[go: up one dir, main page]

WO2020030092A1 - Composition pharmaceutique contenant un composé de m-diamide et application de celle-ci - Google Patents

Composition pharmaceutique contenant un composé de m-diamide et application de celle-ci Download PDF

Info

Publication number
WO2020030092A1
WO2020030092A1 PCT/CN2019/099948 CN2019099948W WO2020030092A1 WO 2020030092 A1 WO2020030092 A1 WO 2020030092A1 CN 2019099948 W CN2019099948 W CN 2019099948W WO 2020030092 A1 WO2020030092 A1 WO 2020030092A1
Authority
WO
WIPO (PCT)
Prior art keywords
active ingredient
compound
pharmaceutical composition
composition containing
hydrogen
Prior art date
Application number
PCT/CN2019/099948
Other languages
English (en)
Chinese (zh)
Inventor
倪珏萍
相君成
吕亮
洪湖
刘吉永
邵佳礼
周丽琪
刘叙杆
Original Assignee
上海泰禾国际贸易有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from CN201910701359.4A external-priority patent/CN110810412B/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 WO2020030092A1 publication Critical patent/WO2020030092A1/fr

Links

Classifications

    • 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
    • A01N37/18—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 the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
    • 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
    • A01N37/34—Nitriles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
    • C07C237/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C255/50—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles

Definitions

  • the present application belongs to the technical field of prevention and control of harmful organisms by pharmaceutical compositions, and relates to a pharmaceutical composition containing an isodiamide compound and an application thereof, and in particular, to a composition containing an isodiamide compound and an agricultural antibiotic and an application thereof.
  • 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.
  • Insecticide compositions have an important role in improving the effectiveness of insecticides, expanding the spectrum of control, and delaying the development of resistance. Therefore, in the art, it is still desired to develop more efficient insecticide compositions or insecticidal bactericidal compositions to meet the needs of agriculture and the forestry industry.
  • the purpose of the present application is to provide a pharmaceutical composition containing an m-diamide compound and its application.
  • the pharmaceutical composition has a synergistic effect, and can prevent and control diseases caused by pests and diseases.
  • the present application provides a pharmaceutical composition containing an m-diamide compound.
  • the pharmaceutical composition includes an active ingredient A and an active ingredient B.
  • the active ingredient A is an amide compound having a structure represented by Formula I.
  • the active ingredient B includes any one or a combination of two other pesticides or fungicides;
  • Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, substituted or unsubstituted 3-10 membered heterocyclic group, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl or C 1 -C 6 haloalkylsulfonyl;
  • Q is selected from C 3 -C 8 cycloalkyl or C 3 -C 8 halocycloalkyl;
  • X is selected from hydrogen, fluorine or trifluoromethyl
  • Y 1 is selected from fluorine, chlorine, bromine, iodine, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, C 2 -C 4 alkenyl , C 2 -C 4 haloalkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 halocycloalkyl, C 1- C 6 alkylcarbonyl, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl or C 1 -C 6 haloalkylsulfonyl;
  • Y 2 is selected from bromine, iodine, cyano, nitro, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, C 2 -C 4 alkenyl, C 2 -C 4 haloalkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 halocycloalkyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl or C 1 -C 6 haloalkylsulfonyl;
  • R 1 is selected from hydrogen, fluorine or methoxy
  • R 2 is selected from fluorine or trifluoromethyl
  • R 3 and R 4 are each independently selected from hydrogen, halogen, cyano, nitro, C 1 -C 6 alkyl , C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl or C 3 -C 8 halocycloalkyl;
  • n represents an integer of 0 to 3 (for example, 0, 1, 2 or 3); W 1 and W 2 are independently an oxygen atom Or sulfur atom.
  • the pharmaceutical composition using the m-bisamide compound having the structure shown by the formula I as described in the present application as the active ingredient A and blended with the active ingredient B has a synergistic effect between the active ingredient A and the active ingredient B.
  • the control effect is significantly improved, and since the active ingredient A can reach an insecticidal activity of more than 80%, or even 90% -100% at a low dose, the effect is fast.
  • the insecticidal activity can be exerted, and a high insecticidal activity can be achieved within 3 days. It can reduce the damage to plants and humans caused by excessive drug concentration, and make less drug residues during application, which is more conducive to environmental protection.
  • the present application provides a pharmaceutical composition containing a compound substituted at the 3-position of m-diamide with an N-cyclopropylmethyl derivative.
  • the pharmaceutical composition includes active ingredient A and active ingredient B.
  • the active ingredient A It is an m-bisamide compound having a structure represented by Formula II, and the active ingredient B includes any one or a combination of other fungicides, insecticides, or acaricides;
  • Z is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylsulfonyl, or C 1 -C 6 haloalkyl Sulfonyl
  • Y is selected from C 1 -C 6 haloalkyl or C 1 -C 6 haloalkoxy;
  • R is selected from hydrogen or methyl.
  • an m-bisamide compound having a structure represented by Formula II is further preferred, and it is compounded with active ingredient B as an active ingredient of a pharmaceutical composition. Good results can be achieved at low doses, resulting in less drug residues and more environmental protection.
  • Z is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethoxy, trifluoromethyl, methanesulfonyl, or trifluoromethanesulfonyl.
  • Y is selected from trifluoromethyl or trifluoromethoxy
  • R is selected from hydrogen or methyl.
  • the m-bisamide compound is any one of the compounds shown in Table 1 below having the general formula II.
  • 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
  • CF 3 is a trifluoromethyl group
  • OCF 3 is a trifluoromethoxy group
  • MeS (O) 2 represents methanesulfonyl
  • CF 3 S (O) 2 represents trifluoromethanesulfonyl.
  • the m-diamide compound is any one or a combination of at least two selected from the following compounds 1-14:
  • the active ingredient B was selected. There are more than 680 known active ingredients of pesticides, and more than 100 commonly used active ingredients. Most of them have different degrees of resistance. Agricultural antibiotics insecticides or fungicides, because they come from biological sources, are environmentally friendly and have low dosages, but they also have drug resistance. In actual production, they have to increase the amount of drugs used.
  • the active ingredient B is selected from any one or a combination of antibiotic bactericides, insecticides, or acaricides in the prior art.
  • the active ingredient B is selected from the group consisting of avermectin, methylaminoavermectin benzoate (formin salt), spinosad, ethyl spinosad, ivermectin, Mibel Any one or a combination of two or more pesticides, fungicides, such as biotin, polyoxin, Jinggangmycin, kasugamycin, and bacteriocin.
  • avermectin methylaminoavermectin benzoate (formin salt), spinosad, ethyl spinosad, ivermectin, Mibel Any one or a combination of two or more pesticides, fungicides, such as biotin, polyoxin, Jinggangmycin, kasugamycin, and bacteriocin.
  • the pharmaceutical composition containing the metadiamide compound is a pharmaceutical composition containing the metadiamide compound (active ingredient A) and the active ingredient B described in Table 2 below, but not Limited to the combinations listed in the table.
  • the medicinal composition containing an m-bisamide compound is a medicinal composition containing the active ingredient A and the active ingredient B described in Table 1, and the active ingredient B is not limited to the above-mentioned antibiotic-based pharmaceutical products.
  • the combined effects of the pharmaceutical composition were tested using harmful organisms such as rice cockroach, rice leaf roller, vegetable diamondback moth, vegetable beet armyworm, eggplant thrips, wheat armyworm, wheat scab, rice sheath blight, A synergistic composition was found.
  • the weight ratio of the active ingredient A and the active ingredient B described herein is 200: 1 to 1: 200, for example, 200: 1, 180: 1, 150: 1, 130: 1, 100: 1, 80: 1, and 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 the metadiamide compound has different preferred weight ratios according to the difference between the active ingredient A and the active ingredient B.
  • the active ingredient is When A and active ingredient B are selected from the components described 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: 50 Compound of formula I: ethyl spinosad 100: 1 ⁇ 1: 100 50: 1 ⁇ 1: 50 Compound of Formula I: Methylavermectin Benzoate 100: 1 ⁇ 1: 100 80: 1 ⁇ 1: 80 Compound of Formula I: Spinosad 100: 1 ⁇ 1: 100 60: 1 ⁇ 1: 60 Compound of Formula I: Polyclonal 100: 1 ⁇ 1: 100 20: 1 ⁇ 1: 20 Compound of formula I: Jinggangmycin 100: 1 ⁇ 1: 100 50: 1 ⁇ 1: 50
  • 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 a pharmaceutical formulation comprising a pharmaceutical composition containing an m-diamide compound as described above and an agrochemically acceptable adjuvant and / or carrier.
  • the weight percentage content of the mesodiamide compound-containing pharmaceutical composition is 0.01-99%, such as 0.01%, 0.1%, 1%, 3%, 5%, 8 %, 10%, 15%, 18%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99%.
  • the agrochemically acceptable adjuvant includes any one or at least one of a dispersant, a wetting agent, an emulsifier, an antifreeze, a thickener, a defoamer, a preservative, a stabilizer, or a colorant. A combination of the two.
  • the dispersant includes lignin sulfonate, alkylphenol polyoxyethylene ether, naphthalenesulfonic acid formaldehyde condensate sodium salt, fatty amine polyoxyethylene ether, fatty acid polyoxyethylene ester, glycerin fatty acid ester polyoxylate Vinyl ether, polycarboxylate, formaldehyde condensate, calcium alkylbenzenesulfonate, alkylphenol polyoxyethylene ether.
  • the wetting agent is selected from the group consisting of sodium lauryl sulfate, alkyl naphthalene sulfonate, pulverized powder BX, polyoxyethylene ether, EO / PO block polyether, fatty alcohol polyoxyethylene ether, and fatty alcohol polyoxylate.
  • the emulsifier is selected from dodecylbenzenesulfonate, alkylnaphthalenesulfonate, alkylsulfonate, alkylphenol polyoxyethylene ether, benzylphenol polyoxyethylene, phenethylphenol polyoxyethylene Ether, fatty amine polyoxyethylene ether.
  • the antifreeze is selected from ethylene glycol, propylene glycol, and glycerol.
  • the thickener is selected from the group consisting of xanthan gum, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl starch, methyl cellulose, sodium starch phosphate, magnesium aluminum silicate, and polyvinyl alcohol.
  • the defoamer is selected from the group consisting of silicone oil, silicone compounds, tributyl phosphate, C10-20 saturated fatty acid compounds, and polyether defoamers.
  • the preservative is selected from the group consisting of formaldehyde, phenyl salicylate, butyl parahydroxybenzoate, and potassium sorbate
  • the stabilizer is selected from triphenyl phosphite, epichlorohydrin, epoxy soybean oil, and silicic acid.
  • Magnesium aluminum, the colorant is selected from the group consisting of azo pigments, titanium oxide, and iron oxide.
  • the carrier includes a filler and / or a solvent
  • the agrochemically acceptable carrier includes a solid carrier and / or a liquid carrier.
  • the solid support includes natural or synthetic clays and silicates, such as natural silica and diatomaceous earth; magnesium silicates such as talc; magnesium aluminum silicates such as kaolinite, kaolin, montmorillonite, and mica; White carbon black, calcium carbonate, light calcium carbonate; calcium sulfate; limestone; sodium sulfate; amine salts such as ammonium sulfate and hexamethylene diamine.
  • Liquid carriers include water and organic solvents.
  • Organic solvents include aromatic hydrocarbons such as xylene, benzene, xylene, toluene, etc .; chlorinated hydrocarbons such as chlorobenzene, vinyl chloride, trichloromethane, dichloromethane, etc .; aliphatic hydrocarbons such as petroleum distillates, Cyclohexane, light mineral oil; alcohols such as isopropanol, butanol, ethylene glycol, propylene glycol, glycerol, and cyclohexanol and their ethers and esters; ketones such as acetone, cyclohexanone, and dimethyl Formamide and N-methyl-pyrrolidone.
  • aromatic hydrocarbons such as xylene, benzene, xylene, toluene, etc .
  • chlorinated hydrocarbons such as chlorobenzene, vinyl chloride, trichloromethane, dichloromethane, etc .
  • the active ingredient may be mixed with a liquid carrier and / or a solid carrier, and auxiliary agents such as emulsifiers, dispersants, stabilizers, wetting agents, adhesives Mixtures, defoamers, antioxidants, etc.
  • auxiliary agents such as emulsifiers, dispersants, stabilizers, wetting agents, adhesives Mixtures, defoamers, antioxidants, etc.
  • the dosage form of the pharmaceutical preparation is a solution, a soluble powder, a soluble granule, an emulsifiable concentrate, a wettable powder, an aqueous emulsion, a suspending agent, a dispersible oil suspending agent, a water-dispersible granule, and a microcapsule suspending agent.
  • Granules, microemulsions, suspension emulsions, microcapsule suspension-suspensions ultra-low-volume liquids, hot aerosols, film-spreading oils, suspended seed coatings, dry powders for seeds, suspensions for seeds, and seeds for Powder dissolving agent, seed treatment dispersible powder, seed treatment emulsion or seed treatment liquid.
  • the dosage form of the pharmaceutical preparation is a solution, a soluble granule, a suspension, an emulsifiable concentrate, a wettable powder, an aqueous emulsion, a water-dispersible granule, a dispersible oil suspension, a microcapsule suspension, and an ultra-low capacity.
  • Liquid, hot aerosol, suspension seed coating or seed treatment dispersible powder is a solution, a soluble granule, a suspension, an emulsifiable concentrate, a wettable powder, an aqueous emulsion, a water-dispersible granule, a dispersible oil suspension, a microcapsule suspension, and an ultra-low capacity.
  • the present application provides the application of the pharmaceutical composition or pharmaceutical preparation containing the metadiamide compound as described above in the prevention, control of plant diseases or insect pests in agriculture, forestry, and horticulture.
  • the medicinal composition or medicinal preparation containing the metadiamide compound described in the present application is suitable for controlling various agricultural, forestry, horticultural pests and sanitary pests that harm rice, corn, wheat, potato, fruit trees, vegetables, other crops and flowers, and Disease.
  • 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 the pharmaceutical
  • the pests include lepidoptera, coleoptera, hemiptera, tarptera, diptera, orthoptera, homoptera, isoptera, hymenoptera, and spider mite
  • said Diseases include diseases caused by semi-known bacteria, ascomycetes, basidiomycetes, and the like.
  • 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 diseases include, but are not limited to, wheat scab, rice sheath blight, rice blast and the like.
  • the method of using the pharmaceutical composition or pharmaceutical preparation is spraying, soil treatment, seed treatment, flight prevention, and the like.
  • 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 and insect pests, which method is: applying an effective dose of the above-mentioned pharmaceutical composition containing metadiamide compounds to a plant disease to be controlled or a growth medium thereof Or pharmaceutical preparations.
  • the effective dose is 10-1000g per hectare, such as 10g, 20g, 50g, 80g, 100g, 120g, 150g, 180g, 200g, 250g, 300g, 350g, 400g, 450g, 500g, 600g, 700g, 800g 900g or 1000g, preferably 20-500g per hectare.
  • composition of the present application may be applied to the disease or its growth medium in the form of a formulation.
  • the compound of the general formula I (especially the compound of the general formula II) is dissolved or dispersed in a carrier as an active ingredient or formulated into a formulation for easier dispersion when used as a fungicide.
  • these chemical preparations can be formulated as solution, emulsifiable concentrate, wettable powder, water emulsion, suspension, dispersible oil suspension, water-dispersible granule, seed treatment, microcapsule suspension, granule, microemulsion , Suspension emulsion, suspension-microcapsule suspension and so on.
  • the pharmaceutical composition of the present application has the following advantages in use:
  • composition of active ingredient A and active ingredient B in this application has a synergistic effect.
  • the amount of the composition used is greatly reduced compared with the single active ingredient alone, and the control effect is significantly improved; due to the significant resistance of active ingredient A to resistant pests
  • the activity also solves the prevention and control of important crop diseases and insect pests such as diploid pupae, diamondback moth, thrips and other important crops.
  • the drug resistance can be delayed after compounding, which is an effective resistance risk management tool and extends the life cycle of the drug.
  • the active ingredient A described in this application is compounded with the active ingredient B of different control objects, which expands the spectrum of control and saves labor costs of medication, and can be applied to vegetables, fruit trees, flowers, cereals, oil, sugar, etc. Crops, horticulture, forestry, health and various diseases and insect pests. In addition, it has extremely high activity against newly emerged Spodoptera frugiperda, which can be used for emergency prevention and control, which is conducive to maintaining environmental ecological security and social stability.
  • Methyl 2-fluoro-3- (N- (cyclopropylmethyl) benzamide) benzoate (13.00 g, 40.88 mmol) was dissolved in methanol (100 mL), and a 10% aqueous sodium hydroxide solution (6.54 g) was added. , 163.52 mmol, 65.4 mL), after stirring at room temperature for 2 h, the reaction was monitored by TLC for completion. The methanol was concentrated and removed under reduced pressure. The concentrated residue was dissolved in water (100 mL) and extracted with ethyl acetate (50 mL). The organic phase was discarded, and the pH of the aqueous phase was adjusted to 7 with a 2M aqueous hydrochloric acid solution.
  • 2-Bromo-6-trifluoromethyl-4-heptafluoroisopropylaniline (0.52 g, 1.28 mmol) was dissolved in tetrahydrofuran (4 mL), and lithium diisopropylaminoamide (0.77 mL) was added dropwise at -70 ° C. , 1.54 mmol), 5 minutes later, a tetrafluorofuran solution of 2-fluoro-3- [N- (cyclopropylmethyl) benzamido] benzoyl chloride synthesized in one step was added dropwise, stirred at -70 ° C for 30 minutes, and raised to Stirring was continued for 30 min at room temperature.
  • a saturated ammonium chloride aqueous solution (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.
  • Methyl 2-fluoro-3-aminobenzoate (2.00 g, 11.82 mmol) was dissolved in 1,2-dichloroethane (65 mL), and cyclopropylmethyl ketone (2.98 g, 35.47 mmol) was sequentially added at room temperature. ), Trifluoroacetic acid (8.08 g, 70.92 mmol) and sodium triacetoxyborohydride (7.51 g, 35.47 mmol). The reaction was heated to 45 ° C. for 1 h. When TLC monitored that the reaction was no longer in progress, the reaction was terminated. A saturated NaHCO 3 solution (50 mL) was added to the reaction solution, and extracted with dichloromethane (80 mL).
  • Formulation example 1 24% compound 6. Jinggangmycin solution
  • composition of the 24% compound 6 ⁇ jinggangmycin solution is shown in Table 5 below:
  • Preparation method Calculate the amount of each material according to the formula. In a 250ml three-necked flask, add deionized water, add propylene glycol methyl ether, then add compound 6, Jinggangmycin, heat to 30-40 ° C and stir for 2 hours. Finally add fat Alcohol polyoxyethylene ether, dissolved uniformly, and filtered to obtain a solution of 24% compound 6. Jinggangmycin.
  • composition of 10% Compound 8 ⁇ Avermectin EC is shown in Table 6 below:
  • Preparation method Calculate the amount of each material according to the formula. In a 250mL three-neck flask, add xylene, add compound 8, avermectin, calcium dodecylbenzenesulfonate, and castor oil polyoxyethylene ether. Stir at 50 ° C for 1.5 hours and filter to obtain 10% Compound 8. Avermectin EC.
  • the 30% compound 4 ⁇ polyoxin wettable powder is shown in Table 7:
  • Preparation method Calculate the amount of each material according to the formula. After mixing compound 4, polyoxin, sodium lauryl sulfate, sodium lignin sulfonate, and kaolin, uniformly pulverize to an average particle size of 10 microns with a jet mill That is, 30% of compound 4 ⁇ polyoxin wettable powder was obtained.
  • Preparation method Calculate the amount of each material according to the formula, dissolve Compound 2, Jinggangmycin, castor oil polyoxyethylene ether, and xylene uniformly at 40-50 ° C as Phase A; deionized water, propylene glycol, and tribenzene Vinylphenol polyoxyethylene ether phosphate is stirred and dissolved uniformly as Phase B; under high shear, add Phase A to Phase B slowly, cut to an average particle size of 1.5 microns, and add 0.1 parts of Carson 10 parts of 1% yellow The original gum solution was stirred for 30 minutes to obtain 25% Compound 2 ⁇ Jinggangmycin water emulsion.
  • Active ingredient A Ethyl spinosad 5 Active ingredient B Fatty alcohol polyoxyethylene ether 1.5 moisturizer Tristyryl phenol polyoxyethylene ether phosphate 2 Dispersant Sodium lignosulfonate 3 Dispersant Propylene glycol 4 antifreeze 1% xanthan gum solution 10 Thickener Casson 0.1 preservative Polydimethylsiloxane 0.2 Silicone defoamer Deionized water Make up 100 Carrier
  • 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, add ethyl poly
  • the bactericidin and compound 8 were sheared uniformly, and then ground to an average particle diameter of 2 microns by a sand mill, and 10 parts of a 1% xanthan gum solution was added and stirred for 30 minutes to obtain 15% of a compound 8 ⁇ ethyl spinosad suspension.
  • Preparation method Calculate the amount of each material according to the formula, and mix compound 3, avermectin, sodium lauryl sulfate, sodium lignin sulfonate, sodium naphthalene formaldehyde polymer sulfonate, ammonium sulfate, corn starch, and kaolin. , Pulverized by an air jet mill to an average particle size of 10 to 15 microns, kneaded by adding 17% of the powder amount, and then granulated by rotary extrusion, dried at 50 ° C for 3 hours, and sieved to obtain 25% compound 3 ⁇ Avermectin 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, add compound 1, methylamino Avermectin benzoate, The organic bentonite and fumed silica were sheared uniformly, and then ground to an average particle diameter of 4 micrometers by a sand mill to obtain a 5% compound 1 ⁇ methylaminoavermectin benzoate dispersible oil suspension agent.
  • Preparation method Calculate the amount of each material according to the formula. Dissolve compound 10, methylamino avermectin benzoate, polyaryl polymethylene polyisocyanate, and xylene uniformly at 40-50 degrees as Phase A. ; Another take deionized water, D-800, propylene glycol, dissolve uniformly, as phase B; under high shear, slowly add phase A to phase B, cut to an average particle size of 2 to 3 microns, and then add the material to In a three-necked flask, hexamethylene diamine was added, and the reaction was stirred at 50 to 60 ° C for 10 hours.
  • Tristyrenol phenol polyoxyethylene ether phosphate, kasson, an antifoaming agent, and a 1% xanthan gum solution were stirred for 1 hour. 35% Compound 10 ⁇ Aminoavermectin Benzoate Microcapsule Suspension was obtained.
  • Bioassay Example 1 Active ingredient A has significant activity against various pests
  • Targets Plutella xylostella 3rd instar larvae, armyworm 3rd instar larvae, diploid pupae 3rd instar larvae, all reared indoors.
  • Plutella xylostella + leaf soaking feeding method With reference to NY / 1154.14-2008, the main operation description is as follows: immerse the clean bract leaf dish in the medicinal solution for 10s, dry it and place it in petri dishes, 4 dishes per dish, put filter paper in the petri dish to moisturize. Ten dishes of Plutella xylostella were received in each dish and repeated three times. It was placed in a light incubator at a temperature of 25 ° C under 14hL: 10hD and cultured. The number of dead and live insects of Plutella xylostella was investigated 3 days after the administration, and the mortality was calculated.
  • Feeding on slime + dipping leaf With reference to NY / 1154.14-2008, the main operation description is as follows: immerse the clean corn leaf section in the medicinal solution for 10s, dry it and place it in petri dishes, 4 pieces per dish, put filter paper in the petri dish to moisturize. Ten dishes of slimeworms were received in each dish, and 3 replicates were performed. It was placed in a light incubator at a temperature of 25 ° C under 14hL: 10hD and cultured. The number of dead and live insects of the armyworm was investigated 3 days after the administration, and the mortality was calculated.
  • Erhuan + rice stalk dipping method With reference to NY / T1154.11-2008, the main operation is as follows: immerse the cleaned rice stalks in the medicinal solution for 10s, remove them, place them in a cool place to dry, put them into finger tubes, and insert 10 third-instar larvae. Each treatment was repeated 3 times. The mouth of the tube was sealed with a black cotton cloth. The rubber band was tied tightly and placed in a light incubator at 28 ° C in the dark. The number of dead worms in P. chinensis was investigated 3 days after the treatment, and the mortality of each treatment was calculated.
  • Bioassay Example 2 The composition of active ingredient A is a compound of formula II 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.
  • Bioassay Example 3 Active ingredient A is a compound of formula II and active ingredient B is avermectin, ivermectin, spinosad, etc., and its activity is tested against Plutella xylostella
  • Target Plutella xylostella 3rd instar larvae, reared indoors.
  • Test agent or combination name Dose mg / L 3d mortality% Theoretical mortality% Synergy effect Joint mode of action Compound 1 0.01 36.67 / / / Avermectin 0.06 70 / / / Ivermectin 0.4 75 / / / Spinosad 0.06 60 / / / Compound 1 + Avermectin 0.01 + 0.06 100 68.35 31.65
  • Bioassay Example 4 The composition of active ingredient A is a compound of formula II and active ingredient and B is methylaminoavermectin benzoate, ivermectin, mibelin
  • Soaking method Soaking method.
  • the operation description is as follows: With reference to NY / 1154.6-2006, the main operation description is as follows: immerse 10 test insects in the medicinal solution for 10s, dry them and place them in petri dishes, put 4 clean corn leaf sections in each dish, and petri dishes Put filter paper inside to moisturize. 3 repetitions. It was placed in a light incubator at a temperature of 25 ° C under 14hL: 10hD and cultured. The number of dead and live insects of the armyworm was investigated 3 days after the administration, and the mortality was calculated.
  • the evaluation method was the same as that in Example 2.
  • Bioassay Example 5 Activity test of a combination of compound 8 and avermectin on pyrene disulfide
  • Insect source 3rd instar larvae of pupae, indoor breeding.
  • Example 1 Rice stalk immersion method, the operation description is described in Example 1.
  • the evaluation method is referred to NY / T1154.7-2006, and the co-toxicity coefficient is used for evaluation.
  • the co-toxicity coefficient (CTC value) of the mixture is calculated according to formula (1), formula (2), and formula (3):
  • TTI A ⁇ P A + B ⁇ P B ⁇ ⁇ (2)
  • CTC co-toxicity coefficient
  • ATI mixed actual virulence index
  • TTI mixed theoretical virulence index
  • the co-toxicity coefficient (CTC) ⁇ 120 of the compounding agent is synergistic; CTC ⁇ 80 is antagonistic; 80 ⁇ CTC ⁇ 120 is additive.
  • Bioassay Example 6 Activity Test of a Composition of Compound 3 and Methyl Avermectin Benzoate on Spodoptera exigua
  • Insect source 3rd instar larvae of Spodoptera exigua, reared indoors.
  • Soaked leaf dish feeding method Soaked leaf dish feeding method. The operation description is as follows: immerse the clean bract leaf dish in the medicinal solution for 10s, dry it, and place it in a 24-well plate. Each well receives one test of beet armyworm, and each handles 24. It was placed in a light incubator at a temperature of 25 ° C under 14hL: 10hD and cultured. The number of dead and alive insects was investigated 3 days after the administration, and the mortality was calculated.
  • Bioassay Example 7 Activity Test of a Compound 1 and Spinosad Composition on Plutella xylostella
  • Insect source Plutella xylostella 3rd instar larvae, reared indoors.
  • Bioassay Example 8 Test of the activity of the composition of compound 9 and ethyl spinosad against Plutella xylostella
  • Insect source Plutella xylostella 3rd instar larvae, reared indoors.
  • Leaf soaking method Operation description Contemporaneous test embodiment 1, statistical evaluation of concomitant test embodiment 5.
  • Bioassay Example 9 Activity test of a compound 12 and avermectin on Plutella xylostella
  • Insect source Plutella xylostella 3rd instar larvae, reared indoors.
  • Leaf soaking method Operation description Contemporaneous test embodiment 1, statistical evaluation of concomitant test embodiment 5.
  • Bioassay Example 10 25% compound 10 ⁇ polyoxin wettable powder (compound 10 mass concentration of 10%, polyoxin mass concentration of 15%) Field control of wheat scab, and armyworm control
  • Crops and metallurgical objects wheat, early flowering period, scab, slime
  • Bioassay Example 11 24% Compound 8 ⁇ Jinggangmycin solution (Compound 8 mass concentration is 12%, Jinggangmycin mass concentration is 12%) Field control of rice leaf curl, and rice sheath blight
  • Crops and targets rice, leaf roller, rice sheath blight

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

L'invention concerne une composition pharmaceutique contenant un composé de m-diamide et une application de celle-ci. La composition pharmaceutique comprend un composant actif A et un composant actif B, le composant actif A étant le composé de m-diamide ayant une structure représentée par la formule I, et le composant actif B étant une combinaison d'un ou deux autres pesticides ou bactéricides quelconques. La composition contenant le composant actif A et le composant actif B possède les effets uniques d'interaction synergique, de lutte contre les nuisibles résistants, d'élargissement d'un spectre d'activité, de lutte contre les insectes transmettant les virus et analogues, et peut efficacement prévenir et traiter diverses maladies et insectes nuisibles sur des cultures telles que le riz, le maïs, le blé, les légumes, les arbres fruitiers, les fleurs, les oléagineuses, les matières sucrières et analogues, ainsi que le jardinage et la sylviculture.
PCT/CN2019/099948 2018-08-10 2019-08-09 Composition pharmaceutique contenant un composé de m-diamide et application de celle-ci WO2020030092A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN201810913917 2018-08-10
CN201810913917.9 2018-08-10
CN201910701359.4A CN110810412B (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
CN201910701359.4 2019-07-31

Publications (1)

Publication Number Publication Date
WO2020030092A1 true WO2020030092A1 (fr) 2020-02-13

Family

ID=69413234

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2019/099948 WO2020030092A1 (fr) 2018-08-10 2019-08-09 Composition pharmaceutique contenant un composé de m-diamide et application de celle-ci

Country Status (1)

Country Link
WO (1) WO2020030092A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023112988A1 (fr) 2021-12-16 2023-06-22 住友化学株式会社 Procédé de lutte contre des arthropodes nuisibles

Citations (4)

* 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
JP2011157294A (ja) * 2010-01-29 2011-08-18 Mitsui Chemicals Agro Inc 有害生物防除組成物
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 (4)

* 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
JP2011157294A (ja) * 2010-01-29 2011-08-18 Mitsui Chemicals Agro Inc 有害生物防除組成物
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

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
OZOE, Y. ET AL.: "Insecticidal 3-benzamido-N-phenylbenzamides Specifically Bind with High Affinity to a Novel Allosteric Site in Housefly GABA Receptors", PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY, vol. 107, no. 3, 26 September 2013 (2013-09-26), pages 285 - 292, XP055683464, DOI: 10.1016/j.pestbp.2013.09.005 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023112988A1 (fr) 2021-12-16 2023-06-22 住友化学株式会社 Procédé de lutte contre des arthropodes nuisibles

Similar Documents

Publication Publication Date Title
CN110810412B (zh) 一种含有间二酰胺类化合物的药物组合物及其应用
KR102445236B1 (ko) m-디아미드계 화합물 및 이의 제조방법과 응용
DE60036290T2 (de) Pyrazolderivate und verfahren zu ihrer herstellung und pestizide die diese als aktive inhaltsstoffe enthalten
CN112661665B (zh) 一种酰胺类化合物及其制备方法和应用
CN108605940A (zh) 一种氟氯虫双酰胺杀虫剂及其应用
WO2018086633A1 (fr) Composition bactéricide comprenant de la benzisothiazolinone et de l&#39;éthylicine
CN103300019A (zh) 一种杀虫组合物
WO2020030092A1 (fr) Composition pharmaceutique contenant un composé de m-diamide et application de celle-ci
WO2015135424A1 (fr) Composition pesticide et procédé de lutte contre les organismes nuisibles
TWI252228B (en) Pesticidal pyrimidine-derivatives
WO2018068773A2 (fr) Composition bactéricide contenant de la benzisothiazolinone et une protéine activatrice d&#39;alternaria tenuissima
WO2018036289A1 (fr) Composition pesticide
WO2020030093A1 (fr) Composition pharmaceutique contenant un composé de m-diamide et son utilisation
CN113767908B (zh) 一种含有间二酰胺类化合物的药物组合物及其应用
WO2020030094A1 (fr) Composition pharmaceutique comprenant un composé méta-diamide et utilisation de celle-ci
CN114716408A (zh) 一类含芳香酰胺的双酰胺类衍生物及其制备方法和应用
CN115067345A (zh) 一种杀菌组合物、制剂及其应用
WO2020030095A1 (fr) Composition pharmaceutique contenant le composé méta-diamide et son utilisation
CN114656373B (zh) 一种氰基取代苯甲酰胺类化合物及其应用
WO2018171252A1 (fr) Composition pesticide contenant de la benzisothiazolinone et du thidiazuron
WO2018171817A1 (fr) Composition miticide contenant des dérivés de spiro-éther
CN116924952A (zh) 一种含硫酰胺类化合物及其制备方法和应用
CN107593728A (zh) 一种杀虫组合物
CN116102493A (zh) 一种酰胺类化合物及其制备方法和应用
CN104904743B (zh) 杀虫组合物

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19847521

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19847521

Country of ref document: EP

Kind code of ref document: A1