amount of a compound of formula I or any of 1.1 to 1.130, or any of pharmaceutical composition 1 or any of 1.1 to 1.48, to an animal or human patient in need. 1.2 If the patient is a human patient, Method 1.1; 1.3 If the patient is an animal patient, Method 1.1 (e.g., veterinary method); 1.4 Method 1.3, where the animal is a domesticated animal (e.g., chicken, turkey, goose, duck, pig, cow, goat, or sheep); 1.5 Methods that do not cause bioaccumulation of compounds in livestock animals; 1.4 1.6 Method 1.4 or 1.5 that does not result in the accumulation of compounds in the food of livestock animals (e.g., meat such as beef, poultry, or pork, or eggs); 1.7 Method 1.6, wherein the food derived from an animal processed according to the method contains less than 5 ppm of the compound, for example less than 4 ppm, or less than 3 ppm, or less than 2 ppm, or less than 1 ppm, or less than 0.5 ppm, or less than 0.1 ppm of the compound; 1.8 If the animal is a non-domesticated draft animal such as a horse, donkey, mule, cattle, llama, or camel, then Method 1.3 1.9 Method 1.3, where the animal is a pet such as a dog, cat, rabbit, ferret, rat, or mouse; 1.10 Any of methods 1.1 to 1.9, wherein the compound or composition is administered orally to a human or animal as a tablet, capsule, liquid solution, oral gel, powder, oral spray, feed additive, dietary bait, saltrick, or nutritional supplement; 1.11 Any of methods 1.1 to 1.9, wherein the compound or composition is administered percutaneously to a human or animal for systemic delivery, for example, as a liquid solution, gel, or patch; 1.12 Any of methods 1.1 to 1.9, wherein the compound or composition is administered topically to a human or animal, for example, to the skin, hair, or fur, for topical (non-systemic) delivery, for example, as a liquid solution, spray, gel (for example, for "spot-on" application), cream, ointment, shampoo, foam, bath, or dip; 1.13 Any of methods 1.3 to 1.9, wherein the compound or composition is administered to an animal using a removable collar that is fitted around the animal's neck; 1.14 The compound or composition is administered to a human or animal as a rapid-acting injection, such as intravenous, subcutaneous, intramuscular, or intraperitoneal injection, in order to provide immediate release of the compound to the animal, according to any of methods 1.1 to 1.9; 1.15 Any of methods 1.1 to 1.9, wherein the compound or composition is administered to a human or animal as a sustained-release injection, such as subcutaneous, intramuscular, or intraperitoneal injection, using a sustained-release or delayed-release vehicle (e.g., a polymer matrix). 1.16 A method for treating, controlling, suppressing, or eradicating infection or parasitism by insects (arthropods) (adult insects, insect eggs, insect larvae, insect nymphs, and / or insect pupae), comprising applying a compound of formula I, or any of 1.1 to 1.130, or any of insecticidal composition 1 or 1.1 to 1.48, to a plant, plant growing medium, product, or location where it is needed; 1.17 Method 1.16 in which the compound or composition is applied to a plant or a growing medium in which a plant grows, for example, a crop, farmland, orchard, vineyard, plantation, or agricultural soil. 1.18 The plant or crop is selected from rice, corn, wheat, sugarcane, potato, rye, oat, barley, millet, soybean, cotton, vegetables (e.g., beans, lettuce, onion, tomato, bell pepper), fruits and nuts (e.g., grapes, apples, citrus fruits, bananas, kiwis, avocados, mangoes, olives, walnuts, peanuts), tea, coffee, tobacco, and cocoa, Method 1.17 1.19 Method 1.16, in which the compound or composition is applied to ornamental plants (e.g., residential or commercial greenhouses, gardens, or lawns); 1.20 When the compound or composition is applied to residential or commercial places, such as houses, apartment buildings, office buildings, manufacturing facilities, hotels, motels, parks, sports facilities (e.g., stadiums, golf courses), and other public places, Method 1.16 1.21 If the compound or composition is applied to a product, for example, a stored food (e.g., grains, fruits, nuts, spices, tobacco), clothing, bedding, furniture, carpets, rugs, and other household items, Method 1.20 1.22 Any one of methods 1.16 to 1.21, wherein the compound or composition is applied as an aerosol spray (for example, as a suspension of solid or liquid particles less than 1 micron in size). 1.23 Any one of methods 1.16 to 1.21, wherein the compound or composition is applied as a liquid spray (for example, a mist of droplets having a droplet size greater than 1 micron). 1.24 Any one of methods 1.16 to 1.21, wherein the compound or composition is applied by dusting (e.g., a mist of solid particles having a particle size greater than 1 micron), or as a bulk liquid, spray, lacquer, paint, or smoke. 1.25 Method 1, or any of 1.1 to 1.24, wherein the method is intended to kill one or more insects (arthropods) (e.g., adult insects, insect eggs, insect larvae, insect nymphs, and / or insect pupae); 1.26, Method 1.25, wherein the insect (arthropod) is selected from one or more of the following: fleas, lice, mites, chiggers, mosquitoes, grasshoppers, locusts, beetles (e.g., cane beetles, thrips, stink bugs, voxelder bugs, scarab beetles, jewel beetles), ants (e.g., carpenter ants, fire ants), cockroaches, termites, flies, aphids, moths, butterflies, and wasps; 1.27 The insect (arthropod) is selected from one or more of the following, for example, as follows, Method 1.25: Acariformes (e.g., ticks and mites; e.g., the superorders Parasitiformes and Acariformes, as well as the orders Ixodida, Mesostigmata, Sarcoptiformes, and Trombidiformes), which include ticks (e.g., ticks of the genera Ixodes, Boophilus, e.g. Boophilus microplus, Amblyomma, Hyalomma, Rhipicephalus, e.g. Rhipicephalus appendiculatus, Haemaphysalis, Dermacentor, Ornithodorus, e.g. Ornithodorus moubata), and mites (e.g., genus Dermanyssus, e.g. Dermanyssus gallinae, genus Ornithonyssus, e.g. Ornithonyssus sylviarum, genus Sarcoptes, e.g. Sarcoptes The genera include scabiei, Psoroptes, Chorioptes, Demodex, Eutrombicula, Tetranychus, Panonychus, and Bryobia (spider mites), Eriophyes (gall mites), Polyphacotarsonemus, and Varroa, including, for example, Varroa destructor); Louses belong to the order Anoplura (e.g., genera Pediculus and Pthirus), Ischonocera (e.g., genera Bovicola, Damalinia, Felicola, Saemundssonia, and Trichodectes), and Amblycera (e.g., genera Holomenopon, Menopon, e.g., Menopon gallinae, Menecanthus, e.g., Menecanthus stramineus, Heterodoxus, e.g., Heterodoxus spiniger); The class Chilopoda (centipedes) includes the order Scutigeromorpha (e.g., the genus Scutigera); Diplopoda (millipedes) are a class that includes Julida, such as the genus Blaniulus; The class Chilopoda (scolopendra) includes the genera Scutigerella, Symphylella, and Henseniella; They belong to the order Isopoda, which includes the genus Oniscus (woodlice); Diptera (including flies and mosquitoes), such as the genera Aedes, Anopheles, Culex, Musca, Hypoderma, Gasterophilus, Simulium, Hylemyia (seed flies), Atherigona and Chlorops (stem miners), Phytomyza (leaf miners), and Ceratitis (fruit flies); These are Hemiptera (true bugs), such as the genera Triatoma, Psylla, Bemisia, Trialeurodes, Aphis, Myzus, Megoura viciae, Phylloxera, Adelges, Phorodon humuli (honey aphid), Aeneolamia, Nephotettix (leafhoppers), Empoasca, Nilaparvata, Perkinsiella, Pyrilla, Aonidiella (red scale insects), Coccus, Pseucoccus, Helopeltis (mosquito bugs), Lygus, Dysdercus, Oxycarenus, and Nezara; They belong to the order Lice (locusts) (e.g., genera Damalinia, Linoqnathus); They belong to the order Fleas (fleas), such as the genera Ctenocephalides, Tunga, and Ceratophyllus; They belong to the order Blattodea (cockroaches), for example, the genera Periplaneta and Blatella; Hymenoptera (sawflies, wasps, and ants), such as the genera Athalia, Cephus (sawflies), Atta (leafcutter ants), Vespula, Dolichovespula, Vespa, Linepithema, Solenopsis, Anoplolepsis, Camponotus, Formica, Myrmica, and Monomorium, such as Monomorium pharaonis; Coleoptera (beetles) include genera such as Ephestia (moths), Anthrens (carpet beetles), Tribolium (grain weevils), Sitophilus (grain weevils), for example Hypothenemus hampei (coffee berry baller), Hylesinus (bark beetles), Anthonomus grandis (cotton weevil), Acalymma (cucumber beetles), Lema, Psylliodes, Leptinotarsa ​​decemlineata (colorado leaf beetle), Diabrotica (corn root worms), Gonocephalum (false horsehair worms), Agriotes (horsehair worms), Dermolepida and Heteronychus (scarabaeid larvae), and Phaedon This includes the genera cochleariae (mustard leaf beetle), Lissorhoptrus oryzophilus (rice water weevil), Melioethes (flower weevils), Ceutorhynchus, Rhynchophorus, and Cosmopolites (root weevils); Lepidoptera (including butterflies and moths, their larvae and caterpillars), for example, the genera Heliothis, e.g., Heliothis virescens (tobacco worm), Heliothis armioera and Heliothis zea; the genera Spodoptera, e.g., S. exempta, S. littoralis (Egyptian armyworm), S. eridania (Southern armyworm), Mamestra configurata (Barth's armyworm); the genera Earias, e.g., E. insulana (Egyptian cotton worm); the genera Pectinophora, e.g., Pectinophora gossypiella (peach nut worm); the genera Ostrinia, e.g., O. nubilalis (European corn borer); Trichoplusia These include the cabbage moth (ni), the genera Pieris (cabbage worms), Laphyqma (armyworms), Agrotis and Amathes (moths), Wiseana (polina moths), Chilo (grape leaf rollers), Tryporyza and Diatraea (sugarcane and rice leaf rollers), Sparuganothis pilleriana (grape leaf rollers), Cydia pomonella (codling moths), Archips (tortricans), and the genera Plutella, such as Plutella xylostella (diamondback moths); The order Thrips (thrips) includes, for example, genera Anaphothrips, Megalothrips, Scirtothrips, Sorgothrips, Frankiniella, and Thrips, such as Thrips tabaci; These are orthopterans, such as the genera Locusta and Schistocerca (grasshoppers), and crickets, such as the genera Gryllus and Acheta; They belong to the order Collembola (springtails), such as the genera Sminthurus and Onychiurus; The order Neoisoptera (termites), such as the genera Odontotermes, Reticulitermes, Heterotermes, and Coptotermes; It belongs to the order Dermaptera (earwigs), for example, the genus Forficula. 1.28 The insect is selected from mites of the superorder Parasitiformes, e.g., mites of the suborder Mesostigmata, e.g., mites of the families Dermanyssidae or Macronyssidae, e.g., mites of the genera Dermanyssus (e.g., Dermanyssus gallinae) or Ornithonyssus (e.g., Ornithonyssus sylviarum), particularly from mites (Dermanyssus gallinae), method 1.25; 1.29 Any of Method 1 or 1.1 to 1.28, wherein the method further includes co-administration of one or more other insecticides (e.g., simultaneously, sequentially, or alternately). 1.30 Method 1.29, wherein the one or more other insecticides are selected from phenylpyrazoles, pyrethroids, neonicotinoids, organochlorine compounds, organophosphate esters, butenolides, carbamates, and diamides (rianoids); 1.31 The one or more other insecticides are fipronil, acetoprole, ethiprole, flufiprole, pyraclofos, pyrafluprole, pyriprole, pyrolane, and vaniliprole, allethrin, bifenthrin, cyfluthrin, cypermethrin, cyphenothrin, deltamethrin, dimefluthrin, esfenvalerate, etofenprox, fenpropatrin, fenvalerate, flucitrinate, flumethrin, imiprothrin, cyhalothrin (e.g., lambdacyhalothrin), metofluthrin, permethrin, phenothrin, prallethrin, resmethrin, silafluofen, fluvalinate (e.g., taufluvalinate), tefluthrin, tetramethyl Method 1.29, selected from tranomethrin, transfluthrin, acetamiprid, clothiandin, dinotefuran, imidacloprid, nitenpyram, nithiazine, thiacloprid, thiamethoxam, aldrin, chlordane, dieldrin, endosulfan, endrin, heptachlor, azamethiphos, azinophosmethyl, chlorpyrifos, diazinon, dichlorvos, fenitrothion, malathion, parathion, parathionmethyl, fosmet, terbuphos, tetrachlorvinphos, flupyradiflon, aldicarb, benziocarb, carbofuran, carbaryl, etiocarb, phenobucarb, oxamyl, methomyl, and chlorantraniliprole; 1.32 The compound or composition is administered to an animal or human patient four times a day, three times a day, twice a day, once a day, once every two days, once every three days, once every four days, once every five days, once every six days, once a week, once every two weeks, once every three weeks, once a month, once every two months, once every three months, or once every six months, according to either Method 1 or 1.1 to 1.31; 1.33 The compound or composition may be applied to a place or product four times a day, three times a day, twice a day, once a day, once every two days, once every three days, once every four days, once every five days, once every six days, once a week, once every two weeks, once every three weeks, once a month, once every two months, once every three months, or once every six months, by Method 1 or any of 1.1 to 1.31, until the application of the compound or composition is no longer required. 1.34 The compound to which the following formula applies: [ka] The compound of formula I is in the form of a free form or a salt, according to method 1, or any of 1.1 to 1.33. 1.35 The compound is applied as an aqueous solution containing an appropriate organic cosolvent (e.g., methanol, ethanol, isopropanol, methoxymethanol, ethoxyethanol, 2-butoxyethanol) according to Method 1 or any of 1.1 to 1.34; 1.36 Method 1.35, wherein the solution comprises 2-butoxyethanol, ethanol, and water. 1.37 The solution comprises 2-butoxyethanol, ethanol, and water in a ratio of 7:2:1 (v / v), for example, the composition comprises a compound of formula I dissolved, dispersed, or suspended in a solution comprising 2-butoxyethanol, ethanol, and water in a ratio of 7:2:1 (v / v), method 1.36; 1.38 Method 1.34, wherein the solution comprises ethanol and water; 1.39 The solution contains ethanol and water in a ratio of approximately 75:25 to 99:1 (v / v), for example, 75:25 to 95:5, or 75:25 to 90:10, or 75:25 to 85:15, or 75:25 to 80:20, or 80:20 to 99:1, or 80:20 to 95:5, or 80:20 to 90:10, or 80:20 to 85 Method 1.38, including in proportions of :15, or 85:15-99:1, or 85:15-95:5, or 85:15-90:10, or 90:10-99:1, or 90:10-95:5, or 95:5-99:1, or approximately 80:20, or approximately 85:15, or approximately 90:10, or approximately 95:5, or approximately 99:1 (v / v). 1.49 The compound is applied as an aqueous suspension containing an organic cosolvent (e.g., methanol, ethanol, isopropanol, methoxymethanol, ethoxyethanol, 2-butoxyethanol) as appropriate, according to Method 1 or any of 1.1 to 1.34; 1.50 Method 1.49, wherein the suspension comprises 2-butoxyethanol, ethanol, and water; 1.51 The suspension comprises 2-butoxyethanol, ethanol, and water in a ratio of 7:2:1 (v / v), for example, the suspension comprises a compound of formula I suspended in a solution comprising 2-butoxyethanol, ethanol, and water in a ratio of 7:2:1 (v / v), Method 1.50 1.52 The suspension comprises ethanol and water, method 1.49; 1.53 The suspension contains ethanol and water in a ratio of approximately 1:99 to 75:25 (v / v), for example, 10:90 to 75:25, or 20:80 to 75:25, or 30:70 to 75:25, or 40:60 to 75:35, or 50:50 to 75:25, or 55:45 to 75:25, or 60:40 to 75:25, or 65:35 to 75:25, or 70:30 to 75:25 (v / v), Method 1.52 1.54 The compound is applied or administered as a composition, wherein the composition contains the compound of formula I in an amount of 0.1 to 1.0%, for example, 0.1 to 0.5%, or 0.2 to 0.3%, or about 0.25% (w / v), according to either Method 1 or 1.1 to 1.40; 1.55 The compound is applied or administered as a composition, the composition is prepared from a concentrate, the concentrate contains the compound of formula I in an amount of 1-20%, for example, 1-15%, or 1-10%, or 1-5% (w / v), and the concentrate is diluted before use with water and / or an organic cosolvent (e.g., methanol, ethanol, isopropanol, methoxymethanol, ethoxyethanol, 2-butoxyethanol), for example, so that the final concentration of the compound of formula I in the composition to be applied or administered is 0.1-1.0%, for example, 0.1-0.5%, or 0.2-0.3%, or about 0.25% (w / v), by either Method 1 or 1.1-1.54; 1.56 The compound or composition is formulated for delivery by spray (e.g., liquid spray or aerosol spray) according to Method 1 or any of 1.1 to 1.55; 1.57 Method 1, or any of 1.1 to 1.56, to treat, control, suppress or eradicate infection or parasitism by an insect (arthropod) (e.g., an adult insect, an egg, a larva, a nymph, and / or a pupa), wherein the insect is Dermanyssus gallinae; 1.58 The mites infect chickens or parasitize chicken coops, chicken enclosures, chicken cages, other chicken enclosures, poultry farms, or chicken feed, by method 1.57; 1.59 Method 1.57, wherein the method is carried out by administering the composition to chickens or by applying the composition to a chicken coop, chicken enclosure, chicken cage, other chicken enclosure, poultry farm, or chicken feed; 1.60 Method 1 or any of 1.1 to 1.59, to treat, control, suppress or eradicate infection or parasitism by insects (arthropods) (e.g., adult insects, insect eggs, insect larvae, insect nymphs, and / or insect pupae), wherein the insect is selected from one or more of the following: fleas, ticks, mites, lice, fire ants, termites, beetles, cockroaches, mole crickets, thrips, cutworms, and weevils;

[0025] In a fourth aspect, the Disclosure provides a compound of Formula I or any of 1.1 to 1.130, or a pharmaceutical composition 1 or an insecticide composition 1 or any of 1.1 to 1.48, for use in treating, controlling, suppressing, or eradicating infection or parasitism by insects (arthropods) (e.g., adult insects, insect eggs, insect larvae, insect nymphs, and / or insect pupae), for example, according to Method 1 or any of 1.1 to 1.60.

[0026] In a fourth aspect, the Disclosure provides the use of a compound of Formula I or any of 1.1 to 1.130, or any of Pharmaceutical Composition 1 or Insecticide Composition 1 or any of 1.1 to 1.48, for treating, controlling, suppressing, or eradicating infection or parasitism by insects (arthropods) (e.g., adult insects, insect eggs, insect larvae, insect nymphs, and / or insect pupae), for example, according to Method 1 or any of 1.1 to 1.60.

[0027] Compounds of formula I and compositions containing such compounds are expected to have broad insecticidal activity. These compounds and compositions are generally effective in killing a variety of arthropods, including chelicerates such as mites, ticks, and arachnids, myriapods such as millipedes, centipedes, and centipedes, and pancrustaceans such as woodlice (malacostraca, isopoda), insects (Insecta), and springtails (Collimera). Therefore, the term "insect" as used herein is understood not to be limited to arthropods of the class Insecta (i.e., true insects), but rather to include a variety of arthropods that are not phylogenetically classified as insects. Similarly, as used herein, the terms “insecticide” and “insecticidal” refer to the properties of a compound or composition that is effective in killing true insects, as well as other arthropods, including chelicerates such as arachnids (ticks, mites, spiders), myriapods, and non-insect pancrustaceans such as woodlice and springtails.

[0028] In particularly preferred embodiments of this disclosure, the compounds and compositions disclosed herein are useful for and used for the control of ticks and mites, which are arthropods belonging to the class Arachnida of the subphylum Chelicerata, for example, the superorders Parasitiformes (mites and ticks) and Acariformes (mites). In particular, the superorder Parasitiformes includes arthropods of the order Ixodida (ticks) and the suborder Mesostigmata (mites), and the superorder Acariformes includes arthropods of the suborders Sarcoptiformes and Trombidiformes (mites).

[0029] The compositions of this disclosure may generally be in solid, liquid, or semi-solid form, including powders, granules, aggregates, blocks, solutions, suspensions, dispersions, emulsions, mists, aerosols, fogs, foams, gels, creams, pastes, ointments, and gums. Liquid compositions include water-miscible concentrates, emulsifying concentrates, flowable suspensions, wettable powders, or soluble powders, which are used to treat substrates or locations that are or may be infected or parasitized by insects (arthropods), including facilities, outdoor or indoor storage or processing areas, containers or equipment, and standing or flowing water.

[0030] The compounds and compositions of this disclosure may generally be administered to animals by being incorporated into feed or suitable orally administered pharmaceutical formulations, edible feeds, saltricks, nutritional supplements, injectors, sprays, baths, immersants, showers, jets, dust, greases, shampoos, creams, or wax coatings.

[0031] The compounds and compositions of this disclosure may be applied to general environments, including stored products, timber, household goods, and facilities for household and industrial use, or to specific locations where pests are present, as sprays, fogs, dusts, fumigants, waxes, lacquers, granules, and baits, as small supplies to waterways, wells, reservoirs, and other flowing or standing water.

[0032] The compounds and compositions according to this disclosure may generally be applied to growing crops as foliar sprays, dusts, granules, fogs, and foams, or as finely divided and encapsulated suspensions of the compounds. These may also be applied as soil and root treatments in the form of liquid drenches, dusts, granules, fumigants, and foams, and as seed treatments in the form of liquid slurries and dusts.

[0033] Solid compositions such as dust, granules, or wettable powders are generally prepared by impregnating a solid diluent with a solution of a compound of formula I in a volatile solvent, evaporating the solvent, and, if necessary, grinding the product to obtain a powder, and further granulating or compressing the product as desired to obtain granules, pellets, or briquettes; or by encapsulating the finely divided active ingredient in natural or synthetic polymers, such as gelatin, synthetic resins, and polyamides. Wetting agents, dispersants, and emulsifiers that may be present in the wettable powder in particular may be of ionic or nonionic type, and may be, for example, sulfolicinoleates, quaternary ammonium derivatives, or products based on condensates of nonylphenol and octylphenol with ethylene oxide, or carboxylic acid esters of anhydrous sorbitol solubilized by etherification of the free hydroxyl group by condensation with ethylene oxide, or mixtures of these types of agents. The wettable powder may be treated with water immediately before use to give a suspension ready for application.

[0034] Liquid compositions may incorporate natural or synthetic polymers, wetting agents, dispersants, or emulsifiers. Liquid compositions may contain wetting agents, dispersants, or emulsifiers of ionic or nonionic type or mixtures thereof, and may be prepared using aqueous, organic, or aqueous-organic diluents, such as acetophenone, isophorone, toluene, xylene, mineral oil, animal oil or vegetable oil, and water-soluble polymers (and mixtures of these diluents).

[0035] The compositions of this disclosure may contain synergistic agents (e.g., piperonyl butoxide or sesamex), stabilizers, other insecticides, acaricides, plant nematodeicides, anthelmintics or anticoccidial agents, fungicides (agricultural or veterinary appropriate, e.g., benomyl, iprodione), fungicides, arthropod or vertebrate attractants or repellents or pheromones, deodorants, fragrances, dyes, taste masking agents, and auxiliary therapeutic agents, such as trace elements. These may be designed to improve potency, persistence, safety, and, if desired, uptake, or to allow the composition to exhibit other useful functions in the same animal or area being treated.

[0036] The compositions of this disclosure may typically contain one or more compounds of formula I and / or the total active ingredient (compounds of formula I and any additional insecticides, synergists, trace elements or stabilizers) in amounts from 0.00001% to 95% by weight, or more specifically from 0.0005% to 50% by weight. The compositions actually employed and their application rates will be selected by farmers, livestock producers, physicians or veterinarians, pest control operators or those skilled in the art to achieve the desired effect.

[0037] Solid and liquid compositions for topical application to animals, timber, storage products, or household goods typically contain one or more compounds of formula I in amounts from 0.00005% to 90% by weight, more specifically from 0.001% to 10% by weight. Solid and liquid compositions for oral or parenteral (including transdermal) administration to animals typically contain one or more compounds of formula I in amounts from 0.1% to 90% by weight. Medicinal feeds typically contain one or more compounds of formula I in amounts from 0.001% to 3% by weight. Concentrates and supplements for mixing with feeds typically contain one or more compounds of formula I in amounts from 5% to 90% by weight, preferably from 5% to 50% by weight. Mineral salts typically contain one or more compounds of formula I in amounts from 0.1% to 10% by weight.

[0038] Dust and liquid compositions intended for application to livestock, people, articles, facilities, or outdoor areas may contain one or more compounds of formula I in amounts from 0.0001% to 15% by weight, and more particularly from 0.005% to 2.0% by weight. Appropriate concentrations in treated water are between 0.0001 ppm and 20 ppm, and more particularly from 0.001 ppm to 5.0 ppm, of one or more compounds of formula I, and may be used therapeutically in aquaculture with appropriate exposure times. Edible feed may contain one or more compounds of formula I in amounts from 0.01% to 5% by weight, preferably from 0.01% to 1.0% by weight.

[0039] When administered to vertebrates parenterally, orally, or by transdermal or other means, the dosage of the compound of formula I depends on the species, age, and health status of the vertebrate, as well as the nature and extent of its actual or potential parasitic infestation by the pest. A single dose of 0.1 to 100 mg, preferably 2.0 to 20.0 mg, per kg of animal body weight, or a dose of 0.01 to 20.0 mg, preferably 0.1 to 5.0 mg, per kg of animal body weight per day for sustained drug administration, is generally appropriate by oral or parenteral administration. By using sustained-release formulations or sustained-release devices, the daily dose required over a period of several months may be combined and administered to the animal in a single dose.

[0040] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art to which this disclosure pertains. Terms used herein are solely for the purpose of describing specific embodiments and are not intended to limit the invention.

[0041] Where a range of values ​​is given, unless the context clearly indicates otherwise (for example, where each carbon atom within the range should be given individually, such as the number of carbon atoms), each intermediate value up to one-tenth of the lower limit is understood to be included in the present invention as a value existing between the upper and lower limits of that range, and any other value or intermediate value within that range. The upper and lower limits of these smaller ranges may also be included independently in smaller ranges, unless there are limits specifically excluded in the given range. Furthermore, where a given range includes one or both of these limits, ranges excluding one or both of these included limits are also included in the present invention.

[0042] The following terms are used to describe this disclosure. If a term is not specifically defined herein, it is given the meaning that, in the context of its use describing this disclosure, will be recognized in the art by those skilled in the art applying that term.

[0043] As used herein and in the claims, the articles “a” and “an” are used to refer to one or more (i.e., at least one) grammatical objects of the article, unless the context clearly indicates otherwise. For example, “an element” means one or more elements.

[0044] As used herein and in the claims, the phrase “and / or” should be understood to mean “one or both” of the elements being combined, i.e., elements that exist in some cases conjunctively and in other cases disjunctively. Multiple elements enumerated with the phrase “and / or” should be interpreted in the same way, i.e., “one or more” of the elements being combined. Other elements, whether related or unrelated to the elements specifically identified by the phrase “and / or” may exist as appropriate. Thus, as a non-restrictive example, when used in combination with non-restrictive expressions such as “comprising,” a reference to “A and / or B” may, in one embodiment, refer to A only (which may appropriately include elements other than B), in another embodiment, refer to B only (which may appropriately include elements other than A), and in yet another embodiment, refer to both A and B (which may appropriately include other elements).

[0045] Where used herein and in the claims, the term “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” should be interpreted as inclusive, that is, including not only the inclusion of at least one of several elements or a list of elements, but also multiple inclusions and additional items not listed as appropriate. Only terms that explicitly indicate the inclusion of a single element, such as “one of ~” or “exactly one of ~” or, as used in the claims, “consisting of ~,” refer to the inclusion of exactly one element from several elements or a list of elements. In general, where used herein, the term “or” should be interpreted as indicating an exclusive choice (i.e., “one or the other, but not both”) only when preceded by an exclusive term such as “either,” “one of ~,” “one of ~,” or “exactly one of ~.”

[0046] Where used herein, the term “approximately” and similar terms relating to numerical values ​​or ranges reflect the fact that there is a certain level of variation that is recognized and acceptable in the art due to practical and / or theoretical limitations. For example, small variations are acceptable due to variations inherent in how a device operates and / or how measurements are taken. Accordingly, the term “approximately” is typically used to encompass values ​​within the standard deviation or standard error. In some embodiments, “approximately” may be interpreted as + / - 10% of the stated value.

[0047] In the claims and specification, all transitional phrases, including "comprising," "including," "carrying," "having," "containing," "involving," "holding," and "composed of," should be understood as open-end, meaning "to include without limitation." Only the transitional phrases "consisting of" and "consisting essentially of" are considered restrictive or semi-closed transitional phrases, respectively.

[0048] Various compounds, compositions, and methods are described using the non-restrictive terms “comprising,” “including,” or “having” various components or processes (to be interpreted as “including without limitation”), but it should also be understood that such compounds, compositions, methods, and devices may essentially consist of, or be composed of, such various components and processes, and such terms should be interpreted as defining essentially closed-member groups. This paragraph is not intended to restrict in any way the meaning of “comprising,” “having,” or “including” (and their other verb forms), and these should be interpreted as non-restrictive phrases meaning “including without limitation,” in accordance with patent law and custom. The intent of this paragraph is simply to show that closed groups defined by the terms “consisting of” or “essentially consisting of” are subgroups encompassed within non-restrictive descriptions, and to provide support for claims using the terms “consisting of” or “essentially consisting of.”

[0049] As used herein and in the claims, the expression “at least one” refers to at least one element selected from any one or more elements contained in a list of elements that includes one or more elements, and does not require that the list of elements include at least one of each element specifically enumerated in that list, nor does it exclude any combination of elements contained in that list. This definition allows for the presence of elements other than those specifically identified in the list of elements referred to by the phrase “at least one,” regardless of whether or not they are related to those specifically identified elements. Therefore, as a non-restrictive example, “at least one of A and B” (or synonymously “at least one of A or B,” or synonymously “at least one of A and / or B”) may, in one embodiment, mean that B is absent (and may appropriately include elements other than B) and at least one A (which may appropriately include two or more A); in another embodiment, mean that A is absent (and may appropriately include elements other than A) and at least one B (which may appropriately include two or more B); and in yet another embodiment, mean at least one A (which may appropriately include two or more A) and at least one B (which may appropriately include two or more B) (and which may appropriately include other elements), and so on.

[0050] In some of the methods described herein that involve multiple steps or actions, it should be understood that, unless otherwise indicated by the context, the order of the steps or actions of the method is not necessarily limited to the order in which the steps or actions of the method are described.

[0051] The terms “co-administration” and “co-administering” or “combination therapy” may refer to both simultaneous administration (administering two or more therapeutic agents at the same time) and staggered administration (administering one or more therapeutic agents at different times than the administration of additional therapeutic agents or drugs), as long as the therapeutic agents remain present in the patient at some, preferably effective, doses simultaneously. In some embodiments, one or more of the compounds described herein are co-administered in combination with at least one additional bioactive agent, such as another anticancer agent. In some embodiments, the co-administration of compounds results in synergistic activity and / or therapy, including anticancer activity.

[0052] The term “effective” may mean, but is not limited to, that the amount / dose of an active medicinal or insecticide component is effective or sufficient to provide the intended result (e.g., treatment, control, suppression, or eradication of infection or parasitism by insects (arthropods) (e.g., adult insects, insect eggs, insect larvae, insect nymphs, and / or insect pupae)) when used in the context of its intended use.

[0053] The effective dose depends on the type and severity of the disease or infestation, the composition used, the route of administration or application, the type of animal or site being treated, co-treatment or application with other insecticides, and other factors recognized by those skilled in the medical field.

[0054] The term "pharmaceutically acceptable" may, but is not limited to, a substance or composition that, when administered to a patient or subject, does not cause a harmful, allergic, or other adverse reaction.

[0055] The term "pharmaceutically acceptable carrier" may refer to, but is not limited to, any solvent, excipient, coating, etc., that is suitable for the administration of a drug to a patient or subject. Such components include diluents, binders, lubricants, dispersants, surfactants, isotonic agents, stabilizers, solubilizers, gelling agents, complexing agents, antioxidants, buffers, fragrances, colorants, and coatings.Suitable solvents and excipients include water, ethanol, dimethyl sulfoxide, polyethylene glycol, polypropylene glycol, poloxamer (ethylene oxide / propylene oxide block copolymer), mannitol, sorbitol, glycerin, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, cellulose acetate, polyvinyl alcohol, polyvinyl acetate, polyvinyl acetate-polyvinyl alcohol copolymer, polyvinylpyrrolidone, polyacrylate, methyl polyacrylate, polymethyl methacrylate, xanthan gum, gum arabic, guar gum, karaya gum, agar, alginic acid, sodium alginate, carrageenan, tragacanth gum, locust bean gum, glucan, gellan gum, sodium lauryl sulfate, sodium laureth sulfate, cocamidopropyl This includes, but is not limited to, betaine, polyoxyethylene sorbitan esters (e.g., polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80), dimethicone, diethyl phthalate, stearic acid, cetyl alcohol, magnesium stearate, magnesium aluminum silicate, silicon dioxide, starch (e.g., pregelatinized starch), sodium starch glycolate, talc, triethyl citrate, glyceryl triacetate, dextrose, maltose, lactose, trehalose, calcium carbonate, dicalcium phosphate, sodium chloride, potassium chloride, sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium citrate, sodium phosphate, sodium acetate, hydrochloric acid, acetic acid, citric acid, tartaric acid, phosphoric acid, propyl gallate, sodium metabisulfite, butylated hydroxyanisole, butylated hydroxytoluene, and alpha-tocopherol.

[0056] The term "insecticidally acceptable" may mean, but is not limited to, substances and compositions that, when applied to a product or location, do not cause unacceptable adverse consequences, such as unacceptable hazardous or environmentally harmful consequences.

[0057] The term “insecticidally acceptable carrier” may mean, but is not limited to, any solvent, excipient, coating, etc. that is compatible with the administration of an insecticide to a product or site. Suitable carriers and excipients include all pharmaceutically acceptable suitable carriers and excipients listed in the paragraph above, and further include methanol, isopropanol, 2-butoxyethanol, ethylene glycol, hexylene glycol, 1,3-propanediol, 1,2-propanediol, diethylene glycol, diethanolamine, aluminum oxide, aluminum silicate, trisodium sulfosuccinate, cobalt propionate, 2-ethylhexyloctadecenoate, ethylene oxide / oleic acid monoethanolamide, 2-butyl propenate polymers and copolymers, sodium dodecylnaphthalenesulfonate, decamethylcyclopentasiloxane, cyclodextrin, sodium silicate, ammonium dodecanoate, sodium benzoate, boric acid, sodium borate, and mica.

[0058] The term "systemic administration" refers to a route of administration, such as enteral or non-enteral, that results in the systemic distribution of a drug, with distribution throughout the body occurring after systemic absorption or accumulation of the drug in the bloodstream. The appropriate form depends, in part, on the route of use or entry, e.g., oral (enteral) administration or parenteral administration (e.g., intravenous injection). Such forms should not prevent the composition or formulation from reaching target cells (i.e., cells to which the negatively charged polymer is desired to be delivered). For example, a pharmacological composition injected into the bloodstream should be soluble. Other factors known in the art include considerations such as toxicity and forms that may prevent the composition or formulation from exerting its effect.

[0059] The terms “patient” or “subject” may refer to cells, tissues, or animals, preferably mammals, such as humans, domestic animals, or companion animals, to which treatment (including prophylactic treatment) using the compositions of this disclosure is provided. For the treatment of an infection, condition, or disease state that is specific to a particular animal, such as a human patient, the term “patient” refers to that particular animal, including domestic animals such as dogs or cats, or domestic animals such as horses, cattle, or sheep.

[0060] As used herein, the term “compound” means any specific compound disclosed herein unless otherwise specified, including tautomers, positional isomers, geometric isomers, and, where applicable, stereoisomers, atropisomers, including their optical isomers (enantiomers) and other stereoisomers (diastereomers), and, where applicable, their salts, hydrates, solvates, polymorphs, and derivatives. Such isomers include both cis and trans isomers in the context of double and triple bonds and cyclic systems. In its contextual use, the term “compound” generally refers to a single compound, but may also include other compounds such as stereoisomers, positional isomers, and / or optical isomers (including racemic mixtures), as well as specific enantiomers or enantiomer-enriched mixtures of the disclosed compound. The term also means any specific chemical compound in which one or more atoms are substituted with one or more different isotopes of the same element (e.g., hydrogen substituted with deuterium). When describing this compound, please note that a large number of substituents and related variables will be explained in particular.

[0061] A "tautomer" refers to a compound whose structure is interchangeable with another compound, differing in the transfer of hydrogen atoms and electrons. Thus, two structures may be in equilibrium through the transfer of π electrons and atoms (usually H). For example, enols and ketones are tautomers because they are rapidly interconverted by treatment with either an acid or a base. Another example of tautomerism is the ac and nitro forms of phenylnitromethane, which are also formed by treatment with an acid or a base. The tautomer form may be related to achieving optimal chemical reactivity and biological activity of the compound of interest.

[0062] Those skilled in the art will understand that the molecules described herein are stable compounds, as outlined below. Where bonds are shown, both double and single bonds are shown or understood within the context of the compounds shown and the well-known rules concerning valence interactions.

[0063] As used herein, “derivative” may mean a composition formed directly from a natural compound, by modification, or by partial substitution. As used herein, “analog” may mean a composition having a structure similar to, but not identical to, a natural compound.

[0064] "Amino" refers to an -NH2 group, "hydroxy" refers to an "-OH" group, "cyano" refers to an -CN group, and "nitro" refers to an -NO2 group. It is understood that both amino and hydroxyl groups can be appropriately substituted, for example, with acyl groups. However, since monoalkylamino groups and dialkylamino groups, as well as alkoxy groups (i.e., alkyloxy groups), are listed separately herein, the term "may be appropriately substituted" when applied to these groups does not intend alkyl substitution of amino and hydroxyl groups.

[0065] "Halo" or "halogen" refers to fluoro(F), chloro(Cl), bromo(Br), or iodine(I).

[0066] As used herein, “alkyl” means a completely saturated acyclic linear or branched hydrocarbon moiety, preferably having 1 to 6 carbon atoms, or in some embodiments having 1 to 4 carbon atoms, or 1 to 3 carbon atoms, and may be substituted as appropriate, as defined herein, unless otherwise specified. Exemplary alkyl groups include methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, or the general formula -C n H 2n+1 This includes, but is not limited to, any other acyclic hydrocarbon group having the same properties.

[0067] As used herein, “alkenyl” means an acyclic, linear or branched unsaturated hydrocarbon moiety having at least one carbon-carbon double bond, preferably having 2 to 6 carbon atoms, or in some embodiments 2 to 4 carbon atoms, or 2 to 3 carbon atoms, and may be substituted as appropriate, as defined herein, unless otherwise specified. Preferably, the group is monounsaturated (having a single carbon-carbon double bond). Examples of alkenyl groups include vinyl and allyl, or the general formula -C n H 2n-1 This includes, but is not limited to, any other hydrocarbon acyclic group having the same properties.

[0068] As used herein, “alkynyl” means an acyclic, linear or branched unsaturated hydrocarbon moiety having at least one carbon-carbon triple bond, preferably having 2 to 6 carbon atoms, or in some embodiments having 2 to 4 carbon atoms, or 2 to 3 carbon atoms, and may be substituted as appropriate, as defined herein, unless otherwise specified. Preferably, the group is monounsaturated (having a single carbon-carbon triple bond). Examples of alkynyl groups include ethynyl and propargyl, or the general formula -C n H 2n-3 This includes, but is not limited to, any other hydrocarbon acyclic group having a double bond or triple bond. As used herein, hydrocarbon radicals having both double and triple bonds are considered alkynyl radicals.

[0069] As used herein, "alkylene" refers to -(CH2) n- means a group, where n is generally an integer from 1 to 10, for example from 1 to 6, and may be substituted as appropriate, as defined herein. If substituted, the alkylene group is preferably substituted with a C1-C6 alkyl group (including a cyclopropyl group or a t-butyl group), more preferably with a methyl group in one or more methylene (CH2) groups, but may be substituted with one or more halo groups, preferably 1 to 3 halo groups, or one or two hydroxyl groups, amino groups, alkoxy groups, cycloalkyl groups, or cycloalkoxy groups, as defined herein.

[0070] The term "C" used herein 1~6 A "haloalkyl" is an alkyl group as defined above, having 1 to 6 carbon atoms, and substituted with at least one, up to the maximum number of halogen atoms (e.g., F, Cl, Br, or I) permitted by the valence of the alkyl group's carbon atoms, and may be further substituted as appropriate, as defined herein. This group may be substituted with multiple atoms of the same halogen or with different halogens. 1~6 Haloalkyls include, for example, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, and 2,2,2-trifluoroethyl.

[0071] As used herein, “alkoxy” means a group of the -O-(alkyl) structure, which may be substituted as appropriate, as defined herein. For example, C 1~6 The alkoxy group is -O-(C 1~6 It is a group having an alkyl structure. The alkoxy radical is bonded to the structure to which it is attached by its oxygen atom.

[0072] As used herein, “cycloalkyl” means a non-aromatic saturated or unsaturated free radical that forms at least one ring, having, for example, 3 to 10 carbon atoms and a corresponding number of hydrogen atoms, and which may be substituted as appropriate, as defined herein. Thus, the term “cycloalkyl” includes a carbon ring having one or more double or triple bonds. Cycloalkyl groups can be monocyclic or polycyclic. In addition to covalent substitution, the individual rings of such polycyclic cycloalkyl groups may have different linkages, such as condensation, crosslinking, and spiro. Exemplary cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornanyl, bicyclo[3.2.1]octanyl, octahydro-pentarenyl, spiro[4.5]decanyl, cyclopropyl, adamantyl, cyclobutyl-substituted, cyclopentyl-substituted cyclobutyl, cyclopropyl-substituted cyclohexyl, and the like. Of course, other cycloalkyl groups will be readily apparent to those skilled in the art in light of the interests of this disclosure.

[0073] As used herein, “cycloalkoxy” means a group of the -O-(cycloalkyl) structure, which may be substituted as appropriate, as defined herein. For example, C 3~6 The cycloalkoxy group is -O-(C 3~6 It is a group having a cycloalkyl structure. The cycloalkoxy radical is bonded to the structure to which it is attached by its oxygen atom.

[0074] As used herein, “halocycloalkyl” means a cycloalkyl group as defined above, wherein at least one and up to the maximum number of halogen atoms (e.g., F, Cl, Br, or I) permitted by the valence of the alkyl group's carbon atoms are substituted, and which may be further substituted as appropriate, as defined herein. The group may be substituted with multiple atoms of the same halogen or with different halogens. Examples of halocycloalkyl groups include 1-fluorocyclopropyl, 2-fluorocyclopropyl, 2,2-difluorocyclopropyl, 2,2-difluorocyclobutyl, 3,3-difluorocyclopentyl, and the like.

[0075] As used herein, “heterocycloalkyl” means any non-aromatic ring system containing a ring atom that is at least one heteroatom (e.g., N, S, or O). This includes monocyclic and fused bicyclic ring systems of 3 to 12 members, as well as any larger polycyclic fused ring systems, provided that the ring system does not contain any aromatic carbocyclic or aromatic heterocyclic rings. Examples of heterocycloalkyl groups include pyrrolidinyl, tetrahydrofuranil, dihydrofuranil, tetrahydropyranil, pyranil, thiopyranil, azidinil, azetidinil, oxyranil, methylenedioxyl, clomenil, barbituryl, isoxazolidinyl, 1,3-oxazolidine-3-yl, isothiazolidinyl, 1,3-thiazolidinyl, 1,3-thiazolidinyl, 1,2-pyrazolidinyl, 1,3-pyrazolidinyl, piperidinyl, thiomorpholinil, 1,2-tetrahydrothiadinyl-2-yl, 1,3-tetrahydrothiadinyl-3-yl, tetrahydrothiadiazine, morpholinil, 1,2-tetrahydrodiazine-2-yl, 1,3-tetrahydrodiazine-1-yl, tetrahydroazepinyl, piperazinyl, and piperidine. -2-Onyl, piperidine-3-Onyl, chromanil, 2-pyrrolinil, 3-pyrrolinil, imidazolidinil, 2-imidazolidinil, 1,4-dioxanil, 8-azabicyclo[3.2.1]octanil, 3-azabicyclo[3.2.1]octanil, 3,8-diazabicyclo[3.2.1]octanil, 2,5-diazabicyclo[2.2.1]heptanil, 2,5-diaza These include bicyclo[2.2.2]octanyl, octahydro-2H-pyrido[1,2-a]pyradinyl, 3-azabicyclo[4.1.0]heptanyl, 3-azabicyclo[3.1.0]hexanyl, 2-azaspiro[4.4]nonanyl, 7-oxa-1-azaspiro[4.4]nonanyl, 7-azabicyclo[2.2.2]heptanyl, octahydro-1H-indolyl, and the like. In general, heterocycloalkyl groups are usually bonded to the main structure via a carbon or nitrogen atom. Naturally, other heterocycloalkyl groups will be readily apparent to those skilled in the art in light of the interests of this disclosure.

[0076] As used herein, “aryl” means any carbocyclic aromatic ring system, i.e., any aromatic ring system containing only carbon atoms as ring atoms. This includes six-membered monocyclic aryl ring systems and nine- or ten-membered fused bicyclic aryl ring systems, including larger fused ring systems, provided that such ring systems contain at least one six-membered aromatic carbocyclic (i.e., a benzene ring) within the fused ring system and the ring atoms are not heteroatoms. Aryls include, but are not limited to, phenyl, naphthyl, phenanthryl, and anthracenyl.

[0077] As used herein, “heteroaryl” means any heteroaromatic ring system, i.e., any aromatic ring system containing a ring atom that is at least one heteroatom (e.g., N, S, or O). This includes five- and six-membered monocyclic heteroaryl ring systems, as well as nine- or ten-membered fused bicyclic heteroaryl ring systems, and includes larger fused ring systems insofar as such ring systems contain at least one aromatic carbocyclic or aromatic heterocyclic ring within the fused ring system and contain at least one heteroatom (e.g., N, S, or O) ring atom (in either the aromatic or nonaromatic ring). Thus, heteroaryls include, but are not limited to, bicyclic fused ring systems selected from aromatic-heteroaromatic, aromatic-heterocyclic, heteroaromatic-carbocyclic, heterocyclic-aromatic, and heteroaromatic-heteroaromatic, as well as larger fused ring systems containing some combinations of benzene, cycloalkane, heterocycloalkane, and heteroaromatic rings.Exemplary heteroaryl groups include furyl, thienyl, thiazolyl, pyrazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrrolyl, triazolyl, tetrazolyl, imidazolyl, 1,3,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,3-oxadiazolyl, 1,3,5-thiadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridadinyl, pyridonyl, 1,2 ,4-triazinyl, 1,2,3-triazinyl, 1,3,5-triazinyl, pyrazolo[3,4-b]pyridinyl, cinnolinyl, pteridinyl, purinyl, 6,7-dihydro-5H-[1]pyridinyl, benzo[b]thiophenyl, 5,6,7,8-tetrahydro-quinoline-3-yl, benzoxazolyl, benzofuranil, isobenzofuranil, benzothiazolyl, benzoisothiazolyl, benzoisoxazolyl, benzimidazolyl, benzothiadi Azolyl, thianaftenyl, isothianaftenyl, benzofuranil, isobenzofuranil, isoindolyl, indolyl, indolidinyl, indazolyl, isoquinolinil, quinolinil, phthalazinyl, quinoxalinil, quinazolinil, naphthyridyl, phenantridinyl, acridinyl, carbazolyl, carbazolinil, permidinyl, phenantrololinil, phenacenyl, pyrrolopyrimidinyl, pyrrolopyrimidinyl, pyridopyrimidinyl, thienopyrimidinyl These include phlopyrimidinyl, phlopyridyl, phlopyrolyl, pyrazoloxazolyl, thienofuranil, imidazothiazolyl, imidazopyridyl, imidazotriazil, imidazopyrimidinyl, pyrazinopyridazinyl, phenothiazinyl, flazanil, phenoxazinyl, pyrazobenzoxazinyl, azaindridinyl, dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyridoxazinyl. For heteroaryl systems in which both the ring carbon atom and the ring heteroatom have open valencies, it is understood that they can form bonds with either of those atomic types (e.g., C bond or N bond).For example, if the pyrazolyl portion is a substituent and is further substituted with other groups, the core structure to which the pyrazolyl is bonded, and any one or more other substituents bonded to the pyrazolyl, may be bonded via a pyrazole ring nitrogen atom (N bond) or a pyrazole ring carbon atom (C bond).

[0078] As used herein, the term “unsubstituted” means that the structure or group shown is further substituted with hydrogen atoms only.

[0079] As used herein, the terms “substituted” or “may be substituted as appropriate” mean that one or more hydrogen atoms of a group or radical are independently replaced by one or more non-hydrogen substituents (i.e., if two or more substitutions occur, each substituent is independent of the other substituents) up to the maximum number of substituents allowed for the chemical structure, substructure, group or radical (e.g., up to five substituents, preferably up to three substituents, often up to one or two substituents on a part). Substituents may be further substituted themselves. Optional substituents, unless otherwise specified, are hydroxyl (-OH), thiol (-SH), carboxyl (-COOH), cyano (-CN), nitro (-NO2), halo (preferably F or Cl), C1-C 20 Alkyl (for example, C1~C 10 Alkyl (C1-C6 alkyl), C2-C 20 Alkenyl (for example, C2~C 10 Alkenyls (C2-C6 alkenyls), C2-C 20 Alkinyl (for example, C2~C 10 Alkynnyl (C2-C6 alkynyl), aryl (e.g., phenyl, naphthyl), heteroaryl (e.g., 5- to 10-membered ring heteroaryls such as azole, diazole, triazole, pyridine, diazine, triazine, and their benzo-condensed derivatives), 5- to 10-membered heterocycloalkyl (containing at least one heteroatom as N, S, or O), C1-C 20 Alkoxy (for example, C1~C 20 Alkoxy, C1-C6 alkoxy), C3-C 20Cycloalkyl (for example, C3~C 10 Cycloalkyl, C3-C6 cycloalkyl), C3-C 20 Cycloalkoxy (for example, C3-C3) 10 Cycloalkoxy (C3-C6 cycloalkoxy), aryloxy (e.g., phenoxy), thioether (thioC1-C6 alkyl or aryl), keto, acyl (preferably C1-C6 acyl), ester or thioester (preferably C1-C6 alkyl or aryl, including alkylene esters, where the bonding is at the alkylene group rather than the ester functional group itself, and the ester functional group is preferably substituted with a C1-C6 alkyl or aryl group), a Mins (including amino(-NH2), mono-C1~C6 alkylaminos, di-C1~C6 alkylaminos, and 5-membered or 6-membered N-containing heterocycloalkyls), carbamates or urethanes (such as N(C0~C6 alkyl)C(O)(OC1~C6 alkyl) groups, which may be optionally substituted), hydrazines or hydrazides, amides (NC(O), preferably substituted with one or two C1~C6 alkyl groups (including carboxamides optionally substituted with one or two C1~C6 alkyl groups)), sulfones (SO2), sulfoxides (S(O)), sulfonamides, alkanols (preferably C1~C6 alkyl or aryl, e.g., (CH2) n OH), or alkanic acid (preferably C1-C6 alkyl or aryl, for example (CH2) n COOH) (where n is an integer from 1 to 10, for example from 1 to 6). The substituents of the present invention may also include a SiR1R2R3 group, where R1 and R2 are as separately described herein, and R3 is H or a C1-C6 alkyl group, preferably R1, R2, and R3 in this context are C1-C3 alkyl groups (including an isopropyl group or a t-butyl group). Additional optional substituents include NHC(O)NH, (CH2) n SH, (CH2) n O(C1~C6 alkyl), (CH2) n C(O)(C1~C6 alkyl), (CH2) nOC(O)(C1~C6 alkyl), (CH2) n C(O)O(C1~C6 alkyl), (CH2) n NHC(O)R1, (CH2) n C(O)NR1R2, (OCH2) n OH, (CH2O) n COOH, C1-C6 alkyl, (OCH2) n O(C1~C6 alkyl), (CH2O) n C(O)(C1~C6 alkyl), (OCH2) n NHC(O)R1, (CH2O) n C(O)NR1R2, S(O)2R s , and S(O)R s (R s is C1-C6 alkyl or (CH2) m It contains an NR1R2 group. Each of the above groups may be directly bonded to the substituted moiety, or alternatively, the substituents may be substituted as appropriate - (CH2) m - may be substituted as appropriate via, or instead of -(OCH2) m -,-(OCH2CH2) m -, or -(CH2CH2O) m -The alkylene group may be bonded to the moiety substituted via the -(CH2) group (preferably an aryl or heteroaryl moiety), and these groups may be substituted with one or more of the above substituents, where m is an integer from 1 to 20, for example, from 1 to 10 or from 1 to 6. m -or-(CH2) n- Groups, or other chains such as ethylene glycol chains, may be substituted at any position on the chain. Since substituents can be substituted themselves, these groups may also include, for example, compounds such as aryl C1-C6 alkyl (e.g., benzyl), halo C1-C6 alkyl (e.g., trifluoromethyl), hydroxy C1-C6 alkyl (e.g., 2-hydroxy-2-methylbutyl), and C1-C6 alkyl-aryl (e.g., tolyl). Preferably, any optional substituent described herein ("primary substituent") may be appropriately substituted itself with only one to three further substituents ("secondary substituents"), and each of the secondary substituents may appropriately be substituted with a single further substituent ("tertiary substituent").

[0080] When describing substituents bonded to various positions on the core structure of formula I (including substituents bonded to substituents), substituents may, in some cases, be referred to using the name of the corresponding compound, and especially in the case of rings, the same substituent may be referred to using the name of the corresponding chemical radical (e.g., having the "-yl" suffix), but it is understood that these terms are interchangeable. For example, when referring to substituent Ar, or heteroaryl ring R bonded to substituent Ar, the terms "pyridine" and "pyridyl" are equivalent, and the terms "morpholine" and "morpholinyl" are also equivalent. Those skilled in the art will recognize that such terms are used, for example, to indicate the bonding of a pyridine ring or a morpholine ring at a given position, and thus convert the ring to a pyridyl or morpholinyl substituent, respectively. Unless otherwise specified, such bonding may occur at any chemically acceptable position on the bonded ring.

[0081] As used herein, the range of carbon atoms including C0 means that carbon is absent and replaced by H (or deuterium). Therefore, the range of carbon atoms C0-C6 includes carbon atoms 1, 2, 3, 4, 5, and 6, where C0 is replaced by H (or deuterium).

[0082] The compound of formula (I) may exist as a tautomer, for example, as a tautomer of an amide (NHC=O) and a hydroxyimine (N=COH). Therefore, R 3 When it is a hydroxyl (-OH) group, it is understood to be tautomerally equivalent to the keto group adjacent to the hydrogenated nitrogen atom: [ka]

[0083] X is -N- and Y is CR 2 And R 2 If is OH, or if Y is -N- and X is CR 1 And R 1 When is OH, similar tautomer equivalents are intended. Such combinations of groups are also within the scope of this application, and such tautomer equivalents are understood to be included. For example, as follows: [ka]

[0084] Exemplary, non-limiting embodiments of this disclosure are further described with reference to the following examples. [Examples]

[0085] Unless otherwise specified, all starting materials and solvents were obtained from commercially available sources (e.g., AcrosOrganics, Merck, AlfaAesar, and TCI) and used without further purification. All reactions were carried out on silica gel 60F. 254 Thin-layer chromatography (TLC) was performed on 0.2 μm thick pre-coated aluminum foil (with UV254 fluorescence indicator) (Sigma-Aldrich) and monitored periodically. The developing plates were air-dried and visualized under UV light (254 / 365 nm) or using KMnO4 solution. Automated flash column chromatography was performed using Biotage® Selekt with a pre-packed silica (50 Å, 20 μM) cartridge.

[0086] 1 HNMR and 13 ¹¹C NMR spectra were recorded at 400 MHz and 101 MHz, respectively, at 298 K, using a BrukerAvance 400 spectrometer with the residual solvent peak as an internal standard. Chemical shifts are reported in ppm(δ), and coupling constants (J) are given in Hertz (Hz). Peak multiplicity is abbreviated as follows: s (singular), bs (broad single), d (double), dd (double double), t (triple), dt (double triple), q (quadruple), p (quintuplet), and m (multiple). Data were acquired using BrukerTopSpin software and processed using MestreNova software.

[0087] High-resolution mass spectrometry (HRMS) spectra were registered using an Agilent Technologies 6540 UHD Accurate Mass Q-TOF LC-MS system, or an Agilent 1290 Infinity Series U-HPLC system (Agilent Technologies, Santa Clara, CA, USA) connected to a Q-TOF 6540 high-resolution mass spectrometer and a 1290 Infinity Series DAD / UV-Vis detector (Agilent Technologies). The purity of the final compound was assessed as >98% using ULC-MS. The analysis was performed according to the method described below. The mobile phase was a mixture of water (solvent A) and acetonitrile (solvent B), both containing 0.1% formic acid. Method: A Phenomenex Luna Omega 1.6 μm (C18, 100 × 2.1 mm) polar column was used at 40°C, with a flow rate of 0.65 mL / min during a 10-minute gradient elution. The gradient elution was as follows: from 99.5:0.5(A / B) to 5:95(A / B) over 8 minutes, then to 5:95(A / B) for 2 minutes, and then back to 99.5:0.5(A / B) over 0.1 minutes. UV detection was the average signal at wavelengths from 190 nm to 640 nm, and the mass spectrum was recorded using a mass spectrometer with positive-mode electrospray ionization.

[0088] The compounds described herein may be synthesized as described herein, by modified methods described herein, or by methods known to those skilled in the art.

[0089] Chemical abbreviations: ACN, acetonitrile; Boc, tert-butoxycarbonyl; CD3OD, deuterated methanol; CDCl3, deuterated chloroform; DCE, dichloroethane; DCM, dichloromethane; DEE, diethyl ether; DIPEA, N,N'-diisopropylethylamine; DMA, dimethylacetamide; DMF, dimethylformamide; DMSO, dimethyl sulfoxide; DMSO-d6, deuterated dimethyl sulfoxide; EA, ethyl acetate; h, time; EtOH, anhydrous ethanol; Et3N, triethylamine; HATU, 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; min, minute; HRMS, high-resolution mass spectrometry; MeOH, methanol; NMR, nuclear magnetic resonance; tBu, tert-butyl; tBuOH, tert-butanol; TLC, thin-layer chromatography; PE, petroleum ether; rt, room temperature.

[0090] chemical synthesis Compounds of general formula (I) may be prepared according to the general synthetic methods described below: N-arylation of 2-aminopyrazole [ka] For example, see CN109134375; IN178903; WO 2004 / 092140. Heterocyclic condensation [ka] For example, Silva et al., Eur. J. Med. Chem., 46(9):4676-4681 (2011); Liu et al., Arch. Org. Chem., 2009(2): 258-268 (2009); de Mello et al., J. Med. Chem., 47(22): 5427-5432 (2004); El-Gohary & Shaaban, Eur. J. Med. Chem. 152(1):126-136 (2018); Kumar et al., Org. Prep. Proc. Intl., 51(1):1-89 (2019); Ibrahim et al., J. Ind. Chem. Soc., 64(6):345-347 (1987); Bhasvar et al., J. See Het. Chem. 51(3):635-641 (2014); Toche et al., J. Het. Chem. 47(2):287-291 (2010); [ka] For example, see CN115304607, Gangurde et al., J. Het. Chem., 51(4):883-890 (2014); Abdelhamid, J. Chem. Res. Synop. 6:208-209 (1993); WO 2015 / 025025; [ka] For example, Chien et al., Tet. Lett. 45(21):4105-4108 (2004); Rizk et al., Chin. J. Chem., 29(7):1451-1459 (2011); Farghaly et al., Bioorg. & Med. Chem. Lett., 22(7):2166-2175 (2014); Colombo et al., J. Het. Chem. 26(4):949-955 (1989).

[0091] Example 1: 1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-6-hydroxy-4-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile [ka] 5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carbonitrile (commercially available) (0.100 g, 0.311 mmol) and 4,4,4-trifluoro-3-oxobutanoate ethyl (commercially available) (0.115 g, 0.091 μL, 0.623 mmol) were stirred in a preheated pressure-resistant tube at 150°C for 18 hours. After cooling, the crude product was purified by automated flash chromatography using silica gel (4 g cartridge, petroleum ether / ethyl acetate gradient from 99:1 to 70:30) to obtain the target compound (36 mg, yield 26%) as a white solid. 1 H NMR (400 MHz,DMSO-d6) δ 13.36 (bs,1H),8.40 (s,2H),7.34 (s,1H); 13 C NMR (101 MHz,DMSO-d6) δ 166.50-166.26 (m),151.26,136.07 (2C),135.36,134.05 (q,J = 34.1 Hz),132.47 (q,J = 35.9 Hz),127.38-127.22 (m),122.61 (q,J = 274.0 Hz),122.15 (q,J = 273.4 Hz),119.16,112.26,110.54,104.49; 19 F NMR (376 MHz,DMSO-d6) δ -61.38,-61.52. HRMS (ESI) m / z [M+Na] + C 15 Calculated value of H4Cl2F6N4O: 462.95586, Measured value: 462.95666.

[0092] Comparative Example 2: N-(3-cyano-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-1H-pyrazole-5-yl)acetamide [ka] To a solution of 5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carbonitrile (commercially available) (0.100 g, 0.311 mmol) in acetic acid (3.0 mL), ethyl 4,4,4-trifluoro-3-oxobutanoate (commercially available) (0.057 g, 0.045 μL, 0.311 mmol) was added, and the mixture was stirred at 120 °C for 24 hours. After cooling, the solvent was evaporated, and the crude product was purified by automated flash chromatography using silica gel (4 g cartridge, 80:20 gradient of petroleum ether / ethyl acetate) to obtain the target compound (46 mg, yield 41%) as a white solid. 1 H NMR (400 MHz,DMSO-d6) δ 10.45 (s,1H),8.33 (s,2H),7.21 (s,1H),2.03 (s,3H); 13 C NMR (101 MHz,DMSO-d6) δ 168.28,140.91,136.02 (2C),135.98,133.57 (q,J = 33.8 Hz),127.13 (q,J = 33.8 Hz),126.87,122.76 (q,J = 274.0 Hz),114.08,101.49,23.51; 19 F NMR (376 MHz,DMSO-d6) δ -61.42. HRMS (ESI) m / z [M+Na] + C 13 Calculated value of H7Cl2F3N4O: 384.98412, measured value: 384.98409.

[0093] Comparative Example 3: N-(3-cyano-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-1H-pyrazole-5-yl)propionamide [ka] To a solution of 5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carbonitrile (commercially available) (0.200 g, 0.623 mmol) in propionic acid (1.5 mL), ethyl 4,4,4-trifluoro-3-oxobutanoate (commercially available) (0.126 g, 0.100 μL, 0.685 mmol) was added, and the mixture was stirred at 120 °C for 24 hours. After cooling, the solvent was evaporated, and the crude product was purified by automated flash chromatography using silica gel (4 g cartridge, 80:20 gradient of petroleum ether / ethyl acetate) to obtain the target compound (35 mg, yield 15%) as a white solid. 1 H NMR (400 MHz,DMSO-d6) δ 10.40 (s,1H),8.33 (s,2H),7.22 (s,1H),2.29 (q,J = 7.5 Hz,2H),1.00 (t,J = 7.5 Hz,3H); 13 C NMR (101 MHz,DMSO-d6) δ 172.02,140.94,136.03,135.99 (2C),133.52 (q,J = 33.8 Hz),127.22-127.01 (m),126.84,122.77 (q,J = 273.9 Hz),114.12,101.61,28.99,9.65; 19 F NMR (376 MHz,DMSO-d6) δ -61.40. HRMS (ESI) m / z [M+H] + C 14 Calculated value of H9Cl2F3N4O: 377.01783, Measured value: 377.01823.

[0094] Example 4: 1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-(difluoromethyl)-6-hydroxy-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile [ka] 5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carbonitrilate (0.050 g, 0.155 mmol) and ethyl 4,4-difluoro-3-oxobutanoate (0.027 μL, 0.187 mmol) were stirred at 150°C for 1 hour in a pressure-resistant tube in a preheated bath. Next, CF3COOH (0.012 μL, 0.155 mmol) was added, and the mixture was stirred overnight at 150°C in a pressure-resistant tube. After cooling, the crude product was purified by automated flash chromatography using silica gel (4 g cartridge, PE:EA gradient from 99:1 to 70:30) to obtain the target compound (12 mg, yield 11%) as a pale yellow solid. 1 H NMR (400 MHz,DMSO-d6) δ 13.02 (bs,1H),8.40 (s,2H),7.46 (t,J = 53.9 Hz,1H),7.15 (s,1H); 19 F NMR (376 MHz,DMSO-d6) δ -61.50,-112.70,-112.8. HRMS (ESI) m / z [MH] - C 15 Calculated value of H5Cl2F5N4O: 420.96878, Measured value: 420.96900.

[0095] Examples 5-16: Additional compounds within the scope of this disclosure may be manufactured according to the following general scheme: [ka]

[0096] The following compounds are prepared according to the same procedure as shown in Examples 1 and 4: [Table 1] [Table 2] [Table 3]

[0097] Example 17: In vivo evaluation To investigate the therapeutic efficacy of the compounds disclosed herein, live chickens infested with mites (Dermanyssus gallinae) were treated topically with a solution of the test compound, and fipronil was used as a positive control. The test solution was prepared by dissolving the test compound in a mixture of 2-butoxyethanol, ethanol, and water (7:2:1) to a final concentration of 0.25% (w / v).

[0098] The test solution is administered using a mechanical spray pump that delivers 0.5 mL of solution with each operation. The test solution is sprayed over the entire body surface of the animal from a distance of 10-20 centimeters, ensuring direct contact between the solution and the animal's skin. The dose applied to each animal is 3 mL / kg, which corresponds to 7.5 mg / kg (kg of live body weight). This dose is achieved using 6 spray operations per kg of body weight per day. This treatment is carried out once a day at 24-hour intervals for 5 days. One animal is left untreated as a negative control.

[0099] Blood samples are collected from each animal before the initial treatment (T=0) and at 24-hour intervals thereafter. Each egg laid after treatment is collected for later analysis.

[0100] Plasma concentration analysis

[0101] Plasma samples are obtained from each blood sample immediately after collection using standard procedures. Plasma is frozen and stored at -80°C until analysis. Next, the samples are thawed at room temperature and extracted by solid-phase extraction (SPE) (Strata-X 33μ Polymeric Reversed Phase, 60 mg / 3 mL, Phenomenex), during which an aliquot (100 μl) of the sample is pre-treated with 300 μl of acetonitrile for protein precipitation. After protein precipitation, the sample is thoroughly vortexed and then centrifuged (12000 rpm, 10 minutes, room temperature). The supernatant is collected, transferred to a clean Falcon tube, and diluted with 3 mL of water. The Strata-X column is conditioned with 2 mL of methanol and 2 mL of water. After conditioning, the sample is loaded, the column is washed with 2 mL of water, the analyte is eluted with 2 mL of methanol, dried under nitrogen, and then resuspended in 100 μl of acetonitrile for mass spectrometry. The recovery rate of this method was calculated by adding a standard substance to untreated plasma and was found to be 72%. Calibration curves were created for both compounds (0.005–10 μM).

[0102] A Thermo Q-exactive mass spectrometer (Thermo Fisher Scientific, Waltham, MA) is used. The LC system, controlled by Chromeleon X-press software, consists of a binary pump, a constant-temperature autosampler, and a column compartment, all of which are Dionex Ultimate 3000 series modules (Thermo Fisher Scientific, Waltham, MA). A volume of 2 μL is injected for each sample. Chromatographic separation of the analytes is performed by reverse-phase chromatography. A Luna Omega 1.6 μm Polar (C18, 2.1 mm × 100 mm) is used, with mobile phases of (A) water and (B) acetonitrile, both containing 0.1% v / v formic acid. The flow rate is 0.400 mL / min during a 12-minute gradient elution as follows: from 99.5:0.5(A / B) to 5:95(A / B) in 10 minutes, at 5:95(A / B) for 2 minutes, and then back to 99.5:0.5(A / B) in 2.5 minutes. The column is operated at a constant temperature of 40°C. The LC eluate is introduced into the Q-Exactive mass spectrometer via an H-ESI source operating in negative mode, with a sheath gas flow rate of 45, auxiliary gas flow rate of 15, spray voltage of 3.5kV, capillary temperature and auxiliary gas heater temperature of 320°C and 350°C respectively, and an S-lens RF level of 50. The Q-Exactive mass spectrometer is operated in FullMS mode with a resolution of 140,000. Data analysis is performed using Qual Browser Thermo Xalibur 4.0.27.13 (Thermo Fisher Scientific) and Lipostar 2.0 (Molecular Discovery Ltd) software.

[0103] The following peak was observed and quantified: fipronil, retention time 9.54 min ([MH] - Ion 434.9318 m / z); fipronyl sulfone, retention time 9.98 min ([MH] - Ion 450.9268 m / z); fipronilamide, retention time 9.97 min ([MH] -Ion 452.9235 m / z); Compound of Example 1, retention time 9.95 min ([MH] - Ion (438.9602 m / z). No metabolites of the compound from Example 1 were observed.

[0104] Plasma analysis results

[0105] The plasma of four chickens was analyzed: two were treated with fipronil, and two were treated with the compound from Example 1. Plasma samples from day 3 and day 5 were analyzed. The plasma sample from chicken 1 on day 3 was found to be unusable due to heterogeneity. The results are shown in the table below: [Table 4] [Table 5]

[0106] These results indicate that the compound in Example 1 exhibits substantially lower systemic absorption and plasma accumulation compared to fipronil.

[0107] Egg concentration analysis

[0108] A modified and optimized QuEChERS protocol was employed to extract compounds from eggs. The shells were removed manually, then each egg was transferred to a clean beaker and homogenized with a small electric mixer. 5 grams of homogenized egg were placed in a 50 mL Falcon tube, 5 mL of water was added, and the sample was shaken for 10 minutes. Next, 10 mL of acetonitrile was added, and the sample was shaken again for 10 minutes. Then, roQ salt (4.0 g MgSO4, 1.0 g NaCl, 1.0 SCTD and 0.5 g SCDS, Phenomenex P / N KS08909) was added to each sample, and the mixture was shaken well for 10 minutes. Subsequently, the samples were centrifuged at 2500 g for 5 minutes at room temperature, and the supernatant was transferred to an HPLC vial for analysis. The same HPLC-MS method as described above was used.

[0109] Egg analysis results

[0110] One egg from each of two chickens was analyzed: one chicken treated with fipronil, and the other treated with the compound from Example 1. Both eggs were 5 days old. The results are shown in the table below as relative peak areas from LC-MS: [Table 6] [Table 7]

[0111] These results indicate that the compound from Example 1 accumulates substantially less in treated chicken eggs compared to fipronil.

[0112] Antiparasitic effectiveness

[0113] To test the efficacy of the compound, live chickens infested with natural mites (Dermanyssus gallinae) were treated topically with a solution of the test compound, using fipronil as a positive control. The test solution was prepared by dissolving the test compound in a mixture of 2-butoxyethanol, ethanol, and water (7:2:1) to a final concentration of 0.25% (w / v). The test solution was sprayed onto the animals from bottom to top using a mechanical spray pump that delivered 0.5 mL of solution per operation to facilitate application and skin penetration. The dose applied to each animal was 3 mL / kg, which corresponds to 7.5 mg / kg (kg of live body weight). This dose was achieved using 6 spray operations per kg of body weight per day. This treatment was carried out once a day at 24-hour intervals for 5 days.

[0114] Two animals were treated with the compound from Example 1, two animals with fipronil, and one animal was left untreated as a negative control. Parasitism by D. gallinae was monitored by checking the density of mites in specific areas of the animal's body (feet, legs, and wings) and comparing the parasitism levels before and after treatment.

[0115] When all pests were eliminated, 100% pest control capability was achieved. For some chemical products, when pests were not completely eliminated, insecticidal capability was measured by averaging the number of parasites located in three different areas of the treated animal at the start and end of the treatment.

[0116] By the fifth day of treatment, all chickens treated with either the compound from Example 1 or fipronil were 100% mite-free. Untreated chickens (negative control) retained a similar number of mites as the initial dose.

[0117] The experiment was repeated using the compounds from Examples 2 and 3 as comparative examples. After 5 days of treatment, the mite infestation level decreased by only about 5-10%, which can be explained by a nonspecific solvent effect on mites.

[0118] Example 18: Metabolic Stability As previously discussed, phenylpyrazole insecticides are plagued by problems and concerns related to their degradation. While phenylpyrazoles such as fipronil degrade slowly in the environment, their metabolic degradation in animals is rapid. Furthermore, the major metabolites of fipronil—sulfones, sulfides, and desulfinyl derivatives—are significantly more toxic, persistent, bioaccumulative, and less selective than the parent compound. (See Leemans et al.)

[0119] Therefore, the metabolic stability of the compounds in Examples 1 and 4 is evaluated to determine whether metabolic degradation produces metabolites of concern.

[0120] In short, human cryopreserved hepatocytes (Gibco, lot HUE125) are added to the incubation wells of a 96-well assay plate in William's E medium at a density of 500,000 cells / mL. The test substrate (compound from Example 1 or 4) is added to the wells at a final concentration of 1 μM. The wells are incubated at 37°C, and stop solution is added to the wells at 0, 30, 60, 120, and 240 minutes. The stop solution is an ice-cold solution (100 μL / well) (2:1, volume / volume) containing 0.5 μM labetalol in acetonitrile. Each time point is tested in triplicate. Analysis is performed by LC-MS.

[0121] LC-MS conditions: Equipment: QExactive Column: Luna Omega 1.6 μm polar C18 100 Å(150x2.1mm) Column temperature: 40℃ Column N:102 + pre-column installed Injection volume: 2 μl Flow rate: 0.40 mL / min Polarity: Negative Eluent A: Water Milli Q + 0.1% FA Eluent B: ACN + 0.1% FA Acquisition method: DDS based on IL acquired using full scan MS + MassMetaSite (other peaks ON)

[0122] The compound from Example 1 is found to be metabolically stable. After 240 minutes, approximately 95.5% of the original compound from Example 1 (RT 11.12 min) is still present, and no specific peaks indicating metabolites are observed.

[0123] The compound of Example 4 is found to be extremely metabolically stable. After 240 minutes, approximately 84.2% of the original compound of Example 4 is still present (RT 10.65), with one major metabolite (RT 9.02, M+ 176) rising to a peak level of 1%. The apparent molecular weight of this metabolite is consistent with that of the N-glucuronide conjugate of the ketototheraper of the 2-hydroxypyridine ring.

[0124] Example 19: Acute toxicity to honeybees The effects of acute oral toxicity and acute contact toxicity of the compound in Example 1 and fipronil will be determined in adult worker bees and European honeybees (Apis mellifera L.). This study will be conducted in accordance with OECD guidelines 213 (oral toxicity) and 214 (contact toxicity) (September 1998).

[0125] In accordance with OECD Trial Guidelines Nos. 213 and 214, a trial is considered effective if: (1) the mean mortality rate of the control group at the end of the trial is 10% or less; and (2) at the end of the trial, the control-adjusted mean mortality rate of the reference group at the tested dose is 50% or more (internal efficacy criteria according to POS BT200).

[0126] Young worker European honeybees are randomly collected on the morning of or the day before use from hives containing a queen, provided with proper nutrition, and in good health and free from disease. They are not treated with chemicals. Hives are derived from colonies in established apiaries, and colonies are regularly inspected according to standard beekeeping practices. All colonies are kept outdoors under field conditions, and the bees forage for food from the environment. The last treatment for Varroa mites was performed in November 2023. The bees are freely supplied with a 50% w / v (or 500 g / L) sucrose aqueous solution prepared with tap water.

[0127] Acute oral toxicity test

[0128] Adult worker bees were exposed to three increasing doses of the test substance dispersed in a 50% (w / v) sucrose aqueous solution (see Table 1) for up to 6 hours (see Section 4.5.1).

[0129] An untreated 50% w / v sucrose solution containing 0.2% of a propanol-aqueous solution (80%-20%) is used as a negative control.

[0130] The mortality rate of the bees will be recorded at 4, 24, and 48 hours and compared to the control value. If the control mortality rate is 10% or less, but the mortality rate increases by more than 10% between 24 and 48 hours, the experiment will be extended up to a maximum of 96 hours.

[0131] Dilute the test substance with a 50% (w / v) sucrose aqueous solution to prepare an oral solution. Anesthetize the bees to be used in the oral test with carbon dioxide for the time necessary for fixation and place them in the test cages. Fast them for 2 hours before treatment. Administer 200 μL (20 μL / bee) of treated diet to each cage using a dispenser (e.g., a syringe without a tip) and weigh the contents before and after filling.

[0132] The overall exposure period is 6 hours, during which consumption is monitored. The feeder is replaced at the end of the 6 hours, or when the treated feed is consumed (usually within 3-4 hours). In either case, the feeder is weighed, and a new feeder containing untreated 50% (w / v) sucrose solution is freely provided, and the average effective dose is calculated based on actual consumption.

[0133] Acute contact toxicity test

[0134] Adult worker bees are exposed to three increasing doses of the test substance (see Table 2) by direct application to the thorax (droplets, see Section 4.5.2). In addition to the test substance group, one control group is treated with propanol-aqueous solutions (80% to 20%).

[0135] The mortality rate of the bees will be recorded at 4, 24, and 48 hours and compared to the control value. If the mortality rate increases by more than 10% between 24 and 48 hours, while the control mortality rate is 10% or less, the experiment will be extended up to a maximum of 96 hours.

[0136] Prepare a contact solution by diluting the test substance with a propanol-aqueous solution (80% to 20%).

[0137] The bees to be used for the contact test are anesthetized with carbon dioxide and treated individually by topically applying 2 μL of the test solution to their thorax using a micro-applicator. The honeybees are then moved to cages and given free access to the sucrose solution.

[0138] Experimental Design [Table 8] [Table 9]

[0139] 200cm 3 Use disposable, well-ventilated cages with an internal volume not less than [amount missing]. Each cage should have a transparent lid to allow proper observation of the bees from the outside. The top of the cage should have at least one hole for inserting a feeder, into which a syringe filled with a 50% (w / v) sucrose solution should be inserted.

[0140] The tests will be conducted under the following conditions: (a) Temperature: 25.00 ± 2.00°C; (b) Relative humidity: 60.00 ± 10.00%. Except during evaluation, the honeybees will be kept in a constant dark place. Throughout the experimental phase, temperature and relative humidity will be continuously recorded using a dedicated data logger with sensors placed near the test unit.

[0141] The test will last 48 hours. If the mortality rate in the test substance treatment group continues to rise above 10% after the first 24 hours, the test period will be extended up to a maximum of 96 hours, provided that the mortality rate in the control group does not exceed 10%.

[0142] Record the number of dead European honeybees per cage at 4, 24, and 48 hours. If an extended observation period is necessary, perform further assessments every 24 hours for up to a maximum of 96 hours. If processed feed remains after 6 hours of exposure, quantitatively estimate the feed consumption per colony.

[0143] Behavioral differences between the control group of European honeybees and the test group of European honeybees will be recorded as follows: [Table 10]

[0144] result

[0145] The data is summarized in tabular form, showing the number of survivors, deaths, and abnormal bees per experimental group. Mortality for each replicate is calculated as a percentage, comparing the number of dead bees to the number of bees introduced at baseline. The mean values ​​for the treatment groups are compared to the mean mortality rates of the respective control groups using Abbott's formula (POS BT 200), modified by Schneider-Ollelli: CM% = ((Mt-Mc) / (100-Mc)) × 100 CM=Mean adjusted mortality rate (%) Mc = Mean mortality rate of the control group (%) Mt = Mean mortality rate of the treatment group (%)

[0146] [Table 11]

[0147] [Table 12]

[0148] These results demonstrate that the compound of the present invention is substantially less toxic to European honeybees than fipronil.

[0149] The examples provided herein are illustrative and are not intended to limit in any way the various aspects and embodiments of the invention described herein.

Claims

1. The general structure is as follows: 【Chemistry 1】 Compounds that are in the form of free bodies or salts, having [In the formula, X is -N- or -CR １ - and; Y is -N- or -CR ２ - and; Z is -CR ３ - and; R １ 、 R ２ 、 and R ３ are each independently selected from H, halo, cyano, nitro, hydroxy, amino, C １～６ alkyl, C ３～６ cycloalkyl, C １～６ haloalkyl, C １～６ alkoxy, C １～６ haloalkoxy, C ３～６ cycloalkoxy, C ３～６ halocycloalkyl, NH(C １～６ alkyl), N(C １～６ alkyl)(C １～６ alkyl), and 3- to 6-membered heterocycloalkyl, and these may each be optionally substituted; Ar is a phenyl or a 5- or 6-membered heteroaryl which may be appropriately substituted with 1 to 5 R groups; R can be any of the following independently: halo, cyano, nitro, hydroxy, amino, and C. １～６ Alkyl, C ３～６ Cycloalkyl, C １～６ Haloalkyl, C １～６ Alkoxy, C １～６ Haloalkoxy, C ３～６ Halocycloalkyl, NH(C) １～６ Alkyl), N (C １～６ (Alkyl) (C １～６ Selected from alkyl groups and 3- to 6-membered heterocycloalkyl groups, each of which may be appropriately substituted.

2. X is -CR １ - and Y is -CR ２ - The compound according to claim 1.

3. The general structure is as follows: 【Chemistry 2】 The compound according to claim 1, having [In the formula, R １ , R ２ , and R are as defined in claim 1.

4. R １ However, halos (e.g., F, Cl), cyanos, C １～３ Alkyl (e.g., methyl, ethyl), and C １～３ The compound according to any one of claims 1 to 3, which is selected from haloalkyl groups (e.g., trifluoromethyl groups) and which may be appropriately substituted with each other.

5. R ２ The compound according to any one of claims 1 to 4, wherein the compound is selected from H, halo (e.g., F, Cl), and cyano.

6. R ３ However, hydroxy, amino, and NH(C) １～６ The compound according to any one of claims 1 to 5, selected from alkyl (e.g., N-methylamino), each of which may be appropriately substituted.

7. The compound according to any one of claims 1 to 6, wherein Ar is a phenyl or a 5- or 6-membered heteroaryl, which may be appropriately substituted with 1 to 5 R groups.

8. The general structure is as follows: 【Transformation 3】 The compound according to claim 1, having [wherein R is as defined in claim 1].

9. Each R independently corresponds to a halo (e.g., F, Cl, Br, I), cyano, nitro, hydroxy, or C. １～６ Haloalkyl (e.g., trifluoromethyl), C １～６ Haloalkoxys (e.g., trifluoromethoxy), and C ３～６ The compound according to any one of claims 1 to 8, selected from halocycloalkyls (e.g., 2,2-difluorocyclopropyl), each of which may be appropriately substituted.

10. The compound according to any one of claims 1 to 8, wherein Ar is selected from 2,6-dichloro-4-trifluoromethyl, 2,6-dichloro-4-trifluoromethoxy, 2,6-dichloro-4-bromo, 2,6-dichloro-4-difluoromethyl, 2,6-dichloro-4-difluoromethoxy, 2,6-dichloro-4-fluoromethyl, 2,6-dichloro-4-fluoromethoxy, 2,6-dichloro-4-methyl, 2,6-dichloro-4-methoxy, 2,4,6-trichloro, 2-chloro-4-trifluoromethoxy, 2-chloro-4-bromo, 2-chloro-4-difluoromethyl, 2-chloro-4-difluoromethoxy, 2-chloro-4-fluoromethyl, 2-chloro-4-fluoromethoxy, 2-chloro-4-methyl, 2-chloro-4-methoxy, 2,4-dichloro, and 2-chloro-4-bromo.

11. The following structure: 【Chemistry 4】 A compound of formula I, which is in the form of a free body or a salt, having the compound.

12. The following structure: 【Transformation 5】 A compound of formula I according to claim 1, having the following characteristics, in the form of a free body or a salt: [In the formula, R １ This is as defined in claim 1.

13. R １ However, halos (e.g., F, Cl), cyanos, C １～３ Alkyl (e.g., methyl, ethyl), C ３～６ Cycloalkyl (e.g., cyclopropyl), and C １～３ The compound according to claim 12, selected from haloalkyls (e.g., trifluoromethyl).

14. A compound according to claim 12, selected from the group consisting of the following, each in the form of a free body or a salt. 【Transformation 6】

15. A pharmaceutical composition or insecticide composition comprising a mixture of an effective amount of the compound according to any one of claims 1 to 14, in the form of a free body or salt, and a diluent or carrier that is pharmaceutically acceptable or insecticide-acceptable.

16. A pharmaceutical or insecticide composition comprising a mixture of an effective amount of the compound according to claim 14, in the form of a free body or salt, and a pharmaceutically acceptable or insecticide-acceptable diluent or carrier, wherein the composition is formulated for delivery by spray (e.g., liquid or aerosol spray).

17. The composition according to claim 16, wherein the composition is a solution containing a compound of formula I dissolved in 2-butoxyethanol, ethanol, and water (in a volume ratio of 7:2:1).

18. A compound or composition according to any one of claims 1 to 14, used to treat, control, suppress or eradicate infection or parasitism caused by insects (arthropods) (e.g., adults, insect eggs, insect larvae, insect nymphs, and / or insect pupae), wherein the insect may optionally be mites (Dermanyssus gallinae), and further, the compound or composition may optionally be administered to chickens, or optionally applied to chicken coops, chicken enclosures, chicken cages, other chicken enclosures, poultry farms, or chicken feed.

19. A compound or composition according to any one of claims 1 to 14, used to treat, control, suppress or eradicate infection or parasitism by insects (arthropods) (e.g., adults, insect eggs, insect larvae, insect nymphs, and / or insect pupae), wherein the insect is one or more insects selected from the group consisting of fleas, ticks, mites, lice, fire ants, termites, beetles, cockroaches, mole crickets, thrips, cutworms, and weevils.

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