Control of resistant pests

Abstract

To provide methods of controlling pesticide-resistant pests.SOLUTION: The present invention relates to methods of controlling pesticide-resistant pests, comprising exposing the pesticide-resistant pests to a compound of formula (I) or a tautomer thereof. (R1 represents -C(=O) R7 or the like; R2 represents H or the like; R3, R4, R5 and R6 each represent H, -C1-10 alkyl or the like; R7 represents H, -C1-10 alkyl or the like).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for controlling pesticide-resistant pests, comprising exposing the pesticide-resistant pests to a pest control dose of the triketone compound of formula (I). [Background technology]

[0002] Pest and disease resistance is a significant agricultural problem, and the incidence of resistance is increasing. In the 1940s, farmers in the United States lost approximately 7% of their crops to pests, a figure that rose to 13% in the 1980s and 1990s, even with the availability of more pesticides. It is estimated that up to 1,000 pest species have developed resistance to one or more pesticides since 1945.

[0003] One example is grain protectants. Grain protectants are pesticides applied to stored grains to prevent damage from harmful species such as the long-grain borer (Rhyzopertha dominica (F.)), grain weevil (Sitophilus oryzae (L.)), confused flour beetle (Tribolium castaneum (Herbst)), sawtoothed grain beetle (Oryzaephilus suranamensis (L.)), and corngrass beetle (Cryptolestes ferrugineus (Stephens)). Grain protectants have been used for decades, and now resistance is a problem. (Daglish, 2008, J Stored Products Research, 44:71-76). For example, in many Australian states, the longhorn beetle cannot be controlled by any organic phosphate or synthetic pyrethroid, and resistance to the insect growth regulator methoprene is common (Daglish, et al. 2013, J Stored Products Research, 54:71-76). Organic phosphate resistance is also common in the sawtooth beetle.

[0004] Resistance to biological agents can emerge in pests that infest agriculturally useful animals such as cattle. For example, the cattle tick is a serious pest of cattle throughout the tropical and subtropical regions of the world. Infestation causes high production losses through weight loss, reduced milk yield, and skin damage. Cattle ticks can also transmit tick-borne fevers such as Babesia and Anaplasma, which can cause high morbidity among susceptible animals.

[0005] Tick ​​control is typically carried out using integrated pest control systems that employ more than one type of biological agent. However, to reduce the development of resistance, a wider range of options for biological agents is needed, particularly those with different mechanisms of action.

Disclosure of the Invention

[0006] The present invention is at least partially based on the discovery that flavones, potassium channel activators, are effective in controlling pesticidal-resistant pests, particularly agriculturally important pests that exhibit resistance to commonly used pesticides, such as stored grain pests and cattle ticks and flies.

[0007] Summary of the Invention In one aspect of the present invention, there is provided a method for controlling pesticidal-resistant pests, the method comprising contacting the pesticidal-resistant pests with a compound of formula (I)

[0008]

Chemical formula

[0009] In another embodiment of the present invention, a method for treating or preventing pest infestation or infection in livestock animals or companion animals, wherein the animal is given formula (I)

[0010] [ka] (In the formula, R1 is -C(=O)R7, -OR8, -SR8, -C 1~10 Hydroxyalkyl, -NR9R 10 Selected from -C(=N-R9)R7, -C(=N-OH)R7, -NO, -NO2, -N(OR8)R7, and -OSO3R8; R2 is hydrogen, -C 1~10 Alkyl, -C 2~10 Selected from alkenyls, aryls, and heteroaryls; R3, R4, R5, and R6 are hydrogen, -C 1~10 Alkyl, -C 3~6 Cycloalkyl, -C 2~10 Alkenyl, -C 1~10 Haloalkyl, -C 1~10 Dihaloalkyl, -C 1~10 Trihaloalkyl, -OR8, -SR8, -NR9R 10 , -(C=N-R9)R7, -NO, -NO2, -NR9OR8, -OSO3R8, -C 1~10 Independently selected from alkylaryl and -C(=O)R7; R7 is hydrogen, -C 1~10 Alkyl, -C 2~10 Alkylaryl, C 3~6 Cycloalkyl, -C 2~10 Alkenyl, -C 1~10 Alkyl heteroaryl, -C 1~10 Haloalkyl, -C 1~10 Dihaloalkyl, -C 1~10 Trihaloalkyl, -C 1~10 Haloalkoxy, -C 1~10Hydroxyalkyl, -C 1~10 Thioalkyl, -C 1~10 Nitroalkyl, -C 1~3 Alkyl OC 1~3 Alkyl, -C 1~3 Alkyl OC 1~3 Haloalkyl, -C 1~3 Alkyl OC 1~3 Dihaloalkyl, -C 1~3 Alkyl OC 1~3 Trihaloalkyl, -OR8, -SR8 and -NR9R 10 selected from; R8 is hydrogen, -C 1~10 alkyl, -C 2~10 alkylaryl, -C 3~6 cycloalkyl, -C 2~10 alkenyl, -C 1~10 alkylheteroaryl, -C 1~10 haloalkyl, -C 1~10 dihaloalkyl, -C 1~10 trihaloalkyl, -C 1~10 haloalkoxy, -C 1~10 hydroxyalkyl, -C 1~10 thioalkyl and -C 1~10 nitroalkyl selected from; R9 and R 10 are hydrogen, -C 1~10 alkyl, -C 2~10 alkylaryl, -C 3~6 cycloalkyl, -C 2~10 alkenyl, -C 1~10 alkylheteroaryl, -C 1~10 haloalkyl, -C 1~10 dihaloalkyl, -C 1~10 independently selected from trihaloalkyl) comprising administering an effective amount of a compound of or a tautomer thereof; A method is provided wherein pest infestation is caused by a population of pests including pesticide-resistant pests.

[0011] In yet another aspect of the invention, a method of controlling a population of pests, the formula (I)

[0012] [ka] (In the formula, R1 is -C(=O)R7, -OR8, -SR8, -C 1~10 Hydroxyalkyl, -NR9R 10 Selected from -C(=N-R9)R7, -C(=N-OH)R7, -NO, -NO2, -N(OR8)R7, and -OSO3R8; R2 is hydrogen, -C 1~10 Alkyl, -C 2~10 Selected from alkenyls, aryls, and heteroaryls; R3, R4, R5, and R6 are hydrogen, -C 1~10 Alkyl, -C 3~6 Cycloalkyl, -C 2~10 Alkenyl, -C 1~10 Haloalkyl, -C 1~10 Dihaloalkyl, -C 1~10 Trihaloalkyl, -OR8, -SR8, -NR9R 10 , -C(=N-R9)R7, -NO, -NO2, -NR9OR8, -OSO3R8, -C 1~10 Independently selected from alkylaryl and -C(=O)R7; R7 is hydrogen, -C 1~10 Alkyl, -C 2~10 Alkylaryl, C 3~6 Cycloalkyl, -C 2~10 Alkenyl, -C 1~10 Alkyl heteroaryl, -C 1~10 Haloalkyl, -C 1~10 Dihaloalkyl, -C 1~10 Trihaloalkyl, -C 1~10 Haloalkoxy, -C 1~10 Hydroxyalkyl, -C 1~10 Thioalkyl, -C 1~10 Nitroalkyl, -C 1~3 Alkyl OC 1~3 Alkyl, -C 1~3 Alkyl OC 1~3 Haloalkyl, -C 1~3 Alkyl OC 1~3Dihaloalkyl, -C 1~3 Alkyl OC 1~3 Trihaloalkyl, -OR8, -SR8, and -NR9R 10 Selected from; R8 is hydrogen, -C 1~10 Alkyl, -C 2~10 Alkylaryl, -C 3~6 Cycloalkyl, -C 2~10 Alkenyl, -C 1~10 Alkyl heteroaryl, -C 1~10 Haloalkyl, -C 1~10 Dihaloalkyl, -C 1~10 Trihaloalkyl, -C 1~10 Haloalkoxy, -C 1~10 Hydroxyalkyl, -C 1~10 Thioalkyl and -C 1~10 Selected from nitroalkyl groups; R9 and R 10 is hydrogen, -C 1~10 Alkyl, -C 2~10 Alkylaryl, -C 3~6 Cycloalkyl, -C 2~10 Alkenyl, -C 1~10 Alkyl heteroaryl, -C 1~10 Haloalkyl, -C 1~10 Dihaloalkyl, -C 1~10 (Selected independently from trihaloalkyls) This includes applying the compound or its tautomers to an environment in which a population of harmful organisms is or is likely to be parasitized or spread; A method is provided for controlling pest populations, including pests resistant to pesticides.

[0013] In a further embodiment of the present invention, a method for protecting a storage plant portion from pest infestation, wherein the plant portion is subjected to formula (I)

[0014] [ka] (In the formula, R1 is -C(=O)R7, -OR8, -SR8, -C 1~10Hydroxyalkyl, -NR9R 10 Selected from -C(=N-R9)R7, -C(=N-OH)R7, -NO, -NO2, -N(OR8)R7, and -OSO3R8; R2 is hydrogen, -C 1~10 Alkyl, -C 2~10 Selected from alkenyls, aryls, and heteroaryls; R3, R4, R5, and R6 are hydrogen, -C 1~10 Alkyl, -C 3~6 Cycloalkyl, -C 2~10 Alkenyl, -C 1~10 Haloalkyl, -C 1~10 Dihaloalkyl, -C 1~10 Trihaloalkyl, -OR8, -SR8, -NR9R 10 , -C(=N-R9)R7, -NO, -NO2, -NR9OR8, -OSO3R8, -C 1~10 Independently selected from alkylaryl and -C(=O)R7; R7 is hydrogen, -C 1~10 Alkyl, -C 2~10 Alkylaryl, C 3~6 Cycloalkyl, -C 2~10 Alkenyl, -C 1~10 Alkyl heteroaryl, -C 1~10 Haloalkyl, -C 1~10 Dihaloalkyl, -C 1~10 Trihaloalkyl, -C 1~10 Haloalkoxy, -C 1~10 Hydroxyalkyl, -C 1~10 Thioalkyl, -C 1~10 Nitroalkyl, -C 1~3 Alkyl OC 1~3 Alkyl, -C 1~3 Alkyl OC 1~3 Haloalkyl, -C 1~3 Alkyl OC 1~3 Dihaloalkyl, -C 1~3 Alkyl OC 1~3 Trihaloalkyl, -OR8, -SR8, and -NR9R 10 Selected from; R8 is hydrogen, -C 1~10 Alkyl, -C 2~10Alkylaryl, -C 3~6 Cycloalkyl, -C 2~10 Alkenyl, -C 1~10 Alkyl heteroaryl, -C 1~10 Haloalkyl, -C 1~10 Dihaloalkyl, -C 1~10 Trihaloalkyl, -C 1~10 Haloalkoxy, -C 1~10 Hydroxyalkyl, -C 1~10 Thioalkyl and -C 1~10 Selected from nitroalkyl groups; R9 and R 10 is hydrogen, -C 1~10 Alkyl, -C 2~10 Alkylaryl, -C 3~6 Cycloalkyl, -C 2~10 Alkenyl, -C 1~10 Alkyl heteroaryl, -C 1~10 Haloalkyl, -C 1~10 Dihaloalkyl, -C 1~10 (Selected independently from trihaloalkyls) This includes contacting the compound or its tautomers, A method is provided for pest infestation, which is caused by a population of pests, including pesticide-resistant pests.

[0015] Detailed description of the invention Unless otherwise defined, all technical and chemical terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention pertains. Any methods and materials similar to or equivalent to those described herein may be used in the practice or testing of the present invention, but preferred methods and materials are described. For the purposes of the present invention, the following terms are defined below.

[0016] The articles “a” and “an” are used herein to refer to one or more (i.e., at least one) grammatical objects of a part of speech. For example, “element” means one element or more than one element.

[0017] As used herein, the term “about” means a quantity, level, value, dimension, size, or amount that varies by approximately 30%, 25%, 20%, 15%, or 10% from the quantity, level, value, dimension, size, or amount of reference.

[0018] Unless otherwise required by the context through clear language or necessary implication, the word “comprise” or variations such as “comprises” or “comprising” shall be used in an inclusive sense, that is, to identify the presence of the specified features, without precluding the presence or addition of further features in the various embodiments of the present invention.

[0019] Where any prior art publication is referenced herein, such reference should be understood not to constitute an endorsement that the publication forms part of the common general knowledge in the art in Australia or any other country.

[0020] As used herein, the term “combination” refers to a compound of formula (I) and at least one second pesticide used simultaneously or sequentially in a single or separate composition, such that the biological activities of each compound overlap or manifest simultaneously in insects.

[0021] As used herein, the term "control" means to eliminate, eradicate or destroy a pest, including preventing the infestation or spread of a pest, repelling a pest from the environment, increasing the mortality rate of a pest, or inhibiting the growth and / or development of a pest, or to prevent the reproduction of a pest.

[0022] As used herein, the term “environment” means an environment in which a compound of formula (I) may be applied to ensure that a pest-resistant organism is exposed to the compound, or an environment in which a compound of formula (I) may be applied because of the possibility of parasitism or spread by a pest-resistant organism. The environment may be an agricultural environment, a domestic environment, an industrial environment, or another environment that is or potentially is a habitat for a pest-resistant organism. An agricultural environment may be an environment for growing commercially important crops, trees or other plants that may be susceptible to parasitism or spread by a pest-resistant organism. An agricultural environment may be an environment for growing commercially important crops, trees or other plants that may be susceptible to parasitism or spread by a pest-resistant organism. An agricultural environment may be an environment in which commercially important livestock animals are kept, for example, pastures, barns, holding pens or milking parlors. Domestic environments include environments in which humans or animals, such as companion animals, reside, and can include indoor environments such as carpets, curtains, cupboards, beds and bedding, animal beds or blankets, or indoor air. Domestic environments can also include outdoor environments such as gardens or animal shelters such as rabbit hutches or dog houses. Industrial environments include environments used for industrial purposes, such as the manufacture, storage, or sale of products. Industrial environments include warehouses, manufacturing facilities, shops, and storage facilities, including pet shops, plant nurseries, and grain storage facilities. Other environments include leisure areas such as parks, stadiums, and exhibition halls, or bodies of water such as rivers, lakes, ponds, or other places where water collects, moves slowly, or stagnates.

[0023] As used herein, the term “alkyl” refers to a linear or branched saturated hydrocarbon group having one to ten carbon atoms. Where appropriate, an alkyl group may have a specific number of carbon atoms, for example, an alkyl group having one, two, three, four, five, or six carbon atoms in a linear or branched arrangement. 1~6It is an alkyl group. Suitable alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, n-pentyl, 2-methylbutyl, 3-methylbutyl, 4-methylbutyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 5-methylpentyl, 2-ethylbutyl, 3-ethylbutyl, heptyl, octyl, nonyl, and decyl.

[0024] As used herein, the term “alkenyl” refers to a linear or branched hydrocarbon group having two to ten carbon atoms and one or more double bonds between carbon atoms. Where appropriate, an alkenyl group may have a specific number of carbon atoms. For example, the C2-C6 in “C2-C6 alkenyl” may be a group having two, three, four, five, or six carbon atoms in a linear or branched arrangement. Examples of suitable alkenyl groups include, but are not limited to, ethenyl, propenyl, isopropenyl, butenyl, butadienyl, pentenyl, pentadienyl, hexenyl, hexadienyl, heptenyl, octenyl, nonenyl, and decenyl.

[0025] As used herein, the term "cycloalkyl" refers to a saturated cyclic hydrocarbon. A cycloalkyl ring can contain a specific number of carbon atoms. For example, a 3-membered to 6-membered cycloalkyl group contains 3, 4, 5, or 6 carbon atoms. Suitable examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0026] As used herein, the term “aryl” is intended to mean any stable monocyclic, bicyclic, or tricyclic carbocyclic system with up to seven atoms in each ring, where at least one ring is aromatic. Examples of such aryl groups include, but are not limited to, phenyl, naphthyl, tetrahydronaphthyl, indanyl, fluorenyl, phenantrenyl, biphenyl, and binaphthyl.

[0027] The term "heteroaryl," as used herein, refers to a stable monocyclic, bicyclic, or tricyclic ring having up to seven atoms in each ring, where at least one ring is aromatic and at least one ring contains one to four heteroatoms selected from the group consisting of O, N, and S. Heteroaryl groups within the scope of this definition include, but are not limited to, acridinyl, carbazolyl, synnolinyl, quinoxalinyl, quinazolinyl, pyrazolyl, indolyl, isoindolyl, 1H,3H-1-oxoisoindolyl, benzotriazolyl, furanyl, thienyl, thiophenyl, benzothienyl, benzofuranyl, benzodioxane, benzodioxin, quinolinyl, isoquinolinyl, oxazo Examples include lyl, isoxazolyl, imidazolyl, pyrazinyl, pyridadinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrahydroquinolinyl, thiazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3,5-triazinyl, 1,2,4-triazinyl, 1,2,4,5-tetradinyl, and tetrazolyl. Specific heteroaryl groups have a 5-membered or 6-membered ring, such as pyrazolyl, furanyl, thienyl, oxazolyl, indolyl, isoindolyl, 1H,3H-1-oxoisoindolyl, isoxazolyl, imidazolyl, pyrazinyl, pyridadinyl, pyridinyl, pyrimidinyl, pyrrolyl, thiazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, and 1,2,4-oxadiazolyl and 1,2,4-thiadiazolyl.

[0028] The term "haloalkyl," as used herein, refers to an alkyl group in which one or more hydrogen atoms of the alkyl group are replaced by a halo atom. Where appropriate, an alkyl group may have a specific number of carbon atoms, for example, a haloalkyl group having one, two, three, four, five or six carbon atoms in a linear or branched arrangement. 1~6These are haloalkyls. Examples of haloalkyls include fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 1,1-difluoroethyl, 2,2-fluoroethyl, 1,1,2-trifluoroethyl, 2,2,2-trifluoroethyl, 3-fluoropropyl, 3,3-difluoropropyl, 3,3,3-trifluoropropyl, 4-fluorobutyl, 4,4-difluorobutyl, 4,4,4-trifluorobutyl, 5-fluoropentyl, 5,5-difluoropentyl, 5,5,5-trifluoropentyl, 6-fluorohexyl, 6,6-difluorohexyl or 6,6,6-trifluorohexyl, chloromethyl, dichloromethyl, trichloromethyl, 1-chloroethyl, 2-chloroethyl, 1,1-dichloroethyl, 2,2-chloroethyl, 1,1,2-trichloroethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 3,3-dichloro Ropropyl, 3,3,3-trichloropropyl, 4-chlorobutyl, 4,4-dichlorobutyl, 4,4,4-trichlorobutyl, 5-chloropentyl, 5,5-dichloropentyl, 5,5,5-trichloropentyl, 6-chlorohexyl, 6,6-dichlorohexyl or 6,6,6-trichlorohexyl, bromomethyl, dibromomethyl, tribromomethyl, 1-bromoethyl, 2-bromoethyl, 1,1-dibromoethyl, 2,2-dibromethyl Examples include bromoethyl, 1,1,2-tribromoethyl, 2,2,2-tribromoethyl, 3-bromopropyl, 3,3-dibromopropyl, 3,3,3-tribromopropyl, 4-bromobutyl, 4,4-dibromobutyl, 4,4,4-tribromobutyl, 5-bromopentyl, 5,5-dibromopentyl, 5,5,5-tribromopentyl, 6-bromohexyl, 6,6-dibromohexyl, or 6,6,6-tribromohexyl.

[0029] As used herein, "halo" refers to fluoro, chloro, bromo, and iodine.

[0030] The terms "hydroxyalkyl," "thioalkyl," and "nitroalkyl" refer to alkyl groups as defined above, in which one hydrogen atom is replaced by a hydroxyl group, a thiol group, or a nitro group, respectively.

[0031] As used herein, the term "alkoxy" refers to an oxygen substituent that is substituted with an alkyl group as defined above. Suitable examples of alkoxy groups include, but are not limited to, -OCH3, -OCH2CH3, -O(CH2)2CH3, -OCH(CH3)2, -O(CH2)3CH3, -OCH2CH(CH3)2, -OC(CH3)3, -O(CH2)4CH3, and -O(CH2)5(CH3).

[0032] The compound of formula (I) can exist in numerous tautomer forms. For example, tautomerism is shown in the following scheme:

[0033] [ka]

[0034] All such tautomer structures are intended to fall within the scope of formula (I).

[0035] Compounds relating to formula (I) may also exist in stereoisomeric form. These compounds may be enantiomers or diastereomers and may exist as individual isomers or in the form of a mixture including a racemic mixture.

[0036] The term "chemical agent-resistant pest" refers to pests such as insects or spiders that have developed resistance to one or more chemical agents previously used to control them. Chemical agent-resistant pests can exist within a pest population. For example, the Tialo strain of the tick *Haemaphysalis microplus* has a resistance profile of approximately 30% fluazuron, 60.6% cypermethrin, 57.6% flumetholone, 16.2% amitraz (amidine), 11.3% DDT, 9.3% chlorpyrifos, and 2.4% dieldrin.

[0037] Method of the present invention In one embodiment, the present invention is a method for controlling pests resistant to a pesticide, wherein the pest resistant to a pest is controlled by formula (I):

[0038] [ka] (In the formula, R1 is -C(=O)R7, -OR8, -SR8, -C 1~10 Hydroxyalkyl, -NR9R 10 Selected from -C(=N-R9)R7, -C(=N-OH)R7, -NO, -NO2, -N(OR8)R7, and -OSO3R8; R2 is hydrogen, -C 1~10 Alkyl, -C 2~10 Selected from alkenyls, aryls, and heteroaryls; R3, R4, R5, and R6 are hydrogen, -C 1~10 Alkyl, -C 3~6 Cycloalkyl, -C 2~10 Alkenyl, -C 1~10 Haloalkyl, -C 1~10 Dihaloalkyl, -C 1~10 Trihaloalkyl, -OR8, -SR8, -NR9R 10 , -C(=N-R9)R7, -NO, -NO2, -NR9OR8, -OSO3R8, -C 1~10 Independently selected from alkylaryl and -C(=O)R7; R7 is hydrogen, -C 1~10 Alkyl, -C 2~10 Alkylaryl, C 3~6 Cycloalkyl, -C 2~10 Alkenyl, -C 1~10 Alkyl heteroaryl, -C 1~10 Haloalkyl, -C 1~10 Dihaloalkyl, -C 1~10 Trihaloalkyl, -C 1~10 Haloalkoxy, -C 1~10 Hydroxyalkyl, -C 1~10 Thioalkyl, -C 1~10 Nitroalkyl, -C 1~3 Alkyl OC 1~3 Alkyl, -C 1~3 Alkyl OC 1~3 Haloalkyl, -C 1~3 Alkyl OC 1~3 Dihaloalkyl, -C 1~3 Alkyl OC 1~3 Trihaloalkyl, -OR8, -SR8, and -NR9R 10 Selected from; R8 is hydrogen, -C 1~10 Alkyl, -C 2~10 Alkylaryl, -C 3~6 Cycloalkyl, -C 2~10 Alkenyl, -C 1~10 Alkyl heteroaryl, -C 1~10 Haloalkyl, -C 1~10 Dihaloalkyl, -C 1~10 Trihaloalkyl, -C 1~10 Haloalkoxy, -C 1~10 Hydroxyalkyl, -C 1~10 Thioalkyl and -C 1~10 Selected from nitroalkyl groups; R9 and R 10 is hydrogen, -C 1~10 Alkyl, -C 2~10 Alkylaryl, -C 3~6 Cycloalkyl, -C 2~10 Alkenyl, -C 1~10 Alkyl heteroaryl, -C 1~10 Haloalkyl, -C 1~10 Dihaloalkyl, -C 1~10(Selected independently from trihaloalkyls) The present invention provides a method comprising exposure to a compound or its tautomers.

[0039] In some embodiments, the compound of formula (I) is of formula (II).

[0040] [ka] (In the formula, R 11 -CR 12 R 13 R 14 or -NR 15 R 16 Selected from; R 12 and R 13 One is hydrogen, and the other is hydroxyl or -OCR 17 R 18 R 19 is or R 12 and R 13 They combine to form an oxo group (=O) or an =N-OH group; R 14 is -CH(CH3)CR 20 R 21 R 22 -CH2CH(CH3)CR 20 R 21 R 22 or -CH(CH3)CH2CR 20 R 21 R 22 and; R 15 and R 16 is hydrogen and C 1~10 Selected independently of alkyl; R 17 , R 18 and R 19 It is selected independently of hydrogen or halo; R 20 , R 21 and R 22 is hydrogen, hydroxyl, halo, NO2 and --OCR 17 R 18R 19 (Selected independently of) It is a compound of or a tautomer of the compound.

[0041] In some embodiments, the compound of formula (I) is of formula (III):

[0042] [ka] (In the formula, R 23 and R 24 One is hydrogen, and the other is hydroxyl or -OCR 27 R 28 R 29 is or R 23 and R 24 They combine to form an oxo group (=O); R 25 -CR 30 R 31 R 32 -CH2CR 30 R 31 R 32 or -CH(CH3)CR 30 R 31 R 32 and; R 26 is H or -CH3; where R 26 If H, then R 25 -CH(CH3)CR 30 R 31 R 32 and; R 27 , R 28 and R 29 It is selected independently of hydrogen or halo; R 30 , R 31 and R 32 (This is independently selected from hydrogen, hydroxyl, halo, NO2, and -OCR5R6R7) It is a compound of or a tautomer of the compound.

[0043] In some embodiments, the compound of formula (I) is as follows:

[0044] [ka]

[0045] [ka]

[0046] [ka] or selected from its tautomers.

[0047] In certain embodiments, the compound of formula (I) is flavesone(1-isobutyroyl-3,3,5,5-tetramethylcyclohexane-2,4,6-trione):

[0048] [ka] Leptosperm (1-valeroyl-3,3,5,5-tetramethylcyclohexane-2,4,6-trione):

[0049] [ka] Or isoleptospermone (1-isovaleroyl-3,3,5,5-tetramethylcyclohexane-2,4,6-trione):

[0050] [ka] Selection is particularly based on Flavesson's selection criteria.

[0051] The compound of formula (I) can be isolated from oil-producing trees, such as trees from the Myrtaceae family, such as Leptospermum scoparium, Eucalyptus grandis, or Eucalyptus cloeziana, especially Leptospermum scoparium.

[0052] In other embodiments, the compound of formula (I) can be prepared synthetically, for example, as described in the pamphlet International Publication No. 2002 / 089587. In one method, 1,3,5-trihydroxybenzene is prepared as shown in Scheme 1:

[0053] [ka] As shown, it can be reacted with RCN in the presence of zinc chloride (Blatt, Org. Synth. Col 11, 1943, 522-523).

[0054] 1-acyl-3,3,5,5-tetramethyl-2,4,6-cyclohexatrione is obtained by slowly adding methyl iodide anhydrous (6 equivalents) to 1-acyl-2,4,6-trihydroxybenzene (1 equivalent) and sodium ethoxide (6 equivalents) in anhydrous methanol, as shown in Scheme 2 (U.S. Patent No. 4,202,840).

[0055] [ka]

[0056] The effective dose of the compound of formula (I) depends on whether the compound is applied to the pest itself, the environment, or to livestock or companion animals or plant parts, and also depends on the uniqueness of the pesticide-resistant pest. Typically, the effective dose falls within the range of 0.1 ppm to about 500,000 ppm, particularly 1 ppm to 200,000 ppm or 1 ppm to 100,000 ppm. In some embodiments in which pests are directly exposed to the compound of formula (I), the effective dose may fall within the range of 10 ppm to 10,000 ppm, or 100 ppm to 10,000 ppm, or 100 ppm to 5,000 ppm, particularly 300 ppm to 5,000 ppm, or 500 ppm to 5,000 ppm, and even more particularly 800 ppm to 2,500 ppm, or 900 ppm to 2,000 ppm. In some embodiments, the effective amount may be between 100 ppm and 1000 ppm, for example, between 200 ppm and 800 ppm, or between 300 ppm and 600 ppm. In other embodiments, the effective amount may be between 600 ppm and 5000 ppm, particularly between 1000 ppm and 2500 ppm. In some embodiments, the effective amount is between 20 ppm and 100 ppm, particularly between 25 ppm and 80 ppm. The effective amount applied to the environment, such as grain in a grain storage facility, may be in the range of 20 ppm to 100 ppm, particularly between 50 ppm and 100 ppm.

[0057] In some embodiments, the pest is an insect resistant to one or more insecticides. In other embodiments, the pest is a spider resistant to one or more arachnoids. In some embodiments, the pest is a population of insects including insects resistant to one or more insecticides, or a population of spiders including spiders resistant to one or more arachnoids.

[0058] Examples of insects or groups of insects that are resistant to one or more insecticides include the following: (a) From the order Lepidoptera, for example, Adoxophyes orana, Agrotis ipsilon, Agrotis segetum, Alabama argillacea, Anticarsia gemmatalis, Argyresthia conjugella, Autographa gamma, Cacoecia murinana, Capua reticulana, Choristoneura fumiferana, Chilo partellus, Choristoneura occidentalis, Cirphis unipuncta), Cnaphalocrocis medinalis, Crocidolomia binotalis, Cydia pomonella, Dendrolimus pini, Diaphania nitidalis, Diatraea grandiosella, Earias insulana, Elasmopalpus lignosellus, Eupoecilia ambiguella, Feltia subterranea, Grapholitha funebrana, Grapholitha molesta, Heliocoverpa armigera, Heliocoverpa virecens Virescens), Heliocoverpa zea, Hellula undalis, Hibernia defoliaria, Hypliantriacunea), apple moth (Hyponomeuta malinellus), Keiferia lycopersicella, Lambdina fiscellaria, white-striped armyworm (Laphygma exigua), Leucoptera scitella, Lithocolletis blancardella, Lobesia botrana, helicopter moth (Loxostege sticticalis), gypsy moth (Lymantria dispar), nonne snail (Lymantria monacha), peach leaf miner (Lyonetia clerkella), tobacco hawk moth (Manduca sexta), banded gypsy moth (Malacosoma neustria), armyworm (Mamestra) brassicae), Mocis repanda, Operophthera brumata, Orgyia pseudotsugata, Ostrinia nubilalis, Pandemis heparana, Panolis flamnea, Pectinophora gossypiella, Phthorimaea operculella, Phyllocnistis citrella, Pieris brassicae, Plathypena scabra, Platynota stultana, Plutella xylostella, Prays citri citri), Prays oleae, Prodenia sunia, Prodenia ornithogalli, Pseudoplusia includens, Rhyacionia fulstranafrustrana), Scrobipalpula absoluta, rice armyworm (Sesamia inferens), tortrix moth (Sparganothis pilleriana), armyworm (Spodoptera frugiperda), Spodoptera littoralis, beet armyworm (Spodoptera litura), Syllepta derogata, Synanthedon myopaeforinis, pine leafminer (Thaumatopoea pityocampa), Tortrix viridana, nettle moth (Trichoplusia ni), dike moth (Tryporyza) *Incertulas* and *Zeiraphera canadensis*, as well as *Galleria mellonella*, *Sitotroga cerealella*, *Ephestia cautella*, and *Tineola bisselliella*; (b) From the order Coleoptera (beetles), for example, the Mexican cotton weevil (Anthonomus grandis), the pear flower weevil (Anthonomus pomorum), Apion vorax, Atomaria linearis, the horned katydid (Blastophagus piniperda), the tortoise beetle (Cassida nebulosa), Cerotoma trifurcata, Ceuthorhynchus assimilis, Ceuthorhynchus napi, Chaetocnema tibialis, Connoderus vespertinus, and Crioceris asparagi. asparagus), Cryptolestes ferrugineus, Dendroctonus rufipennis, Diabrotica longicornis, Diabrotica punctata, Diabrotica virgifera, Epilachna varivestis, Epitrix hirtipennis, Eutinobothrus brasiliensis, Hylobius abietis, Hypera brunneipennis, Hypera postica, Ips Lema bilineata, Lema melanopus, Colorado leaf beetle (Leptinotarsa ​​decemlineata), Limonius californicus, rice water weevil (Lissorhoptrus oryzophilus), melanotus...Melanotus communis, Melighethes aeneus, Melolontha hippocastani, European powder beetle (Melolontha melolontha), Oulema oryzae, Otiorhynchus sulcatus, Otiorhynchus ovatus, Phaedon cochleariae, Phyllopertha horticola, Phyllophaga species, Phyllotreta chrysocephala, Phyllotreta nemorum nemorum), striped flea beetle (Phyllotreta striolata), bean beetle (Popillia japonica), Psylliodes napi, Scolytus intricatus and Sitona lineatus, as well as broad bean weevil (Bruchus rufimanus), bean weevil (Bruchus pisorum), Bruchus lentis, granary weevil (Sitophilus granarius), cigarette beetle (Lasioderma serricorne), sawtoothed beetle (Oryzaephilus surinamensis), long-horned beetle (Rhyzopertha dominica), grain weevil (Sitophilus oryzae), confused flour beetle (Tribolium castaneum), carpet beetle (Trogoderma granarium), and Brazilian bean weevil (Zabrotes subfasciatus); (c) From the order Diptera, for example, Anastrepha ludens, Mediterranean fruit fly (Ceratitis capitata), Contarinia sorghicola, melon fly (Dacus cucurbitae), olive fly (Dacus oleae), Dasineura brassicae, Delia coarctata, Delia radicum, Hydrellia griseola, Hyleniyia platura, Liriomyza sativae, bean leafminer (Liriomyza (trifolii), Mayetiola destructor, Orseolia oryzae, Oscinella frit, Pegomya hyoscyami, Phorbia antiqua, Phorbia brassicae, Phorbia coarctata, Rhagoletis cerasi and Rhagoletis pomonella, as well as Aedes aegypti, Aedes vexans, Aedes albopictus, Anopheles maculipennis, and Chrysomya bezziana), American pygmy flies (Cochliomyia hominivorax), Chrysomya macellaria, man-eating flies (Cordylobia anthropophaga), Culex pipiens, Fannia canicularis, horse flies (Gasterophilus intestinalis), Glossina morcitans* morsitans*, * Haematobia irritans*, * Haplodiplosis equestris*, * Hypoderma lineata*, * Lucilia cuprina*, * Lucilia sericata*, * Musca domestica*, * Muscina stabulans*, * Oestrus ovis*, * Tabanus bovinus*, and * Simulium damnosum*; (d) From the order Thysanoptera, for example, Frankliniella fusca, Frankliniella occidentalis, Frankliniella tritici, Haplothrips tritici, Heliothirips haemorrhoidalis, Scirtothrips citri, Thrips oryzae, Thrips palmi, and Thrips tabaci; (e) From the order Hymenoptera, for example, the turnip sawfly (Athalia rosae), Atta cephalotes, Atta sexdens, Atta texana, Hoplocampa minuta, Hoplocampa testudinea, Iridomyrmex humilis, Iridomyrmex purpureus, house ant (Monomorium pharaonis), Solenopsis geminata, red imported fire ant (Solenopsis invicta), Solenopsis licteri richteri) and Technomyrmex albipes; (f) From the order Heteroptera (suborder Heteroptera), for example, Acrosternum hilare, Blissus leucopterus, Cyrtopeltis notatus, Dysdercus cingulatus, Dysdercus intermedius, Eurygaster integriceps, Euschistus ictericus, Leptoglossus phyllopus, Lygus hesperus, Lygus lineolaris, Lygus pratensis *Tyrantha pratensis*, *Mormidea pictiventris*, *Nezara viridula*, *Piesma quadrata*, *Solubea insularis*, and *Thyanta perditor*;(g) From the order Homoptera, for example, Acyrthosiphon onobrychis, pea aphid (Acyrthosiphon pisum), Adelges laricis, Aonidiella aurantii, Aphidula nasturtii, bean aphid (Aphis fabae), cotton aphid (Aphis gossypii), Aphis pomi, potato aphid (Aulacorthum solani), tobacco whitefly (Bemisia tabaci), Brachycaudus cardui), radish aphid (Brevicoryne brassicae), Dalbulus maidis, Dreyfusia nordmannianae, Dreyfusia piceae, Dysaphis radicola, Empoasca fabae, Eriosorna lanigerum, small brown planthopper (Laodelphax striatella), Macrosiphum avenae, Macrosiphun euphorbiae, Macrosiphon rosae, Megoura Viciae), Metopolophium dirhodum, Peach aphid (Myzus persicae), Myzus cerasi, Leafhopper (Nephotettix cincticeps), Brown planthopper (Nilaparvata lugens), Perkinsiella saccharicida, Phorodon humuli, Psylla serrulatamali), Psylla pyri, Psylla pyricola, Rhopalosiphum maidis, Schizaphis graminum, Sitobion avenae, Sogatella furcifera, Toxoptera citricida, Trialeurodes abutilonea, Trialeurodes vaporariorum, and Viteus vitifoliae; (h) From the order Isoptera, for example, Kalotermes flavicollis, Coptotermes species, Leucotermes flavipes, Macrotermes subhyalinus, Macrotermes darwiniensis, Mastotermes species, Microtermes species, Nasutitermes species, for example, Nasutitermes walkeri, Odontotermes formosanus, Reticulitermes lucifugus, and Termes natalensis; (i) From the order Orthoptera, for example, Grillotalpa gryllotalpa, Locusta migratoria, Melanoplus bivittatus, Melanoplus femurrubrum, Melanoplus mexicanus, Melanoplus sanguinipes, Melanoplus spretus, Nomadacris septemfasciata, Schistocerca americana, Schistocerca peregrina (Peregrina), Stauronotus maroccanus and desert locust (Schistocerca gregaria), as well as European house cricket (Acheta domesticus), Eastern cockroach (Blatta orientalis), German cockroach (Blattella germanica) and American cockroach (Periplaneta americana); (j) From the order Phthiraptera of lice, for example, the order Mallophaga, e.g., the genus Damalina, and the suborder Anoplura, e.g., the genera Linognathus and Haematopinus; (k) From the order Hemiptera of the Hemiptera, for example, the genera Aphis, Bemnisia, Phorodon, Aeneolamia, Empoasca, Perkinsiella, Pyrilla, Aonidiella, Coccus, Pseudococcus, and Helopeltis. , stink bugs (Lygus), Dysdercus, Oxycarenus, Nezara, Aleyrodes, Triatoma, Psylla, Myzus, Megoura, Phylloxera, Adelges, Nilaparvata, Nephotettix or Cimex; (l) From the order Siphonaptera, for example, the genera Ctenocephalides or Pulex; (m) From the order Thysanura, for example, the genus Lepisina; (n) From the order Dermaptera, for example, the genus Forficula; Furthermore (o) From the order Psocoptera, which includes booklice, for example, the genus Peripsocus.

[0059] Insects may develop resistance to one or more insecticides commonly used to control them before resistance develops. For example, insects may develop resistance to one or more insecticides selected from the following: (i) Sodium channel modulators, e.g., pyrethroids, DDT, and methoxychloride. Suitable pyrethroids include acrinatrin, allethrin, bifenthrin, bioallethrin, bioallethrin-S-cyclopentyl, biorethmetrin, cycloprothrin, cyfluthrin, β-cyfluthrin, cyhalothrin, γ-cyhalothrin, λ-cyhalothrin, cypermethrin, α-cypermethrin, β-cypermethrin, θ-cypermethrin, ζ-cypermethrin, cyphenothrin, deltamethrin, dimefluthrin, empenthrin, and esfenvale. Examples include phosphate, etofenprox, fenpropathrin, fenvalerate, flucitrinate, flumethrin, fluvalinate, tau-fluvalinate, halfenprox, imiprothrin, metofluthrin, permethrin, phenothrin, prallethrin, profluthrin, pyrethrin (chrysanthemum), resmethrin, RU15525, silafluofen, tefluthrin, tetramethrin, tralomethrin, transfluthrin, and ZX18901. (ii) Acetylcholinesterase (AChE) inhibitors, such as carbamates or organic phosphates. Suitable carbamates include alanicarb, aldicarb, bengiocarb, benfuracarb, butocarbime, butoxycarbime, carbaryl, carbofuran, carbosulfan, ethiofencarb, phenobucarb, formentanate, furathiocarb, isoprocarb, methiocarb, methomyl, metholcarb, oxamyl, pyrimicarb, propoxer, thiodicarb, thiophanox, triazameate, trimetacarb, and xylylcarb. Suitable organic phosphates include acephate, azamethiphos, adinphos, adinphos-methyl, adinphos-ethyl, kazusaphos, chlorethoxyphos, chlorfenvinphos, chlormephos, chlorpyrifos, chlorpyrifos-methyl, coumaphos, cyanophos, demeton-S-methyl, diazinon, dichlorvos, diclotophos, dimethoate, dimethylvinphos, disulfone, ethione, etoprophos, fanflu, phenamiphos, fenitrothion, fenthion, fothiazate, heptenophos, isofenphos, isoxathion, ma Examples include lathion, mecarbam, methamidophos, methidathion, mevinphos, monoclotophos, naled, omethoate, oxydemeton-methyl, parathion, parathion-methyl, fenthoate, phorate, phosalon, phosmet, phosphamidone, foxim, pirimiphos, pirimiphos-methyl, profenphos, propethamphos, prothiophos, pyraclophos, pyridaphenthion, quinalphos, sulfotep, tebupyrimphos, temephos, terbuphos, tetrachlorvinphos, thiometon, triazophos, trichlorfon, and bamidothion. (iii) GABAergic chloride channel antagonists, such as organic chlorides or fiproles. Suitable organic chlorides include chlordane, endosulfan, and α-enosulfan. Suitable fiproles include ethiprole, fipronil, pyrafluprole, and pyriprole. (iv) Nicotinic acetylcholine receptor agonists, such as nicotine or chloronicotinyl compounds. Suitable chloronicotinyl compounds include acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiocloprid, and thiamethoxam. (v) Allosteric acetylcholine receptor modulators, e.g., spinetram or spinosad. (vi) Chloride channel actuators, such as abamectin, emamectin benzoate, lepimectin, or milbemectin. (vii) A juvenile hormone mimetic selected from hydroprene, quinoprene, methoprene, S-methoprene, phenoxycarb, or pyriproxyfen. (viii) Homophoran feeding blockers, such as pymetrozine or flanicamid. (ix) Mitochondrial ATP synthase inhibitors, such as diafenthiurone or tetradifan. (x) Uncoupling agents for oxidative phosphorylation, e.g., chlorfenapyr or DNOC. (xi) Nicotinic acetylcholine receptor channel blockers, such as bensultap, cartap hydrochloride, thiocyclam, or thiosultap sodium. (xii) Inhibitors of chitin biosynthesis, such as benzoylurea or buprofezin. Suitable benzoylureas include bistriflurone, chlorfluazurone, diflubenzuron, flucycloxurone, flufenoxurone, hexaflumurone, lufenuron, novaron, nobiflumuron, penflurone, teflubenzuron, or triflumuron. (xiii) Molting disruptors, such as cyromazine. (xiv) Ecdysone receptor agonists or disruptors, such as diacylhydrazines. Suitable diacylhydrazines include chromafenozide, halofenozide, methoxyfenozide, or tebufenozide. (xv) Octopamine receptor agonists, such as amitraz. (xvi) Mitochondrial complex I electron transport inhibitors, such as hydramethylnon, acequinosyl, and fluacrypryrim. (xvii) Acetyl-CoA carboxylase inhibitors, such as tetronic acid derivatives or tetramic acid derivatives. Suitable tetronic acid derivatives include spirodiclofen and spiromesfen, and a suitable tetramic acid derivative is spirotetramato. (xviii) Voltage-dependent sodium channel blockers, e.g., indoxacarb or metaflumisone. (xix) Mitochondrial complex IV electron inhibitors, such as phosphine or cyanide. Suitable phosphines include zinc phosphide, aluminum phosphide, calcium phosphide, or phosphine. (xx) Mitochondrial complex IV electron transport inhibitors, e.g., cyenopyrafen (xxi) ryanodine receptor modulators, e.g., chlorantraniliprole, cyantraniliprole, and flubendiamide.

[0060] The spider community includes spiders, harvestmen, scorpions, pseudoscorpions, microscopions, mites and ticks, especially mites and ticks (Acari (Acarina)). Suitable spiders include: (i) Mites, such as tomato rust mite (Aculops lycopersicae), citrus rust mite (Aculops pelekassi), Aculus Schlechtendali, Balusium medicagoense, southern spider mite (Brevipalpus phoenicis), greenhouse spider mite (Brevipalpus californicus), clover mite (Bryobia praetiosa), false clover spider mite (Bryobia rubrioculus), Bryobia species, such as clover mite, mite (Dermanyssus gallinae), yellow mite (Eotetranychus carpini), Lewis's spider mite (Eotetranichus lewisi), Eutetranychus banksia banksia), oriental spider mite (Eutetranychus orientalis), Eriophyes sheldoni, Eryophyes tiliae, Eriophyes inangulis, grape mite (Eriophyes vitis), Halotydeus destructor (red-legged mite), Oligonychus pratensis, mango spider mite (Oligonychus coffeae), Oligonitis oryzae, Oligonychus milleri, apple spider mite (Panonychus ulmi), citrus spider mite (Panonychus citri), Pentareus genus, e.g., blue oat mite, Phyllocoptruta oleivora, tea mite (Polyphagotarsonemus latus), sheep mite (Psoroptes ovis), Sarcoptes mites*Tetranychus scabiei*, *Tetranychus pallidus*, *Tetranychus cinnabarinus*, *Tetranychus kanzawai*, *Tetranychus pacificus*, and *Tetranychus urticae*. (ii) Ticks, such as Amblyomma americanum, Amblyomma variegatum, Argas persicus, Boophilus annulatus, Boophilus decoloratus, Boophilus miccroplus, Dermacentor silvarum, Hyalomma truncatum, Ixodes ricinus, Ixodes rubicundus, Ornithodorus moubata, Otobius megnini Rhipicephalus megnini, Rhipicephalus apendiculatus, Rhipicephalus evertsi, and Rhipicephalus microplus.

[0061] Spiders may be resistant to one or more arachnoids commonly used to control spiders, especially mites or ticks, before resistance develops. For example, spiders may be resistant to abamectin, acequinosyl, acrinatrin, aldicarb, alpha-cypermethrin, amidithione, amiton, amitraz, aramite, arsenic trioxide, azinphos-ethyl, azinphos-methyl, azobenzene, azocyclotin, azothoate, benomyl, benzoximate, benzylbenzoate, bifenazate, bifenthrin, binapacril, bromocyclene, bromophos, bromophos-ethyl, bromopropylate, butocarboxime, campechlor, carbanolate, carba Lil, Carbofuran, Carbophenothione, Carvacrol, Quinomethionate, Chlorbenside, Chlordimeform, Chlorfenapyr, Chlorphenetol, Chlorphensone, Chlorfensulfide, Chlorfenvinphos, Chlorobenzilate, Chloromebform, Chlomethiurone, Chloropropylate, Chlorpyrifos, Chlorthiofos, Clofentezine, Closantel, Coumaphos, Crotamiton, Crotoxyfos, Cyanthoate, Cycloprate, Cyenopyrafren ), cyflumetofen, cyhalotrin, cyhexatin, cypermethrin, cyromazine, DDT, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, diafenthiurone, dialiphos, diazinon, diclofluanide, dichlorvos, dicofol, dieldrin, dienochlor, diflovidazine, dimefox, dimethoate, dinex, dinobton, dinocup, dinoctone, dinopenton, dinosulfone, dinoterbone, dioxation, diphenylsulfone Phosphate, disulfonate, DNOC, endosulfan, endothione, ethione, etoate-methyl, etoxazole, phenazaflor, phenazaquin, fenbutasin oxide, phenothiocarb, fenpropathrin, fenpyroximate, fenson, fentriphanil, fenvalerate, fipronil, fluacrypyrim, fluazuron, flubendimine, flucycloxuron, flucitrinate, fluenetil, flufenoxuron, flumethrin, fluolbenside, fluvalinate, formmethanate,Formothion, formparanate, genit, halfenprox, heptenofos, hexachlorophene, hexythiazox, isocarbophos, lindan, malathion, mecarbum, methacryphos, methamidophos, methiocarb, metholcarb, mevinphos, milbemectin, mipafox, monoclotophos, naled, niflulidide, omethoate, oxamyl, oxydeprophos, oxydisulfonate, parathion, permethrin, fencapton, phorate, fosalon, fosmet, foxim, pirimiphos-methyl, propargit, They may be resistant to one or more arachnids or acaricides selected from propetamphos, propoxer, protidathion, protoate, pyridaben, pyrimidifen, quinalphos, quinthiophos, scradan, sofamide, spirodiclofen, sulfuramide, sulfotep, sulfur, tau-fluvalinate, tebufenpyrad, TEPP, tetrachlorvinphos, tetradiphon, tetrasul, thiocarboxime, thiophanox, thiometon, thioquinox, turingiencin, triatene, triazophos, trichlorfon, and bamidothion.

[0062] The pest may be at any stage of its life cycle, such as an egg, larva, pupa, adult, or nymph. In some embodiments, the pest may be in a larval stage.

[0063] In certain embodiments, the pest is a tick or mite, particularly a tick or mite in its larval stage, particularly a cattle tick in its larval stage.

[0064] In some embodiments, the present invention provides a method for treating or preventing pest infestation in livestock animals or companion animals, wherein the pest infestation is caused by a population of pests, including pesticide-resistant pests. The method involves applying a compound of formula (I) as defined above to the livestock animals or companion animals.

[0065] In some embodiments, the domesticated animals are selected from cattle, sheep, goats, deer, pigs, camels, llamas, alpacas, chickens, and the like. In other embodiments, the companion animals are selected from dogs, cats, rabbits, guinea pigs, hamsters, mice, horses, and the like.

[0066] In some embodiments, the compound of formula (I) may be applied topically, for example by immersion, spraying, pouring, washing, fogging or misting, drenching, or droplet application. In other embodiments, the compound of formula (I) may be applied systemically, for example, in the form of tablets, capsules, chewable tablets, or liquid drenching formulations.

[0067] In some embodiments, the method is for controlling pest infestation or outbreaks or potential pest infestations or outbreaks in environments where pest infestation or outbreaks are caused by populations of pests, including pesticide-resistant pests. The method involves applying a compound of formula (I) as defined above to an environment that is a host for pest infestation or outbreaks, or is at risk of being a host for pest infestation or outbreaks. The environment may be any environment that could be a host for pest infestation or outbreaks, for example, an agricultural environment, a domestic environment, an industrial environment, or a leisure environment. In certain embodiments, the environment is an agricultural environment.

[0068] In some embodiments, the method is used to control pests that infest stored plant products. The method involves contacting the plant product with a compound of formula (I).

[0069] Appropriately, the plant parts to be protected are brought into contact by immersion, spraying, fogging, or misting. Contact can be achieved before or during storage, especially before storage.

[0070] In some embodiments, the plant portion is grain that will be stored, for example, in a silo, before use. This method may be particularly useful for controlling pests that damage grain during storage, where the population of pests includes pesticide-resistant pests, such as those resistant to organic phosphates, such as fenitrothion, malathion, chlorpyrifos-methyl and pirimifos-methyl; and / or synthetic pyrethroids, such as deltamethrin or violethmethrin; and / or insect growth regulators, such as methoprene, and includes populations of the grain weevil (Rhyzopertha dominica), grain weevil (Sitophilus oryzae), confused flour beetle (Tribolium castaneum), sawtoothed grain beetle (Oryzaephilus surinamensis), or rusty-breasted grain beetle (Cryptolestes ferrugineous).

[0071] In some embodiments, the method is used to control pests that infest crops and cause damage to cereal crops in particular, such as rice, wheat, durum wheat, corn, maize, barley, millet, sorghum, oats, rye, lycocephala, teff, phenio, wild rice, and spelt. The method involves contacting the pests with a compound of formula (I) in an agricultural environment. Contact can be made by applying the compound or a composition containing the compound of formula (I) to the crop and / or the soil surrounding the crop, where the crop is likely to be infested with pests or a population of pests, particularly including pesticide-resistant pests. Examples of pests resistant to biological agents include H. destructor (red-legged earth mite), Balusium medicagoense, Pentaleus species such as the blue oat mite, and Bryobia species such as the clover mite, which are resistant to organic phosphates such as chlorpyrifos and / or pyrethroids such as bifenthrin.

[0072] In some embodiments, the compound of formula (I) can be applied without a solvent, while in certain embodiments, the compound of formula (I) is applied in the form of a composition together with an acceptable carrier, diluent, and / or excipient. This also applies to the exposure of pests to the compound of formula (I).

[0073] The composition can be formulated into any suitable composition, such as a spray, aerosol, oil, emulsion, wettable powder, flowable formulation, granular formulation, powder, powder, solution, suspension, emulsion or controlled-release formulation, tablet, capsule, oral solution, shampoo, conditioner, spot-on formulation, liquid or immersion. The composition can be formulated using a solid or liquid carrier as appropriate. The selection of formulation and mode of application depends on the pest being controlled, the environment in which it is controlled, or the animals suffering from the pest, and the appropriate selection is made considering the pest, target, and environment.

[0074] In some embodiments, the formulation may contain natural additives, such as antioxidants and stabilizers. For example, α-tocopherol can be used as an antioxidant, and suitable stabilizers include gum arabic, guar gum, locust bean gum, xanthan gum, kel gum, polyvinyl alcohol, sodium caseinate, and mixtures thereof.

[0075] Examples of solid carriers useful in preparing formulations include clays, such as kaolin clay, diatomaceous earth, water-containing synthetic silicon dioxide, bentonite, fubasami clay, and acid clay; talc; ceramics; and inorganic minerals, such as Celite®, quartz, sulfur, activated carbon, calcium carbonate, and hydrated silica; these solid carriers are either pulverized or granular. Examples of useful liquid carriers include water, alcohols such as methanol and ethanol, ketones such as acetone and methyl ethyl ketone, aromatic hydrocarbons such as benzene, toluene, xylene, ethylbenzene and methylnaphthalene, aliphatic hydrocarbons such as hexane, cyclohexane, kerosene and diesel fuel, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and isobutyronitrile, ethers such as diisopropyl ether and dioxane, acid amides such as N,N-dimethylformamide and N,N-dimethylacetamide, halogenated hydrocarbons such as dichloromethane, trichloroethane and carbon tetrachloride, dimethyl sulfoxide, as well as fish oil, mineral oil, vegetable oils such as olive oil, rapeseed oil, cottonseed oil, soybean oil and sesame oil, and essential oils such as lavender oil, eucalyptus oil, tea tree oil and citrus oil. Solid or liquid carriers can be used alone or in combination. Examples of gas carriers and sprays include butane gas, isobutene, pentane, LPG (liquefied petroleum gas), dimethyl ether, carbon fluoride, and carbon dioxide.

[0076] Examples of surfactants include alkyl sulfates, alkyl sulfonates, alkylaryl sulfone salts, alkylaryl ethers and their polyoxyethylene adducts, polyethylene glycol ethers, polyhydric alcohol esters, sugar alcohol derivatives, sorbitan monolaurate, alkylallylsorbitan monolaurate, alkylbenzene sulfonates, alkylnaphthalene sulfonates, lignin sulfonates, and sulfate salts of higher alcohols. These surfactants can be used alone or in combination.

[0077] Examples of adjuvants for formulations, such as binders and dispersants, include casein, gelatin, polysaccharides such as starch, gum arabic, cellulose derivatives and alginic acid, lignin derivatives, bentonite, sugars and high molecular weight synthetic water-soluble compounds such as polyvinyl alcohol, polyvinylpyrrolidone and polyacrylic acid. Examples of stabilizers include PAP (isopropyl acid phosphate), BHT (2,6-di-tert-butyl-4-methylphenol), BHA (a mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), synergists such as piperonyl butoxide, vegetable oils, mineral oils, fish oils, surfactants and fatty acids, or their esters.

[0078] The emulsifiers that can be used are, appropriately, one or more selected from nonionic or anionic emulsifiers. Examples of nonionic emulsifiers, but not limited to these, include polyoxyethylene alkylphenyl ethers, polyoxyethylene alkyl ethers, polyethylene glycol fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbitol fatty acid esters, and polyoxyethylene polyoxypropylene alkyl ethers. Examples of anionic emulsifiers include alkyl sulfates, polyoxyethylene alkyl ether sulfates, sulfosuccinates, taurine derivatives, sarcosine derivatives, phosphate esters, and alkylbenzene sulfonates. A mixture consisting of polyoxyethylene styrylphenyl ether and calcium allylbenzenesulfonate is preferred. These emulsifiers can be used in an amount of 1 to 20 parts by weight per 100 parts by weight of the composition of the present invention.

[0079] In some embodiments, the compound of formula (I) is formulated as a spray. The spray can be formulated as a liquid for use in atomizers or aerosols. In some embodiments, the liquid solubilizes the compound of formula (I), and here, for example, the liquid or solvent is an oil or a hydrocarbon solvent. In other embodiments, the liquid is an aqueous liquid, and the formulation is in the form of a suspension or emulsion.

[0080] In some embodiments, the composition may include a propellant, such as butane, isobutene, pentane, carbon dioxide, or nitrogen.

[0081] In some embodiments, the spray can be placed locally in the environment or on animals, or applied directly to resistant pests. In other embodiments, the compound of formula (I) can be formulated in a viscous formulation which is immersed in a carrier such as filter paper or fabric and left on the site of pest infestation for contact with the pest. In some embodiments, the compound of formula (I) can be formulated in a slow-release formulation.

[0082] The method of the present invention can be incorporated as part of an integrated pest control system, in which the compound of formula (I) is used in combination with other pesticides, either simultaneously or sequentially. The compound of formula (I) is a potassium channel activator. In some embodiments, the compound of formula (I) is combined with another pesticide having a different mechanism of action. In certain embodiments, pesticide-resistant pests are not resistant to the effects of any of the compounds used in the combination. In some embodiments, the combination of the compound of formula (I) and the second pesticide is in a single composition. In other embodiments, the compound of formula (I) and the second pesticide are in separate compositions. The second pesticide can be selected from any of those enumerated in paragraphs 0059, i) to xxi) or paragraph 0061 above.

[0083] To facilitate understanding and practical implementation of the present invention, certain preferred embodiments are described below as non-limiting examples. [Brief explanation of the drawing]

[0084] [Figure 1] This figure shows the dose-response curves of susceptible populations of H. destructor after exposure to Flaveson at concentrations of 0 mg, 3 mg, 10 mg, 30 mg, 100 mg, 300 mg, 1000 mg, 3000 mg, and 10000 mg ai / L (ppm) at 4, 6, 8, and 24 hours. [Figure 2] This figure shows graphs of dose-response curves for susceptibility and tolerance of H. destructor in populations exposed to Flaveson at concentrations of 0 mg, 3 mg, 10 mg, 30 mg, 100 mg, 300 mg, 1000 mg, 3000 mg, and 10000 mg ai / L (ppm) over 24 hours. [Figure 3] This figure shows graphs of dose-response curves for H. destructor-sensitive and resistant populations after exposure to bifenthrin at concentrations of 0 mg, 0.00001 mg, 0.0001 mg, 0.001 mg, 0.01 mg, 0.1 mg, 1.0 mg, 10 mg, 100 mg, 1000 mg, and 10000 mg ai / L (ppm) over 24 hours. [Figure 4] This figure shows graphs of dose-response curves for H. destructor-sensitive and resistant populations after exposure to chlorpyrifos at concentrations of 0 mg, 0.7 mg, 7.0 mg, 70 mg, and 700 mg ai / L (ppm) over 24 hours. [Figure 5] This figure shows graphs of dose-response curves for susceptible and resistant populations of green peach aphids exposed to flaveson at concentrations of 0 mg, 10 mg, 100 mg, 300 mg, 1000 mg, 2000 mg, 5000 mg, 10000 mg, 30000 mg, and 100000 mg ai / L, and for 48 hours of exposure. [Figure 6]This figure shows graphs of dose-response curves for susceptible and resistant populations of green peach aphids exposed to flaveson at concentrations of 0 mg, 10 mg, 100 mg, 300 mg, 1000 mg, 2000 mg, 5000 mg, 10000 mg, 30000 mg, and 100000 mg ai / L and for 96 hours of exposure. [Figure 7] This figure shows graphs of dose-response curves for susceptible and resistant populations of peach aphids exposed to pyrimicarb at concentrations of 0.025 mg, 0.25 mg, 2.50 mg, 25.0 mg, 250.0 mg, and 2500.0 mg ai / L and for 48 hours of exposure. [Figure 8] This figure shows graphs of dose-response curves for susceptible and resistant populations of peach aphids exposed to pyrimicarb at concentrations of 0.025 mg, 0.25 mg, 2.50 mg, 25.0 mg, 250.0 mg, and 2500.0 mg ai / L and for 96 hours of exposure. [Examples]

[0085] [Example 1] Larval packet test - Bovine tick The larval packet test (LPT) is a variation of the test first described by Stone and Haydock (1962, Bull. Entomol. Res., 563-578, http: / / dx.doi.org / 10.1017 / S000748530004832X) for evaluating field tolerance in the larvae of the cattle tick *Ixodes ventricosus* (*Rhipicephalus microplus*).

[0086] By performing a first LPT assay, we identified the potential range of flaveson acaricidal activity against susceptible-non-resistant field strains (NRFS) of the tick *Haemaphysalis microplus*, using a wide range of concentrations (1 / 10 series), as a reference strain.

[0087] The test compound, flavesone, 6-isobutyryl-2,2,4,4-tetramethylcyclohexane-1,3,5-trione, 96.7% was used. Since its volatility / evaporative properties were unknown, the LPT method was modified to minimize exposure of the active test substance to the atmosphere by incorporating the use of a suitably sized polyethylene plastic sheet to wrap the larval packets.

[0088] In addition, the use of the solvent trichloroethylene (TCE) was eliminated to avoid the time required for evaporation during the preparation of the test strips. Evaporation was minimized by preparing the test solution in olive oil alone as a diluent, immediately wrapping the paper in a plastic sheet, and sealing it with a bulldog clip.

[0089] A stock solution containing 100,000 ppm (10%) flavesone was prepared in olive oil as a diluent (1.035 mL of flavesone (96.7%) versus 8.965 mL of olive oil), and then further diluted in a 1 / 10 series to obtain concentrations of 10,000 ppm, 1,000 ppm, 100 ppm, 10 ppm, and 1 ppm. Olive oil was the only negative control. No positive controls were included in this experiment. Due to the viscosity of the olive oil, all solutions were prepared using the reverse pipetting technique.

[0090] Using a micropipette, 225 μL of each solution was impregnated onto half of a 75 mm x 85 mm Whatman® 541 filter paper sheet in a grid pattern. The paper was immediately folded in half, wrapped in polyethylene plastic, and sealed with three bulldog clips. The impregnated paper was held on an aluminum tray at room temperature for a minimum of 60 minutes to allow dispersion across the grid pattern on the paper before aliquots of larvae. Packets were prepared in duplicate for each concentration, including a negative control.

[0091] Eight drum vials containing approximately 20,000 hatched 7-21 day old NRFS larvae (about 1 g of eggs) were opened and placed on a recessed tray with a small amount of detergent water about 15 to 30 minutes before use. Only larvae that had moved to the top of the vial were used in the assay.

[0092] Using disposable plastic tweezers, approximately 100 larval aliquots were placed into each packet, the packets were resealed, and incubated at 27°C and 85% relative humidity (RH).

[0093] After 24 hours, the larval packets were opened and the number of dead and surviving larvae was counted under a magnifying lamp. The mortality percentage was calculated and, where applicable, the Abbott formula (Abbott, 1925, J. Economic Entomology, 18:256-257):

[0094]

number

[0095] LC 50 Value and LC 99 The values ​​were determined by probit mortality versus log concentration analysis. Probit values ​​were derived from "Transformation of Percentages to Probit's Tables" published by Fisher RA and Yates F. (1938).

[0096] The results are shown in Tables 1 and 2.

[0097] [Table 1]

[0098] LC 50 Value and LC 99 The values ​​were determined and are shown in Table 2.

[0099]

Table 2

[0100] [Example 2] LPT assay using resistant larvae By repeating the LPT assay of Example 1 using a narrow range of flaveson concentrations, a 1 / 2 series, the LC 50 values and LC 99 values were determined.

[0101] The tick strain of Rhipicephalus microplus has resistance to about 30% fluarazuron, 60.6% permethrin (SP), 57.6% flumethrin (SP), 16.2% amitraz (amidine), 11.3% DDT, 9.3% chlorpyrifos (OP) and 2.4% aldrin [2014 Tick acaricide resistance profiling].

[0102] Synthetic pyrethroid (SP) permethrin was included in the assay as a positive control.

[0103] A stock solution of flaveson (100,000 ppm) was diluted 1 / 10 with olive oil (1 mL to 9 mL diluent) to obtain 10,000 ppm, which was then further diluted in a 1 / 2 series (5 mL to 5 mL diluent) to obtain concentrations of 5,000 ppm, 2,500 ppm, 1,250 ppm, 625 ppm, 312.5 ppm and 156.25 ppm.

[0104] For the preparation of the positive control, permethrin, a stock solution at a concentration of 10,000 ppm was prepared in 2:1 trichloroethylene (TCE) / olive oil (0.0352 g of permethrin, 94.8% purity, vs. 10 mL of solvent) as the solvent, and then further diluted in a 1:2 series (5 mL vs. 5 mL of solvent) to also obtain 5,000 ppm, 2,500 ppm, 1,250 ppm, 625 ppm, 312.5 ppm, and 156.25 ppm.

[0105] Flavon paper was prepared as in Example 1.

[0106] Using a micropipette, 670 μL of each solution was impregnated into the permethrin paper and hung on a rack in the draft to allow the paper to dry for at least 60 minutes (evaporation of TCE). The paper was then folded in half and sealed with three bulldog clips and placed on an aluminum tray before aliquoting the larvae. All packets were prepared in duplicate.

[0107] Negative control papers were prepared for both flavone (olive oil only) and the positive control, permethrin (2:1 TCE / olive oil).

[0108] Mortality was determined at 24 hours, and the LC 50 value and LC 99 value were determined by probit mortality vs. log concentration analysis. The dose-response relationship was determined with 24-hour contact exposure. The results are shown in Table 3.

[0109]

Table 3

[0110] For both strains with 1,250 ppm of flavone, some larvae were still waving their legs in the air; however, they did not take steps to indicate survival (flaccid paralysis). For both strains with 2,500 ppm of flavone, no movement was observed and 100% mortality was observed.

[0111] LC between NRFS strain and Tialo strain 50 Data and LC 99 When comparing the data, there was no evidence of cross-tolerance to Flaveson.

[0112] Negative control mortality rates ranged from 0% to 0.51% and were corrected using the Abbott formula where applicable.

[0113] Using probit mortality versus log concentration analysis, LC 50 Value and LC 99 The values ​​were determined and are shown in Table 4.

[0114] [Table 4]

[0115] [Example 3] The experiment in Example 2 was repeated only with NRFS strains, using a 1:2 serial dilution and cypermethrin as a positive control. Flaveson concentrations were 5,000 ppm, 2,500 ppm, 1,250 ppm, 625 ppm, and 312.5 ppm. Cypermethrin concentrations were 1,250 ppm, 652 ppm, 312.5 ppm, 156.25 ppm, 78.125 ppm, and 36.0625 ppm.

[0116] Mortality rate is determined within 24 hours, LC 50 Value and LC 99 The values ​​were determined by probit mortality versus log concentration analysis.

[0117] Similar to Example 2, with 1,250 ppm of flaveson, some larvae were still waving their legs in the air; however, they did not take any steps indicating survival (flaccid paralysis). With 2,500 ppm of flaveson, no movement was observed, and 100% mortality was observed.

[0118] The negative control mortality rate was set to a range of 0% to 1.02%, and was corrected using the Abbott formula where applicable.

[0119] The results are shown in Table 5:

[0120] [Table 5]

[0121] LC 50 values and LC 99 values are shown in Table 6:

[0122] [Table 6]

[0123] [Example 4] In Examples 2 and 3, a 100% mortality rate was recorded after 24-hour contact exposure at a flavone concentration of 1,250 ppm. However, for both the NRFS strain and the Tiarro strain, at this concentration, some larvae were still waving their legs in the air but did not take steps to survive (flaccid paralysis) and were thus found to be near death. This experiment was conducted to confirm whether these larvae would die within an additional 24-hour contact exposure and the mortality rate would be determined at 48 hours.

[0124] The concentrations of 1,250 ppm, 625 ppm, and 312.5 ppm of flavone concentration prepared for Example 3 were used on the same day they were prepared. Duplicate papers were prepared for both the NRFS strain and the Tiarro strain (including the negative control) as described in Example 2.

[0125] The mortality rate was determined at 48 hours, and the LC 50 values and LC 99 values were determined by probit mortality vs. log concentration analysis. The results are shown in Tables 7 and 8.

[0126] The negative control mortality rates ranged between 0.79% and 3.91% and were corrected by using the Abbott formula.

[0127] [Table 7]

[0128] [Table 8]

[0129] [Example 5] Evaluation of Flavesone as a grain protectant The laboratory established an insect population of the long-horned beetle Rhyzopertha dominica (QRD1440) with a history of resistance to organic phosphates, and used pyrethroids in this study.

[0130] Organically produced wheat grains free of residues were used in the study. The wheat's moisture content was maintained at 11%.

[0131] Test solutions of flaveson (25 ppm), deltamethrin (K-Obiol®, 1 ppm), and chlorpyrifos (Reldan®, 5 ppm and 10 ppm) in water were prepared. Water was used as the control sample. Five lots of 240 g wheat were weighed into 1 L glass jars, one jar per treatment and one control.

[0132] The test and control solutions were pipetteed into one of the jars located just above the surface of the grain (one jar per sample) at a ratio equivalent to 10 mL of solution per kg of wheat. The jars were sealed and gently shaken and rotated by hand, then mechanically rotated for 10 minutes. The moisture content was 12%, reflecting the upper limit permitted by the Australian bulk handling company. The day after processing, each 240 g wheat sample was divided into three 80 g replicates and placed in 250 mL glass jars.

[0133] Fifty adult R. dominica (QRD1440) (1 to 3 weeks after emergence) were added to each jar of treated or control wheat. Each jar was covered with filter paper as a lid and stored at 25°C and 55% relative humidity for 14 days. After this, adult insects were recovered by sieving the wheat sample. Mortality rates were recorded. All dead and surviving adults were discarded. The wheat jars were incubated for a further 6 weeks, and the number of offspring was recorded. The results are shown in Table 9:

[0134] [Table 9]

[0135] At 25 ppm of flaveson, QDR1140 long-eared beetle (R. dominica) resistant strains had higher mortality rates than controls and other pesticides used. Flaveson treatment also resulted in the production of fewer F1 offspring.

[0136] [Example 6] Flavesone concentration The experiment in Example 5 was repeated using Flaveson at concentrations of 25 ppm, 50 ppm, and 75 ppm. Water was used as the control.

[0137] The results are shown in Table 10:

[0138] [Table 10]

[0139] [Example 7] Control of a resistant strain of the long-eared burrowing beetle (R. dominica) QRD1440 The experiment in Example 5 was repeated using Flaveson at a concentration of 60 ppm. Water was used as a control.

[0140] The results are shown in Table 11.

[0141] [Table 11]

[0142] [Example 8] A comparative study using susceptible strains of the long-eared borer (R. dominica), QRD14. The experiment in Example 5 was repeated using different concentrations of flaveson to determine the efficacy of the laboratory-cultivated susceptible strain QQRD14 of the long-eared borer (R. dominica).

[0143] The results are shown in Table 12.

[0144] [Table 12]

[0145] [Example 9] Control of Halotydeus destructor (red-legged mite): Dose response in susceptible populations The efficacy of flavesone against H. destructor was determined using the glass vial technique developed by Hoffmann et al. (1997, Exp. Appl. Acarol., 21:151-162), adapted for plastic vials. Susceptible mite populations were collected from Cape weed (Arctotheca calendula) at a site in Victoria (37°40'33”S, 145°07'45”E) known to have no history of insecticide application. Following collection, samples were stored in small plastic containers containing leaf material and paper towels to absorb excess moisture. The containers were kept at 4°C before testing.

[0146] Series dilutions of each insecticide were prepared from the compositions shown in Table 13:

[0147] [Table 13]

[0148] The test composition contained 0.1% Tween 20 nonionic surfactant to aid in the diffusion of the insecticide when coating plastic vials. Tween 20 at this concentration has been previously shown to have no toxic effect against H. destructor. For each insecticide concentration tested—3 mg, 10 mg, 30 mg, 100 mg, 300 mg, 1000 mg, 3000 mg, and 10000 mg ai / L (ppm)—approximately 10 mL of the solution was poured into 15 mL plastic vials, and swirled to ensure complete coating, with any excess liquid removed. Eight vials were coated per concentration and allowed to dry overnight. Control vials were treated in the same manner, but water was used instead of the test composition.

[0149] Eight susceptible H. destructor mites were then placed in each vial along with Vicia sativa leaves. The leaves were added to provide food and increase humidity. The vials were then sealed and left at 18°C. At 4, 6, 8, and 24 hours of exposure, the mites were scored as viable (freely moving), immobile (inhibited movement), or dead (no movement for a 5-second period). Immobile individuals were pooled with dead individuals for analysis, as they inevitably died and therefore did not contribute to the next generation.

[0150] The results for flaveson are shown in Figure 1. Mortality from H. destructor increased dramatically between 100 mg and 300 mg ai / L, and mortality increased with the duration of exposure. At 4 hours of exposure, flaveson at 300 mg ai / L caused an average mortality rate of 55%, while lower doses resulted in lower mortality. All doses above 300 mg ai / L resulted in a 100% mortality rate after 4 hours of exposure. At 8 hours of exposure, the mortality rate at 300 mg ai / L rose to 100%. At lower doses, an increase in mortality was observed at 24 hours.

[0151] [Example 10] Control of Halotydeus destructor (red-legged mite): Dose response in susceptible and resistant populations The experiments described in Example 9 were repeated using susceptible and resistant populations of H. destructor, with the exception that mites were observed at 6 and 24 hours. Resistant populations of H. destructor were collected from lucing grazing land in the Upper South-East region of South Australia, where resistance to synthetic pyrethroids was confirmed in late 2016.

[0152] Data generated in the assay were evaluated for concentrations that caused 50%, 90%, and 99% mortality (lethal concentrations, LC), along with 95% confidence intervals (CIs). These concentrations were estimated from observations of mortality after 24 hours of exposure using binary logistic regression (Robertson & Preisler, 1992, Pesticide Bioassays with Arthropods. CRC: Boca Raton; Venables & Ripley, 2002, Modern Applied Statistics with S. Springer: New York). Population differences were tested by comparing changes in model deviation with and without population factors (different regression intercepts for each population). Differences in regression gradients between populations were tested by comparing changes in model deviation with and without population × dose interaction terms. The resistance ratio of pesticide-resistant populations was calculated using its LC. 50 LCs of susceptible groups 50 The ratio was estimated. All analyses were performed using R3.3. (R Core Team 2017, R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. http: / / www.R-project.org).

[0153] Figure 2 shows the dose-response curves illustrating the effect of Flaveson on susceptible and resistant H. destructor populations after 24 hours of exposure. Flaveson was equally effective against both insecticide-resistant and susceptible populations, as demonstrated by the tight alignment of the dose-response curves for both populations (χ²). 2 (=1.40, df=1, p=0.24). LC 50For flaveson, the values ​​(and 95% CI) were calculated as 40.6 (33.3–49.6) mg ai / L and 34.2 (27.9–41.9) mg ai / L for the susceptible and tolerant populations, respectively, as shown in Table 14. There was no evidence that the regression gradients for concentration differed significantly between the populations (χ²). 2 (=0.01, df=1, p0.91).

[0154] As shown in Figure 3, a significant difference in susceptibility to bifenthrin was observed between the susceptible and resistant populations (χ²). 2 (=167.57, df=1, p=0.0001). Comparing LC50 values ​​between populations showed that the resistant population required approximately 3,500 times the dose of bifenthrin compared to the susceptible population to achieve a 50% mortality rate after 24 hours. This population likely contained a mixture of resistant and susceptible individuals. The LC50 value for the susceptible population of 0.04 (0.03~0.08) mg ai / L is consistent with previous studies using H. destructor collected from this site. The regression coefficients also differed significantly between populations (χ²). 2 (=28.76, df=1, p=0.0001).

[0155] Regarding chlorpyrifos, the dose-response also differed significantly between the insecticide-resistant population and the susceptible population (χ 2 (χ² = 44.13, df = 1, p = 0.0001). The resistant population was 6.5 times more resistant to chlorpyrifos than the susceptible population. This is comparable to the organic phosphate resistance observed in South Australia. There is no evidence that the regression gradients with respect to concentration differed between the populations. 2 (=1.77, df=1, p=0.18).

[0156] LD for 24-hour exposure 50 Value, LD 90 Value and LD 99 The values ​​and confidence intervals are shown in Table 14.

[0157] [Table 14]

[0158] These results demonstrate that flavesone is effective against H. destructor in both susceptible and insecticide-resistant populations, causing a 50% mortality rate within 24 hours at concentrations between 34 and 40 mg ai / L.

[0159] [Example 11] Efficacy of Flaveson on susceptible and resistant populations of the peach aphid. Colonies of the green peach aphid (M. persicae) were established from long-term laboratory cultures of known insecticide-susceptible populations as well as populations previously shown to be resistant to carbamates and synthetic pyrethroids. Each colony was maintained separately on bok choy plants (Brassica napus chinensis) in exclusion cages in a constant temperature room at 24°C with a 16:8 LD photoperiod.

[0160] Laboratory bioassays were used to determine the efficacy of flaveson against the peach aphid (M. persicae) according to the leaf immersion method described by Moores et al. (1994, Pesticide Biochemistry and Physiology, 49, 114-120). A pilot study was conducted first to confirm that the leaf immersion method is appropriate for deriving a clear dose-response for flaveson 500EW against peach aphids (M. persicae) and to determine appropriate percentage ranges and timings for mortality assessment (scored at 24, 48, 72 & 96 hours) (data not shown).

[0161] Bioassays were subsequently performed to determine the efficacy of flaveson against susceptible and resistant populations of the peach aphid (M. persicae) and to calculate LC values. The efficacy of the conventional insecticide, pyrimicarb, was tested for comparison. 1 × 10⁻⁶ of the proposed field area -3 Nine concentrations of flaveson (Table 15) ranging from 1 to 10-fold, and six concentrations of pyrimicarb were sequentially diluted and tested against susceptible and resistant aphid populations along with a water control. Leaf discs (25 mm in diameter) cut from bok choy leaves were submerged in the insecticide solution or water control for 1 second and placed adaxially upward on 10 g / L agar in a 35 mm Petri dish. Six replicate leaf discs were prepared per treatment. After the leaves were air-dried, eight green peach aphid (M. persicae) nymphs were transferred to each insecticide-soaked leaf disc using a fine-bristled paintbrush.

[0162] After introducing the aphids, each petri dish was inverted onto a lid containing 25mm diameter filter paper for humidity control. All petri dishes were then placed in an incubator maintained at 18°C ​​± 2°C with a 16:8 LD cycle photoperiod. At 48 and 96 hours, the aphids were scored as viable (active and freely moving), dead (immobile for a period of 5 seconds), or immobile (inhibited movement). Immobile individuals were pooled with dead individuals for analysis, as they would inevitably die and therefore would not contribute to the next generation.

[0163] [Table 15]

[0164] Data Analysis Dose-response curves were generated by plotting mortality percentages against log concentrations. Mortality data were analyzed using a logistic regression model with random effects. Logistic regression is suitable for analyzing binary response data (i.e., death / survival) with a random effect component of the model to control for the non-independence of mortality scores within replicates. Binary logistic regression (Robertson & Preisler 1992, Pesticide Bioassays with Arthropods, CRC: Boca Ratan; Venables & Ripley 2002, Modern Applied Statistics with S, Springer, New York, http: / / www.stats.ox.ac.uk / pub / MASS4) was used to calculate the concentrations (lethal concentrations, LC) (along with 95% confidence intervals, CI) that resulted in 50%, 90%, and 99% mortality. Population differences were tested by comparing changes in model deviation with and without population factors (different regression intercepts for each population). We tested the differences in regression gradients between populations by comparing the changes in model deviations with and without population × dose interaction terms.

[0165] The analysis was performed using R version 3.3.1 (R Development Core Team 2017. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria, http: / / R-project.org).

[0166] result While the dose-response curves for susceptible and resistant populations exposed to flaveson appeared similar at 48 hours (Figure 5), significant differences between the populations were detected (c²=8.09, df=1, p<0.01). However, by 96 hours, the dose-response curves for susceptible and resistant peach aphid (M. persicae) populations exposed to flaveson were more closely aligned and not significantly different (c²=0.78, df=1, p=0.38) (Figure 6). The LC50 values ​​(and 95% CI) after 96 hours of exposure were estimated as 2,731 (2,259–3,303) mg ai / L for the susceptible population and 3,151 (2,568–3,865) mg ai / L for the resistant population (Table 16). There were no significant differences in the regression gradients between the groups at 48 hours (c²=0.49, df=1, p=0.48) or 96 hours (c²=0.72, df=1, p=0.40).

[0167] [Table 16]

[0168] At 48 and 96 hours, there were no clear differences in dose-response curves between the susceptible and tolerant populations after exposure to pyrimicarb (48 hours: c2=269.9, df=1, p<0.0001; 96 hours: c2=257.5, df=1, p<0.0001) (Figures 7 & 8). Furthermore, the regression gradients differed significantly between the populations (48 hours: c2=66.6, df=1, p<0.0001; 96 hours: c2=107.2, df=1, p<0.0001). The estimated LC50 for the susceptible population at 96 hours with a dose of 18.5 mg ai / L was consistent with previous laboratory studies using the peach aphid (M. persicae) (Umina et al. 2014, Journal of Economic Entomology, 107(4), 1626 1638). The very low mortality rates observed in the resistant population after exposure to pyrimicarb prevented the calculation of meaningful LC values ​​(Table 16).

[0169] This study demonstrates the efficacy of flaveson against the peach aphid (M. persicae). The LC50 of flaveson after 96 hours of exposure ranged from 2,731 to 3,151 mg ai / L. The efficacy of pyrimicarb was very high in the susceptible population and was closely consistent with previously published bioassay data. Resistance to pyrimicarb was confirmed in the insecticide-resistant population. This population is also resistant to synthetic pyrethroids, as demonstrated by pesticide bioassay results and genetic screening (see Umina et al., 2014).

[0170] The dose-response curves for flavesone in susceptible and resistant populations were closely aligned at 96 hours post-exposure. This indicates that flavesone is effective against carbamate-resistant populations of the green peach aphid (M. persicae) and that flavesone has a different mechanism of action than other insecticides in this class. There is some evidence regarding population differences in response at 48 hours. The reasons for this (single or plural) remain unclear, but may reflect natural differences between populations, such as colony health, general cold tolerance, or bacterial endosymbionts.

[0171] [Example 12] Toxicity of Flaveson against Aedes aegypti LVP (L3 larvae of insecticide-susceptible and PRS insecticide-resistant strains). Localized mosquito larval assay techniques were performed.

[0172] Lethal concentration (LC) 50 To determine the values, a dose-response assay was used, with a minimum of 5 point doses of Flaveson diluted in sterile ddH2O, using a minimum of 4 technical replicates per dose (5 mosquitoes per replicate).

[0173] Two mosquito species were used: Aedes aegypti (yellow fever mosquito) Liverpool strain (insecticide susceptible, LVP) and PRS Puerto Rico strain (synthetic pyrethroid resistant) in L3 stage larvae. Negative control: Vehicle Positive controls: Industrial-grade synthetic pyrethroids (SP) and organic phosphates (OP): deltamethrin (SP), permethrin (SP), and malathion (OP). Phenotypic endpoints: Scored for mortality / paralysis at 24, 48, and 72 hours. Dose point (selected from pilot assays not shown): Flaveson: 6.25 μg / mL, 25.0 μg / mL, 50 μg / mL, 75 μg / mL & 100 μg / mL; H2O control Deltamethrin: 1.56 ng / mL, 6.25 ng / mL, 12.5 ng / mL, 25 ng / mL, 50 ng / mL; 0.625% DMSO-negative control Permethrin: 6.25 ng / mL, 12.5 ng / mL, 25 ng / mL, 50 ng / mL, 100 ng / mL; 0.625% DMSO-negative control Malathion: 0.0156 μg / mL, 0.0625 μg / mL, 0.125 μg / mL, 0.25 μg / mL, 1 μg / mL; 0.5% EtOH-negative control

[0174] Using a wide-mouth plastic transfer pipette, larvae were transferred to a 24-well tissue plate at a rate of 5 larvae per well. Water was gently removed from the wells using a 1 mL pipette, and an equal volume of ddH2O was added. An appropriate volume of the test compound was added to each of the four replicated wells per treatment, and the plate was gently rotated to ensure uniform mixing. The plate was placed in a test or growth chamber under constant conditions of 22–25°C and approximately 75–85% relative humidity in a 12-hour light / 12-hour dark cycle. Death and unresponsive larvae were identified at 24, 48, and 72 hours.

[0175] The results are shown in Table 17.

[0176] [Table 17]

[0177] [Example 12] Evaluation of Flavesone as a grain protectant against major storage grain pests resistant to commonly used biocides. insect For this stage of the experiment, five laboratory-established strains (both susceptible and resistant) were considered. The resistant strains listed below represent the grain protection agent resistance genotypes commonly encountered in grain storage in Australia, particularly in the eastern breadbasket: • The long-horned beetle (R. dominica) strain QRD1440 is resistant to OP protective agents and pyrethroids. • The confused flour beetle (T. castaneum) strain QTC279 is resistant to malathion and violethmethrin. • The *C. ferrugineus* strain QCF73 is resistant to phosphine. • The sawtooth flat beetle (O. surinamensis) strain QOS302 is resistant to fenitrothion and chlorpyrifos-methyl. • The weevil (S. oryzae) strain QSO393 is resistant to fenitrothion.

[0178] Test program Grain processing and bioassays This study used organically produced wheat free of residues and insects. The moisture content of the wheat before treatment was maintained at 11%. The chemicals used in these experiments—flavesone, K-Obiol EC Combi (50 g / L deltamethrin, 400 g / L PBO), and reldan (500 g / L chlorpyrifos-methyl)—were obtained from Bio-Gene Technology, Bayer Crop Science, and Dow AgroSciences, respectively. Two concentrations (25 ppm and 60 ppm) were considered for independent flavesone experiments.

[0179] For each strain of borer (internal feeder), R. dominica, and S. oryzae, three lots of 160g wheat were weighed into glass jars (500mL capacity), i.e., one jar per treatment and another jar for control (distilled water only). The solutions for each treatment (prepared at predetermined dilution ratios, individually and in combination) were pipetteed separately into the inside of the glass jar just above the surface of the grain, at a ratio equivalent to 10mL of solution per kilogram of wheat. Distilled water was applied to the control grain at the same ratio as the treatment. All jars were sealed and gently shaken and rotated by hand, then mechanically rotated for 1 hour. The moisture content after treatment was 12%, reflecting the upper limit permitted by the Australian bulk handling company. One day after processing, each 240g lot of wheat was divided into three 80g replicates and placed in separate glass jars (250mL capacity). The procedure for confused flour beetle (T. castaneum), rusty-breasted flat beetle (C. ferrugineus), and sawtooth flat beetle (O. surinamensis) was kept the same except that three lots of 600g wheat per plant were processed. One day after processing, each 600g lot of wheat was divided into three 190g replicates and placed in glass jars (500mL capacity). The remaining 30g of wheat was ground into flour, divided into three 10g lots, and added to the corresponding replicates of the whole wheat so that each replicate totaled 200g. The aim of grinding 5% of each replica into powder was to improve the reproduction of these three pest species, which are external feeders. The above activity was repeated twice over the next two days to produce a total of three replicas for each treatment.

[0180] The bioassay was initiated by adding 50 adult beetles (1-3 weeks after emergence) to each jar of treated or control wheat. Each jar was covered with a filter paper lid and stored in a controlled environment room at 25°C and 55% relative humidity for 2 weeks. After this, the adults were sieved from the wheat and the mortality rate was recorded. Subsequently, all adults (dead and alive) were discarded, and the wheat jars were incubated for a further 6 weeks, during which time the number of adult offspring was recorded. To simultaneously observe offspring emergence, jars containing the grain weevil (S. oryzae) and the sawtoothed flat beetle (O. surinamensis) were incubated at 25°C and 55% relative humidity, while jars containing other species were incubated at 30°C and 55% relative humidity.

[0181] Data Analysis Each dataset is presented in a simple table, along with various adult mortality percentages and the number of surviving adult F1 offspring (mean ± standard error of three replicates), as well as the percentage of offspring reduction calculated from the average number of F1 offspring in treated wheat and untreated control.

[0182] result The effectiveness of Flaveson The control mortality rates in both susceptible and resistant strains of all five species were negligible (0–1.3%) (Tables 18–22). The number of adult offspring produced in the control strains of R. dominica was 234 (QTC14) and 211 (QRD1440), respectively (Table 18); 118 (QTC4) and 321 (QTC279) for T. castaneum (Flour beetle) (Table 19); 360 (QCF31) and 344 (QCF73) for C. ferrugineus (Rusticus ferrugineus) (Table 20); 348 (VOS48) and 412 (QOS302) for O. surinamensis (O. surinamensis) (Table 21); and 716 (LS2) and 610 (QSO393), respectively, for the susceptible and resistant strains of S. oryzae (S. oryzae) (Table 22).

[0183] As expected, 25 ppm of flaveson failed to achieve complete adult mortality in both the susceptible (QRD14) and resistant (QRD1440) strains of the long-eared beetle (R. dominica), but achieved 100% and 88% reduction in offspring, respectively (Table 18). However, upon reviewing the Phase I results, a higher concentration of 60 ppm of flaveson achieved complete control of both adult and offspring in both strains (Table 1).

[0184] For the other four species strains, however, both of the proposed concentrations (25 ppm and 60 ppm) of flaveson failed to achieve complete adult mortality (Tables 19-22); complete offspring reduction was achieved at 60 ppm in *C. ferrugineus* and *O. surinamensis* (Tables 20 and 22). Neither concentration of flaveson was effective against the susceptible (QTC4) and resistant (QTC279) strains of *T. castaneum*, resulting in no adult mortality reduction, with up to 45% offspring reduction for the former and 36% for the latter at the higher concentration of 60 ppm (Table 19). For *C. ferrugineus*, adult mortality rates reached 90% and 62% in the susceptible (QCF31) and resistant (QCF73) strains, respectively, at the highest dose of 60 ppm (Table 20). At a lower dose of 25 ppm, offspring reduction in this species was recorded at a similar level of 75% for both strains, and 100% offspring reduction was recorded at the 60 ppm level (Table 20). In the case of *O. surinamensis*, flaveson at 25 ppm resulted in adult mortality rates of 22% and 0.7% in the susceptible (VOS48) and resistant (QOS302) strains, respectively; and at a higher dose of 60 ppm, adult mortality rates reached up to 91% in the former and 14% in the latter (Table 21). Both proportions of flaveson, however, produced very high percentage offspring reduction (61–99%) at 25 ppm and complete offspring reduction (100%) at 60 ppm in both strains of this species (Table 21). The effectiveness of flaveson against the grain weevil (S. oryzae) was similar to that observed against the confused flour beetle (T. castaneum) (Tables 18 and 22). Both proportions failed to achieve any significant mortality for adults of both strains (Table 22). At 60 ppm, however, flaveson achieved offspring reductions of 29% and 50% in the resistant (QSO393) and susceptible (LS2) strains, respectively (Table 22).

[0185] [Table 18]

[0186] [Table 19]

[0187] [Table 20]

[0188] [Table 21]

[0189] [Table 22]

[0190] [Example 13] Evaluation of the combination of flavesone and chlorpyrifos-methyl (Lerdan) against major storage grain pests resistant to commonly used biological agents. The experiment in Example 12 was repeated using a combination of flavesone and chlorpyrifos-methyl.

[0191] Across all combined treatment experiments, the control mortality rates in both susceptible and resistant strains of all five species were negligible (0–3%) (Tables 23–27). The number of adult offspring produced in the control group of the long-grained grain beetle (R. dominica) was 186 for the susceptible (QRD14) and resistant (QRD1440) strains (Table 23), 59 (QTC4) and 480 (QTC279) for the confused flour beetle (T. castaneum) (Table 24), 467 (QCF31) and 188 (QCF73) for the rusty-breasted flat beetle (C. ferrugineus) (Table 25), 526 (VOS48) and 429 (QOS302) for the sawtooth flat beetle (O. surinamensis) (Table 26), and 720 (LS2) and 565 (QSO393), respectively, for the susceptible and resistant strains of the grain weevil (S. oryzae) (Table 27).

[0192] All experimental combinations of flaveson and chlorpyrifos-methyl, applied at both higher and lower rates, were highly successful against susceptible strains of all five test species, resulting in 100% adult mortality and offspring reduction (Tables 23-27). The efficacy of all these combinations was greatest against resistant strains of the rusty-breasted flat beetle (C. ferrugineus), where complete control of both adults and offspring was achieved (Table 26). Furthermore, with the exception of a 99% offspring reduction in one combination, all these treatments achieved 100% offspring control in resistant strains of the confused flour beetle (T. castaneum) (QTC279), sawtoothed flat beetle (O. surinamensis) (QOS302), and grain weevil (S. oryzae) (QSO393) (Tables 24, 26, and 27). However, complete adult mortality was achieved against resistant strains of the grain borer (R. dominica) (QRD1440) only with the combination of Flaveson 60 + chlorpyrifos-methyl 5, while complete offspring reduction was achieved in grains treated with the combinations of Flaveson 30 + chlorpyrifos-methyl 10, Flaveson 60 + chlorpyrifos-methyl 5, and Flaveson 60 + chlorpyrifos-methyl 10 (Table 23).

[0193] [Table 23]

[0194] [Table 24]

[0195] [Table 25]

[0196] [Table 26]

[0197] [Table 27]

[0198] Table 28 summarizes the efficacy of the chlorpyrifos-methyl and flavesone combination.

[0199] [Table 28]

[0200] [Example 14] Evaluation of the combination of flaveson and deltamethrin (K-Obiol) against susceptible and resistant strains of the long-eared borer (R. dominica). Using a combination of flaveson and deltamethrin, the experiment in Example 12 was repeated with the susceptible QRD14 and resistant QRD1440 strains of the long-eared borer (R. dominica).

[0201] In these experiments, the control mortality rate remained below 1% for both the susceptible and resistant strains of this species, and similar numbers of surviving adult offspring (126 and 125) appeared (Table 29). In all combinations, complete control of both adults and offspring was achieved against the susceptible strain (QRD14), and high levels of control were achieved against the resistant strain (QRD1440) (Table 29). For adults of the resistant strain, all combinations resulted in a mortality rate of 93–100%. Similarly, all combinations resulted in a 99–100% reduction in the offspring of the resistant strain QRD1440 (Table 29).

[0202] The results are shown in Table 29.

[0203] [Table 29]

Claims

[Claim 1] The invention described herein.

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