Derivative of pyrazole, insecticide comprising thereof as active component, intermediate compound, methods for preparing compounds

FIELD: organic chemistry, insecticides, chemical technology.

SUBSTANCE: invention describes derivative of 1-aryl-3-cyano-5-heteroarylalkylaminopyrazole of the general formula (1): wherein A means: (A-1) , (A-2) , (A-3) and (A-4) and wherein X represents C-halogen; R1 represents (C1-C4)-alkyl group or halogen-(C1-C4)-alkyl group; A represents any group among (A-1) - (A-4) wherein R4 represents hydrogen atom or (C1-C4)-alkyl group; n = 0, 1 or 2 under condition that R1 represents halogen-(C1-C4)-alkyl group with exception for perhalogenalkyl group when A represents (A-1) and n = 0, and that n doesn't equal 0 when A represents (A-4). Also, invention describes derivative of pyrazole of the formula (2): wherein A means: (A-1) and Y means: (Y-1) , (Y-2) and (Y-3) wherein X, R2, R3 and R4 have values given above; R5 represents hydrogen atom; A represents (A-1); Y means any group among (Y-1) - (Y-3); Z represents halogen atom that are intermediate compounds used for synthesis of the compound (1). Invention describes methods for preparing compounds of the formula (1) and (2) and insecticide comprising compound of the formula (1) as an active component. Insecticide shows high systemic activity, high safety and reduced harmful effect on environment in vicinity areas of its applying.

EFFECT: improved methods for preparing, valuable insecticide properties of compound.

11 cl, 9 tbl, 19 ex

 

The technical field

The present invention relates to a new derivative of 1-aryl-3-cyano-5-heterooligomerization and means of containing it as active ingredient, for pest control.

Background of the invention

In the field of agriculture and horticulture to date developed and implemented in practical applications in order to control various insect pests of many insecticides.

Examples are known of pyrazole compounds having insecticidal activity, include derivatives of 3-cyano-1-phenylpyrazole having optionally substituted by an amino group in the 5-position described in tiled applications for Japan patent No. 228065/1987, 316771/1988 and 118369/1991, substituted derivatives of 1-aryl-3-cyano-5-(het)arylmethylidene described in application laid on the Japan patent No. 148240/1993, and substituted derivatives of 1-aryl-5-(het)arylmethylidene described in application laid on the Japan patent No. 47768/1989.

However, the compounds described in the above literature are not sufficient to the extent necessary in all aspects such as insecticidal activity spectrum of insecticidal activity, safety and the like, and thus desirable to develop new compounds able to overcome such problems. As a result, as compounds oblad the participating high security, in WO98/45274 describes the new derivatives of 1-aryl-3-cyano-5-heterooligomerization.

However, in this application does not describe a specific compound in which a heterocyclic ring is pyrazinone ring, pyridazine ring or pyrimidine ring.

Compounds described in WO98/45274 and the like are excellent in their insecticidal activity and have reduced toxicity compared to known compounds. In recent years, security for organisms other than the target insect pests, and the environment is required in a larger extent and in the future will be strictly taken measures to protect the environment. Therefore, for the development of pesticides that meet the more stringent requirements, an important problem is the search for compounds with higher security.

In addition, in the effective application of the agent for pest control and application to soil, especially effective against organisms pests, such as the exhaust fluid pests, an important factor is the system activity, so it would be desirable to identify new compounds possessing both of these properties.

Description of the invention

As a result of intensive studies to solve the above problems, the authors of the present invention installed, that connection, in which a specific nitrogen-containing six-membered heterocycle is attached to the amino group in the 5-position of the pyrazol ring pyrazol derivative, derivative of 1-aryl-3-cyano-5-heterooligomerization, shows selective high system activity and has low toxicity to the environment that is shown using toxicity for fish.

Moreover, it was found that a higher effect can be achieved by optimizing the combination of the heteroaryl group and the substituent at 4-position of the pyrazol ring, and had created the invention.

Namely, the present invention relates to a derivative of 1-aryl-3-cyano-5-heterooligomerization represented by the following General formula (1):

A:

(where X represents N or C-halogen, R1represents an alkyl group, alkenylphenol group, alkylamino group, or halogenation group, R2represents a hydrogen atom, alkyl group or acyl group, R3represents a hydrogen atom or alkyl group, And a represents any of groups represented by formulas A-1 to a-4, R4 represents a hydrogen atom, alkyl group, halogen atom, and n represents 0, 1 or 2, provided that R1represents halogenating group, except perhalogenated group when a represents an a-1 and n is 0, and that n is not equal to 0, when a is a a-4), and it contains as active ingredient a means of pest control.

Hereinafter the invention will be explained in detail.

[Compounds of the invention]

In the invention, the substituent R1in the compounds represented by the above General formula (1)represents a linear or branched alkyl group such as methyl group, ethyl group, n-sawn group, isopropyl group, n-bucilina group, isobutylene group, sec-bucilina group or tert-bucilina group; a linear or branched alkenylphenol group such as vinyl group, allyl group, metalllica group or 2-bucinellina group; a linear or branched alkylenedioxy group, such as etinilnoy group or propargyl group; or a linear or branched halogenating group, such as group permetrina, deformational group, triptorelin group, 2-florachilena group, 2-chloraniline group, 2,2,2-triptorelin group, 2,2,2-trichlorethylene group, 3-chloropropyl the group, 3-bromopropyne group, 3,3,3-cryptosporella group, 2,2,3,3-tetrafluoropropyl group, 2,2,3,3,3-pentafluoropropyl group, 2,2-dichloro-3,3,3-cryptosporella group, 2,2-dichloro-3,3,3-cryptosporella group, 1,3-debtor-2-through the group, 1,1,1,3,3,3-hexamer-2-through the group, 3,3,3-trichloropropane group, 4-garbatella group, 4,4,4-triptorelin group or 3,3,4,4,4-pentafluorobutane group. Preferred are C1-C4alkyl group, a C1-C4Alchemilla group, C1-C4Alchemilla group or C1-C4halogenation group. Especially preferred is C1-C4alkyl group or a C1-C4halogenation group. Among them, preferred is a C1-C2alkyl group or a C1-C2halogenation group, and particularly preferred is C1-C2halogenation group, such as permetrina group, deformational group, triptorelin group, 2-florachilena group or 2-chloraniline group.

R2represents a hydrogen atom; a linear or branched alkyl group such as methyl group, ethyl group, n-sawn group, isopropyl group, n-bucilina group, isobutylene group, sec-bucilina group or tert-bucilina group; or a linear, or osvetleniyu acyl group, such as methylcarbamyl group, acylcarnitine group, n-propellerblade group, isopropylcarbodiimide group, n-butylcellosolve group, isobutylamine group, sec-butylcellosolve group or tert-butylcellosolve group. Preferred is C1-C4alkyl group or a C1-C4acyl group. Particularly preferred R2is a hydrogen atom.

R3represents a hydrogen atom or a linear or branched alkyl group such as methyl group, ethyl group, n-sawn group, isopropyl group, n-bucilina group, isobutylene group, sec-bucilina group or tert-bucilina group. Preferred of the above alkyl group is C1-C4an alkyl group. Particularly preferred R3is a hydrogen atom.

And is any of groups represented from A-1 to a-4, and preferred among them is a-1. The invention is characterized by the fact that choose a nitrogen-containing six-membered heterocycle having the above specific structure, and the ring is connected with the amino group in the 5-position of the pyrazol ring via a methylene group.

R4represents a hydrogen atom; a linear or branched alkyl group such as methyl group, ethyl group, n-sawn group, isopropyl group, n-bucilina group, isobutylene group, sec-bucilina group or tert-bucilina group; or a halogen atom such as chlorine atom, fluorine atom or bromine atom. As for the alkyl group, preferred is a C1-C4an alkyl group. Particularly preferred R4is a hydrogen atom.

X represents N or an atom of halogen. Of them, preferred is an atom of halogen, and particularly preferred is an atom of chlorine.

n is any of 0, 1 or 2, and preferably n is 0 or 1, provided that n is 0 when a is a-4.

Moreover, when a is a-1, and n is 0, R1is halogenating group, except perhalogenated group. Of them, preferred is a C1-C4halogenation group, particularly preferred is a1-C2halogenation group, most preferred is C1fluorinated alkyl group, such as permetrina group or deformational group.

As compounds of the above General formula (1) is most preferred are compounds comprising each combination of the preferred substituents as described above for the substituents.

Of them preferred connection involving the combination of the substituents is connection is out, in which each of R2, R3and R4represents a hydrogen atom, X represents a C-CL bond group, and a represents a-1.

In the case when n is not equal to 0, R1preferably represents an alkyl group or halogenation group, more preferably, C1-C4alkyl group or a C1-C4halogenating group, and especially preferably, C1-C2halogenating group. Moreover, in the case when n is 0, R1represents halogenating group, different from perhalogenated group, preferably, C1-C4halogenating group and, particularly preferably, C1-C2fluorinated alkyl group.

Of these compounds, in which R1represents C1halogenating group, i.e. pharmacylow group, deformational group or triptorelin group (except triptorelin group, when n is 0 are preferred because they have high insecticidal activity and low toxicity to fish when used as a means of pest control, especially as active ingredients for insecticides.

Combination of the above substituents, the preferred compounds are 1-(2,6-dichloro-4-trifloromethyl the Nile)-4-formailty-5-(pyrazin-2-ylmethylamino)-pyrazole-3-carbonitrile and 1-(2,6-dichloro-4-triptoreline)-4-trifloromethyl-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile.

[Method of producing compounds of the invention]

As for the method of obtaining compounds of the invention represented by the above General formula (1), the compound can be obtained by formation of the pyrazol ring, and then, if necessary, introduction of, or replacement of a Deputy(s).

Known methods include the methods described in tiled applications for Japan patent No. 316771/1988 and 148240/1993, 47768/1989 and 47768/1989. As an illustration, as a way of using such methods, a method shown in reaction scheme 1

Reaction scheme 1

However, this method has the disadvantage that in the first stage, it uses expensive fluorine-containing reagent. Alternative possible methods described in reaction schemes 2 and 3, but there are similar problems, such as the availability of the starting materials.

Reaction scheme 2

Reaction scheme 3

Moreover, in WO98/45274 described that the derivative of pyrazole with a 4-pyridylmethylamine in the 5-position can be obtained by treating the amino group present at the 5-position of the pyrazole nucleus proizvoda, pyridyl-4-aldehyde and imine formation, asetem recovery imine (reaction scheme 4).

Reaction scheme 4

It is also possible to synthesize the compounds according to the invention in accordance with the method shown above in reaction scheme (4), however, as a result of additional research, the authors of the present invention have found that the methods shown in the following reaction schemes 5-10 are more effective as a means of obtaining derivatives of pyrazole represented by the General formula (1) according to the present patent application. Following General formulas (2) provides intermediate compounds for preparing compounds of General formula (1) in accordance with the above methods.

A:

Y:

(where R2, R3, R4and X have the same meanings as in General formula (1), and R5represents a hydrogen atom, thiocyanatopropyl, Citigroup, which combines two of the pyrazol ring, or mercaptopropyl, Z represents a halogen atom).

Next, methods for producing compounds according to the invention will be illustrated in more detail. The reaction scheme 5-10 marked as way is of obtaining compounds of the invention, the above-mentioned General formula (1). In all cases, R1preferably represents halogenating group containing 1-2 carbon atoms.

Reaction scheme 5

Reaction scheme 6

Reaction scheme 7

Reaction scheme 8

Reaction scheme 9

In reaction scheme 5 shows a method of obtaining a pyrazole derivative of the General formula (1), which includes the processing of the pyrazole derivative of the General formula (2), where R5represents a hydrogen atom, and Y is Y-3, the reagent R1S (O)nX1where R1and n have the same significance as in General formula (1)and X1represents a chlorine atom or a bromine atom X1preferably represents a chlorine atom. When n is 0, a preferred example of the used reagent, R1S(O)nX1is triftormetilfullerenov (CF3SCl), and in this case, the resulting compound is a derivative of pyrazole with trifloromethyl group in 4-position. When n is 1, a preferred example of the used reagent, R1S(O)nX1is triformis finishline (CF 3SOCl), and in this case, the resulting compound is a derivative of pyrazole with trifloromethyl group in 4-position.

This reaction is illustrated next using triftormetilfullerenov and triftormetilfullerenov as representative examples, but this reaction can be carried out similarly in the case of using other reagents.

When using triftormetilfullerenov triftormetilfullerenov can be allocated in advance or it may be formed in situ from sodium salt or potassium salt triftormetilfullerenov acid and chloride tiomila. Next pyrazole sulfonylurea on 4th position by engagement with salt triftormetilfullerenov acid, depending on the reaction conditions.

In reaction R1S(O)nX1used in an amount of from 0.5 to 10.0 molar equivalents, preferably from 0.8 to 5 molar equivalents relative to the compound represented by General formula (2) (where R5represents a hydrogen atom) and the interaction is carried out at a temperature from 0° to 150° C, preferably from 0° to 100° C. the Solvent for use in the reaction include aromatic hydrocarbons such as benzene, toluene or xylene; ketones, such as acetone or methyl ethyl ketone, ha is generowanie hydrocarbons, such as chloroform or methylene chloride; polar solvents, such as tetrahydrofuran or N,N-dimethylformamide. In particular, preferred are toluene and dichloromethane.

When using triftormetilfullerenov interaction can be carried out in the absence of reason, but, preferably, it is carried out in the presence of a base, and use amine, such as pyridine or triethylamine. When using triftormetilfullerenov or salt triftormetilfullerenov acid is used amine, such as dimethylamine, pyridine or triethylamine or an inorganic base such as a carbonate of an alkali metal, in combination with an acid, such as sulfuric acid, hydrochloric acid or toluensulfonate acid. Preferred is a combination of dimethylamine and toluensulfonate acid. You can add them individually, but preferably they are added in the form of a salt of dimethylamine and toluensulfonate acid (tosylate dimethylamine).

In reaction scheme 6 shows a method of obtaining a pyrazole derivative of the General formula (1), where n is 1 or 2, comprising the oxidation of the sulfur atom pyrazole derivative of the General formula (1), where n is 0. Examples of methods include oxidation chemical oxidation using an oxidant and biological oxidation using enzymes or gr the BOV, but commonly used chemical oxidation. During the chemical oxidation of the oxidizing agent is added in an amount of from 0.2 to 5.0 molar equivalents, preferably from 0.25 to 2.0 molar equivalents, to the compound of General formula (2) in the absence or in the presence of a solvent, and the interaction is carried out at a temperature of from -20 to 150° C, preferably from 0 to 20° C.

The oxidizing agent for use in this reaction include hydrogen peroxide, Oxon, m-chloroperbenzoic acid, peracetic acid, periodate sodium, ruthenium tetroxide, ozone, tert-butylhydroperoxide, nitric acid, and the like. Preferred is hydrogen peroxide.

The solvent for use in the reaction may be an organic solvent conventionally used for oxidation, and usually use a hydrocarbon solvent such as toluene or hexane, or a halogenated hydrocarbon solvent such as dichloromethane or chloroform.

Specifically, the interaction according to the invention is usually carried out in the presence of acid. Used acid may be represented by a proton acid or a Lewis acid, but it is preferable proton acid. Examples of the proton of the acid include inorganic acids such as sulfuric acid, hydrochloric acid, nitric acid and phosphoric Ki the lot, diluted sulfuric acid, and organic acids such as acetic acid, formic acid and triperoxonane acid. Preferred is an inorganic acid, and more preferred is sulfuric acid. When using sulfuric acid used diluted sulfuric acid having a concentration of from 60 to 90%, preferably from 75 to 85%. Each of these acids may be used in the form of a mixture with an organic solvent, but preferably the solvent is used the acid.

The preferred combination of oxidant and solvent is a combination of hydrogen peroxide and dilute sulphuric acid.

When interacting optionally, you can add a catalyst to accelerate the oxidation. As the catalyst is usually possible to use a catalyst to accelerate the oxidation of sulfide. Preferred are compounds of ruthenium, a compound of tungsten, a compound of vanadium, the compound of molybdenum, a compound of titanium or the like, and more preferred is a compound of ruthenium. Examples of ruthenium compounds can include trichloride of ruthenium and ruthenium oxide. The amount used of the catalyst is, for example, from 0.01 to 100 mol.%, preferably, from 0.1 to 20 mol.% relative to the source of sulfide.

Interaction osushestvliayut temperatures from -30 to 120° C, preferably from -10° C to room temperature for from 1 to 48 hours, preferably from 1 to 6 hours.

In reaction scheme 7 shows a method of obtaining a pyrazole derivative of the General formula (1), where n is equal to 0, including the processing of the pyrazole derivative of the General formula (2), where R5is thiocyanatopropyl, and Y is Y-3, the connection R1-X2where R1has the same meaning as in General formula (1), and X2represents a halogen atom or trimethylsilyloxy group.

Examples of the reagent for use in this reaction include methyl trifluoromethyl, trifluoromethyl iodide and triftormetilfullerenov. It is preferable to triftormetilfullerenov.

Examples of the solvent for use in the reaction include ether solvents such as tetrahydrofuran, diethyl ether and dimethoxyethane; hydrocarbon solvents such as toluene and xylene; and halogenated hydrocarbon solvents such as dichloromethane and chloroform. Preferred is tetrahydrofuran.

The interaction is preferably carried out in the presence of fluoride compounds and the preferred is tetrabutylammonium fluoride or potassium fluoride.

In the interaction of the reagent R1-X2used in an amount of from 0.5 to 10.0 molar equivalent is allentow, preferably from 0.8 to 5 molar equivalents relative to the compound represented by General formula (2), where R5represents a hydrogen atom. The interaction is carried out at a temperature from -20 to 120° C, preferably from 0° C to room temperature for from 1 to 24 hours, preferably from 1 to 4 hours.

In reaction scheme 8 shows a method of obtaining a pyrazole derivative of the General formula (1), where n is equal to 0, including the processing of the pyrazole derivative of the General formula (2), where R5is mercaptopropyl, and Y is Y-3, the connection R1-X3where R1has the same meaning as in General formula (1), and X3represents a halogen atom.

Examples of the reagent for use in this reaction include trifluoromethyl bromide and iodide, trifluoromethyl.

Examples of the solvent include polar solvents such as DMF and DMSO; hydrocarbon solvents such as toluene and hexane; halogenated hydrocarbon solvents such as dichloromethane and chloroform, basic solvents such as triethylamine and liquid ammonia. Preferred is a polar solvent, such as DMF.

The interaction is preferably carried out in terms of education triptoreline radical, and specific examples include exposure SV is the volume, and the use of a radical initiator, the redox agent and agent carrier of electrons, such as methylviologen.

The interaction is carried out at a temperature from -20 to 120° C, preferably from 0° C to room temperature for from 1 to 24 hours, preferably from 1 to 4 hours.

In reaction scheme 9 shows a method of obtaining a pyrazole derivative of the General formula (1), where n is 0, and R3represents a hydrogen atom, including the processing of pyrazole derivative of the General formula (2), where R5is Citigroup that combines two pyrazol ring, and Y is Y-3, the connection R1-X4where R1has the same meaning as in General formula (1)and X4represents a halogen atom or SO2M (M represents an alkali metal).

Examples of the reagent for use in this reaction include methyl trifluoromethyl, trifluoromethyl iodide and salt triftormetilfullerenov acid.

Examples of the solvent include polar solvents such as DMF and DMSO; hydrocarbon solvents such as toluene and hexane; halogenated hydrocarbon solvents such as dichloromethane and chloroform. Preferred is a polar solvent, such as DMF.

The interaction is preferably carried out in the conditions of formation of triptorelin the CSOs radical, and specific examples include irradiation with light and application of a radical initiator, a redox agent and agent carrier of electrons, such as methylviologen.

In the case of methyl trifloromethyl and iodine trifloromethyl preferably combined use agent radical anion formation of sulfur dioxide. Examples of agent radical-anionic education sulfur dioxide include ditional sodium (Na2SO4), hydroxymethanesulfinic sodium (Rongalit, NaO2SCH2OH, hydroxymethanesulfinic zinc, a mixture of sulfur dioxide and zinc and a mixture of sulfur dioxide and formic acid or a salt thereof.

The interaction is carried out at a temperature from -20 to 120° C, preferably from 0° C to room temperature for from 1 to 24 hours, preferably from 1 to 4 hours.

Reaction scheme 10

In reaction scheme 10 shows a method of obtaining a pyrazole derivative of the General formula (1), where R1represents an alkyl group containing one or more fluorine atoms, including processing pyrazole derivative of the General formula (1), where R1represents an alkyl group containing one or more chlorine atoms or bromine atoms, by fluorinating agent selected from the group comprising hydrogen fluoride, CME is ü hydrogen fluoride and an amine and a metal fluoride.

Used reagent comprises hydrogen fluoride, a mixture of hydrogen fluoride and an amine and a metal fluoride such as potassium fluoride, sodium fluoride or fluoride cobalt. Preferred is a mixture of hydrogen fluoride and an amine. As a solvent it is possible to use a solvent commonly used for fluoridation through the exchange of halogen, and preferred is a polar solvent, such as DMF. R7in the original substance, preferably, is trichlorethylene group, and triptorelin group can be marked as R8.

Methods of obtaining derivatives of pyrazole represented by the General formula (1)shown above, and the preferred methods are shown in reaction schemes 5 and 6.

The following will further illustrate the methods of obtaining the derivatives of pyrazole represented by the General formula (2). When Y is Y-3, pyrazole derivatives represented by the General formula (2) can be obtained in accordance with the methods shown in reaction schemes 11 and 12, on the basis of the compounds represented by the General formula (3) and General formula (4).

Reaction scheme 11

Reaction scheme 12

Reaction scheme 13

Moreover, it is to shown in scheme 13 above, here you can specify the way in which the original substance, the compound of General formula (3), first interacts with A(C=O)-X7with the formation of the amide compound (a compound where Y is Y-1 in the General formula (2)), which is then restored with the formation of compounds, where Y is Y-3 in the General formula (2). You can also specify a different way, where the amide compound (a compound where Y is Y-1 in the General formula (2)) is converted into halogenide connection (connection, where Y is Y-2 in the General formula (2)), which is then restored with the formation of a derivative of pyrazole, where Y is Y-3 in the General formula (2).

The reducing agent for use in the reaction of recovery includes the complex of borane-THF, sodium borohydride, cyanoborohydride sodium, lithium borohydride, sociallyengaged or the like.

The solvent for use in the reaction include polar solvents, for example ethers, such as diethyl ether, dioxane or tetrahydrofuran; alcohols, such as methanol, ethanol or propanol; and the like.

The interaction is carried out at a temperature from -20 to 120° C, preferably from 0° C to room temperature for from 1 to 24 hours, preferably from 1 to 4 hours.

Gloriouse agent for use in galogenirovannyie includes entailed phosphorus, oxychloride of phosphorus, chloride thionyl and the like.

The solvent for use in the reaction include nonpolar solvents such as benzene, toluene and xylene; halogenated solvents such as carbon tetrachloride, chloroform and dichloromethane and ether solvents, such as dimethoxyethane and tetrahydrofuran.

The interaction is carried out at a temperature from 0 to 200° C, preferably from room temperature to 150° C, for 1 to 24 hours, preferably from 1 to 4 hours.

Compounds represented by the General formula (1)can be obtained by a combination of the methods mentioned above. The way to obtain 1-(2,6-dichloro-4-triptoreline)-4-trifloromethyl-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile shown below in reaction scheme 14 as a typical way to obtain.

Reaction scheme 14

[The use of compounds of the invention]

Means for pest control containing compound according to the invention as the active ingredient, has action, overwhelming pests, such as insects and mites, and is effective to deter, displacement and pest control, for example, in many areas of agriculture, forestry, cultivation of crops, in the fishing industry and the care products these areas and in health.

In particular, the connection according to the invention has an excellent effect as an insecticide and acaricide when used to deter, displacement and pest control in agriculture, forestry and the like, in particular, pests that damage crops when they are grown, harvested crops, trees, high-value plants and the like, and pests harmful to health.

Next will be illustrated by concrete applications, pests, suppression, methods of application, and the like, but the invention is not limited to the following descriptions. In addition, these target pests are not limited to specified pests, and pests include imago (the last stage of an insect after all metamorphoses), larvae, eggs and the like.

(A) the Area of agriculture and forestry

A means of pest control containing compound according to the invention as an active ingredient, effectively to deter and control pests such as arthropods, spineless, nematodes, various fungi, and the like that affect agricultural crops such as food crops (such as rice plants, oats, maize, potatoes, sweet potatoes, beans), vegetables (e.g., culture, cabbage, pumpkin, tank is agony, tomatoes, onions), fruit trees (e.g. citrus, apples, grapes, peaches), industrial crops (such as tobacco, tea, sugar beets, sugar cane, cotton, olive), crops for grazing and fodder crops (ash soil, grassy pastures, pasture with plants of the legume family), high-value plants (herbs, flowers and plants for arrangements, garden trees), when growing these crops. In addition, the connection according to the invention is also effective to deter and combat pests during storage of the crop of the above cultures, for example, food grains, fruits, nuts, spices and tobacco and products of their processing, such as drying and grinding. In addition, the compound is also effective for the protection of trees, fallen trees, recycled timber and wood from damage by pests such as termites and beetles.

As a specific pests belonging to classes Athropoda (Arthropods), Mollusca (Mussels) and Nematoda (Nematodes)may be, for example, specify the following. Examples of insects of the genus Arthropoda include the following :

Examples of Lepidoptera include Noctuidae, such as Leucania unipuncta, Heliothis assulata, Barathra brassicae and Plusia peponis; Putellidae, such as Plutella maculipennis; Tortricidae such as Nomoa magnanima and Grapholita molesta; Psychidae, such as Canephora asiatica; Review, such as Lyonetia clerkella; Lithocolletidae, still is as of Lithocolletis ringoniella; Acrolepiidae, such as Acrolepia alliella; Aegeriidae, such as Aegeria molybdoceps; Heliodlnidae, such as Kakivoria flavofasciata; Gelechiidae such as Pectinophora gossypiella; Carposinidae such as Carposina nipponensis; Heterogeneldae, such as Chidocampa flavescens; Pyralidae such as Cnaphalocrocis medinalis, Chilo suppxessalis, and Natarcha derogate; Hesperiidae, such as Parnara quttata; Papilionidae, such as Papilio machaon); Pieridae such as Pieris rapae; Lycaenidae, such as Lampides boeticus; Geometridae, such as Ascotis selenaria cretacea; Sphingidae, such as Herse convolvuli, Notodontidae such as Phalera flavescens; Lymantriidae such as Euproctis subflava; and Arctiidae such as Hyphantna cunea.

Examples of Coleoptera include Scarabaeidae such as Anomala cuprea, Oxycetonia jucunda and Popillia japonica; Buprestidae, such as Agrilus auriventris; Elateridae, such as Melanotus legatus; Coccinellidae, such as Epilachna vigintioctopunctata; Cerambycidae, such as Anoplophora malasiaca and Xylotrechus pyrrhoderus; Chrysomelidae, such as Aulacophora femoralis, Phyllotreta striolata and Donacia provostii; Attelabidae, such as Phynchites heros; Brenthidae, such as Cylas formicarius; and Curculionidae, such as Curculio sikkimensis and Echinocnemus squameus.

Examples Hemiptera include Pentatomidae, such as Plautia stali and Halyomorpha halys; Urostylidae, such as Urochela luteovaria; Coreidae, such as Cletus punctiger; Alydidae, such as Leptocorisa chinensis; Pyrrhocoridae, such as Dysdercus cingulatus; Tingidae, such as Stephanitis nashi; Miridae, such as Deraeocoris amplus; Cicadidae, such as Platypleura kaempferi; Aphrophoridae, such as Dophoara vitis; Tettigellidae, such as Oniella leucocephala; Cicadellidae, such as Arboridia apicalis and Empoasca onukii; Deltocephalidae, such as Nephotettix cincticeps; Delphacidae, such as Laodelphax striatellus and Nilaparvata lugens; Flatidae, such as Geisha distinctissima; Psylloidae, such as the Psylla pynsuga; Aleyrodidae, such as Trialeurodes vaporariorum and Bemisia argentifolii; Phylloxeridae, such as Moritziella costaneivora; Pemphigidae, such as Eriosoma lanigera; Aphididae, such as Aphis gossypii; Myzus persicae and Rhopalosiphum rufiabdomlnalis; Margarodidae, such as Icerya purchasi; Pseudococcidae, such as Planococcus citri; Coccidae such as Ceroplastes rubens; and Diaspididae, such as Quadraspidiotus perniciosus and Pseudaulacaspis pentagana.

Examples Thysanoptera include Thripidae such as Frankliniella occidentalis, Scirtothrips dorsalis and Thrips palmi; and Phlaeothripidae, such as Ponticulothrips diospyrosi and Haplothrips aculeatus.

Examples Hymenoptera include Tenthredinidae, such as Athalia japonica; Argidae, such as Arge mali; Cynipidae, such as Dryocosmus kuriphilus; and Megachilidae, such as Megachile nipponica nipponica.

Examples Dioptera include Cecidomyildae, such as Asphondylia sp.; Tephiridae, such as Zeugodacus cucurbitae; Ephydridae, such as Hydrellia griseola; Drosophilidae, such as Drosophila suzukii; Agromyzidae, such as Chromatomyia horticola and Liriomyza trifolii; and Anthomyiidae such as Hylemya antiqua.

Examples of Orthoptera include Tettigoniidae, such as Homorocoryphus nidtidulus; Gzyllidae, such as Calyptotrypes hihinonis; Gryllotalpidae, such as Gcyllotalpa afrcana; and Acrididae, such as Ochoa japonica.

Examples include Collembola Sminthuridae such as Sminthurus viridis; and Onychiuridae, such as Onychiurus matsumotoi.

Examples Isoptera include Termitidae, such as Odontotermes formosanus, and examples Dermaptera include Labiduridae, such as Labidura riparia.

Below may be mentioned as examples of Arthropoda Crustacea and Arachnida.

Examples of Crustacea Isopoda include Armadillidiidae, such as Armadillidium vulgare.

Examples of Arachnida Acarlna include, such as Tarsonemiae such as Hemitarsonemus latus and Tarsonemus pallidus; Eupodidae, such as Penthaleus major; Tenuipalpidae, such as Brevipalpus lewisi; Tetranychidae such as Tetranychus urticae, Tetranychus kanzawai, Panonychus citri, Panonychus ulmi; Eriophyldae, such as Aculus pelekassi, Aculus schlechtendali and Eriophyyes chibaensis; Acaridae such as Tyrophagus putrescentiae.

As Mollusca Gastropoda examples Gastropoda Mesogastropoda include Rosacea canallculata, and examples Stylommatophora include Achatina fulica, Incilaria bilineata, Milax gagates, C limax vaginal maximus and Acusta despecta.

The following may be mentioned as examples Nematoda Secernentea and Adenophorea.

Examples of Secernentea Tylenchida include Anguinidae, such as Ditylenchus destructor; Tylenchorhynchidae, such as Tylenchorhynchus claytoni; Pratylenchidae, such as Pratylenchus penetrans and Pratylenchus coffeae, Hoplolaimidae, such as Helicotylenchus dihystera; Heterodehdae, such as Heterodera rostochiensis; Meloidogynidae, such as Meloidogyne incognita; Criconematidae, such as Criconemoides: Nothotylenchidae, such as Nothotylencus acris; and Aphelenchoidae, such as Aphelenchoides fragariae.

Examples Adenophorea Dorylaimida include Longidoridae, such as Xiphinema americanum; and Trichdoridae, such as Paratrichodorus porosus.

In addition, the connection according to the invention is also effective to deter, fight, and exclusion of pests that affect or are having a negative effect on natural forests, artificial forest plantations in the green areas of cities and the like. At the same time as specific pests may be noted the following.

Examples of Arthropoda Insecta and Arachnida include the following :

Examples of Lepidoptera include Lymantriidae such as DNA argentata and Lymantria disper japonica Lasiocampidae, such as Dendrolimus spectabilis and Malacosoma neustria; Pyralidae such as Dioryctria abietella; Noctuidae, such as Agrotis fucosa; Tortricidae such as Ptycholomoides aeriferana, Laspeyresia kurokoi, and Cydia cryptomeriae; Arctiidae such as Hyphantria cunea; Nepticulidae, such as Stigmella malella; and Heterogeneidae, such as Parasa consocia.

Examples of Coleoptera include Scarabaeidae such as Anomala rufocuprea and Heptophylla picea; Buprestidae, such as Aqrilus spinipennis; Cerambycidae, such as Monochamus alternatus; Chrysomelidae, such as Lypesthes itoi; Carculionidae, such as Scepticus griseus and Shirahoshizo coniferae; Rbynchophoridae, such as Sipalinus gigas; Scolytidae, such as Tomicus piniperda and Indocryphalus aceris; and Bostcychidae, such as Rhizopertha dominica.

Examples Hemiptera include Aphididae, such as Cinara todocola; Adelgidae, such as Adelges japonicus; Diaspidiae, such as Aspidiotus cryptomeriae; and Coccidae such as Ceroplastes pseudoceriferus.

Examples Hymenoptera include Tenthredinidae, such as Pristiphora erichsoni; Diprionidae, such as Nesodiprion japonica; and Cynipidae, such as Dryocosmus kuriphilus.

Examples Dioptera include Tipulidae, such as Tipula aino; Anthomyiidae such as Hylemya platura; and Cecidomyiidae, such as Contarinia inouyei and Contarinia matsusintome.

Examples of Arachnida Acaria include Oligonychus hondoensis and Oligonychus unuguis.

Examples Nematoda Secernentea Tylencida include Paracytaphelenchidae, such as Bursaphelenchus xylophilus.

A means of pest control containing compound according to the invention as an active ingredient, can be used in the form of any drug or any form of application, obtained by cooking composition, effective in the above agricultural is or forestry, individually, or in combination, or as a mixed preparation with other active compounds, such as insecticides, acaricides, nematicides, fungicides, synergists, plant growth regulators, herbicides and toxic food additives. As specific examples of the above other active compounds may be mentioned the following that their limit.

Active compounds such as insecticides or acaricides:

Examples of organophosphorus funds include

Dichlorvos, Fenitrothion, Malathion, Naled, chlorpyrifos, Diazinon, Tetrachlorvinphos, Fenthion, Isoxathion, Mitigation, Salicion, Arafat, Demeton-S-methyl, Disulfoton, Monochrotophos, Azinphos-methyl, Parathion, Fosalan, Pirimiphos-methyl and Prothiofos. Examples carbamate substances include Metolcarb, Fenobucarb, Propoxur, Carbaryl, Ethiofencarb, Pirimicarb, Bendiocarb, Carbosulfan, Carbofuran, Methomyl and Thiodicarb. Examples of organochlorine agents include Lindane, DDT, Endosulfan, Aldrin and Harden. Examples of PYRETHROID agents include Permethrin, Cypermethrin, deltamethrin, Cigalotrin, Cyfluthrin, Acrinathrin, Fenvalerate, Etofenprox, Selflove, Fluvalinate, Flucythrinate, Bifenthrin, Allethrin, Phenothrin, Fenpropathrin, Cyphenothrin, Permethrin, Resmethrin, Transferrin, Prallethrin, Flufenamic, Halftracks, Imiprothrin. Examples of neon echinoidea agents include Imidacloprid, Nitenpyram, Acetamiprid, Territoty, Thiametoxam and Thiacloprid.

Examples of insect growth regulators, such as phenylbenzophenone include Diflubenzuron, Chlorfluazuron, Triflumuron, Flufenoxuron, Hexaflumuron, Lufenuron, Teflubenzuron, Buprofezin, Tebufenozide, Chromafenozide, Methoxyfenozide and Cyromazine.

Examples of juvenile hormone preparations include Pyriproxyfen, Fenoxycarb, Methoprene and Hydroprene.

Examples of insecticidal substances produced by microorganisms include Abamectin, Milbemectin, Nikkomycin, Emamectin benzoate, Ivermectin and Spinosad.

Examples of other insecticides include Cartap, Resultp, Chlorfenapyr, Diafenthiuron, Nicotine sulfate, Metaldehyde, Fipronil, Pymetrozine, Indoxacarb and Elfenberg.

Examples of acaricides include Dicofol, Fenabrave, Basemat, Tetradifon, Polyactis, Amitraz, Propargite, fenbutatin oxide, Tricyclohexyltin hydroxide, Tebufenpyrad, Pyridaben, Fenpyroximate, Pyrimidifen, Fenazaquin, Clofentezine, Vexations, Achiezer, Chinomethionat, Fanatical, Etoxazole, Bifenazate.

Of nematicides examples of active compounds include methyl isocyanate, Fosthiazate, Oxamyl and Resolvents.

Examples of toxic food additives include monohloruksusnoj acid, Warfarin, Coumatetralyl, Diphacinone.

From the use of fungicides is s active compounds include inorganic compounds of copper, organic compounds of copper, sulfur, MANEB, Thiram, Thiadiazin, Captan, CHLOROTHALONIL, Iprobenfos, Thiophanate methyl, Benomyl, Thiabendazole, Iprodione, Procymidone, Pencycuron, Metalaxyl, Sandhofen, Breton, Triflumizole, Fenarimol, Triforine, Dithianon, Triazine, Fluazinam, Provenzal, Datoteke, Isoprothiolane, Pyroquilon, Iminoctadine acetate, Klometol, Dazomet, Kresoxim methyl.

Examples of active compounds synergists include bis(2,3,3,3-tetrafluoropropyl) a simple ester, N-(2-ethylhexyl)bicyclo[2.1.1]hept-5-ene-2,3-dicarboximide and α -[2-(2-butoxyethoxy)ethoxy]-4,5-methylenedioxy-2-propietary.

Examples of active compounds of herbicides include Bialaphos, Sethoxydim, Trifluralin and Mefenacet. Examples of active compounds of plant growth regulators include introcaso acid, Ethephon and 4-CPA.

Examples of active compounds-repellents include Karan-3,4-diol, N,N-diethyl-m-triamide (Deet), lemon, linalool, citronellal, Menton, hinokitiol, menthol, geraniol and eucalyptol.

A means of pest control according to this invention can be used in any form, and the compound of formula (1) is part of the recipe together with auxiliary additives for pesticides with getting preparative forms, such as, for example, wettable powders, wettable granules, aqueous solutions, emulsifiable concentrates, liquid is, fluid forms, including suspension in water emulsions in water, capsules, dusty, pellets and sprays, which are subsequently used. In the formulation can contain any amount of the active ingredient, but the content is usually in the range from 0.001 to 99.5% by weight of the total amount of active ingredient is selected appropriately in accordance with various conditions such as the type of formulation and method of application. For example, it is preferable to obtain preparative forms so that the content of the active ingredient were ranged from 0.01 to 90% by weight, preferably from 1 to 50% by weight, in wettable powders, wettable granules, aqueous solutions, emulsifiable concentrates, liquids, flowable products, capsules and the like; from about 0.1 to 50% by weight, preferably from 1 to 10% by weight, in doctah and granules; or from about 0.001 to 20% by weight, preferably from 0.01 to 2% by weight in the aerosol.

Adjuvants for pesticides are used to improve the repellent action, overwhelming action and preemptive action against pests, to improve stability preparative forms and their dispersive ability of the pigment, and the like, and used examples include carriers (diluents), surfactants, among the Torah, wetting agents, dispersing agents and leavening agents. Liquid carriers include water; aromatic hydrocarbons such as toluene and xylene; alcohols such as methanol, butanol and glycol; ketones, such as acetone; amides such as dimethylformamide; sulfoxidov, such as dimethyl sulfoxide; methylnaphthalene; cyclohexane; animal or vegetable oils and fatty acids. Examples of solid carriers include clay, kaolin, talc, diatomaceous earth, silicon dioxide, calcium carbonate, montmorillonite, bentonite, feldspar, quartz, aluminum oxide, sawdust, nitrocellulose, starch and gum Arabic (of the Arabian gum). Usually as emulsifiers or dispersing agents can be used surfactants. For example, it is possible to use anionic, cationic, nonionic or amphoteric surfactants, such as sodium higher alcohol sulfate, chloride of stearylamine, polyoxyethylene-alkylphenolate ethers and laurylether. In addition, it is possible to use surfactants, such as polyoxyethylene-nonylphenoxy ether and polyoxyethylene-auriferous ether; wetting agents, such as diallylmalonate; fixing compositions, such as carboxymethyl cellulose and polyvinyl alcohol; and disintegrating agents, such as ligninsulfonate sodium and sodium lauryl sulfate.

Nab is emer, in the case of wettable powders, powder filler obtained by mixing the compounds of General formula (I) as an active ingredient with a solid carrier, a surface-active agent, etc., bulk powder can be used after dilution to a prescribed concentration with water for use. In the case of emulsifiable concentrates, liquid filler obtained by mixing the above compounds as the active ingredient with solvents, surface-active agent, etc. and the liquid filler can be applied after dilution to a prescribed concentration with water for use. In the case of Farrukh Dustov, dust is obtained by mixing the above compounds as the active ingredient with a solid carrier, etc. and it can be used by itself. In the case of granules, the granules are obtained by mixing the above compounds as the active ingredient with a solid carrier, a surface-active agent, etc. with subsequent granulation. Granules can be applied as such. Methods of obtaining the above-mentioned preparative forms of various kinds are not limited to the above-described methods, and the person skilled in the art can choose the appropriate method depending on the type of active ingredient and purpose.

The method of application varies in C is depending on the type and degree of pest infestation, on the form, the form of cultivation and the state growth target crops, trees and the like, but against arthropods, gastropods, nematodes and similar products can normally applied with a concentration of active ingredient ranging from 0.1 to 1000 g, preferably from 1 to 100 g / 10 ar area that is damaged by pests or where it is predicted the possibility of defeat.

As for the specific method of application, the above wettable powders, wettable granules, aqueous solutions, emulsifiable concentrates, liquid, flowable products, including suspensions in water emulsions in water, capsules and the like can be diluted with water and sprayed on crops, trees and the like in amounts ranging from 10 to 1000 liters per 10 ar depending on the type, shape cultivation and the state growth target crops, trees and the like. In addition, in the case of Farrukh Dustov, pellets and sprays, the drug can be used as such on crops, trees and the like within the range described for the above method of application.

In the case when the target pests, primarily affect agricultural crops, trees and the like in the soil, wettable powders, wettable the ranula, aqueous solutions, emulsifiable concentrates, liquid, flowable products, including suspensions in water emulsions in water, capsules and the like may, for example, be diluted with water and used usually in amounts ranging from 5 to 500 liters per 10 ar. Then the drugs can be sprayed uniformly on the soil surface over the entire area of application, or they can irrigate the soil. When drugs are dusty or granules, the drugs themselves can also be sprayed uniformly on the soil surface over the entire area of application. Alternatively, spraying or irrigation, the drug can be used only near the crops, crops, trees and the like for protection against destruction by pests, or soil can be plowed during or after spraying for mechanical dispersion of the active ingredient.

Moreover, the tool for pest control containing compound according to the invention as an active ingredient, may be applied around the plants in a known manner. When such processing can be prevented not only the damage caused by pests in the soil after sowing the seeds, but also the stems and leaves, flowers and fruits of plants can be protected from damage by pests.

In the case of protection above the growing of trees, fell the trees, processed wood products, stored wood from damage by pests such as termites or beetles, you can specify the methods of atomization, spraying, irrigation, or applying oil solution, emulsifiable concentrate, wettable powder or Zola, or spraying means in the form of dust or granules. In such applications tool for pest control containing compound according to the invention as an active ingredient, can be used by itself or in combination, or as a mixed preparation with other active compounds, such as insecticides, acaricide, nematocide, fungicide, repellent and a synergist.

The preparations can contain any amount of the active ingredient, but the content is usually in the range from 0.0001 to 95% by weight of the total quantity of active ingredients. Preferably, the active ingredient is contained in an amount of 0.005 to 10% by weight in doctah, granules and the like in an amount of from 0.01 to 50% by weight in emulsifiable concentrates, wettable powders, sols, and the like. Specifically, in the case of displacement or against termites or beetles drugs can be sprayed on the soil surface or of timber and wood in the amount of from 0.01 to 100 g per 1 m2in terms of the amount of the active ingredient.

(C) the Area of livestock and fish the wow economy

A means of pest control containing compound according to the invention as an active ingredient, effectively to deter, repression and suppression of pests such as arthropods, nematodes, trematodes, tapeworms and protozoa, which are internal or external parasites of animals and Pets, which are the objects of livestock, fisheries or living in homes, and the tool can be used for the prevention and treatment of diseases that cause these parasites.

Subject animals include vertebrates such as cattle, including cows, sheep, goats, horses, pigs and the like; cultural fish, birds, such as poultry, domestic animals and experimental animals, selected from a mammal, including a dog, cat, mouse, rat, hamster, squirrel, ferret, etc., fish and the like.

From pests as examples can be mentioned the following Arthropoda Insecta and Arachnida. Examples Diptera include Tabanidae such as Chrysops japonica, Simulium iwatens and Tabanus trigonus; Mascidae, such as Ophyra leucostoma, Musca domestica and Stomoxys calcitrans; Gasterophilidae, such as Gasterphilus intestinalis; Hypodermidae, such as Hypoderma bovis; Calliphoridae, such as Phaenicia cuprina; Phoridae such as Megaseria spiracularis; Sepsidae, such as Sepsis monostigma: Psychodidae, such as Telmatoscopus albipunctatus and Psychoda alternata; Culicidae, such as Anopheles hyrcanus sinensis, Culex tritaeniorhynchus is Aedes albopictus; Simaliidae, such as Prosimilium hirtipes; Ceratopogonidae, such as Culicoides oxystoma and Culicoides arakawai.

Examples Siphonaptera include Pulicidae, such as Ctenocephalides felis and Ctenocephalides canis.

Examples Anoplura include Echinophthiriidae, such as ematopinus suis and Haematopinus eurysternus; Trichodectidae, such as Damalinia equi; Linognathidae, such as Linognathus vituli; and Menoponidae, such as Mepore gallinae.

Examples of Arthropoda Arachnida include Acarina Ixodidae such as Haemaphysalis longicornis, Ixodes ovatus, BoophiIus microplus and Amblyomma testudinarium; Macronyssidae, such as Ornithonyssus sylviarum; Dermanyssidae such as Dermanyssus gallinae; Demodicidae, such as Demodex suis; Sarcoptidae, such as Notoederes cati and Sarcoptes sylvianum, and Psoroptidae, such as Otodectes cynotis and Psoroptes bovis.

As examples Nematoda Phasmidia can note the following.

Examples Strongylida include Ancylostoma, Stephanurus dentatus, Metastrongylus elongatus, Trichostrongylus and the recommended dose rate.

Examples Platyhelminthes Trematoda include Schistosoma japonicum, Fasciola hepatica, Paramphistomum cervi, Paragonimus wastermanii and Prosthogonimus japonicus.

Examples Cestoda include Anoplocephala pecfoliata, Moniezia expansa, Moniezia benedeni, Raillietina tetragona, Raillietina sp., and Raillietina cesticillus.

Examples of Protozoa Mastigophora include Histomonas and the like, such as Rhizomastigida, Leishmania; Trypanosoma, and the like, such as Tripanpsomidae; Giardia and the like, such as Polymastigida, and Txichomonas and the like, such as Trichomonadia.

In addition, examples of Sarcodina Amoebida include Entamoeba, examples Sporozoa Piroplasmea include Theilaria, and Babesia, and examples Telosporidia include Eimeria, Plasmodium, and Toxoplasma.

A means of pest control that contains the connection is according to the invention as an active ingredient can be used in the form of any drug or any form of application, obtained by the obtaining part, effective for the above areas of agriculture and forestry, individually or in combination, or as a mixed preparation with other active compounds, such as insecticides, acaricide, nematocide, fungicide, synergist, plant growth regulator, herbicide or toxic food additive. Substances referred to in section(A) the Area of agriculture and forestry”, can be mentioned as specific examples of the above other active compounds, but they are not limited.

Specific applications include introduction to feed cattle, domestic animals and the like; in oral administration in the form of a suitable oral-swallow prescription composition, for example, tablets, pills, capsules, paste, gel, drink, medical nutrition, medicinal drink, additional therapeutic feeding large pills a slow-release or device for slow release of the remaining in the gastrointestinal tract, containing a pharmaceutically acceptable carrier and the substance covering the shell; and subcutaneous application in the form of a spray, powder, grease, cream, ointment, emulsion, lotion, medication for applying spots, preparation for irrigation, shampoo and the like.

As ways subcutaneous application is a local application, you can use the device (for example, collars, medallions and ear tags)attached to the animal for local or systemic control of arthropods.

Next will be illustrated by concrete methods of oral administration and subcutaneous administration in the case of use as a deworming drugs, but in the invention methods of application are not limited to the following descriptions.

In the case of oral administration as a therapeutic drink, suspension or dispersion can usually be obtained by dissolving the active ingredient in a suitable non-toxic solvent or in water together with suspiration, such as bentonite, wetting agent or other excipients and, if necessary, may contain protivovspenivayushchie agent. The drink usually contains the active ingredient in an amount of from 0.01 to 1.0% by weight, preferably from 0.01 to 0.1% by mass.

In the case of oral administration as a single form of application of dry solids typically use a capsule, a pill or tablet containing a certain amount of the active ingredient. Such forms of application can be obtained by homogeneous mixing of the active ingredient sprayed with a suitable diluent, filler, baking powder and/or binders such as starch, lactose, talc, magnesium stearate, vegetable gum, and things under the service. Upon receipt of such pay form number and content of antihelminth can optionally be determined depending on the form of an animal host for which it was intended treatment of a parasite species and body weight of the host.

In case of introduction in the form of food, can be specified the ways in which the connection of the active ingredient is homogeneous dispersed in the food, the tool is applied as a foliar top dressing or in the form of balls. To achieve anthelminthic action connection of the active ingredient completely contained in the diet in amounts of from 0.0001 to 0.05% by weight, preferably from 0.0005 to 0.01 mass%.

In the case of a solution or dispersion in excipiente - liquid media, the drugs can be introduced to animals parenterally by injection into the abomasum or intramuscularly, nutritarian or subcutaneous injection. Due to parenteral administration the active ingredient preferably is mixed with a vegetable oil such as peanut oil or cottonseed oil. In this composition the active ingredient is usually contained in an amount of from 0.05 to 50% by weight, preferably from 0.1 to 0.2% by weight. Moreover, the drug is mixed with a carrier, such as dimethyl sulfoxide, a hydrocarbon solvent or the like, can be applied directly or topically on the surface of a large RoGator the livestock or domestic animals by spraying or irrigation.

(C) the Area of health

A means of pest control, containing as active ingredient the compound according to the invention is also effective in the field of health scare, repression and suppression of pests harmful effects on the environment, such as food, clothing and housing, or, alternatively, affect the human body or the moving or carrying pathogens, with the aim of maintaining public health. In particular, the means of pest control according to the invention effectively to deter, repression and suppression of Lepidoptera, Coleoptera, book worms, cockroaches, flies and ticks that affect the houses themselves and the internal and external timber, wood products such as wooden furniture, stored food, clothing, books, animal products (leather, fur, wool, feather and so on), industrial goods (clothes, paper etc), and the like, and have an adverse impact on healthy life. Next will be illustrated by concrete examples of pests in the areas of health.

As arthropods insects, Arthropoda Insecta, can be specified as follows. Examples of Lepidoptera include Lymantciidae, such as Euproctis similis; Lasiocampidae, such as Dendrolimus undans flaveola; Heterogeneidae, such as Parasa consocia; Zygaenidae, such as Aztona funeralis; Pyralidae such as Cadra cautella, Ephestia cautella and Plodia intecpnctella; Gelechiidae such as Sitotroga cerearella; Tineidae such as Tinea pellionella and Tineola bisselliella.

Examples of Coleoptera include Oedemeridae, such as Xanthochroa waterhousei; Meloidae, such as Epicauta qorhami; Staphylinidae, such as Paederus fuscipes; Rhynchophoridae, such as Sitophilus zeamais and Sitophilus oryzae; Brachidae, such as Callosobruchus chinensis, Bruchus pisorum, and Bruchus rufimanus; Tenebrionidae such as Tribolium castaneum; Cucujidae, such as Oryzoephilus surinamensis and Placonotus testaceus; Anobiidae, such as Lasioderma serricorne and Stegobium paniceum; Dermestidae, such as Attagenus unicolor, Anthrenus verbasci and Dermestes maculatus; Ptinidae, such as Gibbium aeguinoctiale; Bostrychidae, such as Dinoderus minutus and Rhizopertha dominica; and Lyctidae, such as Lyctus brunneus.

Examples Hymenoptera Vespidae include, such as Vespa mandarinia; Formicidae, such as Brachyponera chinensis; and Pompilidae, such as Batozonellus annulatus.

Examples Diptera include Culicidae, such as Aedes jaonica; Ceratopogonidae, such as Culicoides sp.; Chironomidae, such as Chironomus dorsalis; Simuliidae, such as Simulium aokii; Tabanidae such as Chrysops japonicus; Mascidae, such as Musca domestica; Anthomyiidae such as Fannia canicularis; Calliphoridae, such as Phormia regina; Sarcophagidae, such as Boettcherisca peregrina; Drosophilidae, such as Drosophila virilis; and Piophilidae, such as Piophila casei.

Examples Siphonaptera include Pulicidae, such as Pulex irritans.

Examples include Collembola Neogastruridae, such as Neograstruna communis.

Examples Blattaria include Blattellidae, such as Blattela germania and Asiablatta kyotensis; and Blattidae, such as Periplaneta ainerlcana, Periplaneta fuliginosa and Periplaneta japonica.

Examples Ortnoptera include Gryllacridoidea, such as Diestrammena japonica and Steropelmatidae.

Examples Anoplura include Pediclidae, such as Pediculus humanus capitis; and Pthiridae, such as Pthirus pubis.

Examples Hemiptera include Cimicidae, such as Cimex lectularius; and Reduriidae, such as Isyndus obscurus.

Examples Isoptera include Phinotermitidae, such as Reticulitermes speratus and Coptotermes formosanus: Kalotermitidae, such as Cryptotermes domesticus, and examples Psocoptera include Trogiidae, such as Lepinotus reticulatus; and Liposcelidae, such as Liposcelis bostrichophius. Examples Thysanura include Lepismatidae, such as Ctenolepisma villosa and Lepisma saccharina.

As examples of Arthropoda Arahnida can note the following.

Examples include Acarina Ixodidae such as Ixodes persulcatus; Macronyssidae, such as Ornithonyssus bacoti; Cheyletidae such as Chelacaropsis moorei; Pyemotidae, such as Pyemotes tritici; Demodicidae, such as Demodex folliculorum; Pyroglyphidae, such as Permatophagoides pteronyssius; Sarcoptidae, such as Sarcoptes scabiei; Trombiculidae, such as Leptotrombidum akamushi; Acaridae such as Tyrophagus putrescentiae and Lardoglyphus konoi; and Carpoglyphidae, such as Carpoglyphus lactis.

Examples Araneae include Clubionidae, such as Chiracanthium japonicum; Heteropodidae, such as Heteropoda venatoria; Pholcidae, such as Spermophora senoculata and Pholcus phalangioides; Urocteidae, such as Uroctea compactilis; and Salticidae, such as Plexippus paykulli and Plexippus setipes.

Examples Scorpiones include Buthidae, such as Isometrus europaeus.

As other Acthropoda (arthropods), examples of Chilopoda Scolopendromorpha include Scolopendridae, such as Scolopendra subspinipes and Otostigmus multispinosus, and examples of Scutigeromorpha include Scutigeridae, such as Thereuonema hilgendorfi. In addition, examples Artropoda Diplopoda Polydesmoidea include Strongylosomidae, such as Oxidus qracilis, and examples Athropoda Crustacea Isopoda include Oniscidae, such as Porcellio scaber. Further examples Annelida Hirudinea Gnathobdellida include Haemadipsidae, such as Haemadipsa zeylanica japonica.

A means of pest control containing compound according to the invention as an active ingredient, can be used in the form of any drug or any forms of applications received by the receiving part, effective in the above-mentioned health, individually or in combination, or as a mixed preparation with other active compounds, such as insecticides, acaricide, nematocide, fungicide, synergist, plant growth regulator, herbicide or toxic food additive. Substances referred to in section(A) the Area of agriculture and forestry”, can be mentioned as specific examples of the above other active compounds, but they are not limited.

The application form means of combating agricultural pests according to the invention can be any shape and protection of the above mentioned animal or vegetable products can be achieved by spraying an oil solution, emulsifiable concentrate, wettable powder, dust or the like, premises plastic parboiling agent, processing, cinder agent or aerosol premise granules, tablets or toxic food additives, spray aerosol. The active ingredient of the pre is respectfully contained in the preparations in amounts of from 0.0001 to 95% by mass.

As the method of application against pests, for example, directly against the damaging arthropods, pathogens of arthropods and the like, can be specified ways of spraying, injection, irrigation, and application of the oil solution, emulsifiable concentrate, wetting powder or the like, spraying dust or the like, spraying, such as a fumigant, protivokomarinaya spiral heated aerosol, including smoke means samovozgorayuschiesya type or chemically active aerosol, smoke tool, including veiling or ULV agent and others. Alternatively, a granule, tablet or toxic food additive can be represented in another form, or floating dust, granules or the like can be applied by adding them to waterways, wells, reservoirs, storage tanks for water and other running water or standing water.

In addition, with the Eastern wananchi, which are also pests in agriculture and forestry, can be treated in a manner similar to described in “(A) agriculture and forestry”. How to add a means of struggle for food of the cattle, so that the manure was contaminated with the active ingredient, is effective against flies, and the method of evaporation into the air using electrical protiva the Marina spiral is effective against mosquitoes.

Drugs that are used shapes can exist in the form of mixed drugs with the above other active ingredients such as insecticides, acaricide, nematocide, fungicides, repellents or synergist, and the active ingredient is preferably contained in the preparations in amounts of from 0.0001 to 95% by weight. By the way, you can also use the drug in combination with other used active connections.

In the case of the protection of homes, wooden furniture and the like from damage by pests such as termites or beetles, you can specify the methods of atomization, spraying, irrigation, or applying oil solution, emulsifiable concentrate, wettable powder or Sol or dispersion agent in the form of dust or granules for home, wooden furniture and the like, and next to them. In such applications the connection according to the invention can be used by itself, or in combination, or as a mixed preparation with other active compounds, such as insecticides, acaricide, nematocide, fungicide, repellent and a synergist.

Any number of connections active ingredient, such as a connection according to the invention may contain drugs, but the content is usually in the range from 0.0001 to 95% by weight of the total amount of active phrases is tov. Preferably, the compounds contained in the amount of 0.005 to 10% by weight in oil solutions, doctah, granules and the like, and in the amount of from 0.01 to 50% by weight in emulsifiable concentrates, wettable powders, sols, and the like. Specifically, in the case of displacement and fighting termites or beetles, the product can be sprayed near or directly on the surface in an amount of from 0.01 to 100 g per 1 m2in terms of the amount of the active ingredient.

When deterrence, displacement and suppression of pests that affect human bodies or transport, or carry pathogens, as methods other than the methods mentioned above, it can be noted oral administration in the form of a suitable oral-swallow prescription composition, for example, tablets, pills, capsules, paste, gel, drink, medical nutrition, medical beverage, medical food additives, big pills a slow-release device or sustained release, so that it was kept in the gastrointestinal tract, containing a pharmaceutically acceptable carrier and covering the shell substance; and intradermal application in the form of spray, powder, grease, cream, ointment, emulsion, lotion, medication for applying stains, preparation for irrigation, shampoo and the like. The specific formulations could the t to be carried out by methods similarly noted in section(C) the cultivation of livestock and fisheries”.

The best way of carrying out the invention

Next, a more detailed explanation of the present invention with reference to examples, but the invention is not limited to the following examples, if they do not go beyond its essence.

Example 1. Obtain 1-(2,6-dichloro-4-triptoreline)-4-trifloromethyl-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile (compound No. 5).

To a mixture of 10.0 g of 5-amino-1-(2,6-dichloro-4-triptoreline)-4-triftormetilfullerenov-3-carbonitrile, 2.5 g of formylpyridine and 80 ml of toluene was added 0.1 g of monohydrate p-toluensulfonate acid and the mixture was heated at the boil under reflux for 10 hours, during which formed was removed the water. After cooling to room temperature, to the mixture was added 30 ml of ice-cold water followed by extraction. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed, bringing it away under reduced pressure, obtaining the crude 1-(2,6-dichloro-4-triptoreline)-4-trifloromethyl-5-(pyrazin-2-ylmethylamino)-pyrazole-3-carbonitrile.

To a solution of 1-(2,6-dichloro-4-triptoreline)-4-trifloromethyl-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile obtained above in methanol (100 ml) was gradually added 0.9 g Bo is sodium hydride. After stirring at room temperature for 1 hour to the mixture was added ice and ethyl acetate, followed by extraction. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate. The residue was purified column chromatography on silica gel, receiving 7.0 g of the compound (No. 5), described below in table 1.

Table 1. Melting point: 169° C.

1H NMR (Dl3): 4,37 (2H, m), for 6.81 (1H, m), 7,74 (2H, d), 8,39 (1H, d), and 8.50 (2H, m)

Example 2. Obtain 1-(2,6-dichloro-4-triptoreline)-4-methylsulfinyl-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile (compound No. 1).

To a mixture of 5.6 g of 5-amino-1-(2,6-dichloro-4-triptoreline)-4-methylsulfonylbenzoyl-3-carbonitrile, 2.0 g of formylpyridine and 60 ml of toluene was added 20 mg of the monohydrate of p-toluensulfonate acid and the mixture was heated at the boil under reflux for 3 hours, during which formed was removed the water. After cooling to room temperature, to the mixture was added 0.1 ml of triethylamine and 30 ml of ice-cold water followed by extraction. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed, bringing it away under reduced pressure, obtaining the crude 1-(2,6-dichloro-4-triptoreline)-4-methylsulfinyl-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile.

To a solution of 1-(2,6-dichloro-4-trifter ethylphenyl)-4-methyl-sulfinil-5-(pyrazin-2-ylmethylamino) pyrazole-3-carbonitrile, obtained above in methanol (50 ml) was gradually added 0.7 g sodium borohydride. After stirring at room temperature for 1 hour to the mixture was added ice and ethyl acetate, followed by extraction. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate. The residue was purified column chromatography on silica gel, receiving of 5.1 g of compound (No. 1), described below in table 1.

Table 1. Melting point: 198° C.

1H NMR (Dl3): to 3.33 (3H, s), 4,18 (2H, d), to 7.15 (1H, t), 7,71 (2H, s), to 8.41 (2H, d), 8,51 (1H, d).

Example 3. Obtain 1-(2,6-dichloro-4-triptoreline)-4-trifloromethyl-5-(1-oxy-pyridine-3-ylmethylamino)pyrazole-3-carbonitrile (compound No. 14).

10 mm N,N-dimethylformamide suspended 0.1 g of 60%sodium hydride was gradually added 5-amino-1-(2,6-dichloro-4-triptoreline) -4-triftormetilfullerenov-3-carbonitrile. After 20 minutes stirring at room temperature was added to a mixture of 3 drops of 15-crown-5-ether, and then 0.3 g of 3-chloromethylpyridine-1-oxide, followed by stirring at room temperature. After standing overnight the mixture was added water and ethyl acetate and the mixture is neutralized 1N hydrochloric acid. After separation of liquids organic layer was washed with saturated saline and then dried over besod the first sodium sulfate.

The residue was purified column chromatography on silica gel, obtaining 0.9 g of the compound (No. 14), described in the following table 1.

Table 1. Melting point: 189-191° C.

1H NMR (CDCl3): of 4.2 to 4.5 (2H, m), 7,03 (1H, d), 7,12 (1H, t), 7,18 (1H, t), 7,74 (2H, s), 8,03 (2H, m).

Example 4. Obtaining N-[3-cyano-1-(2,6-dichloro-4-triptoreline)pyrazole-5-yl]pyrazin-2-carboxamide.

To a mixture of 0.5 g (1.6 mmol) of 5-amino-1-(2,6-dichloro-4-triptoreline)pyrazole-3-carbonitrile, 0.24 g (1.7 mmol) of methylpyridoxine and 0.5 ml of acetonitrile was gradually added at room temperature, 0.3 g (1.6 mmol) of a mixture of 28% CH3ASO/CH3HE. After stirring for 2 hours at room temperature, to the mixture was added 5 ml of water, and then concentrated hydrochloric acid to achieve pH 2, while in the sediment precipitated crystals. To the mixture was added 10 ml of ethyl acetate followed by extraction. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate. After removing sodium sulfate by filtration layer was concentrated, and the obtained crystals were filtered off. The crystals were washed with a small amount of hexane and ethyl acetate and dried, obtaining 0.5 g (yield 77%) of N-[3-cyano-1-(2,6-dichloro-4-triptoreline)pyrazole-5-yl]pyrazin-2-carboxamide.

Example 5. Obtain 1-(2,6-dichloro-4-triptoreline)-5-(pyrazin-2-and is chloromethylene)pyrazole-3-carbonitrile.

A mixture of 139 g (0.33 mol) of N-[3-cyano-1-(2,6-dichloro-4-triptoreline)pyrazole-5-yl]pyrazin-2-carboxamide, to 72.6 g (0.35 mol) of pentachloride phosphorus and 300 ml of toluene was heated at the boil under reflux for 2 hours. Addition was added to a mixture of 5 g of pentachloride phosphorus followed by heating at boiling under reflux for 1 hour. The mixture was cooled to room temperature and left overnight. After stirring for 30 minutes, the crystals were filtered off and washed with toluene. The crystals were dissolved in 1 l of chloroform and the solution was extracted after adding water. The organic layer was washed twice with water and saturated saline and then dried over anhydrous sodium sulfate. The solvent was removed by distillation and the obtained crystals were washed with hexane, getting to 112.2 g (yield 79%) of 1-(2,6-dichloro-4-triptoreline)-5-(pyrazin-2-inflormation)pyrazole-3-carbonitrile.

Example 6. Obtain 1-(2,6-dichloro-4-triptoreline)-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile.

To a suspension of 85 mg (2.2 mmol) sodium borohydride in ethanol (2 ml) gradually dobelli 0.5 g (1.1 mmol) 1-(2,6-dichloro-4-triptoreline)-5-(pyrazin-2-inflormation)pyrazole-3-carbonitrile at a temperature not exceeding 20° C. After stirring at room temperature for 1 hour the mixture was gradually poured into 40 ml of water is La precipitation of crystals. After stirring for 30 minutes, the crystals were filtered off and washed with water until until pH of the filtrate reached 6. Thus obtained crystals were dissolved in ethyl acetate and the solution was extracted after addition of a saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The obtained crystals were filtered off, washed with a small amount of hexane and ethyl acetate and dried, obtaining of 0.42 g (yield 92%) of 1-(2,6-dichloro-4-triptoreline)-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile.

Example 7. Obtain 1-(2,6-dichloro-4-triptoreline)-4-trifloromethyl-5-(pyrazin-2-ylmethylamino)pyrazole

To a solution of 3.0 g of 1-(2,6-dichloro-4-triptoreline)-5-(pyrazin-2-ylmethylamino)pyrazole dissolved in 30 ml of dry methylene chloride under nitrogen atmosphere was added 14 ml of triftormetilfullerenov in dry methylene chloride at room temperature for about 1 hour, followed by stirring overnight. To the mixture was added saturated aqueous sodium hydrogen carbonate solution and the organic layer was washed several times with saturated aqueous sodium hydrogen carbonate solution and water. After this layer was purified column chromatography on silica gel. After removal of the solvent drying in vacumme gave 3,59 g 1 - (2,6-dichloro-4-triptoreline)-4-trifloromethyl-5-(pyrazin-2-ylmethylamino)pyrazole

Example 8. Obtain 1-(2,6-dichloro-4-triptoreline)-4-trifloromethyl-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile

In 1.0 ml of 1,2-dichloroethane suspended 234 mg (1.3 mmol) of triftoratsetofenona potassium, 358 mg (1.6 mmol) of p-toluensulfonate dimethylamine, 413 mg (1.0 mmol) 1-(2,6-dichloro-4-triptoreline)-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile, and then under ice cooling was added 301 mg (2.5 mmol) of chloride tiomila. The mixture was heated to 60°and was stirred for 30 minutes. Then the reaction mixture was analyzed using high performance liquid chromatography by observing the formation of 1- (2,6-dichloro-4-triptoreline) -4-trifluoromethyl-sulfinil-5- (pyrazin-2-ylmethylamino) pyrazole-3-carbonitrile with 11% yield. It is established that the conversion of 1-(2,6-dichloro-4-triptoreline)-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile was 95%.

Example 9. Obtain 1-(2,6-dichloro-4-triptoreline)-4-trifloromethyl-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile

5.0 ml of 1,2-dichloroethane suspended 1,725 g (10.0 mmol) of triftoratsetofenona potassium, 895 mg (4.1 mmol) of p-toluensulfonate dimethylamine, 951 mg (5.0 mmol) of monohydrate p-toluensulfonate acid, and then under ice cooling was added 1,506 g (12.6 mmol) of chloride tiomila. After stirring for 3 hours at room temperature the round to the mixture was added to 1.03 g (2.5 mmol) of 1-(2,6-dichloro-4-triptoreline)-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile and the mixture was heated to 40° C and was stirred for 5 hours. The reaction mixture was neutralized with saturated aqueous sodium hydrogen carbonate solution and then was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate. The solvent drove using distillation under reduced pressure and the resulting oil was purified, highlighting 487 mg (yield 38%) of 1-(2,6-dichloro-4-triptoreline)-4-trifloromethyl-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile.

Example 10. Obtain 1-(2,6-dichloro-4-trifluoromethyl-phenyl)-4-trifloromethyl-5-(pyrazin-2-ylmethylamino)-pyrazole-3-carbonitrile

350 ml and 110 ml of acetonitrile was dissolved 7,89 g (8,88 mmol) of bis(1-(2,6-dichloro-4-triptoreline)-3-carbonitril-5-(pyrazin-2-ylmethylamino)pyrazole-4-yl)-disulfide, 5,44 g (of 31.6 mmol) of triftoratsetofenona potassium and 0.40 g (1,24 mmol) dioxobis(acetylacetonato)molybdenum, and then was added dropwise at room temperature, 3.4 ml (to 27.2 mmol) of an 80%aqueous solution of tert-butylhydroperoxide. In addition, every 4 hours was repeated twice adding 5,44 g (of 31.6 mmol) of triftoratsetofenona potassium and 3.4 ml (to 27.2 mmol) of an 80%aqueous solution of tert-butylhydroperoxide, followed by stirring for 15 hours at room temperature. Then again added 5,44 g (of 31.6 mmol) of triftoratsetofenona potassium and 3.4 ml (to 27.2 mmol) of an 80%aqueous solution of tert-butylhydroperoxide to follow them by stirring for 6 hours. After removal by filtration of precipitated precipitated pale brown crystals from the filtrate was removed acetonitrile using distillation under reduced pressure and added with ethyl acetate, followed by extraction. After washing the organic layer with water, the solvent was removed under reduced pressure and the residue was subjected to purification column chromatography (Hexane/AcOEt2=5/2)to give 0.88 g (1.7 mmol) of pale yellow crystals of 1-(2,6-dichloro-4-triptoreline)-4-trifluoromethyl-sulfenyl-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile from 9.6% output.

Example 11. Obtain 1-(2,6-dichloro-4-trifluoromethyl-phenyl)-4-trifloromethyl-5-(pyrazin-2-ylmethylamino)-pyrazole-3-carbonitrile

In nitrogen atmosphere to 10.1 mg (0.24 mmol) of sodium borohydride was added to a solution in methanol (1.5 ml) 50 mg (0.11 mmol) of 1-(2,b-dichloro-4-triptoreline)-4-thiocyanate-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile, followed by stirring at room temperature for 2 hours. After removal of the solvent from the reaction mixture using distillation under reduced pressure in a nitrogen atmosphere was added 2 ml of DMF. After cooling in a bath with a mixture of dry ice-acetone to the mixture was added a solution in DMF (0.5 ml) of 54.5 mg (0.11 mmol) MONTHS-12 (S-(trifluoromethyl)was 3.7-dinitrobenzamide triftoratsetata), triptoreline agent, produced by Daikin Chemcal Industries Ltd. After stirring for 1 hour at room temperature was added ethyl acetate and water, followed by extraction. The organic layer was subjected to LC-analysis, observing the formation of 1-(2,6-dichloro-4-triptoreline)-4-trifloromethyl-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile out of the area under the curve of 41.7%.

Compounds shown in table 1, were synthesized in accordance with methods described in examples 1-11. Below is data showing the number of connections and NMR data.

No. 2

1H NMR (Dl3): to 3.33 (3H, s), 4,19 (2H, d), to 7.15 (1H, ushort), 7,71 (2H, s), 8, 40 (1H, d), 8,42 (1H, d), 8,51 (1H, d)

No. 3

1H NMR (Dl3): of 1.39 (3H, t), 3,26 (2H, m), 4,34 (2H, d), 6,83 (1H, t), to 7.68 (2H, d), 8,35 (1H, d), of 8.47 (1H, d), 8,51 (1H, s)

No. 4

1H NMR (Dl3): 4,43 (2H, d), of 6.75 (1H, t), is 6.78 (1H, t), of 7.75 (2H, d), to 8.41 (1H, m), and 8.50 (2H, m)

No. 6

1H NMR (Dl3): of 2.56 (3H, s), 4,30 (2H, m), 6,62 (1H, osirm), 7,72 (2H, d), of 8.25 (1H, d), 8,35 (1H, d)

No. 7

1H NMR (Dl3): of 4.66 (2H, d), 5,27 (1H, users), and 5.30 (1H, s), 5,61 (1H, s), 7,76 (2H, s), to 8.41 (1H, d), 8,49 (1H, d), 8,54 (1H, s)

No. 8

1H NMR (CDCl3): a 4.53 (2H, s), to 6.88 (1H, t), 7,71 (2H, s), 8,29 (1H, s), at 8.36 (1H, s), 8,39 (1H, s)

No. 9

1H NMR (Dl3): of 4.35 (2H, m), 6,85 (1H, users), of 7.23 (1H, d), 7,74 (2H, d), 8,69 (1H, d), 9,01 (1H, s)

No. 10

1H NMR (Dl3): is 2.37 (3H, s), the 4.90 (2H, d), 5,27 (1H, m), 7,45 (2H, m), of 7.75 (2H, s), 9,12 (1H, DD)

No. 11

1H NMR (Dl3): and 4.68 (2H, m), of 6.71 (1H, users), 7,47 (1H, d), 7,73 (1H, d), 9,11 (1H, d)

No. 12

1H NMR (Dl3): 4.1 and 4.5 (2H, m), 6,69 (1H, t), 7,10 (2H, d), 7,21 (1H, t), to 7.77 (2H, s), 8,10 (2H, d)

No. 13

1H NMR (Dl3): a 4.3 (2H, m), 7,02 (2H, d), of 7.70 (2H, s), 8,01 (2H, d)

No. 15

1H NMR (Dl3): 4,84 (2H, d), 6.35mm (1H, users), 7,31 (3H, m), to 7.77 (2H, s), 8,15 (1H, m)

X:C-Cl, R2=H, R3=H

Connection # S(O)nR1ATPL°
1SOCH3198
2SO2CH3147-149
3SOC2H5158-162
4SOCHF2178
5SOCF3169
6SOCF3186-188
7SCH2F 119-120
8SCHF2117.118
9SOCF3101-103
10SCH3151-153
11SOCF379-81
12SOCHF2202-204
13SOCF3179
14SOCF3189-191
15SOCF3183-185

The following are examples of compositions for agricultural and horticultural insecticide containing as active ingredient the compound according to the invention, but these are not limited.

<Example 1> Wettable powder

Twenty parts by weight of the compounds according to the invention, 20 parts by weight of Carplex #80 (product name white coal, produced by Shionogi &Co., Ltd.), 52 parts by weight of kaolin gli is s ST Kaolin Clay (product name of kaolinite, produced by Tsuchiya Kaolin K.K.), 5 parts by weight of Sorpol 9047K (product name anionic surfactant manufactured by Toho Chemical Industry Co., Ltd.) and 3 parts by weight Runox P65L (product name anionic surfactant manufactured by Toho Chemical Industry Co., Ltd.) mixed and uniformly crushed, getting a wettable powder containing 20% by weight of the active ingredient.

<Example part 2> Douste:

Two parts by weight of the compounds according to the invention, 93 parts by weight of clay (produced by Nippon Talc K.K.) and 5 parts by weight of Carplex #80 (product name white coal, produced by Shionogi &Co., Ltd.), uniformly mixed and crushed, receiving a dust containing 2% by weight of the active ingredient.

<Example 3> Emulsifiable concentrate

In a mixed solvent consisting of 35 parts by weight of xylene and 30 parts by weight of dimethylformamide, was dissolved 20 parts by weight of the compounds according to the invention was added to a mixture of 15 parts by weight of Sorpol 3005K (product name anionic poverhnosti-active substances produced by Toho Chemical Industry Co., Ltd.), getting emulsifiable concentrate containing 20% by weight of the active ingredient.

<Example of composition 4> Flowing the product

A mixture of 30 parts by weight of the compounds according to the invention, 5 parts by weight of Sorpol 9047K, 3 parts by weight Sorbon T-20 (product name is einoo surfactants, produced by Toho Chemical Industry Co., Ltd.), 8 parts by weight of ethylene glycol and 44 parts by weight of water was ground wet in a Dynomill (produced by Shinmaru enterprises Co.). To the resulting suspension were added 10 parts by weight of 1 wt.% aqueous solution of xanthan gum (polymer of natural origin), followed by mixing and careful grinding, receiving flowable product containing 20% by weight of the active ingredient.

Next will be illustrated by examples of testing agricultural and horticultural insecticide containing as active ingredient the compound according to the invention, but applications are not limited to the following.

The test example 1. Insecticidal effect on larvae of brown rice delphacidae (Nilaparvata lugens)

The rice seedlings were planted in a glass cylinder (inner diameter 3 cm × length: 17 cm) and released back five larvae of the 4th age brown rice delacey. Agricultural and horticultural insecticide of the invention was obtained in accordance with example 3 and diluted with water and 0.5 ml of the resulting emulsion was dissipated into the cylinder through the spray installation (produced by Mizuho Rika) (two-time sequence concentration). The cylinder was kept at a constant room temperature at 25° and death and dying larvae study is Ali 5 days after treatment, receiving the degree of mortality (%), keeping agonizing insect for 1/2 dead insect. The results obtained are presented in table 2 (the numbers of the compounds in table 2 correspond to the numbers in table 1).

Table 2
Connection # Concentration (parts per million)The degree of mortality (%)
1500100
3500100
4500100
5500100
6500100
7500100
9500100
10500100
11500100
12500100
13500100
14500100

The test example 2. Insecticidal effect on larvae of the cabbage moth (Plutella xylostella)

Carved out of a cabbage leaf disc (diameter 6 cm) were soaked for 1 minute in an aqueous suspension of agricultural and horticultural insecticide of the invention, obtained the CSOs in accordance with the example of structure 1, dried in air and placed in a plastic Cup (inner diameter: 7 cm). Five larvae of Plutella xylostella 3rd age released into the Cup (twice a sequence of concentration). The Cup was kept at a constant room temperature at 25° and death and dying larvae examined 4 days after treatment, receiving the degree of mortality (%), keeping agonizing insect fordead insect. The results obtained are presented in table 3 (number of connections in table 3 correspond to the numbers in table 1).

Table 3
Connection # Concentration (parts per million)The degree of mortality (%)
1500100
2500100
3500100
4500100
5500100
6500100
7500100
9500100
10500100
11500100
12500100
13500100
14500100
15500100

The test example 3. Insecticidal effect on larvae of the noctuid ordinary (Spodoptera litura)

Carved out of a cabbage leaf disc (diameter 6 cm) were soaked for 1 minute in an aqueous suspension of agricultural and horticultural insecticide of the invention obtained in accordance with example 1, was dried in air and placed in a plastic Cup (inner diameter: 7 cm). Five larvae of the 3rd age stage of Spodoptera litura were released in the Cup (twice a sequence of concentration). The Cup was kept at a constant room temperature at 25° and death and dying larvae examined 5 days after treatment, receiving the degree of mortality (%), keeping agonizing insect for 1/2 dead insect. The results obtained are presented in table 4 (number of compounds in table 4 correspond to the numbers in table 1).

Table 4
Connection # Concentration (parts per million)The degree of mortality (%)
5500100
6500100
9500100
1150090
13500100
14500100
15500100

The test example 4. Insecticidal effect on the imago (adult) corn rayed bean (Callosobruchus chinensis)

Two radiant beans were placed in a glass cylinder (inner diameter: 3 cm × length: 15 cm) and released over 10 adult Callosobruchus chinensis. Agricultural and horticultural insecticide of the invention was obtained in accordance with example 3 and diluted with water and 0.3 ml of the resulting emulsion was dissipated into the cylinder through the spray installation (produced by Mizuho Rika) (two-time sequence concentration). The cylinder was kept at a constant room temperature at 25° and death and dying larvae examined 4 days after treatment, receiving the degree of mortality (%), keeping agonizing insect fordead insect. The results obtained are presented in table 5 (the numbers of the compounds in table 5 correspond to the numbers in table 1).

table 5
Connection # Concentration (parts per million)The degree of mortality (%)
1500100
2500100
3500100
4500100
5500100
6500100
9500100
10500100
11500100
12500100
13500100
14500100
15500100

The test example 5. Insecticidal effect on larvae of the peach aphid (Myzus persicae)

Water was placed in a bottle with a screw tube (volume: 10 ml) and was placed petiole Japanese radish and inoculable 5-6 adults Myzus persicae on the sheet. After insulinopenia the bottle was placed in a glass cylinder (diameter: 0.5 cm, height: 15 cm) with a grid floor and insects were left to develop supported at a constant room temperature at 25° C for 3 days. Adults with leaves removed and leaves the submersible is whether in an aqueous solution of agricultural and horticultural insecticide, obtained according to the invention in accordance with the composition of example 3, about 5 seconds, and then returned in a glass cylinder (double sequence of concentration). The cylinder was kept at a constant room temperature of 25° and the number of insects on the leaves were counted on day 4 after treatment to obtain the degree of mortality (%). The results obtained are presented in table 6 (the number of connections in the table correspond to the numbers in table 1).

Table 6
Connection # Concentration (parts per million)The degree of mortality (%)
1500100
2500100
3500100
4500100
5500100
7500100
8500100
9500100
10500100
12500100
13500100
14500100

Example ispy is Denmark 6. Insecticidal effect on larvae of brown rice delphacidae (Nilaparvata lugens)

The roots of young seedlings of rice (height: about 10 cm), planted in a plastic Cup, washed with water and washed away the soil, so as not to damage the delicate roots. The stalk was premerlani urethane tip (diameter: 3 cm, height: 2 cm)having a secant line and the roots were inserted into the Erlenmeyer flask, which was previously placed 50 ml of a solution of the agent (dilute aqueous solution of an agricultural and horticultural insecticide of the invention obtained in accordance with example composition 1) (2-3 young rice seedlings/flask). Urethane tip reinforcing wedge throat bulb to lock the rice seedlings. Put down a glass tube (diameter: 3 cm height: 5 cm), fixed wedge in urethane tip and fixed with tape. The flask in such a state kept at a constant room temperature of 25° C for 3 days. Five larvae of brown rice delacey was placed in a glass tube and then the tube was closed urethane tip, followed by keeping at a constant room temperature at 25° With (two-time sequence concentration).

Death and dying larvae examined 4 days after treatment, receiving the degree of mortality (%), keeping the ago is serouse insect for dead insect. This test was carried out on three solutions agent, differing in the concentration of the active ingredient. The results are presented in table 7 (the number of connections in the table correspond to the numbers in table 1).

As comparative compounds similarly tested compounds I-V, each of which has the following structure (compound I is described in application laid on the Japan patent No. 316771/1988, compounds II and III are described in the examples WO9845274 and compounds IV and V are included in the claims WO9845274, but not included in the claims of this application).

td align="center"> 100
Table 7
The degree of mortality (%) at each concentration of the active ingredient
Connection # of 3.1 parts per million0.8 parts per million0.2 parts per million
1100100100
3100100100
4100100100
5100100
7100100100
8100100100
9100100100
10100100100
14100100100
Connection comparison
I926733
II5020-
III10010092
IV100100100
v958055

Brown rice delphacidae (Nilaparvata lugens) is a highly problematic insect pests, which is harmful, as described in the example test 1, but sufficient efficiency can be achieved by applying a dusting agent on the stems and leaves, provided that the detection is delayed or that a sufficient amount of the agent is distributed on the roots.

Because this type of insect is typical dwelling around the roots of rice plants or the like, and damage to plants due to the suction of the fluid, b is more effective way of combating insects can be a method of soil treatment agent (processing granules) before widely occurring outbreaks of occurrence of these species. However, to achieve a high effect of control required system property (property infiltration and migration into the body of the plant) the nature of the agent. As can be seen from table 6 all connections according to the invention and compounds III and IV show insecticidal activity due to high system properties against this highly problematic insect pests, but the compounds I, II and III had a clearly lower action than the compounds of the invention due to lower activity.

Example test 7. The toxicity study fish using Oryzias latipes

This sample test is one example of research on the safety of agricultural and horticultural insecticides in relation to the environment.

Ten mg of each compound was dissolved in 1 ml of DMSO and 0.05 ml portion of this solution was added to glass chemical beaker containing 1 liter of distilled water to obtain an aqueous solution containing 0.5 parts per million In aqueous solution were placed five fish Oryzias latipes (adults, the average weight of 360 mg) and mortality was determined 48 hours to calculate the degree of mortality (%) 5 fish on 1 lot/glass, single sequence). The results are presented in table 8 (the number of connections in the table correspond to the numbers in table 1).

Similarly, p is the iMER test 6, the connection I described in application laid on the Japan patent No. 316771/1988, compounds II and III described in the examples WO9845274 and compounds IV and V are included in the claims WO9845274, but not included in the claims of this application, subjected to investigation as comparative compounds.

As can be seen from table 8, all tests for compounds I-V showed a high rate of fish mortality, but the deaths were not observed in the case of compounds of the invention. Thus, the compounds according to the invention are highly efficient even if the agent against used directly in the aqueous system, for example, in the case of the rice fields.

Example test 8: Insecticidal effect on the cat flea

On a round filter (diameter: 10 cm) was added dropwise 0.7 ml of a solution of the agent is diluted to a predetermined concentration. After drying, the filter was placed on the bottom of the cylinder (diameter: 10 cm × height: 30 cm), released back ten fleas and mortality was determined on day 1 and on day 2 after processing for calculating the degree of mortality (%) based on the results. The results are presented in table 9 (the number of connections in the table correspond to the numbers in table 1).

Table 9
Connection # The number of test agent (mg/filter)The degree of mortality (%)
50,7100
70,7100

Industrial applicability

Derivatives of 1-aryl-3-cyano-5-prasidialkabinette invention are novel compounds having excellent insecticidal action and a broad spectrum of insecticidal activity, they also exhibit high system activity and reduced toxicity to the environment, such as toxicity to fish. Therefore, derivatives can be used as agents for combating pests of agriculture.

1. Derivative of 1-aryl-3-cyano-5-heterooligomerization General formula (1):

where X is halogen, R1represents a C1-C4alkyl group or Halogens1-C4alkyl group, R2and R3represent a hydrogen atom, And represents any of groups represented above by formulas A-1 to a-4, where R4represents a hydrogen atom or a C1-C4 alkyl group, n represents 0, 1 or 2, provided that R1is Halogens1-C4alkyl group, with the exception perhalogenated group when a represents an a-1 and n is 0, and that n is not equal to 0, when a is a a-4).

2. Derivative of 1-aryl-3-cyano-5-heterooligomerization according to claim 1, where a represents the a-1 and R4represents a hydrogen atom or a C1-C4alkyl group.

3. Derivative of 1-aryl-3-cyano-5-heterooligomerization according to any one of claims 1 and 2, where R1represents halogenating group containing from 1 to 2 carbon atoms.

4. 1-(2,6-Dichloro-4-triptoreline)-4-formailty-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile and 1-(2,6-dichloro-4-triptoreline)-4-trifloromethyl-5-(pyrazin-2-ylmethylamino)pyrazole-3-carbonitrile.

5. Derivative of 1-aryl-3-cyano-5-heterooligomerization according to any one of claims 1 to 4 as an active ingredient for pest control.

6. Insecticide containing as active ingredient a derivative of 1-aryl-3-cyano-5-heterooligomerization according to any one of claims 1 to 4.

7. A derivative of pyrazole of the General formula (2):

A:Y:

where X, R2, R3and R4have the same values as specified for the General formula (1), and R5represents a hydrogen atom, And represents a-1, Y represents any of the groups Y-1 ÷ Y-3, Z represents a halogen atom.

8. A method of obtaining a pyrazole derivative of the General formula (1), where n is equal to 0, including the processing of the pyrazole derivative of the General formula (2), where R5is a thiocyanate group, a represents an a-1 or a-3, R4represents hydrogen and Y is Y-3, the connection R1-X2where R1has the same values as specified for the General formula (1), and X2represents a halogen atom or trimethylsilyloxy group.

9. A method of obtaining a pyrazole derivative of the General formula (2), where Y is Y-1, R2represents a hydrogen atom, R4represents hydrogen or C1-C4alkyl includes treatment pyrazole derivative of the General formula (3)

where X is halogen, R5represents a hydrogen atom, nitrogen-containing six-membered heterocyclic compound represented by the formula a-C(=O)-X7where a represents a-1, X7is a CNS group having 1-6 carbon atoms.

10. With the persons receiving halogenerator compounds of General formula (2), where Y is Y-2, And represents a-1, Z represents a chlorine atom or a bromine atom, including the processing of amide compounds of General formula (2), where Y is Y-1, And represents a-1, R4and R2represent a hydrogen atom, pentachloride phosphorus or pentabromide phosphorus.

11. A method of obtaining a pyrazole derivative of the General formula (2), where Y is Y-3, And represents a-1, R2, R3and R4represent a hydrogen atom, including the restoration halogenerator compounds represented by the General formula (2), where Y is Y-2 and a represents a-1.



 

Same patents:

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new compound of the formula (I) or its pharmaceutically acceptable salt or solvate wherein X represents CH or nitrogen atom (N); Z represents CH; R1 represents hydrogen atom; R2 and R3 can be similar or different and represent (C1-C6)-alkoxy-group that is optionally substituted with halogen atom, hydroxyl, (C1-C4)-alkoxycarbonyl, amino-group wherein one or two hydrogen atom are optionally replaced for (C1-C4)-alkyl that is optionally substituted with hydroxyl or (C1-C4)-alkoxy-group, the group R12R13N-C(=O)-O- wherein R12 and R13 can be similar or different and represent hydrogen atom or (C1-C4)-alkyl substituted optionally with (C1-C4)-alkoxy-group or the group R14-(S)m- wherein R14 represents phenyl or saturated or unsaturated 5-7-membered heterocyclic group substituted optionally with (C1-C4)-alkyl; m = 0 or 1; R4 represents hydrogen atom; R5, R6, R7 and R8 can be similar or different and represent hydrogen atom, halogen atom, (C1-C4)-alkyl, (C1-C4)-alkoxy-group or nitro-group under condition that R5, R6, R7 and R don't represent hydrogen atom simultaneously; R9 represents hydrogen atom, (C1-C6)-alkyl or (C1-C4)-alkylcarbonyl wherein alkyl fragment of indicated (C1-C6)-alkyl or (C1-C4)-alkylcarbonyl is optionally substituted with (C1-C4)-alkoxy-group; R10 represents hydrogen atom or (C1-C6)-alkyl; R11 represents (C1-C6)-alkyl, (C2-C6)-alkenyl or (C2-C6)-alkynyl (wherein each (C1-C6)-alkyl, (C2-C6)-alkenyl and (C2-C6)-alkynyl is substituted optionally with halogen atom or (C1-C6)-alkoxy-group), or R15-(CH2)n- wherein n is a whole number from 0 to 3; R15 represents naphthyl or 6-membered saturated or unsaturated carbocyclic or saturated or unsaturated 5-7-membered heterocyclic group that are substituted optionally with halogen atom, (C1-C6)-alkyl or (C1-C6)-alkoxy-group. Also, invention relates to variants of compounds of the formula (I). Compounds elicit antitumor activity and don't effect on cytomorphosis. Also, invention relates to pharmaceutical composition based on above described compounds, to a method for treatment of such diseases as malignant tumor, diabetic retinopathy, chronic rheumatism, psoriasis, atherosclerosis, Kaposi's sarcoma, and to a method for inhibition of vascular vessels angiogenesis.

EFFECT: valuable medicinal properties of compounds and composition.

22 cl, 4 tbl, 186 ex

FIELD: organic chemistry, medicine, hormones, pharmacy.

SUBSTANCE: invention relates to new biologically active compounds that act as agonists of peptide hormone vasopressin. Invention describes the compound of the general formula (1) or its pharmaceutically acceptable salt wherein V represents a covalent bond or NH; X is taken among CH2, oxygen atom (O) and N-alkyl; Z represents sulfur atom (S) or -CH=CH-; R1 and R2 are taken independently among hydrogen (H), fluorine (F), chlorine (Cl), bromine (Br) atom and alkyl; R3 is taken among hydroxyl group (OH), O-alkyl and NR4R5 wherein each R4 and R5 represents independently hydrogen atom (H) or alkyl, or both represent -(CH2)q-; p = 0, 1, 2, 3 or 4; q = 4 or 5. Also, invention describes a pharmaceutical composition eliciting agonistic activity with respect to V2-receptors, a method for treatment of enuresis, nicturia and diabetes insipidus, method for control of enuresis and a method for treatment of enuresis and a method for treatment of diseases associated with damage in blood coagulability. Invention provides preparing new compounds eliciting useful biological properties.

EFFECT: valuable medicinal properties of compounds.

17 cl, 31 ex

FIELD: organic chemistry, pharmaceutical composition.

SUBSTANCE: new isoindoline-1-on-glucokinase activators of general formula I , as well as pharmaceutically acceptable salts or N-oxide thereof are disclosed. In formula A is phenyl optionally substituted with one or two halogen or one (law alkyl)sulfonyl group, or nitro group; R1 is C3-C9cycloalkyl; R2 is optionally monosubstituted five- or six-membered heterocyclic ring bonded via carbon atom in cycle to amino group, wherein five- or six-membered heteroaromatic ring contains one or two heteroatoms selected form sulfur, oxygen or nitrogen, one of which is nitrogen atom adjacent to carbon atom bonded to said amino group; said cycle is monocyclic or condensed with phenyl via two carbon atoms in cycle; said monosubstituted with halogen or law alkyl heteroaromatic ring has monosubstituted carbon atom in cycle which in not adjacent to carbon atom bonded to amino group; * is asymmetric carbon atom. Claimed compounds have glucokinase inhibitor activity and useful in pharmaceutical composition for treatment of type II diabetes.

EFFECT: new isoindoline-1-on-glucokinase activators useful in treatment of type II diabetes.

23 cl, 3 dwg, 43 ex

FIELD: organic chemistry, biochemistry, pharmacy.

SUBSTANCE: invention relates to new compounds of the formula (I):

eliciting inhibitory activity with respect to metalloproteinases and wherein R1 means phenoxy-group wherein phenyl residue can be substituted with one or some halogen atoms, hydroxy-, (C1-C6)-alkoxy-group, (C1-C6)-alkyl, cyano- or nitro-group; R2 means pyrimidine, pyrazine or its N-oxide or phenyl substituted with -SO2NR3R4 wherein R3 and R4 can be similar or different and mean hydrogen atom, direct-chain or branch-chain (C1-C6)-alkyl that can be substituted once or some times with the group OH, N(CH3)2, or it can be broken by oxygen atom, or it represents COR5 wherein R5 means (C1-C)-alkyl group that can be substituted with NH2. Also, invention relates to a pharmaceutical composition comprising above said compounds.

EFFECT: valuable biochemical properties of compounds and composition.

5 cl, 1 sch, 1 tbl, 10 ex

FIELD: organic chemistry, heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention relates to nitrogen-containing heterocyclic derivatives of the formula (I): A-B-D-E (I) wherein A means 5- or 6-membered heteroaryl comprising one or two nitrogen atoms in ring; B means ethenylene; D mean phenylene; E means group -N(COR)-SO2-G wherein G means phenyl; R means 5- or 6-membered heteroaryl or heteroarylmethyl comprising one or two nitrogen atoms in ring, or group -(CH2)n-N(R5)R6 wherein n means a whole number from 1 to 5; R5 and R6 are similar or different and mean: hydrogen atom, (C1-C6)-alkyl, hydroxyalkyl, aminoalkyl; or R5 and R6 in common with nitrogen atom can form 5-7-membered cyclic amino-group -N(R5)R6 that can comprise, except for nitrogen atom, also oxygen, sulfur or nitrogen atom as a component forming the ring, or their N-oxides. Compounds of the formula (I) elicit anticancer activity and can be used in medicine.

EFFECT: valuable medicinal properties of compounds.

10 cl, 1 tbl, 24 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of piperazinylalkylthiopyrimidine of the formula (I): wherein R1 represents hydrogen atom, (C1-C4)-alkyl, (C1-C4)-alkanoyl or di-(C1-C4-alkyl)-amino-(C1-C4-alkyl); R2 means hydrogen atom or benzyl substituted with 1-3 substitutes taken among the group consisting of (C1-C4)-alkyl, (C1-C4)-alkoxy-group, di-(C1-C4-alkyl)-amino-group, hydroxyl group and halogen atom; n = 2, 3 or 4, and to its pharmaceutically acceptable acid addition salt. Also, invention describes a method for preparing compounds and pharmaceutical composition based on thereof. Compounds are useful for treatment of diseases arising as result of the central nervous system injury.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

14 cl, 3 tbl, 26 ex

The invention relates to organic chemistry and can find application in medicine

The invention relates to new nitrogen-containing aromatic 6-membered cyclic compounds of the formula (I) or their pharmaceutically acceptable salts, demonstrating excellent selective PDE V inhibitory activity

Thrombin inhibitors // 2221808
The invention relates to compounds of formula I, the values of the radicals defined in the claims and their pharmaceutically acceptable salts

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new compound of the formula (I) or its pharmaceutically acceptable salt or solvate wherein X represents CH or nitrogen atom (N); Z represents CH; R1 represents hydrogen atom; R2 and R3 can be similar or different and represent (C1-C6)-alkoxy-group that is optionally substituted with halogen atom, hydroxyl, (C1-C4)-alkoxycarbonyl, amino-group wherein one or two hydrogen atom are optionally replaced for (C1-C4)-alkyl that is optionally substituted with hydroxyl or (C1-C4)-alkoxy-group, the group R12R13N-C(=O)-O- wherein R12 and R13 can be similar or different and represent hydrogen atom or (C1-C4)-alkyl substituted optionally with (C1-C4)-alkoxy-group or the group R14-(S)m- wherein R14 represents phenyl or saturated or unsaturated 5-7-membered heterocyclic group substituted optionally with (C1-C4)-alkyl; m = 0 or 1; R4 represents hydrogen atom; R5, R6, R7 and R8 can be similar or different and represent hydrogen atom, halogen atom, (C1-C4)-alkyl, (C1-C4)-alkoxy-group or nitro-group under condition that R5, R6, R7 and R don't represent hydrogen atom simultaneously; R9 represents hydrogen atom, (C1-C6)-alkyl or (C1-C4)-alkylcarbonyl wherein alkyl fragment of indicated (C1-C6)-alkyl or (C1-C4)-alkylcarbonyl is optionally substituted with (C1-C4)-alkoxy-group; R10 represents hydrogen atom or (C1-C6)-alkyl; R11 represents (C1-C6)-alkyl, (C2-C6)-alkenyl or (C2-C6)-alkynyl (wherein each (C1-C6)-alkyl, (C2-C6)-alkenyl and (C2-C6)-alkynyl is substituted optionally with halogen atom or (C1-C6)-alkoxy-group), or R15-(CH2)n- wherein n is a whole number from 0 to 3; R15 represents naphthyl or 6-membered saturated or unsaturated carbocyclic or saturated or unsaturated 5-7-membered heterocyclic group that are substituted optionally with halogen atom, (C1-C6)-alkyl or (C1-C6)-alkoxy-group. Also, invention relates to variants of compounds of the formula (I). Compounds elicit antitumor activity and don't effect on cytomorphosis. Also, invention relates to pharmaceutical composition based on above described compounds, to a method for treatment of such diseases as malignant tumor, diabetic retinopathy, chronic rheumatism, psoriasis, atherosclerosis, Kaposi's sarcoma, and to a method for inhibition of vascular vessels angiogenesis.

EFFECT: valuable medicinal properties of compounds and composition.

22 cl, 4 tbl, 186 ex

FIELD: organic chemistry, heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention relates to new heterocyclic compounds corresponding to general formulas: (I) , (II) , (Ia) and (Ib) wherein substitutes have values given in the description. Such compounds are reversible inhibitors of cathepsins S, K, F, L and B. Also, invention relates to a method for preparing these compounds, pharmaceutical composition eliciting inhibitory activity with respect to cysteine proteases and to a method for modulation of autoimmune diseases, treatment of Alzheimer's disease and osteoporosis.

EFFECT: improved method for preparing, valuable medicinal properties of compounds.

42 cl, 106 ex

FIELD: organic chemistry, medicine, hormones, pharmacy.

SUBSTANCE: invention relates to new biologically active compounds that act as agonists of peptide hormone vasopressin. Invention describes the compound of the general formula (1) or its pharmaceutically acceptable salt wherein V represents a covalent bond or NH; X is taken among CH2, oxygen atom (O) and N-alkyl; Z represents sulfur atom (S) or -CH=CH-; R1 and R2 are taken independently among hydrogen (H), fluorine (F), chlorine (Cl), bromine (Br) atom and alkyl; R3 is taken among hydroxyl group (OH), O-alkyl and NR4R5 wherein each R4 and R5 represents independently hydrogen atom (H) or alkyl, or both represent -(CH2)q-; p = 0, 1, 2, 3 or 4; q = 4 or 5. Also, invention describes a pharmaceutical composition eliciting agonistic activity with respect to V2-receptors, a method for treatment of enuresis, nicturia and diabetes insipidus, method for control of enuresis and a method for treatment of enuresis and a method for treatment of diseases associated with damage in blood coagulability. Invention provides preparing new compounds eliciting useful biological properties.

EFFECT: valuable medicinal properties of compounds.

17 cl, 31 ex

FIELD: organic chemistry, pharmaceutical compositions.

SUBSTANCE: invention relates to substituted 3-oxo-1,2,3,4-tetrahydroxinoxalines of general formula 1 , wherein R1 represents substituted sulfanyl or substituted sulfonyl group, containing as substituent optionally substituted C1-C4-alkyl, optionally substituted C3-C8-cycloalkyl, aryl-(C1-C4)alkyl optionally substituted in aril or alkyl group, heterocyclyl-(C1-C4)alkyl optionally substituted in heterocycle or alkyl group; R2 and R3 independently represent hydrogen, halogen, CN, NO2, optionally substituted hydroxyl, optionally substituted amino group, optionally substituted carboxylic group, optionally substituted carbamoyl group, optionally substituted arylcarbonyl group or optionally substituted heterocyclylcarbonyl group; R4 and R5 independently represent hydrogen or inert substituent. Claimed compounds are high effective kaspase-3 inhibitors and are useful in production of pharmaceutical compositions for treatment of diseases associated with excess apoptosis activation, as well as for experimental investigations of apoptosis in vivo and in vitro. Also disclosed are pharmaceutical composition in form of tablets, capsules or injections in pharmaceutically acceptable package, as well as method for production thereof and therapy method.

EFFECT: pharmaceutical composition for apoptosis treatment and investigation.

6 cl, 3 dwg, 8 ex, 1 tbl

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to new compound: N-[2-hydroxy-3(1-piperidinyl)-propoxy]-pyridine-1-oxyde-3-carboxyimidoyl chloride, stereoisomers thereof acid additional salts useful in treatment of pathological insulin resistance.

EFFECT: new compound useful in medicine.

5 cl, 10 tbl, 10 ex

FIELD: organic chemistry, pharmaceutical composition.

SUBSTANCE: new isoindoline-1-on-glucokinase activators of general formula I , as well as pharmaceutically acceptable salts or N-oxide thereof are disclosed. In formula A is phenyl optionally substituted with one or two halogen or one (law alkyl)sulfonyl group, or nitro group; R1 is C3-C9cycloalkyl; R2 is optionally monosubstituted five- or six-membered heterocyclic ring bonded via carbon atom in cycle to amino group, wherein five- or six-membered heteroaromatic ring contains one or two heteroatoms selected form sulfur, oxygen or nitrogen, one of which is nitrogen atom adjacent to carbon atom bonded to said amino group; said cycle is monocyclic or condensed with phenyl via two carbon atoms in cycle; said monosubstituted with halogen or law alkyl heteroaromatic ring has monosubstituted carbon atom in cycle which in not adjacent to carbon atom bonded to amino group; * is asymmetric carbon atom. Claimed compounds have glucokinase inhibitor activity and useful in pharmaceutical composition for treatment of type II diabetes.

EFFECT: new isoindoline-1-on-glucokinase activators useful in treatment of type II diabetes.

23 cl, 3 dwg, 43 ex

FIELD: organic chemistry, heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention relates to nitrogen-containing heterocyclic derivatives of the formula (I): A-B-D-E (I) wherein A means 5- or 6-membered heteroaryl comprising one or two nitrogen atoms in ring; B means ethenylene; D mean phenylene; E means group -N(COR)-SO2-G wherein G means phenyl; R means 5- or 6-membered heteroaryl or heteroarylmethyl comprising one or two nitrogen atoms in ring, or group -(CH2)n-N(R5)R6 wherein n means a whole number from 1 to 5; R5 and R6 are similar or different and mean: hydrogen atom, (C1-C6)-alkyl, hydroxyalkyl, aminoalkyl; or R5 and R6 in common with nitrogen atom can form 5-7-membered cyclic amino-group -N(R5)R6 that can comprise, except for nitrogen atom, also oxygen, sulfur or nitrogen atom as a component forming the ring, or their N-oxides. Compounds of the formula (I) elicit anticancer activity and can be used in medicine.

EFFECT: valuable medicinal properties of compounds.

10 cl, 1 tbl, 24 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention proposes two variants of the improved method for preparing anti-ulcerous therapeutic agents of the formula (I): wherein radicals R1-R6 have values given in cl. 1 and cl. 2 of the invention claim. Method involves interaction of corresponding sulfides with m-chloroperoxybenzoic acid in acetone or a mixture acetone/water as a solvent. According to the first variant pH value of the reaction mixture is increased to the value above 7 after the reaction interaction and solvent is removed and crystals of compound of the formula (I) are separated. According to the second variant the interaction is carried out at pH ≥ 7.0 followed by addition of water if necessary and compound of the formula (I) crystals are separated. Invention is directed for preparing omeprazole or pantoprazole preferably. Invention provides preparing the end products of high purity and with high yield.

EFFECT: improved preparing method.

9 cl, 3 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of benzodiazepine. Invention describes a derivative of benzodiazepine of the formula (I): wherein dotted lines show the possible presence of a double bond; R1, R2, R3, R4 and R5 are given in the invention claim; n represents 0, 1, 2, 3 or 4; X represents sulfur atom (S) or -NT wherein T is give in the invention claim; A represents hydrogen atom, (C6-C18)-aryl group substituted optionally with one or more substitutes Su (as given in the invention claim) or (C1-C12)-alkyl; or in alternative variant R4 and R5 form in common the group -CR6=CR7 wherein CR6 is bound with X and wherein R6 and R7 are given in the invention claim, and their pharmaceutically acceptable salts with acids or bases. It is implied that compounds corresponding to one of points (a)-(e) enumerated in the invention claim are excluded from the invention text. Also, invention describes methods for preparing compounds of the formula (I) and a pharmaceutical composition eliciting the hypolipidemic activity. Invention provides preparing new compounds eliciting the useful biological properties.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

20 cl, 6 tbl, 192 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a group of new derivatives of 4,5-dihydro-1H-pyrazole of the general formula (I):

wherein R means phenyl, thienyl or pyridyl and these indicated groups can be substituted with (C1-C3)-alkoxy-group or halogen atom; R1 means phenyl that can be substituted with (C1-C3)-alkoxy-group or pyridyl group; R2 means hydrogen atom or hydroxy-group; Aa means one group among the following groups: (i) , (ii) , (iii) , (iv) or (v) ; R4 and R5 mean independently from one another hydrogen atom or (C1-C8)-branched or unbranched alkyl; or R4 means acetamido- or dimethylamino-group or 2,2,2-trifluoroethyl, or phenyl, or pyridyl under condition that R5 means hydrogen atom; R6 means hydrogen atom at (C1-C3)-unbranched alkyl; Bb means sulfonyl or carbonyl; R3 means benzyl, phenyl or pyridyl that can be substituted with 1, 2 or 3 substitutes Y that can be similar or different and taken among the group including (C1-C3)-alkyl or (C1-C3)-alkoxy-group, halogen atom, trifluoromethyl; or R3 means naphthyl, and its racemates, mixtures of diastereomers and individual stereoisomers and as well as E-isomers, Z-isomers and mixture of E/Z-compounds of the formula (I) wherein A has values (i) or (ii), and its salt. These compounds are power antagonists of Cannbis-1 (CB1) receptor and can be used for treatment of psychiatric and neurological diseases. Except for, invention relates to a pharmaceutical composition used for treatment of some diseases mediated by CB1-receptor, to a method for preparing this composition, a method for preparing representatives of compounds of the formula (I) wherein Aa means group of the formulae (i) or (ii), intermediate compounds used for preparing compounds of the formula (I) and to a method for treatment of some diseases mediated by CB1-receptor.

EFFECT: valuable medicinal properties of compounds.

16 cl, 9 ex

Up!