WO2020030095A1 - Composition pharmaceutique contenant le composé méta-diamide et son utilisation - Google Patents

Composition pharmaceutique contenant le composé méta-diamide et son utilisation Download PDF

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Publication number
WO2020030095A1
WO2020030095A1 PCT/CN2019/099951 CN2019099951W WO2020030095A1 WO 2020030095 A1 WO2020030095 A1 WO 2020030095A1 CN 2019099951 W CN2019099951 W CN 2019099951W WO 2020030095 A1 WO2020030095 A1 WO 2020030095A1
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Prior art keywords
active ingredient
compound
pharmaceutical composition
weight ratio
mesodiamide
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PCT/CN2019/099951
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English (en)
Chinese (zh)
Inventor
邵佳礼
相君成
刘吉永
周丽琪
马文静
倪珏萍
杜伟霞
侯爽
章海挺
丁福栋
吕亮
关龙
庄彩霞
龙从勇
Original Assignee
上海泰禾国际贸易有限公司
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Priority claimed from CN201910702251.7A external-priority patent/CN110810413B/zh
Application filed by 上海泰禾国际贸易有限公司 filed Critical 上海泰禾国际贸易有限公司
Publication of WO2020030095A1 publication Critical patent/WO2020030095A1/fr

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
    • A01N37/46—N-acyl derivatives
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N41/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom
    • A01N41/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom containing a sulfur-to-oxygen double bond
    • A01N41/10—Sulfones; Sulfoxides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N51/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds having the sequences of atoms O—N—S, X—O—S, N—N—S, O—N—N or O-halogen, regardless of the number of bonds each atom has and with no atom of these sequences forming part of a heterocyclic ring
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
    • A01N57/10—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-oxygen bonds or phosphorus-to-sulfur bonds
    • A01N57/16—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-oxygen bonds or phosphorus-to-sulfur bonds containing heterocyclic radicals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
    • A01N57/26—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-nitrogen bonds
    • A01N57/28—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-nitrogen bonds containing acyclic or cycloaliphatic radicals

Definitions

  • CN101208009A discloses that a composition containing a metadiamide compound has an insecticidal effect, and various types of pesticides and fungicides of various structure types in the prior art are widely used in various crops. With the continuous use of pesticides, pests and diseases will become resistant to some existing pesticide products, and the insecticidal activity of existing pesticide varieties may not always meet the needs of many agricultural practices.
  • H is a hydrogen atom
  • F is a fluorine atom
  • Cl is a chlorine atom
  • Br is a bromine atom
  • I is an iodine atom
  • CN is a cyano group
  • NO 2 is a nitro group
  • Me is a methyl group
  • OMe is a methoxy group
  • CH 2 Cl is monochloromethyl
  • CCl 3 is trichloromethyl
  • CHF 2 is difluoromethyl
  • CH 2 F is monofluoromethyl
  • CF 3 is trifluoromethyl
  • OCF 3 Is trifluoromethoxy
  • c-Pr is cyclopropyl
  • c-Bu is cyclobutyl
  • c-Pent is cyclopentyl
  • c-Hex is cyclohexyl, in the group Represents the group attachment position.
  • C1-C6 alkyl refers to a straight or branched chain alkyl group having 1 to 6 carbon atoms, and includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, and n-butyl Base, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl and the like.
  • C1-C6 alkoxy refers to a straight or branched chain alkoxy group having 1 to 6 carbon atoms and includes, without limitation, methoxy, ethoxy, n-propoxy, isopropoxy And terbutoxy.
  • C1-C6 haloalkyl refers to a linear or branched alkyl group having 1 to 6 carbon atoms substituted with a halogen atom, and includes, without limitation, trifluoromethyl, difluoromethyl, 1,1,1- Trifluoroethyl, pentafluoroethyl, heptafluoron-propyl, heptafluoroisopropyl and the like.
  • C3-C8 cycloalkyl refers to a cyclic alkyl group having 3 to 8 carbon atoms on the ring, and includes, without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Cycloheptyl, cyclooctyl, etc.
  • the molar ratio of the compound of the general formula III to the compound of the general formula IV is 0.5-2: 1, for example, 0.5: 1, 0.8: 1, 1: 1, 1.2: 1, 1.4: 1, 1.5: 1, 1.8 : 1 or 2: 1.
  • the organic base is triethylamine, N, N-diisopropylethylamine, N, N-dimethylaniline, pyridine, sodium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, sodium tert-butoxide Or any one or a combination of at least two of potassium tert-butoxide.
  • the inorganic base is any one or a combination of at least two of sodium hydroxide, potassium hydroxide or sodium hydride.
  • the solvent for the reaction in step 1- (i) is selected from the group consisting of dichloromethane, chloroform, toluene, ethyl acetate, acetone, acetonitrile, tetrahydrofuran, dioxane, N, N-dimethylformamide, di Any one or a combination of at least two of methyl sulfoxide or hexamethylphosphoryl triamine.
  • the molar ratio of the compound of general formula V to the compound of general formula VI is 0.5-2: 1, for example, 0.5: 1, 0.8: 1, 1: 1, 1.2: 1, 1.4: 1, 1.6: 1, 1.8 : 1 or 2: 1.
  • step 1- (ii) is performed in the presence of a basic substance, which is an organic base and / or an inorganic base.
  • the organic base is triethylamine, N, N-diisopropylethylamine, N, N-dimethylaniline, pyridine, sodium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, sodium tert-butoxide Or any one or a combination of at least two of potassium tert-butoxide.
  • the inorganic base is any one or a combination of at least two of sodium hydroxide, potassium hydroxide or sodium hydride.
  • the solvent for the reaction in step 1- (ii) is selected from the group consisting of dichloromethane, chloroform, toluene, ethyl acetate, acetonitrile, tetrahydrofuran, dioxane, N, N-dimethylformamide, dimethyl Any one or a combination of at least two of sulfoxide or hexamethylphosphoryltriamine.
  • a compound of the general formula VIII and a compound containing an LG group such as thionyl chloride, oxalyl chloride, phosgene, phosphoryl chloride, phosphorus pentachloride, phosphorus trichloride, and thionyl bromide are known by a known method.
  • a compound represented by general formula II Triphosgene, phosphorus tribromide or isopropyl chloroformate, etc.
  • the molar ratio of the compound of the general formula II to the compound of the general formula IX is 0.5-2: 1, for example, 0.5: 1, 0.8: 1, 1: 1, 1.2: 1, 1.4: 1, 1.6: 1, 1.8 : 1 or 2: 1.
  • step 1- (v) the reaction described in step 1- (v) is performed in the presence of a basic substance, which is an organic base and / or an inorganic base.
  • the organic base is trimethylamine, triethylamine, diisopropylethylamine, tri-n-butylamine, pyridine, piperidine, 3-methylpyridine, 2,6-dimethyl Any one or a combination of at least two of pyridine, N-methylmorpholine, 3-methylimidazole, 4-N, N-dimethylaminopyridine, an alkali metal alcoholate, and lithium amine.
  • the inorganic base is any one or a combination of at least two of alkali metal hydroxides, carbonates or phosphates.
  • the alkali metal hydroxide is any one or a combination of at least two of lithium hydroxide, sodium hydroxide, or potassium hydroxide.
  • the carbonate is any one or a combination of at least two of sodium bicarbonate, sodium carbonate or potassium carbonate.
  • the phosphate is dipotassium hydrogen phosphate and / or trisodium phosphate.
  • the solvent of the reaction in step 1- (v) is a halogenated hydrocarbon, an aromatic hydrocarbon, a chain or cyclic ether, an ester, a ketone, a nitrile or an aprotic polar inert solvent. Any one or a combination of at least two.
  • the halogenated hydrocarbon is any one or a combination of at least two of dichloromethane, chloroform, or carbon tetrachloride.
  • the aromatic hydrocarbon is any one or a combination of at least two of benzene, toluene, xylene, chlorobenzene or dichlorobenzene.
  • the chain or cyclic ethers are any one or a combination of at least two of diethyl ether, tetrahydrofuran, dioxane, or 1,2-dimethoxyethane.
  • the ester is ethyl acetate and / or butyl acetate.
  • the ketone is any one or a combination of at least two of acetone, methyl isobutyl ketone and cyclohexanone.
  • the nitriles are acetonitrile and / or propionitrile.
  • the aprotic polar inert solvent is 1,3-dimethyl-2-imidazolinone, sulfolane, dimethylsulfoxide, N, N-dimethylformamide, N-methylpyrrolidone, Any one or a combination of at least two of N, N-dimethylacetamide or hexamethylphosphoramide.
  • the reaction temperature in step 1- (v) is -70 ° C or more and the boiling point of the reaction solvent, for example, -70 ° C, -50 ° C, -30 ° C, -10 ° C, -5 ° C, 0 °C, 15 °C, 25 °C, 30 °C, 35 °C, 40 °C, 45 °C, 50 °C, 60 °C, 70 °C, 75 °C, 80 °C, 85 °C, 90 °C, etc. Perform the reaction.
  • the reaction time in step 1- (v) is 0.5-48 hours, such as 0.5 hours, 1 hour, 3 hours, 5 hours, 8 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours , 23 hours, 25 hours, 28 hours, 30 hours, 33 hours, 35 hours, 38 hours, 40 hours, 44 hours, or 48 hours.
  • the compound of the general formula I of the present application can be prepared by another method as follows:
  • a compound of the general formula X and thionyl chloride, oxalyl chloride, phosgene chloride, phosphoryl chloride, phosphorus pentachloride, phosphorus trichloride, thionyl bromide, triphosgene, and tribromide are made by a known method in this step.
  • Phosphoride, isopropyl chloroformate and the like are reacted to prepare a compound represented by the general formula XI containing an LG group.
  • the compound represented by the general formula XI is reacted with the compound represented by the general formula IX under the same conditions as described in 1- (v) to prepare a compound represented by the general formula XII.
  • the aromatic carboxylic acid amide derivative having a nitro group represented by the general formula XII can be reduced to produce an aromatic carboxylic acid amide derivative having an amine group represented by the general formula XIII.
  • Examples of the reduction reaction include a method using a hydrogenation reaction and a method using a metal compound (such as stannous chloride) or a metal (zinc powder, iron powder, etc.).
  • a metal compound such as stannous chloride
  • a metal such as zinc powder, iron powder, etc.
  • the hydrogenation reaction method can be used in a suitable solvent in the presence of a catalyst, under normal pressure or under pressure, in a hydrogen atmosphere.
  • a catalyst in the hydrogenation reaction include palladium catalysts such as palladium-carbon, cobalt catalysts, ruthenium catalysts, and platinum catalysts.
  • the solvent include alcohols such as methanol and ethanol; aromatic hydrocarbons such as benzene and toluene; chain or cyclic ethers such as diethyl ether and tetrahydrofuran; and esters such as ethyl acetate.
  • the pressure of the hydrogenation reaction is 0.1-10 MPa, for example, 0.1 MPa, 0.5 MPa, 0.8 MPa, 1 MPa, 1.5 MPa, 2 MPa, 3 MPa, 4 MPa, 5 MPa, 6 MPa, 7 MPa, 8 MPa, 9 MPa, or 10 MPa.
  • the temperature of the hydrogenation reaction is -20 ° C or higher and the boiling point of the reaction solvent, for example, -20 ° C, -10 ° C, -5 ° C, 0 ° C, 5 ° C, 10 ° C, 15 ° C, or 20 ° C. , 25 ° C, 30 ° C, 35 ° C, 40 ° C, 45 ° C, 50 ° C, 60 ° C, 70 ° C, 75 ° C, 80 ° C, etc., or the reaction is carried out at the boiling point of the solvent, which is the reflux state.
  • the time of the hydrogenation reaction is 0.5-48 hours, such as 0.5 hours, 1 hour, 3 hours, 5 hours, 8 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours, 23 hours, 25 Hours, 28 hours, 30 hours, 33 hours, 35 hours, 38 hours, 40 hours, 44 hours, or 48 hours.
  • the method using a metal compound or a metal is performed in any one or a mixed solvent of at least two of methanol, ethanol, or ethyl acetate.
  • the active ingredient B is selected from any one or a combination of at least two fungicides, insecticides or acaricides currently available.
  • the active ingredient B is selected from the group consisting of nicotine, rotenone, veratridine, matrine, dermatol, mineral oil, imazapyr, thiamethoxam, imidacloprid, clothianidin, clothianidin, and pyrimidine Insecticides, nitenpyram, dimethoxam, piperididin, chlorothiline, flufenamid, flufenamid, triflumezopyrim, flupyradifurone (chemical name 4-[(6- Chloro-3-pyridylmethyl) (2,2-difluoroethyl) amino] -furan-2 (5H) one), spinosad, ethyl spinosad, chlorpyrifos, methyl chlorpyrifos, dimethoate, Dimethoate, Dichlorvos, Triazophos, Phoxim, Thiazophos, Diazphos, Malathion, Methamidophos, Hydra
  • B is not selected from the group consisting of avermectin, methylaminoavermectin benzoate, spinosyn, ethyl spinosad, ivermectin, mibemycin, thiamethoxam, imidacloprid, clothianidin, Clothianidin, acetamiprid, nitenpyram, dipyridam, epoxipyram, flupurone, flufenacil, nitrflufenid, pymetrozine, thiazidone, trifluorobenzimid , Dichlorothiapyrimidine, diprofen, pyrifluquinazon, benzpyrimoxan, anisoleconazole, tebuconazole, prothioconazole, cyclopropazol, azoxystrobin, oxystrobin, pyraclostrobin , Picoxystrobin, metalaxyl, metalaxyl, flupro
  • the active ingredient B is selected from the group consisting of fenpyram, thiamethoxam, clothianidin, imidacloprid, acetamiprid, nitenpyram, diflubenzuron, flufenacil, triflumezopyrimide, and triflumezopyrim , Flupyradifurone, spinosyn, ethyl spinosad, chlorpyrifos, triazophos, chlorfenapyr, fipronil, fipronil, fipronil, deltamethrin, beta-cypermethrin, beta-cyhalothrin, Bifenthrin, fenvalerate, fenvalerate, tefluthrin, beta-cypermethrin, avermectin, methylaminoavermectin benzoate, pymetrozine, ethiprole, flubendicarb Urea, l
  • the active ingredient B is selected from the group consisting of fenpyram, thiamethoxam, imidacloprid, acetamiprid, nitenpyram, fenflufenacil, flufenacil, triflumezopyrim, flupyradifurone, and more Bactericidin, ethyl spinosad, chlorpyrifos, pyracronil, fipronil, deltamethrin, beta-cyhalothrin, bifenthrin, fenvalerate, fenvalerate, tefluthrin , Beta-cyhalothrin, avermectin, avermectin benzoate, pymetrozine, ethiprole, flubendicarb, flubenzuron, fluazinam, butyl ether urea, flubenzuron, alpha Oxfenazide, Nitrofen, Acetofen, Te
  • the medicinal composition containing the metadiamide compound is a medicinal composition comprising the metadiamide compound (active ingredient A) and the active ingredient B as the active ingredients described in Table 2 below:
  • the weight ratio of the active ingredient A and the active ingredient B described in this application is 200: 1-1: 200, for example, 200: 1, 180: 1, 150: 1, 130: 1, 100: 1, 80: 1 , 60: 1, 40: 1, 20: 1, 10: 1, 1: 1, 1:10, 1:30, 1:50, 1:80, 1: 100, 1: 120, 1: 140, 1 : 160, 1: 180 or 1: 200.
  • the pharmaceutical composition containing a metadiamide compound has different preferred weight ratios according to the active ingredient A and active ingredient B contained in it.
  • the active ingredient A and the active ingredient B of the amide compound pharmaceutical composition are selected from the ingredients shown in Table 3, their preferred weight ratios and particularly preferred weight ratios are shown in Table 3.
  • Active ingredient A Active ingredient B Preferred weight ratio Particularly preferred weight ratio Compound of formula I: Avermectin 100: 1-1: 100 50: 1-1: 10 Compound of formula I: lambda-cyhalothrin 100: 1-1: 100 60: 1-1: 5 Compound of formula I: ethyl spinosad 100: 1-1: 100 20: 1-1: 20 Compound of formula I: Deltamethrin 50: 1-1: 50 10: 1-1: 10 Compound of Formula I: Fenpropathrin 50: 1-1: 50 10: 1-1: 10 Compound of Formula I: Methylavermectin Benzoate 100: 1-1: 100 20: 1-1: 20 Compound of formula I: flubendicarb 50: 1-1: 50 20: 1-1: 20 Compound of formula I: flubenzuron 50: 1-1: 50 20: 1-1: 20 Compound of Formula I: Pyridaben 50: 1-1: 50 10: 1-1: 10 Compound of formula I: chlorantranili
  • the m-diamide compound may also be replaced with a tautomer, an enantiomer, a diastereomer or a salt thereof.
  • a pharmaceutical composition containing the tautomer, enantiomer, diastereomer, or a salt of the m-diamide compound can also exert the same properties as the m-diamide-containing compound described in the present application.
  • the pharmaceutical composition has the same action effect, good insecticidal effect and fast-acting effect at a low dose.
  • the present application provides the application of the pharmaceutical composition containing an m-bisamide compound as described above for controlling plant diseases or insect pests in agriculture, forestry, and horticulture.
  • the pharmaceutical composition containing an amide compound of the present application is suitable for controlling various agricultural and forestry, horticultural pests, and health pests and diseases that harm rice, corn, wheat, potatoes, fruit trees, vegetables, other crops, and flowers.
  • the pests include lepidoptera, coleoptera, hemiptera, tarptera, diptera, orthoptera, homoptera, isoptera, hymenoptera, and spider mite pests.
  • the pests include but are not limited to: cotton bollworm, diamondback moth, Spodoptera exigua, Spodoptera litura, Pieris rapae, diploid pupae, pupae trichoderma, big pupae, Spodoptera frugipera, rice leaf roller, rice Thrips, western flower thrips, melon thrips, onion thrips, ginger thrips, mango thrips, peach aphid, cotton aphid, alfalfa aphid, apple yellow aphid, wheat aphid, jumping beetle, stink bug, gray planthopper, Brown planthopper, white-backed planthopper, termite, mosquito fly, spider mite, citrus red spider.
  • the composition of the present application has a wide range of applications, and the scope of plants or crops to be applied mainly includes the following categories: vegetables, cucumbers, loofahs, watermelons, melon, pumpkins, hanging melon, spinach, celery, cabbage, cabbage, gourd, pepper, eggplant , Tomato, shallot, ginger, garlic, leek, strawberry, lettuce, kidney bean, cowpea, broad bean, radish, carrot, potato, yam; cereal, wheat, barley, corn, rice, sorghum; fruit tree, apple, pear, banana , Citrus, grape, lychee, mango; flowers, peony, rose, flamingo; oil crops, peanuts, soybeans, rape, sunflower, sesame; sugar crops, sugar beets, sugar cane; other crops, such as potatoes, sweet potatoes, tobacco and Tea; horticulture, forestry, home health, public health areas, etc .; the above-listed plants or crops have no limiting effect on the scope of use of pesticide
  • the present application provides the use of a pharmaceutical composition containing an m-bisamide compound as described above in seed treatment of plants, crops, or flowers.
  • the present application provides a method for controlling plant diseases, which method is: applying an effective dose of a pharmaceutical composition containing an m-diamide compound as described above to a plant disease to be controlled or a growth medium thereof. Or a pharmaceutical formulation as described above.
  • 2,6-Dibromo-4-heptafluoroisopropylaniline (0.91g, 2.22mmol) was dissolved in tetrahydrofuran (4mL), and lithium diisopropylaminoamide (1.30mL, 2.66mmol) was added dropwise at -70 ° C. After 5 min, a one-step solution of tetrahydrofuran was added dropwise, and the mixture was stirred at -70 ° C for 30 min. The temperature was raised to room temperature and stirred for 30 min. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL).
  • N- [2-Bromo-4- (1,1,1,2,3,3,3-heptafluoroprop-2-yl) -6-trifluoromethylphenyl] -2-fluoro-3- Nitrobenzamide (1.28 g, 2.0 mmol) was dissolved in dimethyl sulfoxide (15 mL), sodium borohydride (155 mg, 4.0 mmol) was added in portions, and the temperature was raised to 60 ° C for 4.0 h. The reaction solution was cooled to room temperature, and 50 mL of water was added to the reaction solution. The mixture was extracted with 50 mL of ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography. (The eluent was petroleum ether: ethyl acetate 85: 15), 0.8 g of a yellow oil was obtained, and the yield was 71%.
  • Formulation example 1 20% compound 9 ⁇ furanid solution (the concentration refers to the sum of the concentrations of compound 9 and furanid in its solution)
  • Preparation method Calculate the amount of each material according to the formula. After compound 616, avermectin, sodium lauryl sulfate, sodium lignin sulfonate, and kaolin are mixed evenly, use an air jet mill to pulverize to an average particle size of 10 microns. That is, 30% of compound 616 ⁇ avermectin wettable powder was obtained.
  • Preparation method Calculate the amount of each material according to the formula, dissolve compound 627, acephate, castor oil polyoxyethylene ether, and xylene uniformly at 40-50 ° C as phase A; deionized water, propylene glycol, and three Styrylphenol polyoxyethylene ether phosphate is stirred and dissolved uniformly as phase B; under high shear, phase A is slowly added to phase B, sheared to an average particle diameter of 1.5 microns, and 0.1 part of carson 10 parts 1% The xanthan gum solution was stirred for 30 minutes to obtain a 15% compound 627 ⁇ acephate aqueous emulsion.
  • Preparation method Calculate the amount of each material according to the formula, stir and dissolve the deionized water, propylene glycol, tristyryl phenol polyoxyethylene ether phosphate, sodium lignin sulfonate, carson, and defoamer, and add acetazole Shear with compound 628 uniformly, and then grind it to an average particle size of 2 micrometers with a sand mill. Add 10 parts of a 1% xanthan gum solution and stir for 30 minutes to obtain 38% compound 628 ⁇ ethaconazole suspension.
  • Preparation method Calculate the amount of each material according to the formula, and mix compound 632, chlorantraniliprole, sodium lauryl sulfate, sodium lignin sulfonate, sodium naphthalene formaldehyde polymer sulfonate, ammonium sulfate, corn starch, and kaolin Homogeneous, pulverized to an average particle size of 10-15 microns by a jet mill, kneaded with 17% of the powder, and then granulated by rotary extrusion, dried at 50 ° C for 3 hours, and sieved to obtain 25% of the compound 632. Chlorantraniliprole water dispersible granules.
  • Preparation method Calculate the amount of each material according to the formula, stir and dissolve methyl oleate, fatty acid polyoxyethylene ether, and styrylphenol polyoxyethylene ether, and add compound 636, methylamino avermectin benzoate,
  • the organic bentonite and fumed silica were uniformly sheared, and then ground to an average particle diameter of 4 microns by a sand mill to obtain 15% of a compound 636 ⁇ methylaminoavermectin benzoate dispersible oil suspension agent.
  • the corn seedling feeding method was used for the activity test. Cut the above-ground part of fresh corn seedlings grown indoors, about 10cm, and set aside. The corn seedlings were immersed in the medicinal solution for 10s, and after being dried in a cool place, cut into 3 to 5 cm leaf sections, and placed in a petri dish, and placed 3 corn seedlings per dish. Ten 10th instar larvae of the armyworm were inserted into each well and repeated three times. Place in a light incubator at 25 ° C, and culture in the dark. 1,2,3 days after treatment, the reaction symptoms were investigated, and the mortality was calculated.
  • the concentration of some of the compounds of the present application is 1 ppm
  • the control effect on the armyworm ie, the mortality of the armyworm
  • the serial numbers of the compounds are: 2, 4, 5, 9, 11, 12, 13, 45, 168, 278, 281, 282, 309, 510, 526, 527, 528, 536, 554, 555, 556, 562, 566, 567, 569, 579, 599, 600, 601, 606, 607, 620, 623, 624, 625, 626, 630, 637, 640, 644, 645, 646, 649, 650, 673.
  • Test system Thrips populations that naturally occur on soybeans grown in greenhouses, with a base of occurrence greater than 100 heads per compound leaf, and thrips are in the active phase. (Sensitivity of the population to the medicament. Monitoring results under the same conditions: ethyl polysterilization 50mg / L dose of 66.55% after 6 days).
  • Test agent 5% SL (compound 5% + emulsifier 5% + solvent make up 100%) for each compound.
  • the pharmaceutical composition containing the active ingredient compound 616 and beta-cypermethrin has a synergistic effect on cotton bollworm.
  • Mother liquor preparation According to the proportion and dosage of the test design, weigh a certain amount of the original drug, dissolve it with N, N-dimethylformamide (DMF), and then add 0.05% Tween 80 water to prepare a mother liquor of a certain concentration.
  • DMF N, N-dimethylformamide
  • Preparation of medicinal solution 5 to 7 doses are set for each ratio. According to the design of the experiment, the mother liquor is diluted to the test dose in turn.
  • the co-toxicity coefficient (CTC value) of the mixture is calculated according to formula (1), formula (2), and formula (3):
  • LC 50 of M-mixture, unit is milligram per liter (mg / L).
  • the percentage content of PA-A agent in the mixture is percentage (%);
  • the percentage content of PB-B agent in the mixture is percentage (%).
  • composition containing the active ingredient compound 627 and avermectin has a synergistic effect on diospyridine
  • Mother liquor preparation According to the proportion and dosage of the test design, weigh a certain amount of the original drug, dissolve it with N, N-dimethylformamide (DMF), and then add 0.05% Tween 80 water to prepare a mother liquor of a certain concentration.
  • DMF N, N-dimethylformamide
  • Preparation of medicinal solution 5 to 7 doses are set for each ratio. According to the design of the experiment, the mother liquor is diluted to the test dose in turn.
  • Medicament treatment immerse the prepared rice stems in the medicinal solution for 10s, dry them and put them into finger tubes, and then put the test insects into the finger tubes with rice stems, 10 heads per tube, each treatment 30 Head test insect.
  • the same medicament is performed in order from low concentration to high concentration, and a blank control and a solvent control are set. After treatment, it was placed in a light incubator at a temperature of 28 ⁇ 1 °C and a light-dark ratio of 16h: 8h.
  • the co-toxicity coefficient (CTC value) of the mixture is calculated according to the formula of the biological test example 1:
  • the co-toxicity coefficient (CTC) ⁇ 120 of the compounding agent is synergistic; CTC ⁇ 80 is antagonistic; 80 ⁇ CTC ⁇ 120 is additive.
  • composition containing the active ingredient compound 628 and indoxacarb had synergistic effects on Spodoptera exigua.
  • Mother liquor preparation According to the proportion and dosage of the test design, weigh a certain amount of the original drug, dissolve it with N, N-dimethylformamide (DMF), and then add 0.05% Tween 80 water to prepare a mother liquor of a certain concentration. Preparation of medicinal solution: 5 to 7 doses are set for each ratio. According to the design of the experiment, the mother liquor is diluted to the test dose in turn.
  • DMF N, N-dimethylformamide
  • the co-toxicity coefficient (CTC value) of the mixture is calculated according to the formula of the biological test example 1:
  • the co-toxicity coefficient (CTC) ⁇ 120 of the compounding agent is synergistic; CTC ⁇ 80 is antagonistic; 80 ⁇ CTC ⁇ 120 is additive.
  • Test target brown planthopper, 3rd instar nymph.
  • the rice seedlings were immersed in the medicinal solution for 10s, and then filled into disposable cups. Each cup received 15 insects, sealed with plastic wrap, and treated 45 test insects. When dipping, the same medicament is performed in order from low concentration to high concentration, and a blank control and a solvent control are set.
  • the number of dead insects was investigated 3d after the treatment.
  • the DPS (v16.05) statistical analysis software was used to calculate the LC 50 value of each agent and its 95% confidence limit.
  • the co-toxicity coefficient (CTC) ⁇ 120 of the compounding agent is synergistic; CTC ⁇ 80 is antagonistic; 80 ⁇ CTC ⁇ 120 is additive.
  • Drug configuration drug name: compound 627, thiamethoxam, are the original drug.
  • Mother liquor preparation According to the proportion and dosage of the test design, weigh a certain amount of the original drug, dissolve it with N, N-dimethylformamide (DMF), and then add 0.05% Tween 80 water to prepare a mother liquor of a certain concentration.
  • DMF N, N-dimethylformamide
  • Medicinal treatment immerse the nymph leaves in the medicinal solution for 10s, insert it into a penicillin bottle filled with water, seal it, dry it, cover it with a transparent plastic cup, repeat 15 to 30 aphids each time, and repeat the treatment 3 times.
  • the same medicament is performed in order from low concentration to high concentration, and a blank control and a solvent control are set.
  • After the treatment it was placed in an observation room with an indoor temperature of 19 to 26 ° C., a humidity of 35% to 65%, and a culture rack with 14Lh: 10Dh light.
  • the co-toxicity coefficient (CTC) ⁇ 120 of the compounding agent is synergistic; CTC ⁇ 80 is antagonistic; 80 ⁇ CTC ⁇ 120 is additive.
  • Test target Tetranychus cinnabarinus, adult mite.
  • Drug name Compound 510, biphenylhydrazine ester, are the original drug.
  • Mother liquor preparation According to the proportion and dosage of the test design, weigh a certain amount of the original drug, dissolve it with N, N-dimethylformamide (DMF), and then add 0.05% Tween 80 water to prepare a mother liquor of a certain concentration. Preparation of medicinal solution: 5 to 7 doses are set for each ratio. According to the design of the experiment, the mother liquor is diluted to the test dose in turn.
  • DMF N, N-dimethylformamide
  • Medicament treatment immerse the mite-leaving leaf in the medicinal solution for 10s, insert it into a penicillin bottle filled with water, seal it, dry it, and cover it with a transparent plastic cup. Each repetition is 15 or more mites, and each treatment is repeated 3 times. .
  • the same medicament is performed in order from low concentration to high concentration, and a blank control and a solvent control are set. After the treatment, it was placed in an observation room with an indoor temperature of 19 to 26 ° C., a humidity of 35% to 65%, and a culture rack with 14Lh: 10Dh light.
  • the co-toxicity coefficient (CTC value) of the mixture is calculated according to the formula of the biological test example 1:
  • the co-toxicity coefficient (CTC) ⁇ 120 of the compounding agent is synergistic; CTC ⁇ 80 is antagonistic; 80 ⁇ CTC ⁇ 120 is additive.
  • Bioassay Example 11 The composition of active ingredient A is a compound of formula I and active ingredient B is avermectin, methylamino avermectin benzoate, ethyl spinosad, etc. Activity test
  • Target 3rd instar larvae of pupae, indoor breeding.
  • Theoretical mortality 1-(1-mortality of active ingredient A at this dose) (1-mortality of active ingredient B at this dose)
  • Synergistic effect ⁇ 20 means significant synergy; 10 ⁇ synergistic effect ⁇ 20, synergistic effect; -10 ⁇ synergistic effect ⁇ 10, synergistic effect; synergistic effect ⁇ -10, antagonistic, negative value The greater the degree of antagonism.

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  • Agronomy & Crop Science (AREA)
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  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
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  • Wood Science & Technology (AREA)
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Abstract

La présente invention concerne une composition pharmaceutique contenant un composé méta-diamide et son utilisation. La composition pharmaceutique comprend un ingrédient actif A et un ingrédient actif B. L'ingrédient actif A est un composé méta-diamide ayant une structure telle que présentée dans la formule I, et l'ingrédient actif B comprend n'importe lequel ou une combinaison de deux autres bactéricides, insecticides ou acaricides. L'ingrédient actif A et l'ingrédient actif B ont un effet de synergie, la quantité d'utilisation de la composition est grandement réduite comparée à celle d'un insecticide ayant un ingrédient actif unique, l'effet de régulation est grandement amélioré, et le profil de régulation est élargi. Ladite composition peut être appliquée à diverses maladies des plantes et ravageurs insectes de plantes telles que les légumes, les arbres fruitiers, les fleurs, les céréales, les plantes oléagineuses et les plantes sucrières ainsi que celles dans le domaine de l'horticulture et de la foresterie, et peut retarder le développement de la résistance aux médicaments.
PCT/CN2019/099951 2018-08-10 2019-08-09 Composition pharmaceutique contenant le composé méta-diamide et son utilisation WO2020030095A1 (fr)

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CN201810913917 2018-08-10
CN201910702251.7A CN110810413B (zh) 2018-08-10 2019-07-31 一种含有间二酰胺类化合物的药物组合物及其应用
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101208009A (zh) * 2005-07-27 2008-06-25 三井化学株式会社 有害生物防除组合物
CN102119143A (zh) * 2008-08-13 2011-07-06 三井化学Agro株式会社 酰胺衍生物、含有该酰胺衍生物的有害生物防除剂及其使用方法
CN108586279A (zh) * 2018-06-26 2018-09-28 上海泰禾国际贸易有限公司 一种间二酰胺类化合物及其制备方法和应用

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101208009A (zh) * 2005-07-27 2008-06-25 三井化学株式会社 有害生物防除组合物
CN102119143A (zh) * 2008-08-13 2011-07-06 三井化学Agro株式会社 酰胺衍生物、含有该酰胺衍生物的有害生物防除剂及其使用方法
CN108586279A (zh) * 2018-06-26 2018-09-28 上海泰禾国际贸易有限公司 一种间二酰胺类化合物及其制备方法和应用

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