Insecticide compositions containing compounds with inhibitor activity against acyl-coa:cholesterol acyltransferase or salts thereof as active ingredients

FIELD: insecticides.

SUBSTANCE: invention relates to insecticide compositions containing one or more compounds of formulae 2-11 with inhibitor activity against acyl-CoA or salts thereof as active ingredients. Said compounds have insecticide activity against pest nymph.

EFFECT: insecticides of improved safety and effectiveness.

2 cl, 3 ex, 9 dwg

 

This invention relates to the use of certain compounds and their salts having inhibitory action on the activity of acyl COA:cholesterylester (AST), as insecticide.

Synthetic organic insecticides are widely used to improve crops, destroying harmful insects, especially in the woods. However, prolonged and improper use of such insecticides for several decades has led to the destruction of biological protective systems the use of natural enemies, abnormal multiplication of harmful insects, or the development of resistance to insecticides, the development of toxicity in non-target organisms, including humans, pollution and so on.

Because of the side effects gradually decreased use of synthetic organic insecticides and, in particular, their application in everyday life in 2004 decreased by 50% compared with application in 1993. Therefore there is an urgent need to develop new insecticides to improve the yield of agricultural products. In addition, the global market for biological products increased by more than 5 trillion Korean won, and is also expected to increase in the domestic market of biological insecticides to about 94 billion Korean won. More tor the, with the development of bioengineering technologies, predicted even greater market insecticides.

Insecticides fall into insects through the oral cavity, skin, and spiracles. When insecticides are on the target insect, some of them decompose and become non-toxic, while others are activated, become more toxic and accumulate in the body or excreted from the body. When applying insecticide on insect only part of the applied insecticide has insecticidal activity to a target. Usually, because of the existence of several factors that hinder the penetration of the insecticide to the target in the body of the insect, only a fraction of the applied pesticide reaches the place of action and destroys the physiological and biochemical functions insect, eventually killing the insect. Therefore, in the implementation or development of insecticides largely ignored their effects, mechanisms of action and metabolism, affecting their effective concentrations in the body of an insect.

Currently available insecticides are classified according to the way the nerve poisons, but which affect the transmission of nerve impulses along the axon, inhibitors of energy production, growth regulators and insect sex pheromones. The insect growth regulators units is alauda on inhibitors of juvenile hormone and chitin synthesis inhibitors.

Nerve poisons kill insects by abnormal stimulation, excitation or inhibition of the nervous system.

The neuron is the smallest unit that makes up the nervous system, usually has one long thin fiber protruding from the cell body called the axon. Through its end, the axon comes into contact with a dendrite or another neuron, forming a specialized structure called a "synapse". The nerve impulse is transmitted along the axon. When the nerve impulse reaches the end of the axon, neurotransmitter, acetylcholine (hereinafter designated as "ACh") is immediately released from the synaptic vesicles into the synapse between the presynaptic and postsynaptic membranes. Released ACh binds with its receptor in the postsynaptic membrane, stimulating postsynaptic neuron. Thus, the nerve impulse is transmitted from one neuron to another neuron.

Immediately after the transmission of nerve impulses from the presynaptic membrane to the postsynaptic membrane ACh released from synaptic vesicles, is hydrolyzed by acetylcholinesterase (hereinafter designated as "AChE"), which stands out from the postsynaptic membrane. AChE has two types of actions: education customers, responsible for the destruction of negative ions and esters, and the hydrolysis of ACh.

So when ACh accum is niruetsya in the postsynaptic membrane at the site of binding to its receptor after transmission of the nerve impulse in the postsynaptic membrane you may experience excessive anxiety and convulsions. Therefore, ACh turns into choline and acetic acid under the influence of AChE. Choline is passed into the presynaptic membrane for re-use and turns into ACh into synaptic vesicles.

In this regard, when the insecticides that inhibit the activity of AChE in relation to the decomposition of ACh, which are primarily organophosphorus compounds and carbamates, are used to combat insects, ACh begins to accumulate in the synapse, and the transmission of nerve signals becomes abnormal, thereby causing convulsions, paralysis and, ultimately, death. It is known that insecticides based on organophosphorus compounds and carbamates inhibit the decomposition ACh mostly affecting the active site of AChE.

These chemical compounds relatively quickly penetrate into the insect through the skin, the joining surfaces of the nervous system, and cause failure in the transmission of nerve impulses and, after a certain latent period, symptoms of abnormal behavior, excessive nervous activity, severe convulsions, and, ultimately, paralysis and death.

The insect growth regulators kill insects by interfering in the synthesis of chitin and, consequently, in the formation of the cuticle of the insect, and are classified as inhibitors of juvenile hormone is in and chitin synthesis inhibitors.

Usually insects detoxify absorbed insecticides, digesting them with the help of various enzymes associated with oxidation, recovery, hydrolysis and the like. However, some insecticides receive even more toxicity in the metabolism. This change is called "activation", and insecticides are activated mainly by oxidation reactions.

Insects have a hard outer shell body (exoskeleton) instead of the skin. Unlike the skin of vertebrates, the exoskeleton of insects has structural functions, such as maintaining body shape, support muscles and hardness, and has a different chemical composition. The exoskeleton or cuticle) shall be discharged insects during growth. Thus, the formation of the cuticle is very important for the growth of insects. The exoskeleton of insects (leather) is a multilayer structure with three functional domains: the cuticle, the epidermis and the main membrane. The cuticle can be divided into two layers: epicuticula and procuticle. Chitin, which is absent in vertebrates, is a major component of the cuticle. Synthesis of chitin is the main objective in the implementation of the intention to kill the insect and inhibited especially insecticides, any abscopal dropping shells of insects that eventually kills the insect.

Procuticle exoskeleton h is Contracting out contains a large amount of chitin, which is a linear polymer of N-acetylglucosamine units. Unlike nerve poisons, when shedding inhibitors enter the insect through the mouth or the stigma, the cuticle of the insect is not formed normally, and thus is blocked insect moulting. The molting inhibitors inhibit the biosynthesis of chitin in the inner layer of endocuticle in procuticle without affecting the formation of epicuticular consisting of hardened proteins. Although the detailed mechanism of their action is not identified, it is known that the molting inhibitors inhibit the enzyme associated with the biosynthesis of chitin, which is the main component of procuticle, inhibiting the polymerization of UDP-N-acetylglucosamine.

Sex pheromones are also used to kill insects. Usually the male insects are caught using involving males pheromones emitted by females of the insect, and, ultimately, killed. However, sex pheromones are not effective on the field.

Some of the insecticides act by physically smothering pests, covering their skin emulsion oil. However, modern insecticides mainly affect the nervous system or enzymes associated with energy formation, which is essential for maintaining the life of the insect. In particular, we have developed and applied N. the practice of insecticides, acting on functions specific to insects, for example, inhibit the biosynthesis of education chitin, which forms the cuticle layer, or block the formation of juvenile hormone.

Physiology of insects described by many researchers. Recent studies have focused on enzymes or receptors associated with metabolism and exposure to molecular biological methods.

As a result of these studies it was found that the cholesterol in insects is required for the formation of the plasma membrane and waxes in the cuticle, as well as for transport of lipids in the blood or the lymph. Cholesterol can be replaced by a 22-dehydrocholesterol or 7-dihydroergosterol, and data connections, so called "alternative connections". However, the alternate connection cannot be used for the synthesis of hormones molting in insects.

Lipid components in insects are weakly hydrophilic, and therefore difficult transferred between tissues via the blood or lymph. Insects solve this problem with the help of transport proteins. Phospholipids, cholesterol, carbohydrates, juvenile hormones and even lipid materials derived from food or penetrating through the shell of the body, are transferred into the state linking to transfer proteins.

In particular, juvenile hormones are present in the status and binding for transport or binding proteins in the blood or the lymph. Binding proteins serve as carriers for juvenile hormones, as well as protect juvenile hormones from the attacks of non-specific esterases. However, specific to juvenile hormone esterase can destroy juvenile hormones regardless of their binding with binding proteins. Therefore, the titer of juvenile hormone in the blood or lymph is determined in accordance with the quantity allocated by allatoona body, and activity of juvenile hormone esterase.

Allatum body, secreting juvenile hormones, demonstrates a periodic action during larvae development and reproduction of adult stages, and its high activity in the secretion of hormones is closely related to the change in its volume. At high activity cells allatum body, secreting hormones that develop with increasing intracellular organelles in the cytosol. Some sources described that the juvenile hormones of insects inhibit metamorphosis insects, and insects, thus, shed at lower titers of juvenile hormone.

Many researchers have studied the physiology of insects, particularly enzymes or receptors associated with metabolism, using methods of molecular biology. However, the transport of hormones and the preservation of Sterol has been studied very rarely.

Because insects are unable to synthesize sterols, who m required as one of the vital nutrients. Most insects use plant sterols, turning them into cholesterol. Cholesterol is required for the biosynthesis of the molting hormone, and participates in the formation of the plasma membrane with phospholipids.

On the other hand, it is known that inhibitors of acyl COA:cholesterylester influence the prevention and treatment of hypertension in humans. In particular, at the present time is their development as therapeutic agents for hypertension, which have a new mechanism of action that is associated with the mechanism of seizures of atherosclerosis. Acyl COA:cholesterylester, which catalyzes the acylation of cholesterol is involved in the absorption of cholesterol in the small intestine, the synthesis of VLDL (VLDL) in the liver, and accumulation of cholesterol in acylated form in fatty tissues and walls of blood vessels. It is also known that acyl COA:cholesterylester involved in the development of atherosclerosis and is used for the development of agents for the treatment of hypertension with a new way of doing things. Representative examples of inhibitors of acyl COA:cholesterylester are chemically synthesized urea, amides, and phenols. Among them some samples of drugs tested for activity in vivo, are currently undergoing preclinical studies for the applications as therapeutic agents for atherosclerosis. However, currently there are no reports regarding the clinical use of inhibitors of acyl COA:cholesterylester.

Based on the fact that insects for growth and reproduction usually require sterols, the authors of this invention have discovered that insects die, if inhibited Sterol-allerease enzyme involved in the storage or transport of sterols, and developed new safe insecticides that can kill insects through a recently identified mechanism of action.

Conducting research for the present invention, taking into account the new concept inhibitory targets, Sterol-Alliluyeva enzyme, which plays a critical role in the formation of sterols for the preservation of various hormones during Sterol metabolism in larval stage of the insect, the authors of this invention have found, identified and cleared new compounds with insecticidal action from natural sources, and determined their molecular structure. With the help of the research system in accordance with this invention was carried out the analysis of do of selected compounds and other synthetic organic compounds inhibiting effect on the activity of acyl COA:cholesterylester. Insecticidal studies on two insect larvae, helped with the so opening, what compounds that have inhibitory activity against the above enzyme can kill the larvae.

Therefore, the object of this invention is the use of compounds having inhibitory action on the activity of acyl COA:cholesterylester, or their salts as an effective ingredient of the insecticide.

The above and other objects, features and advantages of this invention will be better understood from the below detailed description together with the accompanying drawings, in which:

the figure 1 presents1H-NMR spectrum of peripherin And (formula 1) in accordance with this invention;

the figure 2 presents1H-NMR spectrum of phenylpropene And (formula 2) in accordance with this invention;

the figure 3 presents1H-NMR spectrum of phenylpropene In (formula 3) in accordance with this invention;

the figure 4 presents1H-NMR spectrum of phenylpropene With (formula 4) in accordance with this invention;

the figure 5 presents1H-NMR spectrum of pheophorbide And (formula 5) in accordance with this invention;

the figure 6 presents a graph showing insecticidal activity of peripherin And in accordance with this invention larvaePlutella xylostellaL;

the figure 7 presents a graph showing the s insecticidal activity of the compounds of formula 5-11 in accordance with this invention larvae Plutella xylostellaL;

the figure 8 presents a graph showing the influence of phenylpropene a, b and C in accordance with this invention on the mass loss larvaeTenebrio molitorL, and

the figure 9 presents a photograph showing insecticidal activity of peripherin And, phenylpropene And and and pheophorbide in accordance with this invention larvaeTenebrio molitorL, where the degree of growth of larvae compared to the control group.

To achieve the above objective, this invention is an insecticidal composition comprising compounds with inhibitory effect on acyl COA:cholesterylester, or their salts, as effective ingredients.

Detailed description of the present invention are presented below.

The present invention presents an insecticidal composition containing the compounds having inhibitory activity against acyl COA:cholesterylester, or its salt, as an effective ingredient. This invention is presented in detail insecticidal composition containing as an effective ingredient a compound selected from the group comprising compounds represented by formulae 1-11 below.

[Formula 1]

[Formula 2]

[Formula 3]

[Formula 4]

[Formula 5]

[Formula 6]

[Formula 7]

[Formula 8]

[Formula 9]

[Formula 10]

[Formula 11]

Compounds of formula 1-11 can be obtained by chemical synthesis or by extraction from plants or microorganisms.

Among the compounds in accordance with this invention, the compounds of formulas 1-4 receiving method, comprising the cultivation ofPenicillium griseofulvumF1959, extraction of cultured cells with ethyl acetate and chromatography of the obtained extract.

An ethyl acetate extract obtained fromPenicillium griseofulvumF1959, is subjected to chromatography to obtain compounds of formulas 1-4. At the stage of chromatography, preferably applied by chromatography on a column of silica gel with subsequent high-speed liquid chromatography. Preferably, when carrying out chromatography on a column of silica gel as solvent a mixture of chloroform and methanol, and during the high-speed liquid chromatography as solvent a mixture of acetonitrile and water.

Compounds of formula 1-11 possess inhibitory activity against acyl COA:cholesterylester, and due to this action have insecticidal activity against larvae of insects.

In the experimental examples presented below, based on the fact that insects largely require sterols for growth and largely use the Sterol-alleluya enzymes involved in the maintenance and transport of sterols and activation and destruction of hormones, evaluate compounds in accordance with this invention to determine their insecticidal action. It was found that these compounds possess insecticidal activity by inhibiting acyl COA:cholesterylester, which is involved in the preservation and transport of sterols during metabolism of sterols.

Compounds in accordance with this invention, which possess inhibitory activity against acyl COA:cholesterylester, can be used to control harmful insects, including harmful arthropods (e.g., harmful insects and harmful mites and harmful nematodes. In addition, the compounds in accordance with this invention can be used for effective control of harmful insects with increased resistance to conventional insecticides.

In the case of application to the operation of effective ingredients of insecticidal compositions of the compounds in accordance with this invention, without adding other ingredients, can be used by themselves or in the form of their salts (acceptable in agriculture salts with inorganic acids such as hydrochloric acid or sulfuric acid, or organic acids such as p-toluensulfonate acid). However, compounds in accordance with this invention are usually mixed with solid carriers, liquid carriers, gaseous carriers or bait, or absorb them in basic materials, for example, a porous ceramic plate or non-woven fibers, to which is added a surfactant, and, optionally, other additives, and then they receive various forms, for example, oil sprays, emulsifiable concentrates, wettable powders, flowable granules, dusty, aerosols, Smoking compositions, such as mists, evaporated composition, Camtasia composition, toxic baits, and sheet or polymeric compositions to control ticks.

Each of the above compositions may contain one or more compounds in accordance with this invention as an effective ingredient in an amount of from 0.01 to 95 wt. -%

The solid carriers used in the compositions may include fine powders or granules or clay (e.g. kaolin, diatomaceous earth, bentonite, fubasami and the number clay), synthetic hydrogenated silicon oxide, talc, ceramics, other inorganic minerals (e.g., silicate, quartz, sulfur, activated carbon, calcium carbonate and hydrogenated silicon dioxide) and chemical fertilizers (e.g. ammonium sulfate, ammonium phosphate, ammonium nitrate, urea and ammonium chloride).

Liquid carriers include water, alcohols (e.g. methanol, ethanol etc), ketones (e.g. acetone and methyl ethyl ketone), aromatic hydrocarbons (e.g. toluene, xylene, ethylbenzene and methylnaphthalene), aliphatic hydrocarbons (e.g. hexane, cyclohexane, kerosene and light oil), esters (e.g. ethyl acetate and butyl acetate), NITRILES (e.g. acetonitrile and isobutyronitrile), ethers (e.g. diisopropyl ether and dioxane), acid amides (e.g. N,N-dimethylformamide and N,N-dimethylacetamide), halogenated hydrocarbons (e.g. dichloromethane, trichloroethane and carbon tetrachloride), dimethyl sulfoxide, vegetable oils (e.g. soybean oil and cottonseed oil).

Gaseous media or propellants may include freon gas, butane gas, LPG (liquefied petroleum gas), dimethyl ether and gaseous carbon dioxide.

Basic materials for toxic baits can include components bait (for example, powders of cereals, vegetable oils, sugars and kristallicheskuyu cellulose), antioxidants (for example, dibutylaminoethanol and nordihydroguaiaretic acid), preservatives (for example, dehydroacetic acid), agents for preventing accidental eating of children poisoned baits (for example, powder of red pepper) and attractants (e.g., the smell of cheese and onion).

Examples of surfactants may include alkyl sulphates, alkyl sulphonates, alkylarylsulphonates, simple alkylacrylate esters and their polyoxyethylene derivatives, simple polietilenglikolya esters, esters of polyvalent alcohols and alcohol derivatives of sugars.

Examples of other auxiliary agents, such as adhesive agents and dispersing agents include casein; gelatin; polysaccharides, such as starch, Arabic gum, cellulose derivatives and alginic acid; derivatives of lignin; bentonite; sugars; and synthetic water-soluble polymers such as polyvinyl alcohol, polyvinylpyrrolidone and polyacrylic acid.

In addition, as an auxiliary agents can be used stabilizers, including PAP (phosphate, isopropyl acid), BHT (2,6-di-tert-butyl-4-METHYLPHENOL), BHA (mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), vegetable oils, mineral oils, surfactants, fatty acids and esters of fatty acids.

In the beam of application of the compounds in accordance with this invention as agricultural pesticides, acaricides or nematicides, put them in the amount of usually from 0.1 to 100 g per 10 acres of land. If compositions such as emulsifiable concentrates, wettable powders or flowable granules applied after dilution with water, the concentration of the coating is usually from 1 to 100000 h/million Granules, dusty and the like is applied without dilution. If the compounds in accordance with this invention is used as a pesticide, acaricide or nematicide to prevent epidemics, emulsifiable concentrates, wettable powders, flowable granules and other compositions used after dilution with water to 0.1 to 500 ppm, but the oil sprays, aerosols, Smoking song, poisonous baits, protivobakteritsidny plate and the like is used as such.

If the compounds in accordance with this invention is used as a pesticide or acaricide to control ectoparasites in animals, for example, agricultural livestock, such as cows and pigs, and domestic animals such as cats and dogs, the compounds and their salts are used in veterinary system known methods of parasite control, for example, by oral administration in the form of tablets, capsules, mixtures, boluses, the feed and suppositories; parenterally by introducing, for example, by injection, or skin introduction, for example, in the form of a spray oil or water, R is the target, bathing or spot application; or known non-system methods with the use of molded articles, such as collars or ear tags (tags). In such cases, the compounds in accordance with this invention are used in quantities of from 0.01 to 100 mg per kg animal body.

Compounds in accordance with this invention can be applied in the form of a mixture or individually, but simultaneously with the pesticide composition and method in accordance with this invention can be applied to other insecticides, nematicides, acaricides, and repellents, fungicides, herbicides, plant growth regulators, synergists, fertilizers, agents that improve the soil and/or animal feed.

EXAMPLES

In more detail, the invention is explained in the following examples and accompanying drawings. However, the examples are presented only to illustrate this invention, and this invention is not limited to the examples.

Example 1: Obtaining compounds with inhibitory effect on acyl COA:cholesterylester

Obtaining compounds with inhibitory effect on the activity of acyl COA:cholesterylester

(1)Penicillium griseofulvumF1959 used in this invention, isolated from soil collected in Ulsan, Geyongsangbuk-do, Korea, identify as "Penicillium griseofulvumthe through mycological research, and placed in XTS (Korean collection for type cultures) in KRIBB, Korea, and assign an inventory number XTS VR.

Using frozen strain (10% glycerol, -80° (C) the selected fungus prepare the inoculum by insulinopenia in 1-liter Erlenmeyer flask with a reflective partition containing 100 ml of medium for planting: 0.5% glucose, 0.2% yeast extract, 0.5% polypeptide, 0,1%2NRA4, of 0.05% MgSO4·7H2O (sterilized after adjusting pH to 5.8), followed by incubation with vigorous stirring at a temperature of 29°C for 18 hours. 20 ml of the first culture inoculant in 5 l Erlenmeyer flask with a reflective partition containing 1 liter of the following culture medium: 2% soluble starch, 0.4% of aytona, 0.3% of Pharmamedia, 0,1%2NRA4, of 0.05% MgSO4·7H2O, 0.3% of CaCO3, 0.2% of NaCl (sterilized after adjusting pH to 5.8), and grown with vigorous stirring at a temperature of 29°C for 120 hours.

(2) the Fermentative broth culture obtained in stage (1) above, extracted with an equal volume of ethyl acetate (EtOAc) under stirring. The sample is extracted with ethyl acetate sample concentrate under pressure, getting oily brown extract.

The extract obtained is subjected to chromatography on a column of silica gel (chloroform:methanol=99:1, 98:2, 97:3, 95:5, 90:1% about/about, 4 volume compared with silica gel). Fractions analyzed to determine the distribution of compounds using thin layer chromatography, the fractions with the same compounds are combined and examined for inhibitory activity against acyl COA:cholesterylester. Fractions with inhibitory action collect elute with a mixture of chloroform/methanol (95:5 to 90:10% V/V) and eluate concentrate under pressure to obtain a yellowish brown oily extract.

(3-1) Yellowish-brown extract is subjected to high speed liquid chromatography to obtain active fractions containing the compound of peripherin (formula 1). High-speed liquid chromatography is performed on a column OSD (20×250 mm, YMC Company with the detector ultraviolet radiation, where the connection peripherin determined at 322 nm.

Connection peripherin, namely peripherin And (formula 1), and elute from the column OSD solvent acetonitrile:water (45:55 by volume) at a flow rate of 8 ml/minute for 11 minutes.

The active fraction is concentrated under pressure and clean again, getting colorless crystals, peripherin And (formula 1). The connection output is 13 mg on fermentation in 1 liter of medium for 120 hours.

(3-2) Also, the active fraction containing compounds in accordance with this and the finding of formulas 2-4, receive, exposing yellow-brown extract obtained in stage (2), high-speed liquid chromatography. High-speed liquid chromatography is performed on a column OSD (20×250 mm, YMC Company with the detector ultraviolet radiation, where the connection peripherin determined at 320 nm.

Phenylpropan And (formula 2), phenylpropan In (formula 3) and phenylpropan With (formula 4) elute from the column OSD solvent acetonitrile:water (75:25 by volume) at a flow rate of 8 ml/min for 15 minutes, 26 minutes and 49 minutes, respectively.

Every active fraction is concentrated under pressure and clean again, receiving a colorless amorphous crystals, phenylpropan And (formula 2), phenylpropan In (formula 3) and phenylpropan With (formula 4). Phenylpropan a, b and C are obtained from the output of 2.9 mg, 3 mg and 3.1 mg, respectively fermentation in 1 liter of medium for 120 hours.

Determination of molecular structures of the compounds in accordance with this invention, which has inhibitory effects on Sterol metabolism in insects

(1) Spectroscopy in the visible ultraviolet

The analysis in the visible ultraviolet carried out to determine the molecular structure of the compounds obtained by chromatography. Detail obtained crystallized compounds dissolved in 100% methanol and analyzed for definition wide-angle the wavelengths, the corresponding absorption peaks, using a spectrometer visible ultraviolet (Shimadzu Company, UV-265).

In the compounds show maximum absorbance at 232 and 322 nm in the UV spectrum, which shows that the compounds of pyridine or phenyl rings.

(2) Infrared spectroscopy

Infrared (IR) spectroscopy carried out as follows. 2 mg of each of the obtained crystallized compounds dissolved in chloroform, applied to AgBr box, dried and analyzed on a BioRad spectrometer FT/IR (BioRad Digilab Division, FTS-80).

In the compounds show absorption peaks around 3550 cm-1, 1740 cm-1and 1702 cm-1. The infrared absorption spectrum indicates the presence of groups, groups C=O, groups C=O, respectively, in organic compounds.

(3) Mass spectrometry

To determine the molecular weight compounds conduct mass spectrometry with high resolution using a mass spectrometer VGZAB-7070.

In the result, it was found that peripherin And (formula 1), phenylpropan And (formula 2), phenylpropan In (formula 3), phenylpropan With (formula 4) and pheophorbide And (formula 5) have a molecular weight of 583, 581, 508, 450 and 592, respectively.

(4) Analysis of NMR

NMR analysis carried out to determine the molecular structure of crystallized compounds. 10 mg of each crystallized connection totally what Yu dried, dissolved in CDCl3placed in 5-mm NMR tube and analyzed using NMR spectrometer Varian Unity-500.1H-NMR spectrum obtained when 500,13 MHz. The results are presented in figures 1-4.

The molecular structure of the compounds of formulas 1-4 determined using tests(1)-(4).

Experimental example 1: the Research activity of the compounds in accordance with this invention in relation to AST

Evaluate the inhibitory activity of the compounds in accordance with this invention against acyl COA:cholesterylester (hereinafter designated as "AST") using the method developed by Braceros, with minor modifications (Brecher. P and C. Chen, Biochimica Biophysica Acat 617:458-471, 1980). According to this method, the activity against ACAT determined using liver microsomes as a source AST with substrates of cholesterol and14With labeled oleoyl-COA. The radioactivity of the reaction product of ester cholesterol assess how activity against AST.

In detail, get the reaction mixture as follows. Cholesterol and Triton WR-1339, dissolved in acetone, suspended in water and after removal of the acetone in the gaseous nitrogen was added potassium phosphate buffer (pH 7.4, final concentration: 0.4 M). In order to stabilize the response of enzymes to the mixture bovine serum albumin to a final conc is of 30 μm. Then added to the mixture of the sample dissolved in DMSO. The reaction mixture is pre-incubated at 37 ° °C for 30 minutes Then initiate the enzymatic reaction by adding a solution of [1-14C]-oleoyl coenzyme a to a final concentration of 0.04 µci. After 30 min incubation at 37 ° °the reaction is stopped by adding 1 ml isopropanol-heptane. Then to the resulting reaction mixture is added 0.6 ml of n-heptane and 0.4 ml of CWR buffer. The mixture is well stirred and allowed to stand at room temperature for 2 minutes. After separation of the phases, 200 µl of the supernatant was placed in a scintillation vial. After adding in a test tube with 4 ml of scintillation cocktail (Lipoluma, Lumac Co.) the number of synthesized cholesterol oleate was measured on a scintillation counter (Packard Delta-200). Inhibitory activity against ACAT calculated according to the following equation 1:

Inhibitory activity (%)=[1-(T-/S -)]×100,

where T: pulse/min in the test reaction mixture, which contains a compound in accordance with this invention together with the source of the enzyme;

From: imp/min in the control reaction mixture that does not contain the connection, but contains the source of the enzyme; and

In: pulse/min in another control reaction mixture that does not contain the source of the enzyme, which contains about the connection.

As a result, pirprofen And (formula 1) is set to the IC50(IC50: concentration of compound required to inhibit 50% activity of ASAT) 35 ng/ml, the value of the IC50designed to 0.060 in nm, since this compound has a molecular weight of 583.

Phenylpropan And (formula 2) is set to the IC50500 ng/ml, the value of the IC50calculated at 86 nm, since this compound has a molecular weight of 581.

Phenylpropan In (formula 3) is set to the IC506.5 µg/ml, the value of the IC50designed at 12.8 μm, since this compound has a molecular weight of 508.

Phenylpropan With (formula 4) is set to the IC507.2 µg/ml, the value of the IC50calculated at 16,0 μm, since this compound has a molecular weight of 450.

Pheophorbide And (formula 5) is set to the IC50of 1.3 µg/ml, the value of the IC50designed with a 2.2 μm, since this compound has a molecular weight of 592.

In addition, when used in concentrations of 20 μg/ml and 100 μg/ml compound of formula 6-11 demonstrate activity against ACAT 92.4% and 99.2 percent; 96,6% and 97.8%; 84,5% and 93.8%; 93,4% and 98.4%; 17.6% and 82,0%; and 84.8% and 89.6 per cent respectively.

Experimental example 2: study of the inhibitory activity of the compounds in accordance with this invention larvaePlutella xylostellaL.

LarvaePlutella xylostellaL used as experimental n is Contracting out in this test, get them from Insect Research Lab, Korean Research Institute of Bioscience and Biotechnology (KRIBB), Oun-dong, Yusong-ku, Taejon, Korea. After careful weighing appropriate amounts of the compounds in accordance with this invention, which has inhibitory activity against ACAT, dissolved in acetone, mixed with nine volumes of 100 ppm initial solution Triton X-100 and periodically diluted, getting active solutions of compounds. Prepare meals for the growth of larvae ofP. xylostellaL as follows: cabbage leaves are the same height cut into disks (3.0 cm in diameter)and immersed in solutions of the active compounds for 30 seconds and dried under a canopy within 60 minutes. Each impregnated with active compound discs are placed in a Petri dish (55×20 mm) with a disk of filter paper. Then 10 larvae of the second ageP. xylostellaL is placed on each leaf disc with a soft brush that will not damage the larvae and grown in an incubator (25±1°C, 40-45% RH, 16L:8D). After 24 hours and 48 hours of burn mortality. The control group not treated with the active compounds in accordance with this invention, but is grown on leaf discs treated with a 10% mixture of acetone and nine volumes of 100 ppm initial solution Triton X-100. This biological study on the leaf disks was performed three times and LC50 (50% lethal concentration) are calculated according to the method Punched, advanced Finney (1982).

As shown in figure 6, if larvaeP. xylostellaL handle from 0.001 to 1 mg peripherin And (formula 1), among the compounds in accordance with this invention, which has inhibitory activity against ACAT, and insecticidal activity of the compounds evaluated with an interval of 24 hours, peripherin And shows continuous insecticidal effect depending on dose, compared with the control group.

As shown in figure 7, if larvaeP. xylostellaL handle 1 mg of each compound of formula 5-11, and insecticidal activity of the compounds evaluated with an interval of 24 hours, the connection with high in vitro inhibitory activity against ACAT exhibit strong insecticidal activity, while compounds with relatively low inhibitory activity against ACAT show weak insecticidal activity compared with each control group. These results show that in vitro inhibitory activity of compounds against ASAT correlated with their insecticidal action.

Experimental example 3: study of the inhibitory activity of the compounds in accordance with this invention larvaeTenebrio molitorL.

Among the compounds in accordance with this invention, the inhibitor is th activity against ACAT, phenylpropan a, b and C (2-4) test for weight reduction in insect larvae. In this test as an experimental use insect larvaeTenebrio molitorL, which are obtained from laboratory to study insects KRIBB, Korea. Healthy larvae of the second age (10-12 mm)Tenebrio molitorL is taken within 24 hours before testing. Each of the compounds of formula 2-4 dissolved in 10% acetone to a final concentration of 1 mg/ml and periodically diluted. 1 ml of diluted compound is mixed with 1 g of wheat bran, commonly used as food. The resulting mixture was placed in a glass Petri dish (90×20 mm) and the Petri dish was placed in a desiccator for approximately 2 hours under pressure to remove organic solvent. After weighing the 10 most motile larvaeTenebrio molitorL for each test are placed in a Petri dish (87×15 mm) with a filter paper disk, together with a mixture of compounds in accordance with this invention and wheat bran. Then the larvae are grown at a temperature of 25±1°ri relative humidity of 40-45% at 16-hour light/8 hour dark cycle. After 72 hours the mass and feeding larvae record every three days. This study conducted three times and the control group treated with 10% acetone. The results are presented on Fig and 9.

As pok is connected to Fig, if larvaeTenebrio molitorL handle 1 mg phenylpropene a, b or C (formula 2-4), mixed with 10 g of wheat bran and weight of larvae is fixed at 3 and day 7, the compounds show a constant decrease mass effect compared to the control groups.

In addition, whenTenebrio molitorL handle 1 mg peripherin And (formula 1), phenylpropene a and C (formulas 2 and 4) or pheophorbide And (formula 5), where each of them is mixed with 10 g of wheat bran, assess the growth inhibitory action of the compounds. As shown in Fig.9, the inhibition of growth of the larvae takes place in all larvaeTenebrio molitorL treated with these compounds. In particular, when processing philipiraino And with high inhibitory activity against ACAT, most insectsTenebrio molitorL dies on stage larvae and pupae, and some of them die from premature formation of pupae. In addition, in the processing of other compounds, more than 50% of insectsTenebrio molitorL dies on stage larvae and pupae, and the surviving larvae observed inhibition of growth, and the number of surviving larvae is significantly reduced. Moreover, the surviving larvae less mobile compared with the control group. These results show that the compounds in accordance with this invention have larvicide effect through the inhibition of the growth of l is of the escarpment.

As described above, the present invention relates to insecticidal compositions containing compounds with inhibitory activity against ACAT, or its salt as an effective ingredient. Compounds with inhibitory activity against ACAT, have excellent insecticidal action, inhibiting Sterol metabolism in insects. Therefore, the compounds in accordance with this invention can be used as a safe and effective insecticides. In addition, some of the compounds having inhibitory activity against ACAT, can be easily derived fromPenicillium griseofulvumF1959.

1. Insecticidal composition containing the compounds having inhibitory effect on acyl COA:cholesterylester, or salts thereof, where the compound is one or more of the group comprising compounds represented by formulae 2-11 as an effective ingredient:

[Formula 2]

[Formula 3]

[Formula 4]

[Formula 5]

[Formula 6]

[Formula 7]

[Formula 8]

[Formula 9]

[Formula 10]

[Formula 11]

2. Insecticidal composition according to claim 1, in which the compounds of formula 2-4 receiving method including:

cultivation of Penicillium griseofulvum F1959;

extraction of cultured cells with ethyl acetate and chromatography of the obtained extract.



 

Same patents:

FIELD: organic chemistry, agriculture.

SUBSTANCE: claimed method includes application of herbicidal effective amount of (a) 2-(2'-nitro-4'-methylsulfonylbenzoyl)-1,3-cyclohexanedione or agronomically accepted salt thereof and (b) N-isopropyl-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-4-(4'-fluoroxyacetanilide) on determinate locus, wherein mass ratio of (a):)(b) is from 1:20000 to 55:1. Disclosed is herbicidal composition containing (a) and (b) components in abovementioned ratio.

EFFECT: effective controlling of wide spectrum weed; decreased consumption of herbicides.

10 cl, 13 tbl, 1 ex

FIELD: organic chemistry, fungicides.

SUBSTANCE: invention relates to composition containing A) one arylamidine derivative of formula I , wherein R1 represents hydrogen; R2 and R3 are the same or different and represent C1-C8-alkyl; R4 represents C1-C8-alkyl; R5 represents C1-C8-alkyl; m = 1; R6 represents phenyl, substituted by the same or different substitutes selected from halogen or halo-(C1-C8)-alkyl; A represents -O-; and B) another known fungicidal agent selected from fluquinconazole and fenpropimorph, wherein mass ratio of (F) and (B) is 0.13<=A/B<=6.0. Also disclosed are method for combating of phytopathogenic fungi of agriculture cultures using effective and non-phytotoxic amount of abovementioned composition, as well as product for simultaneous, separate and alternate or sequential application of A compound and B compound in mass ratio of 0.13<=A/B<=6.0.

EFFECT: fungicidal compositions with improved and stable activity.

7 cl, 1 tbl, 1 ex

FIELD: herbicides, agriculture.

SUBSTANCE: invention relates to herbicidal composition for controlling of weed plants in cereal crops. Claimed composition contains dicamba alkali or ammonium salts (I), benzenesulfonyl urea derivatives (II), and chlorosulfoxyme alkali or ammonium salts (III) in sinergetically effective ratio, namely I:II:III ratio of (5.0-25):1:(0.1-0.8). Composition is applied in forms of humactable powders or water dispersable granules. Also described are method for controlling of weed plants, evaluation of storage stability thereof, herbicidal activity, etc.

EFFECT: improved herbicidal composition.

2 cl, 7 tbl, 6 ex

FIELD: organic chemistry, herbicides.

SUBSTANCE: invention describes novel derivatives of the formula (I): wherein R1 are similar or different and mean hydrogen atom (H),-CN, (C1-C8)-alkyl, (C1-C8)-alkoxy-group; A means phenyl, pyrazolyl wherein each of them is bound to X through carbon atom and substituted with one or two radicals comprising (C1-C8)-alkyl, (C1-C8)-halogenalkyl; X means oxygen atom (O); R2 and R3 mean H; m means O; R6 means H, (C1-C8)-alkyl, (C1-C8)-alkylsulfonyl substituted with halogen atom; B means [(C1-C8)-alkyl]-carbonyl, [(C3-C6)-cycloalkyl]-carbonyl wherein each radical is not substituted or substituted with one or some radicals chosen from a row comprising halogen atom, (C1-C8)-alkoxy-group and [(C1-C8)-alkoxy]-carbonyl, (C1-C8)-alkylsulfonyl substituted with halogen atom, [(C2-C8)-alkenyl]-carbonyl, phenylcarbonyl substituted with one some radicals chosen from a row comprising halogen atom, (C1-C8)-alkyl and -NO2, or di-[(C1-C8)-alkyl]-aminosulfonyl, formyl or group of the formula -CO-CO-R1 wherein R1 means (C1-C8)-alkyl or phenyl-substituted [(C2-C8)-alkenyl]-carbonyl, furancarbonyl, thienylcarbonyl, halogen-substituted phenylaminocarbonyl, dimethylaminosulfonyl or group of the formula: or wherein W means oxygen or sulfur atom; T means O; R11 means unsubstituted (C1-C8)-alkyl or substituted with halogen atom; R12 and R13 are similar or different and mean H, unsubstituted (C1-C8)-alkyl, with exception for N-hydroxy-N-[(6-phenoxy-2-pyridyl)methyl]-acetamide, and a herbicide agent comprising compound of the formula (I) and accessory substances used usually in preparing agents for plants protection. Proposed compounds possess the herbicide activity and therefore they can be used agriculture.

EFFECT: valuable properties of compounds and agents.

3 cl, 2 tbl, 8 ex

FIELD: agriculture.

SUBSTANCE: invention describes a composition used in stimulating growth and development of agricultural crops. The composition comprises molybdenum and copper compounds, alkanolamine, water and citric acid taken in the following mole ratio in mixture: molybdenum compounds : copper compounds : citric acid : alkanolamine = 1:(2-8):(1-10):(4-80), respectively, in the following ratio of components, wt.-%: mixture of molybdenum compounds, copper compounds, alkanolamine and citric acid in the mole ratio given above, 0.5-65, and water, the balance. The proposed composition is used for stimulating growth and development of agriculture crops, enhancing their quality and output and can be used for their leaf feeding and for presowing treatment of seeds.

EFFECT: valuable properties of composition.

2 tbl, 7 ex

Herbicide agent // 2303872

FIELD: organic chemistry, herbicides.

SUBSTANCE: invention describes a herbicide agent comprising a combination of active components consisting of (a) substituted thene-3-ylsulfonylaminocarbonyl triazolinone of the general formula (I) wherein R1 means alkyl with 1-6 carbon atoms; R2 means alkyl with 1-6 carbon atoms; R3 means alkyl, alkoxy-, alkylthio-group with 1-6 carbon atoms, cycloalkyl with 3-6 carbon atoms; R4 means alkyl with 1-6 carbon atoms, cycloalkyl with 3-6 carbon atoms, or its salt, and (b) compound chosen from group of herbicides given in the description and taken in the synergetic ratio. The proposed agent shows synergetic effect.

EFFECT: valuable property of herbicide agent.

6 cl, 107 tbl, 1 ex

FIELD: agriculture.

SUBSTANCE: claimed method includes treatment of cereal cultures in from tillering period to starting of stem elongation with environmentally friendly agent, namely electroactivated aqueous anolyte solution whish represents water treated in anode chamber of apparatus for electrochemical activation with positive redox potential of +600 - +700 mV and anolyte consumption of 100-150 l/hectare.

EFFECT: increased plant productivity and decreased disease progression.

1 tbl

FIELD: agriculture.

SUBSTANCE: claimed method includes treatment of cereal cultures in from tillering period to starting of stem elongation with environmentally friendly agent, namely electroactivated aqueous anolyte solution whish represents water treated in anode chamber of apparatus for electrochemical activation with positive redox potential of +600 - +700 mV and anolyte consumption of 100-150 l/hectare.

EFFECT: increased plant productivity and decreased disease progression.

1 tbl

FIELD: agriculture.

SUBSTANCE: claimed method includes seeds spraying with mixture of titus herbicide (30 g/hectare) and banvel herbicide (300 ml/hectare) with addition of surfactant-trend (300 ml/hectare) with consumption of processing liquid of 300 l/hectare.

EFFECT: method for weed controlling of increased effectiveness.

1 tbl

FIELD: chemical plant protection.

SUBSTANCE: invention provides herbicidal agent containing (A) herbicidally active amount of one compound described by general formula I, wherein R1 represents C1-C6-alkyl, R2 hydrogen, R4 halogen or C1-C6-alkyl, R4, R5, and R5 are hydrogen atoms, R7 represents C1-C6-alkyl, and a=2; and (B) antidote-active amount of one compound of general formula II or III, in which R8, R9, R10, independently from each other, represent C1-C4-alkyls, weight ratio of herbicide-to-antidote component ranging from 3:1 to 0.75:1. Method of controlling weeds among cultural plants consists in a treatment of weeds with herbicidal agent.

EFFECT: achieved high selectivity of herbicidal agent when used in wheat and corn crops.

5 cl, 7 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: invention relates to incecticidal/acaricidal agent of synergetic action having general formula I wherein W, Y and Z are independently hydrogen or C1-C4-alkyl; A and B together with carbon atom to which they are bonded form C3-C6-cycloalkyl monosubstituted with C1-C4-alkoxyl; G is carbon or -COOR, wherein R is C1-C4-flkyl and compound selected from group containing chloropyriphos, oxydimenton methyl, acephat, methiocarb, thiocarb, pyrimicarb in synergic ratio.

EFFECT: agent of high efficiency to control pests and mites.

2 cl, 8 tbl, 7 ex

FIELD: organic chemistry, herbicides.

SUBSTANCE: invention describes a synergetic composition with the effective content of components (A) and (B) wherein (A) means herbicide chosen from the group of compounds of the formula (I): wherein R1, R2, R, X, Y and Z have values given in the invention claim or their salts; (B) means one or some herbicides among the following groups: (B1) selective herbicides with activity in some dicotyledonous cultures against monocotyledonous and dicotyledonous weeds; (B2) selective herbicides with activity in some dicotyledonous cultures against dicotyledonous weeds; (B3) selective herbicides with activity in some dicotyledonous cultures with preferable effect against monocotyledonous weeds. Also, invention describes a method for control against weeds using the proposed composition. Using the combination of proposed herbicides results to the synergetic effect.

EFFECT: valuable herbicide properties of composition.

3 cl, 7 tbl, 2 ex

FIELD: organic chemistry, insecticides.

SUBSTANCE: invention describes insecticide composition comprising the active amount of one pyridine compound of the formula (I)

or its salt wherein Y represents halogenalkyl group comprising from 1 to 2 carbon atoms and halogen atoms from 1 to 5; m = 0; Q represents compound of the formula:

wherein X represents oxygen atom; R1 and R2 represent independently hydrogen atom, alkyl group comprising from 1 to 6 carbon atoms and substituted with cyan-group, and one insecticide taken among carbofuran, carbosulfan, cipermethrin, bifentrin, acetamiprid, chlorfauazuron, fluphenoxuron, piriproxiphen, spinosad, emamectine benzoate, avermectin, buprophezin and fipronil taken in the weight ratio of compound of the formula (I) and other insecticide = from 1:2 to 100:1. The composition provides stable and strong effect and eradicates insects.

EFFECT: strong insecticide effect of composition.

4 cl, 11 tbl, 5 ex

FIELD: herbicides, agriculture.

SUBSTANCE: invention describes a herbicide composition comprising components in the following their contents, g/l: phenmedifam, 30-160; desmedifam, 30-160; mixture of non-ionogenic and anion-active surface-active substance, 150-350; liquid carboxylic acid amide, 20-200; co-solvent, 30-300; citric acid, 2-6; 1-phenyl-(1,2,4-triazole-4-yl)urea, 2-20; solvent, the balance, up to 1 l. The composition can comprise additionally ethofumezat in the amount 30 g/l. Invention provides the development of herbicide composition based on phenmedifam and desmedifam possessing the enhanced herbicide activity that allows reducing doses of preparations in their consumptions.

EFFECT: improved herbicide activity of composition.

2 cl, 2 tbl, 1 ex

The invention relates to the field of plant protection products that can be used against weeds in tolerant or resistant crops sugar beet and which as a herbicide biologically active substances contain a combination of two or more herbicides

Herbicide agent // 2303872

FIELD: organic chemistry, herbicides.

SUBSTANCE: invention describes a herbicide agent comprising a combination of active components consisting of (a) substituted thene-3-ylsulfonylaminocarbonyl triazolinone of the general formula (I) wherein R1 means alkyl with 1-6 carbon atoms; R2 means alkyl with 1-6 carbon atoms; R3 means alkyl, alkoxy-, alkylthio-group with 1-6 carbon atoms, cycloalkyl with 3-6 carbon atoms; R4 means alkyl with 1-6 carbon atoms, cycloalkyl with 3-6 carbon atoms, or its salt, and (b) compound chosen from group of herbicides given in the description and taken in the synergetic ratio. The proposed agent shows synergetic effect.

EFFECT: valuable property of herbicide agent.

6 cl, 107 tbl, 1 ex

FIELD: synthesis of biologically active compounds.

SUBSTANCE: invention provides novel N6-substituted adenine-based heterocyclic compounds depicted by general formula I: , for which meanings of radicals are presented in description, and pharmaceutically acceptable salts thereof manifesting anticancer, mitotic, immunosuppressive, and antiaging activities for vegetable, animal, and human cells, and methods for preparation thereof. Included are also pharmaceutical compositions, cosmetic preparations, and growth regulators, which contain indicated derivatives as active components. Application of indicated derivatives for preparing therapeutical preparations, and cosmetic preparations are also described.

EFFECT: expanded synthetic possibilities in adenine series and increased choice of various biologically active agents.

10 cl, 10 dwg, 9 tbl, 14 ex

FIELD: agriculture.

SUBSTANCE: claimed method includes treatment of vegetative sunflower plants with 2-(N-4-fluorophenyl)amido-3-amino-4,6-dimethylthieno-[2,3-b]-pyridine in amount of 200 g/hectare.

EFFECT: new method for increase in sunflower productivity.

2 tbl

FIELD: agriculture.

SUBSTANCE: claimed method includes treatment of vegetative sunflower plants with 2-(N-4-phenylethyl)amido-3-amino-4,6-dimethyl-5-chlorothieno-[2,3-b]-pyridine in amount of 200 g/hectare.

EFFECT: new method for increase in sunflower productivity.

2 tbl

FIELD: agriculture.

SUBSTANCE: claimed method includes treatment of vegetative sunflower plants with {1,2,4-triazole-[1,5-a]-pyrimidyl-2-thio}-4-fluoroacenanyl in amount of 200 g/hectare.

EFFECT: new method for increase in sunflower productivity.

2 tbl

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