Insecticidal isoxazolines

FIELD: chemistry.

SUBSTANCE: invention describes isoxazolines of formula (I), in which A denotes C or N; R denotes C1-4 haloalkyl; X denotes identical or different halogens or C1-4 haloalkyl; l equals 0, 1 or 2; Y denotes halogen or C1-4 alkyl, C1-4alkoxy, C1-4haloalkyl, cyano, nitro, amino, C1-4 alkylcarbonylamino, benzoylamino or C1-4 alkoxycarbonylamino; m equals 1 or 1; and G denotes any group selected from heterocyclic groups given in the description, and a method of producing said compounds and use as insecticides for controlling the population of harmful insects or arthropods.

EFFECT: high efficiency of using said compounds.

11 cl, 28 ex, 4 tbl

 

The invention relates to novel isoxazolines, methods for their preparation, their use as insecticides and their new intermediates and their use for combating animal pests.

In WO 2005/085216 indicated that replaced isoxazolines benzamide suitable as means to control animal parasites.

Were detected new isoxazolines the following formula (I)

where a represents C or N;

R represents a C1-C4-halogenated;

X represents identical or different halogen or1-C4-halogenated;

l is 0, 1 or 2;

Y represents independently from each other halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-halogenated, cyano, nitro, amino, C1-C4-alkylcarboxylic, benzoylamine or1-C4-alkoxycarbonyl;

m is 0 or 1; and

G represents any group selected from the heterocyclic groups represented by the formulas from G-1 to G-9:

in which

Z presented yet a halogen, methyl, methylthio, trifluoromethyl, cyano, nitro or amino; and

n is 0 or 1.

The compounds of formula (I) according to the present invention can be obtained by a method in which

(a) compounds of the formula (II)

where A, Y, m and G have the values as above, and Hal represents halogen, interact with the compounds of the formula (III)

where R, X and l have the same meanings as described above, in the presence of inert solvents and, if necessary, in the presence of base

or

(b) compounds of the formula (IV)

where A, R, X, l, Y, m and Hal have the meanings as stated above, interact with the compounds of the formula (V)

where G has the same meaning as above, in the presence of inert solvents and, if necessary, in the presence of a base, or

(C) if G is a

the compounds of formula (Ia)

where A, R, X, l, Y and m have the values as above, interact with halogenation means in the presence of inert solvents,

or

(d) if G is a

the compounds of formula (VI)

where A, R, X, l, Y and m have the values, the AK above, interact with the compounds of the formula (VII)

where R1represents alkyl, in the presence of inert solvents,

or

(e) if G is a

the compounds of formula (VI) interact with 1,2-deformalization in the presence of a base,

or

(f) if G is a

where Rf represents performanceline the compounds of formula (VIII)

where A, R, X, l, Y, m, Hal and Rf have the same meanings as described above, interact with azide compounds in the presence of inert solvents,

or

(g) if G is a

the compounds of formula (VI) interact with azide compounds and trialkylaluminium in the presence of inert solvents,

or

(h) in the case when a is a C, and at least one of (Y)mis a 3-NH2the compounds of formula (Ib)

where R, X, l, Y, m and G have the same meanings as above, restored in the presence of inert solvents,

or

(i) in the case when "A" is, and at least one of (Y)m is a 3-NH-R2in which R2represents acyl, alkoxycarbonyl, halogenoacetyl the Nile or alkylsulfonyl:

the compounds of formula (IC)

where R, X, l, Y, m and G have the same meanings as above, restore the compounds of the formula (IX)

where R2has the same meaning as described above, and T represents halogen or hydroxy,

in the presence of inert solvents and, if necessary, in the presence of a base.

According to the present invention, the isoxazolines of the formula (I) possess high insecticidal activity. Moreover, it was found that the new compounds of formula (I) exhibit pronounced biological properties and are particularly suitable for combating animal pests, in particular insects, arachnids and round worms, encountered in agriculture, in forests, in the protection of stored products and in the protection of materials and sector hygiene and veterinary.

In this description, the term "alkyl" means1-4alkyl straight or branched chain such as methyl, ethyl, n - or ISO-propyl, n-, ISO-, echoed tert-butyl. The alkyl group may be substituted or is substituted by at least one suitable alternate, selected from the substituents denoted in this text, Y.

Examples of the alkyl fragment in each of the terms "alkoxy", "halogenated", "Alcock is carbonylation and alkylcarboxylic" are examples above for "alkyl".

Alkylcarboxylic or benzoyl may be not substituted or is substituted by at least one suitable alternate, selected from the substituents denoted in this text, Y.

The term "halogen" means fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.

Examples of halogen fragment "halogenoalkane" represent examples mentioned above for the term "halogen".

Among the compounds of formula (I) according to the present invention, preferred examples are examples of the formula (I), in which

And is a C;

R represents an optionally substituted C1-4halogenated;

X represents identical or different halogen or optionally substituted C1-4halogenated;

l is 0, 1 or 2;

Y represents identical or different halogen, C C1-4-alkyl, C1-4-alkoxy, C1-4-halogenated, cyano, nitro, amino, C1-4-alkyl-carbylamine, benzoylamine,1-4alkoxy-carbylamine, which may be optionally substituted;

m is 0 or 1; and

G represents any group selected from the heterocyclic groups represented by the following formulas from G-1 to G-9:

where Z represents halogen, methyl, methylthio, trifluoromethyl, cyano, nitro or amino, and

n is 0 or 1.

Also, among the compounds of formula (I) according to the present invention, preferred examples are examples of the formula (I), in which a represents N;

R represents an optionally substituted C1-4halogenated;

X represents identical or different halogen or optionally substituted C1-4halogenated;

l is 0, 1 or 2;

Y represents identical or different halogen, C1-4-alkyl, C1-4-alkoxy, C1-4-halogenated, cyano, nitro, amino, alkyl-carbylamine, benzoylamine, C1-4alkoxy-carbylamine, which may be optionally substituted;

m is 0 or 1; and

G represents any group selected from the heterocyclic groups represented by the following formulas from G-1 to G-9:

where Z represents Galaga is, methyl, methylthio, trifluoromethyl, cyano, nitro or amino, and

n is 0 or 1.

Among the compounds of formula (I) according to the present invention, particularly preferred examples are examples of the formula (I), in which;

And represents C or N;

R represents a trifluoromethyl or pentafluoroethyl;

X represents identical or different fluorine, chlorine, bromine or trifluoromethyl;

l is equal to 0,1 or 2;

Y represents identical or different halogen, C1-2-alkyl, C1-2-alkoxy, C1-2-halogenated, cyano, nitro, amino, C1-2alkylcarboxylic, benzoylamine,1-2alkoxycarbonyl;

m is 0 or 1; and

G is any one of the heterocyclic groups represented by the following formulas from G-1 to G-9:

where Z represents halogen, methyl, methylthio, trifluoromethyl, cyano, nitro or amino, and

n is 0 or 1.

Among the compounds of formula (I) according to the present invention, particularly preferred examples are examples of the formula (I), in which;

And represents C or N;

R represents reformer or pentafluoroethyl;

X represents identical or different fluorine, chlorine, bromine or trifluoromethyl;

l is 0, 1 or 2;

Y represents identical or different halogen, C1-2-alkyl, C1-2-alkoxy, C1-2-halogenated, cyano, nitro, amino, C1-2-alkyl-carbylamine, cyclopropyl-carbylamine, benzoylamine, C1-2-alkoxy-carbylamine or C1-2-alkyl-sulfonylamino;

m is 0, 1 or 2; and G represents any one of the heterocyclic groups represented by the following formulas from G-1 to G-9:

where Z represents halogen, methyl, methylthio, trifluoromethyl, cyano, nitro or amino; and

n is 0 or 1.

The compounds of formula (I) according to the present invention contain asymmetric carbon atoms and therefore include an optical or geometric isomers or a mixture of the corresponding isomers of variable composition. The present invention relates both to the pure isomers and mixtures of isomers.

The above method of obtaining (a) can be represented by the following reaction scheme when, for example, 3-cyano-N-hydroxy-4-(1H-1,2,4-triazole-1-eventlistenerlist and 1,3-dichloro-5-[1-(trifluoromethyl)vinyl]benzene used as starting reagents.

The above method of obtaining (b) can be represented by the following reaction scheme when, for example, 3-(4-fluoro-3-nitrophenyl)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole and 1H-1,2,4-triazole are used as starting reagents.

The above method of obtaining (s) can be represented by the following reaction scheme when, for example, 5-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]-2-(1H-pyrazole-1-yl)-benzonitrile used as a source of reagent, and N-chlorosuccinimide used as halogenation tools.

The above method of obtaining a (d) can be represented by the following reaction scheme when, for example, 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]aniline and 2,5-dimethoxy-tetrahydrofuran is used as initial reagents.

The above method of obtaining (e) can be represented by the following reaction scheme when, for example, 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]aniline and 1,2-diformyl-hydrazine are used as initial reagents.

The above method of obtaining a (f) can be represented by the following reaction scheme when, for example, N-{4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-di is hydrosocial-3-yl]phenyl}-2,2,2-cryptgetkeyparam and sodium azide are used as initial reagents.

The above method of obtaining a (g) can be represented by the following reaction scheme when, for example, 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]aniline, utilitarian and sodium azide are used as initial reagents.

The above method of obtaining a (h) can be represented by the following reaction scheme when, for example, 1-{4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]-2-nitrophenyl}-1H-1,2,4-triazole are used as starting reagent and restore.

The above method of obtaining (i) can be represented by the following reaction scheme when, for example, 5-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]-2-(1H-1,2,4-triazole-1-yl)aniline and acetylchloride used as initial reagents.

The source reagent used in the method of obtaining (a), namely the compounds of formula (II)are novel compounds and can be obtained by the interaction of the compounds of formula (X)

where A, Y, m and G have the values as above, with halogenation agents.

Compounds of the above formula (X) can be obtained by the interaction of the compounds of formula (XI)

where A, Y, m, and have the following meaning, as described above, with hydroxylamine or its salts.

The compounds of formula (XI) can be obtained by the interaction of, for example, compounds of formula (XII)

where A, Y, m and Hal have the meanings as indicated above, with compounds of the formula (V).

The compounds of formula (XII) are well known, and their examples include: 4-fermentology, 3,4-differentally, 2-chloro-4-fermentology, 3-chloro-4-fermentology, 3-bromo-4-fermentology, 4-fluoro-3-iodobenzaldehyde, 4-fluoro-3-methylbenzaldehyde, 4-fluoro-3-triftormetilfosfinov, 2-fluoro-5-formylbenzoate and 3-chloronicotinamide.

The above aldehydes can be synthesized, for example, by the method described in Journal of Medicinal Chemistry, 2003, vol.46, pp.4232-4235.

Well-known examples of compounds of the formula (XI) are known and include:

4-(1H-pyrazole-1-yl)benzaldehyde, 4-(1H-imidazol-1-yl)benzaldehyde, 4-(1H-1,2,3-triazole-1-yl)benzaldehyde and 4-(1H-1,2,5-triazole-1-yl)benzaldehyde. These compounds are described in Journal of Medicinal Chemistry, 1998, vol.41, pp.2390-2410. 6-(1H-imidazol-1-yl)-nicotinamide (described in WO 88/00468 A), 3-fluoro-4-(1H-imidazol-1-yl)benzaldehyde and 3-chloro-4-(1H-imidazol-1-yl)benzaldehyde (described in WO 2005/115990 A); 3-bromo-4-(1H-pyrrol-1-yl)benzaldehyde and 3-bromo-4-(1H-imidazol-1-yl)benzaldehyde, which are described in WO 2005/016862 A; 3-fluoro-4-(1H-pyrazole-1-yl)benzaldehyde and 3-fluoro-4-(1H-1,2,4-triazole-1-yl)benzaldehyde, which are described in WO2002/046204 A.

Preferred examples of the new compounds among the compounds of formula (XI) include:

5-formyl-2-(1H-1,2,4-triazole-1-yl)benzonitrile,

5-formyl-2-(4-nitro-1H-pyrazole-1-yl)benzonitrile and

5-formyl-2-(1H-tetrazol-1-yl)benzonitrile.

Many of the compounds of formula (X) are new and have not been described in the prior art. This also applies to the compounds of the following formula (Ha)

where A, Y and m have the values as above, and G1has a value such as G, provided that G1is not 1H-imidazol-1-yl, when a is a C and m is 0. N-[4-(1H-imidazol-1-yl)-phenyl]hydroxylamine has been described in WO 95/29163 A.

Typical examples of compounds of formula (X) include the reaction of 3-bromo-4-(4-nitro-1H-pyrazole-1-yl)benzaldehyde, the reaction of 3-bromo-4-(4-cyano-1H-pyrazole-1-yl)benzaldehyde, 5-[(hydroxyimino)methyl]-2-(4-nitro-1H-pyrazole-1-yl)benzonitrile, 5-[(hydroxyimino)methyl]-2-(4-cyano-1H-pyrazole-1-Il)benzonitrile, the oxime of 4-(1H-1,2,4-triazole-1-yl)benzaldehyde, the reaction of 3-chloro-4-(1H-1,2,4-triazole-1-yl)benzaldehyde, the reaction of 3-bromo-4-(1H-1,2,4-triazole-1-yl)benzaldehyde, the reaction of 3-methyl-4-(1H-1,2,4-triazole-1-yl)benzaldehyde, the reaction of 4-(1H-1,2,4-triazole-1-yl)-3-trifluoromethyl-benzaldehyde, 5-[(hydroxyimino)methyl]-2-(1H-1,2,4-triazole-1-yl)-benzonitrile, oxime 6-(1H-1,2,4-triazole-1-yl)nicotinamide and 5-[(hydroxyimino)methyl]-2-(1H-tetrazol-1-yl)-benzonitrile.

Compounds of formula (II), (X) and (Ha) include optical or geometric isomers or a mixture of the corresponding isomers of variable composition. The present invention relates both to the pure isomers and mixtures of isomers.

Also, halogenation tools used in obtaining the compounds of formula (II), generally known to the specialist in the art and include, for example, chlorine, bromine, iodine, N-chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide, 1,3-dichloro-5,5-dimethylhydantoin, 1,3-dibromo-5,5-dimethylhydantoin, designed tetrachloride and sodium hypochlorite.

Typical compounds of formula (II), which are used as starting reagents in the method of obtaining (a)include, for example:

3-bromo-N-hydroxy-4-(4-nitro-1H-pyrazole-1-yl)-benzonorbornadiene, 3-bromo-N-hydroxy-4-(4-cyano-1H-pyrazole-1-yl)-benzonorbornadiene, 3-cyano-N-hydroxy-4-(4-nitro-1H-pyrazole-1-yl)-benzonorbornadiene, 3-cyano-N-hydroxy-4-(4-cyano-1H-pyrazole-1-yl-benzoquinoneimine, N-hydroxy-4-(1H-1,2,4-triazole-1-yl)-benzonorbornadiene, 3-chloro-N-hydroxy-4-(1H-1,2,4-triazole-1-yl)-benzonorbornadiene, 3-bromo-N-hydroxy-4-(1H-1,2,4-triazole-1-yl)-benzoquinoneimine, N-hydroxy-3-methyl-4-(1H-1,2,4-triazole-1-yl)-benzoquinoneimine, N-hydroxy-4-(1H-1,2,4-triazole-1-yl)-3-Cryptor-methylbenzyloxycarbonyl, cyano-N-hydroxy-4-(1H-1,2,4-triazole-1-yl)-benzonorbornadiene, N-hydroxy-6-(1H-1,2,4-triazole-1-yl)pyridine-3-carboxymethylated and 3-cyano-N-hydroxy-4-(1H-tetrazol-1-yl)-benzonorbornadiene.

The compounds of formula (III), which is used as the other reagents in the method of obtaining (a)include known compounds described, for example, in the Journal of Organic Chemistry, 1991, vol.56, pp.7336-7340 tel; ibid 1994, vol.59, pp.2898-2901; and in 1999, vol.95, pp.167-170; and WO 2005/05085216 A.

Also, the compounds of formula (III) can be synthesized by the methods described in these publications.

Typical examples of compounds of the formula (III) include:

[1-(trifluoromethyl)vinyl]benzene, 1,3-debtor-5-[1-(trifluoromethyl)vinyl]benzene, 1-chloro-3-[1-(trifluoromethyl)vinyl]benzene, 1,3-dichloro-5-[1-(trifluoromethyl)vinyl]benzene, 1-trifluoromethyl-3-[1-(trifluoromethyl)vinyl]benzene, 1-trifluoromethyl-4-[1-(trifluoromethyl)vinyl]benzene and 1,3-bis(trifluoromethyl)-5-[1-(trifluoromethyl)vinyl]benzene.

The method of obtaining (a) may be carried out by methods described in WO 2004/018410 And WO 2005/085216 or A Tetrahedron, 2000, vol.56, pp.1057-1064.

The reaction of the method of obtaining (a) can be performed in a suitable diluent or solvent. Their examples include aliphatic hydrocarbons (hexane, cyclohexane, heptane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, chlorobenzene etc.), alcohols (methanol, ethanol, isopropanol and others), ethers [diethyl ether, disutility ether, dimethoxyethane (DME, tetrahydrofuran, dioxane and others], amides acids [dimethylformamide (DMF), dimethylacetamide (DMA), N-organic and others], NITRILES (acetonitrile, propionitrile and others), dimethylsulfoxide (DMSO), water, or mixtures of these solvents.

The reaction of the method of obtaining (a) can be performed using a base, such as, for example, alkali metal base, such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium methylate, sodium ethylate or tert-butyl potassium; organic bases such as triethylamine, diisopropylethylamine, tributylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, picoline, lutidine, databaseconnect, or diazabicyclo the imidazole.

The reaction of the method of obtaining (a) can be carried out in a wide temperature range. The reaction can be conducted at a temperature in the range typically from about -78 to about 200°C. and preferably -10 to 150°Stacie, this reaction can be carried out at elevated pressure or at reduced pressure, however, it is preferable to conduct the reaction under normal pressure. The reaction time is from 0.1 to 72 hours, preferably from 1 to 24 hours.

When the method of obtaining (a), for example, from 1 to 2 molar equivalents of the compounds of the formula (III), and is 1 molar equivalent to a small excess of base is introduced into the reaction based on 1 mol of the compounds of the formula (II) in a solvent, as, for example, DMF, obtaining the target compound of formula (I).

The compounds of formula (IV), which are used as starting reagents in the method of obtaining (b), are known and described, for example, in WO 2005/085216 A.

Typical examples of compounds of the formula (IV) include:

5-(3,5-dichlorophenyl)-3-(4-forfinal)-5-(trifluoromethyl)-4,5-dihydroisoxazole, 3-(4-forfinal)-5-[3-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydroisoxazole, 5-[3,5-bis(trifluoromethyl)phenyl]-3-(4-fluoro-phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole, 3-(3-chloro-4-forfinal)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole, 3-(3-chloro-4-forfinal)-5-[3-(trifluoromethyl)-phenyl]-5-(trifluoromethyl)-4,5-dihydroisoxazole, 5-[3,5-bis(trifluoromethyl)phenyl]-3-(3-chloro-4-forfinal)-5-(trifluoromethyl)-4,5-dihydroisoxazole, 3-(3-bromo-4-forfinal)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole, 3-(3-bromo-4-forfinal)-5-[3-(trifluoromethyl)-phenyl]-5-(trifluoromethyl)-4,5-dihydroisoxazole, 5-[3,5-bis(trifluoromethyl)phenyl]-3-(3-bromo-4-forfinal)-5-(trifluoromethyl)-4,5-dihydroisoxazole, 5-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]-2-perbenzoate, 2-fluoro-5-{5-(trifluoromethyl)-5-[3-(trifluoromethyl)phenyl]-4,5-dihydroisoxazole-3-yl}-benzonitrile, 5-{5-[3,5-bis(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl}-2-perbenzoate, 3-(4-fluoro-3-nitrophenyl)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole, 3-(4-chloro-3-nitrophenyl)-5-(3,5-dichlorophenyl)-5-(three is tormentil)-4,5-dihydroisoxazole, 3-(4-fluoro-3-nitrophenyl)-5-[3-(trifluoromethyl)-phenyl-5-(trifluoromethyl)-4,5-dihydroisoxazole, 5-[3,5-bis(trifluoromethyl)-phenyl]-3-(4-fluoro-3-nitrophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole and 3-(6-chloropyridin-3-yl)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole.

The compounds of formula (V), which are used as starting reagents in the method of obtaining (b), are well known in the field of organic chemistry, and their typical examples include:

1H-imidazole, 1H-pyrazole, 4-methyl-1H-pyrazole, 4-fluoro-1H-pyrazole, 4-chloro-1H-pyrazole, 4-bromo-1H-pyrazole, 4-iodine-1H-pyrazole, 4-nitro-1H-pyrazole, 4-methyl-1H-pyrazole, 3-trifluoromethyl-1H-pyrazole, 4-trifluoromethyl-1H-pyrazole, 4-cyano-1H-pyrazole, 1H-1,2,3-triazole, 1H-1,2,4-triazole, 1H-tetrazole, 5-methyl-1H-tetrazole and 5-(methylthio)-1H-tetrazol.

These azoles can be synthesized by the methods described in Journal of Medicinal Chemistry, 2005, vol.48, pp.5780-5793, Monatshefte fur Chemie, 1993, vol.124, pp.199-207, and Tetrahedron Letters, 1996, vol.37, pp.1829-1832.

The reaction of the method of obtaining (b) can be carried out in a suitable diluent or solvent. Their examples include: aliphatic hydrocarbons (hexane, cyclohexane, heptane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, chlorobenzene etc.), ethers [diethyl ether, disutility ether and dimethoxyethane (DME), tetrahydrofuran, dioxane and others], amides acids [dimethylformamide (DMF), dimethylacetamide (DMA), N-organic and others], NITRILES (acetone is home to the thrill, propionitrile and others), dimethylsulfoxide (DMSO), water, or mixtures of these solvents.

The reaction of the method of obtaining (b) can be performed using a base, such as, for example, alkali metal base, such as lithium hydride, sodium hydride, potassium hydride, lithium amide, sodium amide, diisopropylamide lithium utility, tert-utility, trimethylsilylmethyl, hexamethyldisilazide lithium, sodium carbonate, potassium carbonate, sodium acetate, potassium acetate, sodium methylate, sodium ethylate or tert-butyl potassium, or organic bases such as triethylamine, diisopropylethylamine, tributylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, picoline, lutidine, databaseconnect, diazabicyclo or imidazole.

The reaction of the method of obtaining (b) can be carried out in a wide temperature range. The reaction can be conducted at a temperature in the range typically from about -78 to about 200°C. and preferably -10 to 150°Stacie, this reaction can be carried out at elevated pressure or at reduced pressure, however, it is preferable to conduct the reaction under normal pressure. The reaction time is from 0.1 to 72 hours and preferably from 1 to 24 hours.

When the method get (b), for example, from 1 to 3 molar equivalents of the compounds of the formula (V) enter into the reactions is based on 1 mol of the compounds of the formula (IV) in the presence of from 1 to 3 molar equivalents of a base in a solvent, as, for example, DMF, obtaining the target compound of formula (I).

The compounds of formula (Ia), which are used as starting reagents in the method of obtaining (C)correspond to part of the compounds of formula (I).

Examples of halogenation tools include the same compounds, examples of which are given earlier.

The reaction method of producing (s) can be carried out in a suitable diluent or solvent. Their examples include: aliphatic hydrocarbons (hexane, cyclohexane, heptane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, chlorobenzene etc.), ethers [diethyl ether, disutility ether, dimethoxyethane (DME), tetrahydrofuran, dioxane and others], amides acids [dimethylformamide (DMF), dimethyl ndimethylacetamide (DMA), N-organic and others], NITRILES (acetonitrile, propionitrile and others), dimethylsulfoxide (DMSO) or mixtures of these solvents.

The reaction method of producing (s) can be performed using halogenation means, such as, for example, chlorine, bromine, iodine, N-chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide, 1,3-dichloro-5,5-dimethylhydantoin, 1,3-dibromo-5,5-dimethylhydantoin or sodium hypochlorite.

The reaction method of producing (s) can be performed in a wide temperature range. The reaction can be conducted at a temperature in the range typically from about -78 to about 200°C. and preferably -10 to 150°Stacie, d is nnow the reaction can be carried out at elevated pressure or at reduced pressure, however, it is preferable to conduct the reaction under normal pressure. The reaction time is from 0.1 to 72 hours, and preferably from 0.1 to 24 hours.

When the method get (), for example, from 1 molar equivalent to a small excess of N-chlorosuccinimide injected into the reaction based on 1 mol of the compounds of formula (Ia) in a diluent, such as, for example, DMF, obtaining the target compound of formula (I).

The compounds of formula (VI), which are used as starting reagents in the method of obtaining (d), are known and described, for example, in WO 2005/085216 And, and their typical examples include:

4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]aniline, 2-chloro-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]aniline, 2-bromo-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]aniline, 4-{5-[3-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl}aniline, 2-chloro-4-{5-[3-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl}aniline, 2-bromo-4-{5-[3-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]aniline, 4-{5-[3,5-bis(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl} aniline, 2-chloro-4-{5-[3,5-bis(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl}aniline and 2-bromo-4-{5-[3,5-bis(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl}aniline.

The compounds of formula (VII), which are the source the reagents in the method of obtaining (d), are well-known compounds, and their typical examples include:

2.5-dimethoxytetrahydrofuran and 2.5-detoxification.

The reaction according to the method of obtaining (d) can be carried out in a suitable diluent or solvent, and examples include aliphatic hydrocarbons (hexane, cyclohexane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, chlorobenzene etc.), ethers [diethyl ether, disutility ether, dimethoxyethane (DME), tetrahydrofuran, dioxane and others], amides acids [dimethylformamide (DMF), dimethylacetamide (DMA), N-organic and others], acids (acetic acid, etc.), NITRILES (acetonitrile, propionitrile and others), dimethylsulfoxide (DMSO) or mixtures of these solvents.

A method of obtaining a (d) can be performed in a wide temperature range. The reaction can usually be carried out at a temperature in the range from about 0 to about 200°C. and preferably at a temperature from room temperature up to about 150°C. Also, the reaction can be carried out at elevated pressure or at reduced pressure, however, it is preferable to conduct the reaction under normal pressure. The reaction time is from 0.1 to 72 hours and preferably from 1 to 24 hours.

When the method of obtaining (d), for example, from 1 to 5 molar equivalents of 2,5-dialogseminarierna injected into a reaction from the calculations is that on 1 mol of the compounds of the formula (VI) in a solvent, such as, for example, acetic acid, obtaining the target compound of formula (I).

The compounds of formula (VI), which are used as starting reagents in the method of obtaining (e)are identical to the compounds described in the above-mentioned production method of (d).

Also known compound is 1,2-deformalization, which is a starting material.

When the method of obtaining (e), compounds of formula (VI) interact with 1,2-deformalization in the presence of a base and trialkylsilanes, whereby it is possible to obtain the corresponding compounds of formula (I).

Examples of trialkylaluminium may include: trimethylchlorosilane, triethylchlorosilane and trimethylamine.

The method of obtaining (e) can be performed according to the method described in The Journal of Organic Chemistry, 2001, vol.44, pp.3157-3165.

The reaction of the method of obtaining (e) can be performed using a base, such as, for example, organic bases such as triethylamine, diisopropylethylamine, tributylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, picoline, lutidine, databaseconnect, diazabicyclo or imidazole.

The reaction of the method of obtaining (e) can be carried out in a wide temperature range. The reaction can be conducted at a temperature in the range typically from about 0 to about the olo 200°C and preferably from about 0 to about 150°Stacie, this reaction can be carried out at elevated pressure or at reduced pressure, however, it is preferable to conduct the reaction under normal pressure. The reaction time is from 0.1 to 72 hours, preferably from 1 to 24 hours.

When the method of obtaining (e), for example, from 1 to 5 molar equivalents of 1,2-deformalization, from 1 to 10 molar equivalents of the base and from 1 to 25 molar equivalents trialkylaluminium injected into the reaction based on 1 mol of the compounds of the formula (VI) in a large excess of pyridine, obtaining the target compound of formula (I).

The compounds of formula (VIII), which are used as starting reagents in the method of obtaining (f)are new compounds, and get them to the interaction of the compounds of formula (XIII)

where A, R, X, l, Y, m and Rf have such meanings as above, with tetrachloride carbons and trivalent phosphorus compounds of the formula (XIV)

where L represents a C4-8-alkyl or aryl.

The compounds of formula (XIII) are also new compounds and can be obtained by the interaction of the compounds of the formula (VI) with halides performancelevel acids or anhydrides performancelevel acid in the presence of a base.

The above tetrachloride carbon are known and connections. Specific examples of tetrachloride carbon include carbon tetrachloride and chetyrehhloristy carbon. Phosphorus compounds of the formula (XIV) are known, and specific examples may include: tributylphosphine and triphenylphosphine.

The above halides performancelevel acids or anhydrides performancelevel acid are well known compounds.

Examples of these compounds include the anhydride triperoxonane acid anhydride pentafluoropropionic acid and anhydride heptacosanoic acid.

Specific examples of the azide compounds for use in the method of obtaining (f) include lithium azide and sodium azide.

A method of obtaining a (f) can be performed according to the method described in Japanese Patent Application (KOKAI) Publication No. 2005-154420 A.

The reaction according to the method of obtaining (f) can be carried out in a suitable diluent or solvent, and examples include aliphatic hydrocarbons (hexane, cyclohexane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, chlorobenzene etc.), ethers [diethyl ether, disutility ether, dimethoxyethane (DME), tetrahydrofuran, dioxane and others], amines (pyridine, kallidin), acid amides [dimethylformamide (DMF), dimethylacetamide (DMA), N-organic and others], NITRILES (acetonitrile, propionitrile and others), dimethyl sulfoxide (DMSO) or compounds which these solvents.

A method of obtaining a (f) can be performed in a wide temperature range. The reaction can be conducted at a temperature in the range typically from about -78 to about 200°C. and preferably at a temperature from room temperature, i.e. from about 20°C. to about 150°C. Also, the reaction can be carried out at elevated pressure or at reduced pressure, however, it is preferable to conduct the reaction under normal pressure. The reaction time is from 0.1 to 72 hours, preferably from 1 to 24 hours.

When is a method of obtaining a (f), for example from 1 to 2 mole equivalents of azide compounds is introduced into the reaction based on 1 mol of the compounds of the formula (VIII) in a solvent, for example acetonitrile, obtaining the target compound of formula (I).

The compounds of formula (VI), which are used as starting substances in the production method of (g), identical to the compounds represented as starting compounds for the method of obtaining (d). Also, azide compounds are identical to the compounds described in the above-mentioned production method of (f).

In addition, trialkylaluminium are known compounds, and specific examples may include: triethylorthoformate and triethylorthoformate.

The reaction according to the method of obtaining (g) can be carried out in a suitable diluent or solvent, and examples include aliphatic hydrocarbons (hexane, cyclohexane and other), aromatic hydrocarbons (benzene, toluene, xylene, chlorobenzene etc.), ethers [diethyl ether, disutility ether, dimethoxyethane (DME), tetrahydrofuran, dioxane and others], amides acids [dimethylformamide (DMF), dimethylacetamide (DMA), N-organic and others], acids (acetic acid, propionic acid, etc.), NITRILES (acetonitrile, propionitrile and others), dimethylsulfoxide (DMSO) or mixtures of these solvents.

A method of obtaining a (g) can be performed in a wide temperature range. The reaction can be conducted at a temperature in the range typically from about 0 to about 200°C. and preferably at a temperature from room temperature, i.e. from about 20°C. to about 150°C. Also, the reaction can be carried out at elevated pressure or at reduced pressure, however, it is preferable to conduct the reaction under normal pressure. The reaction time is from 0.1 to 72 hours, preferably from 1 to 24 hours.

When is a method of obtaining a (g), for example from 1 to 3 molar equivalents of azide compounds and from 1 to 10 molar equivalents of trialkylaluminium injected into the reaction based on 1 mol of the compounds of the formula (VI) in a solvent, for example acetic acid, obtaining the target compound of formula (I).

A method of obtaining a (g) can be made by the method described in Journal of Medicinal Chemistry, 2000, vol.43, pp.953-970.

The compounds of formula (Ib), as the art of compounds of formula (I), included in the present invention.

Examples of reduction reaction in the production method of (h) include reaction using zinc, iron or tin chloride and hydrogenation reactions using catalysts such as palladium catalyst, Nickel catalyst, cobalt catalyst, rhodium catalyst, a ruthenium catalyst or a platinum catalyst.

The reaction of the method of obtaining a (h) can be carried out in a suitable diluent or solvent, and examples include aliphatic hydrocarbons (hexane, cyclohexane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, chlorobenzene etc.), ethers [diethyl ether, disutility ether and dimethoxyethane (DME), tetrahydrofuran, dioxane and others], acids (acetic acid, propionic acid, etc.), esters (ethyl acetate, ethylpropane and others), water or a mixture of these solvents.

A method of obtaining a (h) can be performed in a wide temperature range. The reaction can be conducted at a temperature in the range typically from about 0 to about 200°C. and preferably at a temperature from room temperature, i.e. from about 20°C. to about 150°C. Also, the reaction can be carried out at elevated pressure or at reduced pressure, however, it is preferable to conduct the reaction under normal pressure. The reaction time is from 0.1 to 72 hours, predpochtitelno 0.5 to 24 hours.

When is a method of obtaining a (h), for example, from 3 to 5 molar equivalents of tin chloride and a catalytic amount of concentrated hydrochloric acid added per 1 mol of the compounds of formula (Ib) in a solvent, for example ethanol, obtaining the target compound of formula (I).

The compounds of formula (Ic) as part of the compounds of formula (I) included in the present invention.

Also, the compounds of formula (IX) are known compounds, and their typical examples include: acetylchloride, propionitrile, isobutyrate, cyclopropanecarbonyl, benzoyl chloride, methylcarbonate, ethylchloride, methansulfonate and benzoic acid.

The reaction of the method of obtaining (i) can be carried out in a suitable diluent or solvent, and examples include aliphatic hydrocarbons (hexane, cyclohexane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, chlorobenzene etc.), ethers [diethyl ether, disutility ether and dimethoxyethane (DME), tetrahydrofuran, dioxane and others], amides acids [dimethylformamide (DMF), dimethylacetamide (DMA), N-organic and others], NITRILES (acetonitrile, propionitrile and others), dimethylsulfoxide (DMSO), water or a mixture these solvents.

The reaction of the method of obtaining (i) can be performed using a base, such as base Selo the aqueous metal, such as, for example, lithium hydride, sodium hydride, potassium hydride, lithium amide, sodium amide, diisopropylamide lithium utility, tert-utility, trimethylsilylmethyl, hexamethyldisilazide lithium, sodium carbonate, potassium carbonate, sodium acetate, potassium acetate, sodium methylate, sodium ethylate or tert-butyl potassium, or organic bases such as triethylamine, diisopropylethylamine, tributylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylaniline, 4-tert-butyl-N,N-dimethylaniline, pyridine, picoline, lutidine, databaseconnect, diazabicyclo or imidazole.

The reaction of the method of obtaining (i) may be used as a condensing means, for example 1,3-dicyclohexylcarbodiimide or 1-ethyl-3-(3'-dimethylamino-propyl)carbodiimide or its salts.

When the method of obtaining (i), for example, from 1 to 2 molar equivalents of the compounds of formula (IX) is injected into the reaction based on 1 mol of the compounds of formula (Ic) in the presence of from 1 to 2 molar equivalents of a base in a solvent, for example THF, obtaining the target compound of formula (I).

Compounds of formula (II), (Ha), (VIII) and (XIII), which is used to produce compounds of formula (I)are new compounds.

Formula (VIII) and (XIII) can register protest to submit the following formula (XV):

where A, R, X, l, Y and m have so the e value, as described in the text, and M represents a group represented by the following formula:

where Rf and Hal have the meaning as described in the text.

The compounds of formula (I) according to the present invention possess high insecticidal activity. Moreover, the compounds of the present invention exhibit high activity against pests of animals and, thus, can be used for pest control animals.

Accordingly, the compounds represented by formula (I) according to the present invention, can be used as insecticides or to obtain compositions for pest control animals.

In the present invention, all compounds, compositions and compounds having insecticidal action on pests, in this text referred to as insecticide.

In addition, the active compound represented by the formula (I) according to the present invention, show the result when combating harmful insects, not with the phytotoxicity relative to cultivated plants.

Accordingly, the compounds of the present invention can be used to fight a lot of different pests of animals. In particular, to fight against sucking insects, biting insects and other plant pests, damage is s stored products pests and hygienic aspect. In addition, the compounds of the present invention can be applied to such a struggle, such as the extermination and destruction of these pests.

Examples of such pests include:

From Insects, parasites of Coleoptera, for example, Callosobruchus Chinensis, Sitophilus zearnais, Tribolium castaneum, Epilachna vigintioctomaculata, Agriotes fuscicollis, Anomala rufocuprea, Leptinotarsa decemlineata, Diabrotica spp., Monochamus altematus, Lissorhoptrus oryzophilus, Lyctus bruneus and Aulacophora femoralis;

parasites of Lepidoptera, for example, Lymantria dispar, Malacosoma neustria, Pieris rapae, Spodoptera litura, Mamestra brassicae, Chilo suppressalis, Pyrausta nubilalis, Ephestia cautella, Adoxophyes orana, Carpocapsa pomonella, Agrotisfucosa, Galleria mellonella, Plutella maculipennis, Heliothis virescens and Phyllocnistis citrella; parasites Heteroptera, for example, Nephotettix cincticeps, Nilaparvata lugens, Pseudococcus comstocki, Unaspis yanonensis, Myzus persicas, Aphis pomi, Aphis gossypii, Phopalosiphum pseudobrassicas, Stephanitis nashi, Nazara spp., Trialeurodes vaporariorm and Pshylla spp.;

parasites of Bajracharya, for example, Thrips palmi and Franklinella occidental;

parasites of Orthoptera, for example, Blatella germanica, Periplaneta americana, Gryllotalpa africana and Locusta migratoria migratoriaodes;

parasites Isoptera, for example Reticulitermes speratus and Coptotermes formosanus; and

parasites of Diptera, for example, Musca domestica, Aedes aegypti, Hylemia platura, Culex pipiens, Anopheles sinensis, Culex tritaeniorhychus and Liriomyza trifolii;

and of the Acarina, for example, Tetranychus cinnabarinus, Tetranychus urticae, Panonychus citri, Aculops pelekassi and Tarsonemus spp.

Other examples of pests include:

From roundworms, for example, Meloidogyne incognita, Bursaphelenchus lignicolus Mamiya et Kiyohara, Aphelenchoides besseyi, Heterodera glycines, and Pratylenchus spp.

In addition to the CSO, it was found that the new compounds of the present invention is active against parasites of animals and, thus, they can effectively be used to combat various malicious animal parasites (endo - and ectoparasites), such as, for example, in the field of veterinary, insects and parasitic worms.

Examples of such parasites of animals may include the following pests:

Of insects, e.g., Gastrophilus spp., Stomoxys spp., Trichodectes spp., Rhodnius spp., Ctenocephalidescanis, Cimx lecturius, Ctenocephalides felis and Lucila cuprina.

Of the Acarina, for example, Ornithodoros spp., Ixodes spp. Boophilus spp.

As mentioned earlier, veterinary areas, i.e. in the field of veterinary medicine, the active compounds according to the present invention is active against animal parasites (ecto - and endoparasites), such as hard ticks, soft ticks, cestocide mites, chigger mites, flies (stinging and licking), parasitic larvae of flies, lice, hair lice, bird mites, hematophagous biting, a parasite of birds and fleas.

These parasites include:

From squad Anoplurida, for example, Haematopinus spp., Linognathus spp., Pediculus spp., Phtirus spp., Solenopotes spp.; examples are: Linognathus setosus, Linognathus vituli, Linognathus ovillus, Linognathus oviformis, Linognathus pedalis, Linognathus stenopsis, Haematopinus asini macrocephalus, Haematopinus eurysternus, Haematopinus suis, Pediculus humanus capitis, Pediculus humanus corporis, Phylloera vastatrix, Phthirus pubic, Solenopotes capillatus;

From squad Mallophagida and suborders Amblycerina and Ishnocerina, for example, Trimenopon spp., Menopon spp., Trinoton spp., Bovicola spp., Werneckiella spp., Lepikentron spp., Damalina spp., Trichodectes spp., Felicola spp.; examples are: Bovicola bovis, Bovicola ovis, Bovicola limbata, Damalina bovis, Trichodectes canis, Felicola subrostratus, Bovicola caprae, Lepikentron ovis, Werneckiella equi;

From the order Diptera and the suborders Nematocerina and Brachycerina, for example, Aedes spp. Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., Odagmia spp., Wilhehnia spp., H. spp., Atylotus spp., Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp., Gasterophilus spp., Hippobosca spp., Lipoptena spp., Melophagus spp., Rhinoestrus spp., Tipula spp., examples are: Aedes aegypti, Aedes albopictus, Aedes taeniorhynchus, Anopheles gambiae, Anopheles maculipennis, Calliphora erythrocephala, Chrysozona pluvialis, Culex quinquefasciatus, Culex pipiens, Culex tarsalis, Fannia canicularis, Sarcophaga carnaria, Stomoxys calcitrans, Tipula paludosa, Lucilia cuprina, Lucilia sericata, Simulium reptans, Phlebotomus papatasi, Phlebotomus longipalpis, Odagmia omata, Wilhelmia equina, Boophthora erythrocephala, Tabanus bromius, Tabanus spodopterus, Tabanus atratus, Tabanus sudeticus, H. ciurea, Chrysops caecutiens, Chrysops relictus, Haematopota pluvialis, Haematopota italica, Musca autumnalis, Musca domestica, Haematobia irritans irritans, Haematobia irritans exigua, Haematobia stimulans, Hydrotaea irritans, Hydrotaea albipuncta, Chrysomya chloropyga, Chrysomya bezziana, Oestrus ovis, Hypoderma bovis, Hypoderma lineatum, Przhevalskiana silenus, Dermatobia hominis, Melophagus ovinus, Lipoptena capreoli, Lipoptena cervi, Hippobosca variegata, Hippobosca equina, Gasterophilus intestinalis, Gasterophilus haemorroidalis, Gasterophilus species, Gasterophilus nasalis, Gasterophilus nigricornis, Gasterophilus pecorum, Braula coeca;

From squad Siphonapterida, for example, Pulex spp., Ctenocphalides spp., Tunga spp., Xenopsylla spp., Ceratophyllus spp.; examples are: Ctenocephalides canis, Ctenocephalides felis, Pulex irritans, Tunga penetrans, Xenopsylla cheopis;

From squad Heteropterida, for example, Cimex spp., Triatoma spp., Rhodnius spp., Panstrongylus spp.;

From squad Blattarida, for example, Blatta orientalis, Periplaneta americana, Blattela germanica, Supella spp.(for example, Suppella longipalpa);

From the subclass of the Acari (Acarina) and detachments of the Meta - and Mesostigmata, for example Argas spp., Ornithodorus spp., Otobius spp., Ixodes spp., Amblyomma spp., Rhipicephalus (Boophilus) spp, Dermacentor spp., Haemophysalis spp., Hyalomma spp., Dermanyssus spp., Rhipicephalus spp.(the main genus of ticks with multiple owners) Ornithonyssus spp., Pneumonyssus spp., Raillietia spp., Pneumonyssus spp., Sternostoma spp., Varroa spp., Acarapis spp.; examples are: Argas persicus, Argas reflexus, Ornithodorus moubata, Otobius megnini, Rhipicephalus (Boophilus) microplus, Rhipicephalus (Boophilus) decoloratus, Rhipicephalus (Boophilus) annulatus, Rhipicephalus (Boophilus) calceratus, Hyalomma anatolicum, Hyalomma aegypticum, Hyalomma marginatum, Hyalomma transiens, Rhipicephalus evertsi, Ixodes ricinus, Ixodes hexagonus, Ixodes canisuga, Ixodes pilosus, Ixodes rubicundus, Ixodes scapulahs, Ixodes holocyclus, Haemaphysalis concinna, Haemaphysalis punctata, Haemaphysalis cinnabarina, Haemaphysalis otophila, Haemaphysalis leachi, Haemaphysalis longicorni, Dermacentor marginatus, Dermacentor reticulatus, Dermacentor picrus, Dermacentor albipictus, Dermacentor andersoni, Dermacentor variabilis, Hyalomma mauritanicum, Rhipicephalus sanguineus, Rhipicephalus bursa, Rhipicephalus appendiculatus, Rhipicephalus capensis, Rhipicephalus turanicus, Rhipicephalus zambeziensis, Amblyomma americanum, Amblyomma variegatum, Amblyomma maculatum, Amblyorama hebraeum, Amblyomma cajennense, Dermanyssus gallinae, Ornithonyssus bursa, Ornithonyssus sylviarum, Varroa jacobsoni;

Detachment of Actinedida (Prostigmata) and Acaridida (Astigmata), for example, Acarapis spp., Cheyletiella spp., Ornithocheyletia spp., Myobia spp., Psorergates spp., Demodex spp., Trombicula spp. Listrophorus spp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypodectes spp., Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp., Laminosioptes spp.; examples are: Cheyletiella yasguri, Cheyletiella blakei, Demodex canis, Demodex bovis, Demodex ovis, Demodex caprae, Demodex equi, Demodex caballi, Demodex suis, Neotrombicula autumnalis, Neotrombicula desaleri, Neoschongastia xerothermobia, Trombicula akamushi, Otodectes cynotis, Notoedres cati, Sarcoptis canis, Sarcoptes bovis, Sarcoptes ovis, Sarcoptes rupicaprae (=S. caprae), Sarcoptes equi, Sarcoptes suis, Psoroptes ovis, Psoroptes cuniculi, Psoroptes equi, Chorioptes bovis, Psoergates ovis, Pneumonyssoidic Mange, Pneumonyssoides caninum, Acarapis woodi.

The active compounds of formula (I) according to the present invention are also suitable for combating arthropods which attack agricultural animals, such as cattle, sheep, goats, horses, pigs, donkeys, camels, Buffalo, rabbits, chickens, turkeys, ducks, geese, honeybees, other domestic animals, such as dogs, cats, birds in cages, aquarium fish and animals, which are known as a test, such as, for example, hamsters, Guinea pigs, rats and mice.

By combating the arthropods planned to reduce mortality and to improve performance (in the case of meat, milk, wool, hides, eggs, honey and the like) to provide a more economical and simple animals through the use of combinations of active compounds according to the present invention.

In veterinary about the Asti and the animals they are applied in a known manner enteral introduction to the form, for example, tablets, capsules, drinks, large doses of drugs, granules, pastes, boluses, the introduction of food, suppositories; parenterally introduction, such as, for example, injection (intramuscular, subcutaneous, intravenous, intraperitoneally and the like), implants, nazalnam application, dermal application in the form of, for example, bathing or dipping, spraying, pouring and point of application, washer, insert and with the help of shaped articles containing active compound, such as collars, ear tags, tail tags, bandage on a limb, pasture leash, timer and things like that. The active compounds can be produced in the form of a shampoo or in the form of suitable preparations, used in aerosols, non-pressurized sprays, such as sprays and atomizers.

When used for livestock, poultry, Pets and the like, the active compounds of formula (I) can be used as drugs (e.g., powders, wettable powders ["WP"], emulsions, emulsifiable concentrates, ["EU"], liquid, homogeneous solutions and suspension concentrates ["SC"]), which contain the active compounds in an amount of from 1 to 80 wt.%, directly or after dilution (e.g., dilution in 100-10000 times), or in the form of baths with the reagent.

Also, it was found that AK is active compounds of the present invention have potential insecticidal action against insects, which destroy industrial materials.

The following insects may be mentioned as examples and are preferred, but not limiting:

Beetles, such as

Hylotrupes bajulus, Chlorophorus pilosis, Anobium punctatum, Xestobium rufovillosum, Ptilinus pecticornis, Dendrobium pertinex, Ernobius mollis, Priobium carpini, Lyctus brunneus, Lyctus africanus, Lyctus planicollis, Lyctus linearis, Lyctus pubescens, Trogoxylon aequale, Minthes rugicollis, Xyleborus spec. Tryptodendron spec. Apate monachus, Bostrychus capucins, Heterobostrychus brunneus, Sinoxylon spec. Dinoderus minutus.

Heminoptera, such as

Sirex juvencus, Urocerus gigas, Urocerus gigas taignus, Urocerus augur.

Termites, such as

Kalotermes flavicollis, Cryptotermes brevis, Heterotermes indicola, Reticulitermes flavipes, Reticulitermes santonensis, Reticulitermes lucecnuugus, Mastotermes darwiniensis, Zootermopsis nevadensis, Coptotermesformosanus.

Seinajoki, such as Chechulina ordinary.

Industrial materials in this context are understood as meaning non-living materials, such as, preferably, plastics, adhesives, glues, paper and cardboard, leather, wood, products of wood and paint.

If necessary, ready-to-use composition for the protection of industrial materials and containing at least one compound of the present invention may also contain additional active ingredients, such as at least one insecticide and/or at least one fungicide. Suitable insecticides and/or fungicides preferably represent insecticides and NGF is icidi, mentioned in this text.

Compounds of the present invention can also be used to protect against the buildup on objects, in particular hulls, screens, nets, buildings, anchors and signal systems, which are in contact with sea water or brackish water.

In addition, the compounds of the present invention, alone or in combination with other active ingredients, can be used as tools against biofouling.

In the hygiene sector, it was found that the active compounds according to the present invention are also suitable for combating animal pests, especially to protect residential areas, in terms of hygiene and food storage. Found that they are particularly active against insects, arachnids and mites, which can be found in enclosed spaces such as, for example, dwellings, factory premises, offices, driver's cab and the like. To combat these pests, they can be used in insecticide products for residential premises, alone or in combination with other active ingredients and auxiliary ingredients. They are active against susceptible and resistant species and against all stages of development.

These pest animals include:

From squad Scorpionidea, for example, Buthus occitanus;

From the order Acarina, such as the er, Argas persicus, Argas reflexus, Bryobia ssp., Dermanyssus gallinae, Glyciphagus domesticus, Ornithodorus moubata, Rhipicephalus sanguineus, Trombicula alfreddugesi, Neutrombicula autumnalis, Dermatophagoides pteronissimus, Dermatophagoides forinae;

From the order Araneae, for example, Aviculariidae, Araneidae;

From the order Opiliones, for example, Pseudoscorpiones chelifer, Pseudoscorpiones cheiridium, Opiliones phalangium;

From the order Isopoda, for example Oniscus asellus, Porcellio scaber;

From the order Diplopoda, for example Blaniulus guttulatus, Polydesmus spp.;

From the order Chilopoda, for example Geophilus spp.;

From the order Zygentoma, for example, Ctenolepisma spp., Lepisma saccharina, Lepismodes inquilinus;

From the order Blattaria, for example, Blatta orientalies, Blattella germanica, Blattella asahinai, Leucophaea maderae, Panchlora spp., Parcoblatta spp., Periplaneta australasiae, Periplaneta americana, Periplaneta brunnea, Periplaneta fuliginosa, Supella longipalpa;

Detachment of Saltatoria, for example, Acheta domesticus;

From the order Dermaptera, for example Forficula auricularia;

From the order Isoptera, for example, Kalotermes spp., Reticulitermes spp;

From the order Psocoptera, for example, Lepinatus spp., Liposcelis spp;

From the order Coleoptera, for example, Anthrenus spp., Attagenus spp., Dermestes spp., Latheticus oryzae, Necrobia spp., Ptinus spp., Rhizopertha dominica, Sitophilus granarius, Sitophilus oryzae, Sitophilus zeamais, Stegobium paniceum;

From the order Diptera, for example Aedes aegypti, Aedes albopictus, Aedes taeniorhynchus, Anopheles spp., Calliphora erythrocephala, Chrysozona pluvialis, Culex quinquefasciatus, Culex pipiens, Culex tarsalis, Drosophila spp., Fannia canicularis, Musca domestica, Phlebotomus spp., Sarcophaga camaria, Simulium spp., Stomoxys calcitrans, Tipula paludosa;

From the order Lepidoptera, for example, Achroia grisella, Galleries mellonella, Plodia interpunctella, Tinea cloacella. Tinea pellionella, Tineola bisselliella;

From the order Hymenoptera, for example, Camponotus herculeanus, Lasius fuliginosus, Lasius niger, Lasius umbratus, Monomorium pharonis, Paravespula spp., Tetramorium caespitum;

From the order Anoplura, for example, Pediculus humanus capitis, Pediculus humanus corporis. Pemphigus spp., Phylloera vastatrix, Phthirus pubis;

From the order Heteroptera, for example, Cimex hemipterus, Cimex lectularius, Rhodinus prolixus, Triatoma infestans.

In the sector of hygiene application of the present invention can be implemented separately or in combination with other suitable active ingredients, such as, for example, insecticides or fungicides, preferably specified in the text, and active ingredients selected from phosphoric esters, carbamates, pyrethroids, neo-nicotinoids, growth regulators.

In General, the present invention can be implemented in a way appropriate to the form of the application. Suitable forms of application include aerosols, non-pressurized sprays, such as sprays and atomizers, automatic devices generate mists, sprays, foams, gels, products for evaporator evaporator plates made of cellulose or polymer, evaporators liquids, gel and membrane evaporators, evaporators based on propellers, evaporative systems, which do not consume energy (passive evaporative system), antimolnoe napkins, antimolnoe bags and antimolnoe gels in the form of granules or powders, baits for spilling or luring installations.

The company is and, the active compounds according to the present invention can be produced in the form of conventional drugs. For various applications, in particular in agriculture and in the hygiene sector, examples of drugs, particularly when used as insecticides, include solutions, emulsions, wettable powders, dry loose preparations, suspensions, powders, foams, pastes, tablets, granules, aerosols, impregnated with active compound of natural and synthetic products, microcapsules, tools, covering seeds, medicines combustion chamber (for example, fumigators and fume cartridges, cans and balls), ULV cold aerosol) and warm aerosols).

Each of these drugs, you can get known in their essence by the way. For example, at least one active compound is mixed with developers, in particular liquid solvents or carriers; liquid gas diluents or carriers; or solid diluents or carriers and, optionally, surface-active substances (such as, for example, anionic, cationic and nonionic surfactants), in particular emulsifiers and/or dispersing agents, and/or a foaming agent, thus obtaining the drugs.

When using water as a developer, for example, an organic solvent can also be used shall be as an auxiliary solvent.

Examples of liquid solvents or carriers may include aromatic hydrocarbons (e.g. xylene, toluene and alkylnaphthalene), chlorinated aromatic or aliphatic hydrocarbons (e.g. chlorobenzene, ethylthiourea and methylenchloride), aliphatic hydrocarbons [for example, cyclohexane, paraffins (for example, fractions of mineral oil)], alcohols (for example, benzyl alcohol, isopropanol, ethanol, butanol, glycol and its ethers and esters), ketones (e.g. acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone), strongly polar solvents such as dimethylformamide and dimethyl sulfoxide), cyclic carbonates (for example, ethylene carbonate resulting, propylene carbonate), pyrrolidine (for example, N-octylpyrimidine, N-organic), ethers (for example, onomatology ether of diethylene glycol and monopropylene ether of diethylene glycol), lactones (for example, butyrolactone and water.

Examples of liquid gas solvents or carriers may include those solvents or carriers, which are a gas at normal temperature and pressure, such as aerosol propellants such as freon, propane, nitrogen, carbon dioxide and halogenated hydrocarbons. Examples of solid solvents may include minerals natural minerals (e.g. kaolins, clays, talc, chalk, quartz, attapulgite, mon is morillonite or diatomaceous earth) and minerals, synthetic minerals (for example, highly dispersed silicic acid, alumina and silicate).

Examples of solid carriers for granules can include crushed and fractionated rocks (for example, calcite, marble, pumice, thick and dolomite), synthetic granules of inorganic or organic powders, organic materials (such as sawdust, coconut shells, rods corn cobs and tobacco stalks).

Examples of emulsifiers and/or foaming agents may include non-ionic and anionic emulsifiers (for example, polyoxyethylene esters of fatty acids, polyoxyethylene alcohol ethers, fatty acids (for example, alkylarylsulphonates ether), alkyl sulphonates, alkyl sulphates and arylsulfonate] and albumin hydrolysates.

Dispersing means include the spent sulfite liquor lignin and methylcellulose.

Binders can also be used in preparations (powders, granules and mulgirigala concentrates). Examples of binders may include carboxymethyl cellulose, natural or synthetic polymers (for example, gum Arabic, polyvinyl alcohol and polyvinyl acetate).

The dye can also be used in the present invention. Examples of coloring agents may include inorganic pigments (e.g. iron oxide, titanium oxide and Prussian blue is), organic dyes, such as alizarin dyes, azo dyes and metal-phthalocyanine dyes, and, in addition, indicator nutrients such as salts of iron, manganese, boron, copper, cobalt, molybdenum or zinc.

The preparation may contain the above-mentioned active ingredient in an amount of generally from 0.1 to 95 wt.%. of the total weight of the preparation, and preferably from 0.5 to 90 wt.%.

The active compounds of formula (I) according to the present invention may exist in the form of a mixture with other active compounds such as insecticides, poisonous baits, bactericides, acaricides, nematicides, fungicides, growth regulators or herbicides in the forms of commercially used drugs and used in the form obtained from these drugs. In this text the examples above insecticides may include organic phosphor means, carbonate tools, substances carboxylate-type substances chlorinated hydrocarbon type and insecticidal materials obtained from microorganisms.

The active compounds of formula (I) according to the present invention may exist in the form of a mixture with synergists, and examples of their products and business forms may include commercially used form. Synergists by themselves do not necessarily need to be active and present with the battle connections a synergistic effect of the active compounds.

Such active ingredients or synergists are, for example, the following.

Compounds acting as fungicides:

Inhibitors of nucleic acid synthesis, such as Benalaxyl, benalaxyl-M, bupirimate, hirasaki, clothingon, dimethirimol, ethirimol, parallaxis, hymexazol, metalaxyl, metalaxyl-M, operas, oxadixyl and oxolinic acid.

Inhibitors of mitosis and cell division, such as benomyl, carbendazim, dietphenterm, fuberidazole, pencycuron, thiabendazole, thiophanate-methyl and toxemic.

Inhibitor of respiratory complex I, such as defimation.

Inhibitors of respiratory complex II, such as boscalid, carboxin, fanforum, flutolanil, parameter, mepronil, oxycarboxin, pentopia and leflunamide.

Inhibitors of respiratory complex III, such as AZOXYSTROBIN, cyazofamid, dimoxystrobin, anestrous, famoxadone, fenamidone, fluoxastrobin, kresoximmethyl, metamyosyn, orysastrobin, pyraclostrobin and picoxystrobin.

Decoupler, such as dinocap and fluazinam.

Inhibitors of ATP production, such as fentin acetate, fentin chloride, fentin hydroxide and silthiofam.

The inhibitor of the biosynthesis of amino acids and proteins, such as andapril, blasticidin-S, cyprodinil, kasugamycin, hydrochloride hydrate kasugamycin is, mepanipyrim and Pyrimethanil.

Inhibitors of signal transmission, such as fenpiclonil, fludyoksonil and jenoxifen.

Inhibitors of fat synthesis and membranes, such as chlozolinate, iprodione, procymidone, vinclozolin, aspropirgos, potassium aspropirgos, edifenphos, iprobenfos (IBP), isoprothiolane, pyrazophos, tolclofos-methyl, biphenyl, iodosorb, propamocarb and propamocarb hydrochloride.

Inhibitors of ergosterol biosynthesis, such as fenhexamid, azaconazole, bitertanol, bromuconazole, tsyprokonazolu, diclobutrazol, difenoconazole, diniconazole, diniconazole-M, epoxiconazole, itaconate, fenbuconazole, Fluconazol, flusilazol, flutriafol, vorconizole, vorconizole-CIS, hexaconazole, kabekona, ipconazole, metconazole, myclobutanil, paclobutrazol, penconazole, propiconazole, prothioconazole, simionato, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, uniconazole, voriconazole, imazalil, imazalil sulfate, Expocentr, fenarimol, flurried, nuarimol, pirivenas, triforine, peyratout, prochloraz, triflumizole wineconsole, Aldemar, dodemont, dodemont acetate, fenpropimorph, tridemorph, fenpropidin, spiroxamine, naftifine, peribuccal and terbinafine.

Inhibitors of the synthesis of cell membranes, such as benthiavalicarb, bialaphos, dimethomorph, floorf, iprovalicarb, polyoxin, palikari and validamycin A.

<> Inhibitors of melanin biosynthesis, such as napropamide, diclocil, phenoxyl, phtalic, peregian and tricyclazole.

Compounds that cause resistance, such as acibenzolar-8-methyl, provenzal and tadini.

MultiSite compounds such as captafol, Captan, CHLOROTHALONIL, copper salts include copper hydroxide, copper naphthenate, copper oxychloride, copper sulphate, copper oxide, oxin-copper and Bordeaux liquid, dichlofluanid, dithianon, dodine, dodine in the form of a free base, ferbam, forfait, guazatine, guazatine acetate, iminoctadine, iminoctadine aveilut, iminoctadine triacetate, marcopper, MANCOZEB, MANEB, metiram, metiram zinc, propineb, sulphur and sulphur preparations containing calcium polysulfide, thiram, tolyfluanid, zineb and Tsira.

Compounds with unknown mechanism of action, such as Librada, bentazon, bantomsin, capsaicin, carvon, quinoline of Meteosat, chlorpicrin, kurane, cyflufenamid, having cymoxanil, dazomet, dibakar, declomycin, dichlorophen, dicloran, difenzoquat, difenzoquat the methyl sulfate, diphenylamine, ethaboxam, verison, flamethower, glucolipid, fluopicolide, perimed, hexachlorobenzene, 8-hydroxyquinolin sulfate, arunamarin, metasurfaces, metrafenone, methylisothiocyanate, millionizer, natamycin, Nickel dimethyldithiocarbamate, nitrates-isopropyl, Actelion, oxamate, oxidation, pentachlorophenol and with whom Lee, 2-phenylphenol and salt, piperalin, propanoic-sodium, probenecid, pyrrolnitrin, hintzen, telital, Tecnatom, triazoxide, trihemic, Suriname and 2,3,5,6-tetrachloro-4-(methylsulphonyl)pyridine, N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide, 2-amino-4-methyl-N-phenyl-5-thiazolecarboxamide, 2-chloro-N-(2,3-dihydro-1,1,3-trimethyl-1H-inden-4-yl)-3-pyridinecarboxamide, 3-[5-(4-chlorophenyl)-2,3-dimethylisoxazole-3-yl]pyridine, CIS-1-(4-chlorophenyl)-2-(1H-1,2,4-triazole-1-yl)cycloheptanol, 2,4-dihydro-5-methoxy-2-methyl-4-[[[[1-[3-(trifluoromethyl)-phenyl]ethylidene]amino]oxy]methyl]phenyl]-3H-1,2,3-triazole-3-one (185336-79-2), methyl 1-(2,3-dihydro-2,2-dimethyl-1H-inden-1-yl)-1H-imidazole-5-carboxylate, 3,4,5-trichloro-2,6-pyridinedicarboxylic, methyl 2-[[[cyclopropyl[(4-methoxyphenyl)imino]methyl]thio]methyl]-alpha-(methoxymethyl)-benzoate, 4-chloro-alpha-propenyloxy-N-[2-[3-methoxy-4-(2-propenyloxy)phenyl]ethyl]-benzazimide, (2S)-N-[2-[4-[[3-(4-chlorophenyl)-2-PROPYNYL]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulphonyl)amino]-butanamide, 5-chloro-7-(4-methylpiperidin-1-yl)-6-(2,4,6-tryptophanyl)[1,2,4]triazolo[1,5-a]pyrimidine, 5-chloro-6-(2,4,6-tryptophanyl)-N-[(1R)-1,2,2-trimethylpropyl][1,2,4]triazolo[1,5-a]pyrimidine-7-amine, 5-chloro-N-[(1R)-1,2-dimethylpropyl]-6-(2,4,6-tryptophanyl) [1,2,4]triazolo[1,5-a]pyrimidine-7-amine, N-[1-(5-bromo-3-chloropyridin-2-yl)ethyl]-2,4-dichloronicotinic, N-(5-bromo-3-chloropyridin-2-yl)methyl-2,4-dichloronicotinic, 2-butoxy-6-iodine-3-propelle soprano-4-one, N-{(Z)-[(cyclopropylmethoxy)imino] [6-(deformedarse)-2,3-differenl]methyl}-2-benzazimide, N-(3-ethyl-3,5,5-trimethylcyclohexyl)-3-formylamino-2-hydroxybenzamide, 2-[[[[1-[3(1-fluoro-2-phenylethyl)oxy]phenyl ethylidene] amino] oxy]methyl]-alpha-(methoxyimino)-N-methyl-Alfie-benzazimide, N-{2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl}-2-(trifluoromethyl)benzamide, N-(3',4'-dichloro-5-forbiden-2-yl)-3-(deformity)-1-methyl-1H-pyrazole-4-carboxamide, N-(6-Methoxy-3-pyridinyl)-cyclopropanecarboxamide, 1-[(4-methoxyphenoxy)methyl]-2,2-dimethylpropyl-1H-imidazole-1-carboxylic acid, O-[1-[(4-methoxyphenoxy)methyl]-2,2-dimethylpropyl]-1H-imidazol-1-thiocarbonate acid, 2-(2-{[6-(3-chloro-2-methylphenoxy)-5-ftorpirimidinu-4-yl]oxy}phenyl)-2-(methoxyimino)-N-methylacetamide.

Compounds acting as microbicides, such as bronopol, dichlorophen, nitrapyrin, Nickel dimethyl-dithiocarbamate, kasugamycin, Actelion, francebuy acid, oxytetracycline, provenzal, streptomycin, telital, copper sulphate and other products from copper.

Compounds acting as insecticidal agents and/or acaricides and/or nematicides:

inhibitors of acetylcholinesterase (AChE), such as carbamates, such as, for example, alankar, aldicarb, aldoxycarb, allistar, aminocarb, bendiocarb, benfuracarb, bofenkamp, betacar, butocarboxim, butoxycarboxim, karber is l, the carbofuran, carbosulfan, cloethocarb, dimetilan, ethiofencarb, fenobucarb, fanatical, formetanate, furathiocarb, isoprocarb, METAM-sodium, methiocarb, methomyl, metolcarb, oxamyl, pirimicarb, promecarb, propoxur, thiodicarb, thiofanox, trimeter, CMS, killchar and triazamate; and

such as organophosphates, such as, for example, Arafat, azamethiphos, azinphos(-methyl, -ethyl), bromophos-ethyl, Kompaniets (-methyl), autotypes, cadusafos, carbophenothion, chlorethoxyfos, Chlorfenvinphos, chlormephos, chlorpyrifos (-methyl-ethyl), coumaphos, cyanofenphos, cyanophos, chlorfenvinfos, demeton-S-methyl, demeton-S-methylsulfone, dialifos, diazinon, dichlofenthion, dichlorvos/DDVP, dicrotophos, dimethoate, dimethylene, dioxybenzone, disulfoton, EPN, ethion, ethoprophos, etrimfos, famphur, fenamiphos, fenitrothion, fensulfothion, fenthion, flupirtine, fonofos, formation, tomatlan, fosthiazate, heptenophos, iodofenphos, iprobenfos, isazofos, isofenphos, isopropyl O-salicylate, isoxathion, Malathion, mecarbam, methacrifos, metamidophos, mitigation, mevinphos, monocrotophos, naled, omethoate, oxydemeton-methyl, parathion (-methyl-ethyl), pentat, Fort, fozalon, phosmet, phosphamidon, fastcars, phoxim, pirimiphos (-methyl-ethyl), profenofos, propafol, propetamphos, prothiofos, procoat, pyraclofos, predatation, predation, finalpos, sabots, sulfotep, sulprofos, tenopir MPOs, temephos, terbufos, tetrachlorvinphos, thiometon, triazophos, trichlorfon, vamidothion.

Modulators of the sodium channel/potentialization blockers, sodium channel, such as pyrethroids, such as, for example, acrinathrin, allethrin (d-CIS-TRANS, d-TRANS), beta-cyfluthrin, bifenthrin, bioallethrin, bioallethrin-S-cyclopentyl-isomer, bioeconomical, bioprotein, bioresmethrin, lovepotion, CIS-cypermethrin, CIS-resmethrin, CIS-permethrin, claritin, cicloprofen, cyfluthrin, cigalotrin, cypermethrin (alpha, beta, theta, Zeta), cyphenothrin, deltamethrin, empenthrin (1R-isomer), esfenvalerate, etofenprox, fenfluthrin, fenpropathrin, generatin, fenvalerate, lubricant, flucythrinate, flavandiols, flumethrin, fluvalinate, tupfenrock, gamma cigalotrin, imiprothrin, kadethrin, lambda cigalotrin, metofluthrin, permethrin (CIS-, TRANS-), phenothrin (1R-TRANS isomer), prallethrin, perflutren, protrudent, piezotron, resmethrin, RU 15525, selflove, Tau-fluvalinate, tefluthrin, tarletan, tetramethrin (-1R - isomer), tralomethrin, transfluthrin, ZXI 8901, pyrethrins (pyrethrum);

DDT; oxadiazine, such as, for example, indoxacarb.

Agonists/antagonists of the acetylcholine receptor, such as chloronicotinyl, such as, for example, acetamiprid, clothianidin, dinotefuran, Imidacloprid, nitenpyram, nithiazine, thiacloprid, thiamethoxam, nicotine, bensol the AP, cartap.

The acetylcholine receptor modulators, such as spinosyn, such as, for example, spinosad.

Antagonists of GABA-regulated chloride channels, such as organochlorine compounds, such as, for example, camphechlor, chlordane, endosulfan, gamma-HCH, HCH, heptachlor, lindane, Methoxychlor;

Pipoly, such as, for example, acetarsol, ethiprole, fipronil, perflubron, periphral and unilibro.

Activators chloride channels, such as Machine, such as, for example, avermectin, emamectin, emamectin benzoate, ivermectin, milbemycin, litigatin, leemartin, selamectin, doramectin, eprinomectin and moxidectin.

The juvenile hormone mimetics, such as, for example, giovanola, epitonin, fenoxycarb, hydroprene, CANopen, methoprene, pyriproxyfen and triplen. Agonists latrophilin receptor, such as depsipeptide, preferably circular depsipeptide, in particular, 24-membered cyclic depsipeptide, for example emodepside.

Agonists/disintegrator ecdysone, such as diacylhydrazines have, such as, for example, chromafenozide, halogenated, methoxyfenozide, tebufenozide.

Inhibitors of chitin biosynthesis, such as benzoylacetone, such as, for example, bistriflate, chlorfluazuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, enflurane, phone benturan, triflumuron; buprofezin; chromatin.

Inhibitors of oxidative phosphorylation, ATP disintegrator, such as diafenthiuron; ORGANOTIN compounds such as, for example, azocyclotin, cyhexatin, fenbutatin oxide.

Decoupler of oxidative phosphorylation by interruption of the H-proton gradient, such as pyrrole, such as, for example, chlorfenapyr; dinitrophenol, such as, for example, binapacryl, dinobuton, dinocap, DNOC.

Inhibitors of electron transfer on the website I like METI's, such as, for example, fenazaquin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad, toppenberg; hydramethylnon; dicofol.

Inhibitors of electron transport at site II, such as rotenone.

Inhibitors of electron transport at site III, as acehenese, flociprin.

Microbial disintegrator putting in membrane insects, such as lines of Bacillus thuringiensis.

Inhibitors of fat synthesis, such as tetronic acids, such as, for example, spirodiclofen, spiromesifen; tetralogie acid, such as, for example, spirotetramat (registration number CAS: 203313-25-1) and 3-(2,5-dimetilfenil)-8-methoxy-2-oxo-1-azaspiro[4.5]Dec-3-EN-4-yl ethylcarbamate (also known as: 3-(2,5-dimetilfenil)-8-methoxy-2-oxo-1-azaspiro[4.5]Dec-3-ene-4-jatiluwih ester of carbonic acid, registration number CAS: 382608-10-8); carboxamide such to the to, for example, flonicamid.

Aktobemunaygas agonists, such as, for example, amitraz.

The inhibitors of magnesium-stimulated ATPase, such as dicarboxamide propargylamines acid, such as, for example, flubendiamide; analogues of nereistoxin, such as, for example, thiocyclam hydrocalc, thiosulfat-sodium.

Biologicals, hormones or pheromones, such as azadirachtin, Bacillus spec, Beauveria spec, Coleman, Metarrhizium spec, Paecilomyces spec, thuringiensin, Verticillium spec.

Active compounds with unknown or non-specific mode of action, such as fumigants, such as, for example, aluminum phosphide, methyl bromide, sulphuryl fluoride is; inhibitors of power, such as, for example, cryolite, flonicamid, pymetrozine; mite growth inhibitors, such as, for example, clofentezine, etoxazole, hexythiazox; midflame, banknotes, benoxinate, bifenazate, bromine-propilot, buprofezin, chinomethionat, Chlordimeform, Chlorobenzilate, chlorpicrin, clotiazepam, ciclope, titlemedium, dicyclanil, tenoxicam, pentaphenyl, flibanserin, lufenuron, lotensin, gossiper, hydramethylnon, yapanlar metaxades, kerosene, piperonylbutoxide, potassium oleate, pyridalyl, sulfuramid, tetradifon, tetrasul, triuralin and verboten.

The content and the concentration of the active compounds of the formula (I) according to the present invention in a commercially usable form can be widely is to ariyavamsa.

In particular, the concentration of the active compounds of the formula (I) according to the present invention can range from 0.0000001 to 100% by weight, preferably from 0.00001 to 1% wt. and more preferably from 0.0001 to 0.5 wt.%.

According to the present invention the compounds of formula (I) for use in the traditional way corresponded to the working forms.

The application is carried out in a manner suitable for used forms.

In agricultural areas, i.e. in the field of protection of plants, all plants and plant parts can be processed in accordance with the present invention. Plants must be understood in this context as meaning all plants and plant populations such as desired and undesired wild plants or crop (including naturally occurring crop). Crops can be a plant that you can get the traditional methods of breeding and optimization of plants, or by using methods of biotechnology and genetic engineering, or a combination of these methods, including genetically modified plants, including cultivated varieties of plants, protected or unprotected rights of plant breeders. Plant parts should be understood as meaning all parts and organs of plants above or below ground level, such as the East, leaf, flower and root, examples which may be mentioned include leaves, needles, stems, petioles, flowers, fruit bodies, fruits, grains, roots, tubers and underground shoots. Plant parts also include material that is collected in the form of harvest, and the material for the vegetative and generative reproduction, for example cuttings, tubers, rhizomes, shoots and crops.

Processing plants and parts of plants according to the present invention the compound of the present invention is carried out directly or by the effect of the compound on the environment, the natural environment or storage space by traditional processing methods, for example by watering (drenching), drip irrigation, spraying, spray, spatter, randomly making, dusting, foaming, spreading in the form of a powder for dry seed treatment, a solution for seed treatment, a water-soluble powder for seed treatment, a water-soluble powder for processing in the form of a suspension or by creating a cover and, in the case of breeding material, particularly in the case of seeds, furthermore, dry processing, handling suspension, the processing liquid coating one or more layers. You can also apply the active compounds by the method of ultra-low volume or injection of a drug with an active connection is whether the active compounds in the soil.

Compounds of the present invention is particularly suitable for seed treatment. So, most of the damage to crops caused by pests occurs in the early stages - when the seed is exposed to attack during storage and after placing the seed into the soil during or immediately after germination of the plants. This phase is especially dangerous, as the roots and shoots of the growing plant are particularly sensitive and even minor damage can lead to death of the whole plant. Protection of seed and germinating plants through the use of suitable compositions containing the compound of the present invention is, therefore, of the greatest interest.

Pest control by treating the seed of plants has been known for a long time and is subject to ongoing improvements. However, seed treatment often causes a number of difficulties are not always able to cope successfully. Thus, it is desirable to develop methods of protection of seed and germinating plants, in which it is possible to do without additional protections crops after planting or after emergence of the plants, or in which the use of additional funds, at least, reduced. It is also desirable to optimize the amount of active compound used in the ACOM way, to ensure maximum protection of seed and germinating plants from attack by pests, but without damaging the plant itself used to be an active compound. In particular, the methods of treatment of seed should also be considered internal insecticidal properties of genetically modified plants to achieve optimum protection of the seed and the germinating plant with a minimum quantity of protection of crops.

In agriculture, the dosage of active compound/standard introduction commonly used in the processing method of the present invention, is a processing leaves: from 0.1 to 10,000 g/ha, preferably from 10 to 1000 g/ha, more preferably from 50 to 300 g/ha; in case of impregnation or drip application, the dosage can be reduced; for seed treatment: from 2 to 200 g per 100 kg of seed, preferably from 3 to 150 g per 100 kg of seeds; for soil treatment: from 0.1 to 10,000 g/ha, preferably from 1 to 5000 g/ha

As mentioned earlier, it is possible to treat all plants and their parts according to the present invention. In the preferred embodiment, handle species of wild plants and crops, or plants obtained by conventional biological methods of cultivation, such as crossing or merging of protoplasm, and their parts. In another preferred the equipment embodiment, handle genetically modified plants and crops, obtained by means of genetic engineering, optionally in combination with conventional methods (Genetically Modified Organisms), and parts thereof. The terms "parts" and "parts of plants" were disclosed above.

Particularly preferably, in accordance with the present invention, process plants from a number of vegetable crops, which in each case are commercially available or are in use. Crops should be understood as meaning plants with new properties ("features"), which were obtained by conventional breeding, mutagenesis or recombinant DNA technologies. They may represent a culture, bio - or genotypes.

Genetically modified plants or plant culture (obtained by genetic engineering)which preferably should be processed in accordance with the present invention include all plants which, due to the genetic modification, received genetic material which imparted these plants particularly advantageous, useful features. Examples of these features are better plant growth, increased tolerance to high or low temperatures, increased tolerance to drought or salt content in the water or soil, improved flowering, easier harvest, ush the counter maturation, higher yields, better quality and/or higher nutritional value of the collected products, the best stability during storage and/or suitability for processing of the collected products. Below and disclosed in detail examples of such features are the best data protection of the plants against animal and microbial pests, such as insects, mites, phytopathogenic fungi, bacteria and/or viruses, and also increased resistance of these plants to some herbicide active compounds. Examples of genetically modified plants which may be mentioned are the important crops such as cereals (wheat, rice), maize, soybeans, potatoes, sugar beets, tomatoes, peas and other varieties of vegetables, cotton, tobacco, rape and also fruit plants (with the fruits apples, pears, citrus fruits and grapes), and particular emphasis on maize, soybeans, potatoes, cotton, tobacco and oilseed rape. Features, which has special significance, in particular, are improved protection of the plants against insects, arachnids, worms and slugs and snails by toxins formed in the plants, in particular formed in the plants by the genetic material from Bacillus thuringiensis (for example by the genes CryIA(a), CryIA(b)CryIA(c), CryIIA, CryIIIA, CryIIIB2, Cry9c, Cry2Ab, Cry3Bb and CryIF and that is also combinations thereof) (hereinafter referred to in this text "Bt plants"). Features, which also have particular importance are enhanced protection of plants against fungi, bacteria and viruses due to genes systemic acquired resistance (SAR), systemin, phytoalexins, elicitors and resistance genes and correspondingly expressed proteins and toxins. Features, which also have particular importance are the increased resistance of plants to some herbicide active compounds, such as imidazolinones, sulfonylureas, glyphosate or phosphinotricin (for example the "PAT" gene). Genes that provide the desired characteristics may also be present in genetically modified plants in combination with each other. Examples of "Bt plants"which may be mentioned are maize, cotton varieties, soybean varieties and potato varieties which are sold under the trade names YIELD GARD® (for example maize, cotton, soybean), KnockOut® (for example maize), StarLink® (for example maize), Bollgard® (cotton), Nucotn® (cotton) and NewLeaf® (potato). Examples of herbicide-tolerant plants that you can specify are maize, cotton varieties and soybean varieties which are sold under the trade names Roundup Ready® (tolerance to glyphosate, for example maize, cotton, soya). Liberty Link® (tolerance to phosphinotricin is, for example, pane), IMI® (tolerance to imidazolinones) and STS® (tolerance to sulfonylureas, for example, corn). Herbicide-resistant plants (plants bred in a traditional way for resistance to the herbicide)that you can specify include the varieties sold under the brand name Clearfield® (for example maize). Of course, these provisions are also applicable to vegetable crops with genetic data features or where it is necessary to develop these genetic features, but these crops will be developed and/or sold in the future.

These plants can handle an active compound of the present invention using the method, with special advantages. The preferred ranges stated above for the active connection is also applicable to processing plants.

When the active compounds according to the present invention are used in the hygiene sector, in particular use against pests of hygiene, or pests of stored materials, they are resistant against alkali or calcium substances and provide excellent residual impacts on trees and soil.

Further, the present invention will be disclosed in more detail using examples, but the present izaberete the ie is not limited to these examples.

The Synthesis example 1 (synthesis of the source reagent).

2-fluoro-5-formylbenzoate (1.0 g, 6.71 mmol) and 1H-1,2,4-triazole (0.56 g, 8.05 mmol) was dissolved in DMF. Potassium carbonate (1.1 g, 8.05 mmol) was added to the solution, which was stirred at 120°C for 6 hours. The temperature of the reaction solution was brought to room temperature and added to a solution of water and ethyl acetate to separate an organic layer and an aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and dried over anhydrous magnesium sulfate. After separating the drying means by filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified column chromatography on silica gel (hexane/ethyl acetate)to give 0.60 g of 5-formyl-2-(1H-1,2,4-triazole-1-yl)benzonitrile (TPL: 134-141°C, yield: 43%).

The Synthesis example 2 (synthesis of the source reagent)

5-formyl-2-(1H-1,2,4-triazole-1-yl)benzonitrile (1.58 g, 7.97 mmol) and hydroxylamine hydrochloride (0.67 g, 9.57 mmol) was dissolved in a mixed solvent of THF-water (4:1). Sodium acetate (0.92 g, 11.2 mmol) was added to the solution, which was stirred at room temperature for 4 hours. After completion of the reaction was added to the reaction solution, water and ethyl acetate to separate an organic layer and an aqueous layer was extracted with what dilatatum. The organic layers were combined, washed with water and dried over anhydrous magnesium sulfate. After separating the drying means by filtration, the filtrate was concentrated under reduced pressure, getting 1.56 g of 5-[(hydroxyimino)methyl]-2-(1H-1,2,4-triazole-1-yl)benzonitrile (TPL: 198-200°C, yield: 87%).

Example of Synthesis 3

N-chlorosuccinimide (0.41 g, 3.04 mmol) was added to a mixture obtained by dissolving 5-[(hydroxyimino)methyl]-2-(1H-1,2,4-triazole-1-yl)benzonitrile (0.59 g, 2.77 mmol) in DMF, and the mixture was stirred for 2 hours. Then to the mixture was added 1,3-dichloro-5-[1-(trifluoromethyl)vinyl]benzene (0.82 g, 3.04 mmol). Dissolved in the DMF triethylamine (0.31 g, 3.29 mmol) was added dropwise to the above mixture while cooling with ice. Upon completion of the addition the mixture was stirred 2 hours at the same temperature and then stirred for another 4 hours after the temperature of the mixture was compared with room temperature. After completion of the reaction was added to a solution reaction, water and ethyl acetate to separate an organic layer and an aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and dried over anhydrous magnesium sulfate. After separating the drying means by filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified column chromatography n is silica gel (hexane/ethyl acetate), getting 0.51 g of 5-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl)-2-(1H-1,2,4-triazole-1-yl)benzonitrile (TPL: 118-125°C, yield: 39%).

Example of Synthesis 4

5-[3,5-bis(trifluoromethyl)phenyl]-3-(4-fluoro-3-nitrophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole (0.40 g, 0.82 mmol) and 1H-tetrazole (0.09 g, 1.22 mmol) was dissolved in DMF. Potassium carbonate (0.17 g, 1.25 mmol) was added to the solution, which was stirred at 60°C for 6 hours. The temperature of the reaction solution was brought to room temperature and added to a solution of water and ethyl acetate to separate an organic layer and an aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and dried over anhydrous magnesium sulfate. After separating the drying means by filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified column chromatography on silica gel (hexane/ethyl acetate)to give 0.06 g of 1-(4-{5-[3,5-bis(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl}-2-nitrophenyl)-2H-tetrazole (TPL: 147-149°C, yield: 13%) and 0.28 g of 1-(4-{5-[3,5-bis(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl}-2-nitrophenyl)-1H-tetrazole (TPL: 173-175°C, yield: 60%).

Example of Synthesis of 5

3-(4-fluoro-3-nitrophenyl)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole (0.6 g, 1.42 mmol) and 1H-1,2,4-Tr the azole (0.12 g, 1.70 mmol) was dissolved in DMF. Potassium carbonate (0.24 g, 1.70 mmol) was added to the solution, which was stirred at 60°C for 6 hours. The temperature of the reaction solution was brought to room temperature and added to a solution of water and ethyl acetate to separate an organic layer and an aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and dried over anhydrous magnesium sulfate. After separating the drying means by filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified column chromatography on silica gel (hexane/ethyl acetate)to give 0.66 g of 1-{4-[5-[3,5-dichlorophenyl]-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]-2-nitrophenyl}-1H-1,2,4-triazole (TPL: 64-72°C, yield: 94%).

Example of Synthesis 6

1H-pyrazole (0.06 g, 0.89 mmol) was dissolved in DMF. Sodium hydride (60%, 0.06 g, 0.89 mmol) was added to the solution under ice cooling, and then the temperature of the solution was brought to room temperature. The solution was stirred for 0.5 hours and again cooled with ice. Was added dropwise to the mixture dissolved in DMF 5-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]-2-perbenzoate (0.30 g, 0.74 mmol). Upon completion of the addition the temperature of the reaction solution was brought to room temperature and the solution was stirred for 3 hours. After completion of the reaction dobavlyali solution of water and ethyl acetate to separate an organic layer and an aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and dried over anhydrous magnesium sulfate. After separating the drying means by filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified column chromatography on silica gel (hexane/ethyl acetate)to give 0.2 g of 5-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]-2-(1H-pyrazole-1-yl)benzonitrile (TPL: 169-176°C, yield: 57%).

Example of synthesis of 7

5-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]-2-(1H-pyrazole-1-yl)benzonitrile (0.43 g, 0.95 mmol) was dissolved in DMF. N-chlorosuccinimide (0.14 g, 1.05 mmol) was added to the solution which was then stirred at room temperature for 2 hours and at 80°C for 2 hours. After completion of the reaction was added to a solution of water and ethyl acetate to separate an organic layer and an aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and dried over anhydrous magnesium sulfate. After separating the drying means by filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified column chromatography on silica gel (hexane/ethyl acetate)to give 0.2 g of 2-(4-chloro-1H-pyrazole-1-yl)-5-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]benzonitrile (TPL: 190-191°C, yield: 41%).

4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]aniline (0.30 g, 0.80 mmol) and 2,5-dimethoxytetrahydrofuran (0.26 g, 2.00 mmol) was dissolved in acetic acid. The solution was boiled under heating for 0.5 hours. The temperature of the reaction solution was brought to room temperature and added to a solution of water and ethyl acetate to separate an organic layer and an aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and dried over anhydrous magnesium sulfate. After separating the drying means by filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified column chromatography on silica gel (hexane/ethyl acetate)to give 0.22 g of 5-(3,5-dichlorophenyl)-3-[4-(1H-pyrrol-1-yl)phenyl]-5-(trifluoromethyl)-4,5-dihydroisoxazole (TPL: 206-208°C, yield: 61%).

Example 9 Synthesis

4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]aniline (0.30 g, 0.80 mmol) and 1,2-deformalization (0.18 g, 2.00 mmol) suspended in pyridine. The triethylamine (0.57 g, 5.6 mmol) and trimethylchlorosilane (1.30 g, 12.0 mmol) was sequentially added to a liquid suspension under ice cooling. Then the solution was boiled under heating for 4 hours. The temperature of the reaction solution was brought to room temperature and then the reaction solution is time to relax is whether water, receiving sediment. The precipitate was washed with a small amount of ethyl acetate and dried, obtaining 0.14 g of 4-{4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]phenyl}-4H-1,3,4-triazole (TPL>250°C, yield: 39%).

Example 10 Synthesis

4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]aniline (1.25 g, 3.33 mmol) and triethylamine (0.40 g, 3.95 mmol) was dissolved in dichloromethane. The dichloromethane solution of the anhydride triperoxonane acid (0.80 g, 3.81 mmol) was added to the solution under ice cooling, and the mixture was stirred at room temperature for one hour. Upon completion of the reaction, the reaction solution was washed with water and dried over anhydrous magnesium sulfate. After separating the drying means by filtration, the filtrate was concentrated under reduced pressure, obtaining 1.55 g of N-{4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]phenyl}-2,2,2-trifurcated (TPL: 45-52°C, yield: 99%).

Example 11 Synthesis

N-{4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]phenyl}-2,2,2-triptorelin (1.30 g, 2.76 mmol) and triphenylphosphine (1.00 g, 3.81 mmol) was dissolved in dichloromethane. Carbon tetrachloride (0.60 g, 3.90 mmol) was added to the solution at 30°C, and the resulting solution was boiled under heating for 5 hours. After completion of the reaction the crude product obtained concentri is consistent reaction solution under reduced pressure, was purified column chromatography on silica gel (hexane/ethyl acetate)to give 1.20 g of N-{4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]phenyl}-2,2,2-cryptgetkeyparam (yield: 89%).

Example 12 Synthesis

N-{4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]phenyl}-2,2,2-cryptgetkeyparam (0.125 g, 0.255 mmol) was dissolved in acetonitrile. Sodium azide (0.05 g, 0.769 mmol) was added to the solution which was then stirred at room temperature for 15 hours. After completion of the reaction was added to a solution of water and ethyl acetate to separate an organic layer and an aqueous layer was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. After separating the drying means by filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified column chromatography on silica gel (hexane/ethyl acetate)to give 0.10 g of 1-{4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]phenyl)-5-(trifluoromethyl)-1H-tetrazole (TPL: 147-151°C, yield: 79%).

Example of Synthesis 13

4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]aniline (0.40 g, 1.07 mmol) and utilitarian (0.30 g, 2.02 mmol) was dissolved in acetic acid. Sodium azide (0.10 g, 1.54 mmol) was added to the solution, which then is ipatio under heating for 5 hours. After completion of the reaction was added to a solution of water and ethyl acetate to separate an organic layer and an aqueous layer was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. After separating the drying means by filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified column chromatography on silica gel (hexane/ethyl acetate)to give 0.25 g of 1-{4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]phenyl}-1H-tetrazole (TPL: 198-199°C. (decomposition), yield: 55%).

Example 14 Synthesis

1-{4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]-2-nitrophenyl}-1H-1,2,4-triazole (0.53 g, 1.12 mmol) and the dihydrate tin chloride (1.01 g, 4.49 mmol) suspended in ethanol. In addition, to the solution was added a catalytic amount of concentrated hydrochloric acid. The reaction solution was heated at 60°C for 4 hours. After completion of the reaction the temperature of the reaction solution was brought to room temperature. Water and ethyl acetate were added to the solution, which neutralize with potassium carbonate with vigorous stirring. The suspension was filtered through celite. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and dried over anhydrous sulfate is m magnesium. After separating the drying means by filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified column chromatography on silica gel (hexane/ethyl acetate)to give 0.38 g of 5-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]-2-(1H-1,2,4-triazole-1-yl)aniline (TPL: 244-246°C, yield: 73%).

Example 15 Synthesis

5-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]-2-(1H-1,2,4-triazole-1-yl)aniline (0.29 g, 0.66 mmol) and pyridine (0.08 g, 0.98 mmol) was dissolved in THF. To the resulting solution at room temperature was added acetylchloride (0.05 g, 0.69 mmol), and stirred the solution for 1 hour. After completion of the reaction solution were added water and ethyl acetate. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and dried over anhydrous magnesium sulfate. After separating the drying means by filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified column chromatography on silica gel (hexane/ethyl acetate)to give 0.17 g of N-{5-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-yl]-2-(1H-1,2,4-triazole-1-yl)phenyl}ndimethylacetamide (TPL: 230-233°C, yield: 51%).

The compounds of formula (I) according to the present invention, is obtained analogously to the synthesis of the original Reagan the s and examples of synthesis to obtain the final products, shown in Table 1, and specific examples of the intermediates are shown in Tables 2-4.

Among the above examples of synthesis of compounds corresponding to the final products are shown in Table 1.

In the following tables. Me means methyl, Et means ethyl, Prcyclomeans cyclopropyl, and Ph means phenyl.

Biological test example 1:

Test for larvae of Spodoptera litura

Preparation of test chemical solution

Solvent: dimethylformamide 3 parts by mass

Emulsifier: polyoxyethyleneglycol ether 1 part by weight

To obtain a preparation of a suitable active compound, 1 part by weight of active compound was mixed with the stated amounts of solvent and emulsifier, and the resulting mixture was diluted with water to a certain concentration.

Test method

The potato leaves were dipped in the test solution, diluted with water up to a certain concentration. After drying in air to remove the chemical solution leaves were placed in a Petri dish with a diameter of 9 cm, which was released 10 larvae of Spodoptera litura 3rd age stage. The Petri dish was placed in a chamber components is that with a temperature of 25°C, was added in potato leaves after 2 days and 4 days to reveal the number of dead larvae after 7 days, computing thus insecticidal ratio of the chemical solution.

In this test calculated the average value of the results in two Petri dishes in the same partition.

The results of the test

In the above biological test 1, the above connection№№2, 4, 5, 7, 8, 12, 13, 16, 17, 18, 19, 21, 23, 24, 25, 26, 27, 28, 29, 38, 47, 48, 52, 72, 86, 89, 90, 91, 93, 94, 96, 97, 98, 99, 100, 101, 103, 104, 105, 106, 107, 109, 114, 122, 123, 152, 126, 127, 132, 133, 134, 135, 136, 141, 148, 150, 151, 153, 154, 157, 160, 161, 162, 165, 166, 171, 176, 178 and 181, as typical examples, had the effect of pest control that insecticidal ratio was 100% effective component concentration of 500 ppm

Test for Tetranychus urticae (test spray)

Test method

50-100 adults of Tetranychus urticae was inoculable on the leaves of beans in the phase of the second sheet, which were grown in pots with a diameter of 6 cm After one day on the sheets in sufficient quantity sprayed using a spray gun having a certain concentration of water diluted solution containing previously received active connection. Then the leaves were placed in a greenhouse and after 7 days was calculated acaricide coefficient of the chemical solution.

The results of the test

The above connection№№16, 21, 38, 80, 85, 89, 90, 94, 97, 98, 101, 103, 104, 109, 114, 123, 125, 126, 127 132, 134, 135, 136, 150, 151, 153, 157, 160, 161, 165 and 181, as typical examples, had the effect of pest control that acaricide ratio was 98% or more in an effective component concentration of 100 ppm

Biological test example 3:

Test for Aulacophora femoralis (test spray)

Test method

The cucumber leaves was immersed in a test solution, diluted with water up to a certain concentration. After the solution of the chemical substance was air-dried leaves were placed in a plastic Cup, which was placed sterilized soil. 5 Aulacophora femoralis 2nd stages were released into the soil, the number of dead insects was determined after 7 days, thus computing the insecticidal ratio of the chemical solution.

The results of the test

The above connection№№21, 25, 38, 64, 80, 85, 86, 89, 90, 91, 94, 97, 98, 99, 100, 101, 103, 104, 106, 107, 109, 114, 122, 126, 127, 132, 134, 135, 136, 147, 148, 150, 151, 153, 154, 157, 160, 161, 165, 166, 171 and 181, as typical examples, had the effect of pest control, what insecticidal ratio was 100% effective component concentration of 500 ppm

Biological test example 4:

Test for Myzus persicas resistant organic phosphor means and urethane tools

Test method

The eggplant was inoculable Myzus persicas resistant to phosphoric means of the m and urethane means, the rate of about 200 units per plant. Having a certain concentration of water diluted solution containing previously received the active compound was sprayed on eggplant in sufficient quantities by means of a spray through one day after inoculation. Eggplant was left in the greenhouse at 28°C, to calculate the insecticidal ratio after 24 hours after spraying of the solution. In this case, the test was repeated two times.

The results of the test

The above compound No. 38, 101, 135 and 153, as typical examples, had the effect of pest control that insecticidal ratio was 100% effective component concentration of 500 ppm

Biological test example 5:

Test for larvae of Lucilia cuprina

20 mg of active compound was dissolved in 1 ml of dimethyl sulfoxide. To obtain a suitable drug (e.g., 100 ppm), the solution of active compound is diluted with water to the required concentration (for example, 1 part by weight of a solution of the active compound with 199 parts by weight of water).

Approximately 20 larvae of Lucilia cuprina placed in the tube, which is approximately 1 cm3horse meat and 0.5 ml of the preparation being tested active compounds. After 48 hours efficacy active compound is defined as the % mortality of the larvae. 0%none of the lychee is the AC did not die, 100%: all larvae were killed.

In this test the above connection№№8, 9, 12, 14, 16, 17, 18, 19, 20, 30, 36, 38, 40, 42, 43, 44,45, 46, 54, 55, 58, 59, 60, 61, 62, 63, 66, 67, 68, 70, 80, 88, 89, 91, 93, 94, 76, 77, 78, 82, 71, 72, 73, 75, 84 demonstrated mortality of larvae>95% at 100 ppm after 2 days.

Biological test example 6:

Test for Musca domestica

20 mg of active compound are dissolved in 1 ml of dimethyl sulfoxide. To obtain a suitable drug (e.g., 100 ppm), the solution of active compound is diluted with water to the required concentration (for example, 1 part by weight of a solution of the active compound with 199 parts by weight of water).

0.2 ml of this preparation of active compound is applied from a pipette onto the sponge (about Ø 1.5 cm), which was moistened in 0.8 ml of sugar solution. Sponge and 10 experimental animals are placed in a Cup (4×4 cm, height 2 cm) and cover.

After 48 hours to determine the activity of the drug active compounds. Here 100% means that all the flies have been killed; 0% means that none of the flies were killed.

In this test the above connection№№8, 9, 14, 16, 18, 19, 20, 30, 36, 40, 42, 43, 44, 45, 46, 55, 58, 60, 61, 62, 66, 67, 68, 70, 80, 88, 89, 91, 93, 94, 76, 77, 78, 82, 71, 72, 73, 75, 84 demonstrated mortality of larvae of>95% at 100 ppm after 2 days.

Biological test example 7:

Test for cat fleas/oral administration

20 mg of active compound are dissolved in 1 ml di is ethylsulfonyl. To obtain a suitable drug (e.g., 100 ppm), the solution of active compound is diluted by the blood of cattle corresponding to the desired concentration (for example, 1 part by weight of a solution of the active compound with 199 parts by weight of the blood of cattle).

20 hungry adult fleas (Ctenocephalides felis, the line "Georgi") is placed in a chamber (Ø 5 cm), the top and bottom of which are closed with gauze. The metal cylinder, the bottom of which is covered with a polymer film, is placed on the camera. The cylinder contains a drug blood/active connection, which can be absorbed by fleas through the polymer film. While the blood is heated to 37°C, the temperature in the region of cameras with fleas set at the level at room temperature.

After the desired time determine the mortality in %. Here 100% means that all fleas were killed; 0% means that none of the flea did not die.

In this test, the above connection№№8, 9, 12, 14, 16, 17, 18, 19, 20, 30, 36, 38, 40, 42, 43, 44, 54, 58, 60, 61, 62, 66, 67, 80, 88, 89, 91, 93, 94, 76, 77, 78, 82, 71, 72, 73, 75, 84 demonstrated mortality >80% at 100 ppm after 2 days.

Biological test example 8:

Rhipicephalus (Boophilus) microplus; injection

20 mg of active compound are dissolved in 1 ml of dimethyl sulfoxide, lower concentration obtained by dilution in the same solvent.

The test is carried out in five p is verenex with fully fed female animals ticks of cattle, collected at least 24 hours after they fell from the owner. 1 μl of the solutions injected in the abdomen, and mites are transferred into cups for cultivation, and kept in a chamber with controlled conditions.

The activity test after 7 days on the deposition of fertile eggs. Eggs, fertility which are not externally visible, store in a glass tube in a Cabinet with adjustable conditions until larvae hatch in about 42 days. 100% of the activity means that no tick not laid fertile eggs.

In this test the above connection№№8, 9, 12, 14, 16, 17, 18, 20, 30, 36, 38, 40, 42, 43, 44, 45, 46, 63, 66, 67, 68, 70, 80, 88, 89, 91, 93, 94, 76, 77, 78, 82, 71, 72, 73, 75, 84 demonstrated activity of>90% at 20 µg/tick after 7 days.

Example of preparation 1 (pellet)

25 parts of water was added to a mixture of 10 parts of the compound (No. 26) of the present invention, 30 parts of bentonite (montmorillonite), 58 parts of talc and 2 parts of lignin sulfonate, and the resulting mixture was mixed for a sufficient time and were granulated in a granulating the form of 10-40 mesh by extrusion granulator, followed by drying at 40-50°C. to obtain granules.

Example of preparation 2 (pellet)

95 parts of clay particles of the material with particle size in the range from 0.2 to 2 mm were placed in a rotary mixer. 5 parts of the compound (No. 72) this izobreteny is sprayed together with a liquid solvent for uniform wetting of the particles during rotation of the agitator and then dried at 40-50°C with the formation of granules.

Example of preparation 3 (emulsifiable concentrate)

30 parts of compound No. 107) of the present invention, 55 parts of xylene, 8 parts polyoxyethyleneglycol ether and 7 parts of Las calcium were mixed and stirred to obtain emulsifiable concentrates.

Example of preparation 4 (wettable powder)

15 parts of the compound (No. 91) of the present invention, 80 parts of a mixture of white carbon black (powder water amorphous silicon oxide) and powder clay (1:5), 2 parts of Las sodium and 3 parts of the condensation product alkylnaphthalene sodium and formalin grinded and mixed to obtain a wettable powder.

Example of preparation 5 (dry loose product)

20 parts of the compound (No. 114) of the present invention, 30 parts of sodium lignin sulfonate, 15 parts of bentonite and 35 parts of calcined diatomaceous earth were thoroughly stirred. To the mixture was added water, and then the mixture was extrudible through a 0.3 mm screen and dried for the formation of dry loose drugs.

1. The isoxazolines of the formula (I)

where
And represents C or N;
R represents a C1-4halogenated;
X represents identical or different Halogens or With1-4halogenated;
1 is equal to 0, 1 or 2;
Y represents, independently from each other, halogen, C-4 alkyl, C1-4alkoxy, C1-4halogenated, cyano, nitro, amino, C1-4alkylcarboxylic, benzoylamine or1-4alkoxycarbonyl; m is 0 or 1; and
G represents a heterocyclic group selected from the group consisting of the following groups from G-1 to G-9:


where
Z represents halogen, methyl, methylthio, trifluoromethyl, cyano, nitro or amino; and
n is 0 or 1.

2. Compounds according to claim 1, in which
And represents C or N;
R represents a trifluoromethyl or pentafluoroethyl;
X represents, independently of one another, fluorine, chlorine, bromine or trifluoromethyl;
1 is equal to 0, 1 or 2;
Y represents, independently from each other, halogen, C1-2alkyl, C1-2alkoxy, C1-2halogenated, cyano, nitro, amino, C1-2alkylcarboxylic, benzoylamine or1-2alkoxycarbonyl;
m is 0 or 1; and
G is selected from heterocyclic groups represented by the formulas from G-1 to G-9:

where
Z represents halogen, methyl, methylthio, trifluoromethyl, cyano, nitro or amino; and
n is 0 or 1.

3. Composition for combating harmful insects or arthropods, containing at least one compound of formula (I) as the active connection.

4. A method of combating harmful insects, characterized in that at least one compound according to claim 1 or 2 influence of harmful insects and/or their habitat.

5. A method of combating harmful insects, characterized in that a composition according to claim 3 influence of harmful insects and/or their habitat.

6. The use of compounds according to claim 1 or 2 for pest insects.

7. The use of a composition according to claim 3 for pest insects.

8. The method of obtaining compounds of formula (I) according to claim 1, characterized in that the compound of formula (II)

in which A, Y, m and G have the same meanings as described in claim 1, and Hal means halogen,
subjected to interaction with the compound of the formula (III)

where R, X and l have the meanings as defined in claim 1,
in the presence of an inert solvent, and optionally in the presence of a base.

9. The method of obtaining compounds of formula (I) according to claim 1, from which causesa fact, the compound of formula (IV)

where A, R, X, l, Y and m have the meanings as defined in claim 1, and Hal means halogen, is subjected to the interaction with compounds of the formula (V)

where G has the meaning as indicated in claim 1,
in the presence of an inert solvent, and optionally in the presence of a base.

10. The compounds of formula (II)

where A, Y, m and G have the meanings as defined in claim 1, and Hal means halogen, which are intermediates for producing compounds of formula (I).

11. The compounds of formula (X)

where A, Y, m and G1have the meanings as defined in claim 1, provided that when a represents C, and m is 0, G1is not 1H-imidazol-1-yl, which are intermediates for producing compounds of formula (I).



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel azoles of general formula 1A and 1B and pharmaceutically acceptable salts thereof, having activity on hepatitis C and hepatitis GBV-C virus. Said compounds have NS5A viral protein ligand properties and can be used as active components for a pharmaceutical composition and a medicinal agent for treating diseases caused by said viruses. In general formula 1A and 1B, the solid lines accompanied by dotted lines denote a single or double bond, wherein if one of them is a single bond, the other is a double bond; X and Y optionally assume different values and denote a nitrogen, oxygen or sulphur atom or a NH group; R1 and R2 optionally denote identical radicals 2.1-2.20, in which the asterisk (*) indicates site of the bond to azole fragments. Said fragments and values of A and B are given in the claim.

EFFECT: more value of the compounds.

10 cl, 1 tbl, 16 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: this invention relates to new compounds with formula (I) possessing the properties of mGLuR2 antagonists, to their obtainment methods, their application for production of medicines for prevention and treatment of disorders wherein mGLuR2 plays the activation role (in particular - central nervous system disorders). In formula (I) either any of X and Y represents N while the other represents CH or each of X and Y represents N; A represents aryl representing phenyl or 5- or 6-membered heteroaryl containing in the cycle 1-3 atoms selected from among nitrogen, oxygen or sulphur, the heteroaryl selected from among amidazolyl, [1,2,4] oxadiazolyl, pyrrolyl, 1H-pyrazolyl, pyridinyl, [1,2,4] triazolyl, tiazolyl and pyrimidinyl, each of them substitutable by C1-6-alkyl; B represents H, cyano or represents a possibly substituted aryl selected from among phenyl or possibly substituted by 5- or 6-membered heteroaryl containing in the cycle 1-3 atoms selected from among nitrogen, oxygen or sulphur where the substitutes are selected from the group consisting of nitro, C1-6-alkyl, possibly substituted hydroxy, NRaRb where Ra and Rb independently represent H, C1-6-alkyl etc. R1 represents H, a halogen atom, C1-6-alkyl, possibly substituted hydroxy, C1-6-alcoxy, C1-6-halogenoalkyl, C3-6-cycloalkyl represents H cyano, a halogen atom, C1-6-halogenoalkyl, C1-6-alcoxy, C1-6-halogenoalcoxi-, C1-6-alkyl or C3-6-cycloalkyl R3 represents a halogen atom, H, C1-6-alcoxy, C1-6-halogenoalkyl, C1-6-alkyl, C3-6-cycloalkyl, C1-6-halogenoalcoxy R4 reprsents H or halogeno.

EFFECT: creation of new compounds of formula (I) possessing mGLuR2 antagonist properties.

104 cl, 465 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I)

, where: n equals 0, 1, 2; G denotes CH2, CHR3; R1 denotes H, C1-C6-alkyl, C3-C6-alkenyl, -CH2Ph; R2, R3, R4 independently denote H, CH3, -CH2F, -CHF2, CF3; A denotes 1,4-Ph, 1,3-Ph, which can be optionally substituted with 1-4 substitutes selected from halogen, C1-C4-alkyl, C1-C4alkoxy, fluorinated C1-C4-alkyl and fluorinated C1-C4alkoxy; E denotes NR5, where R5 denotes H, C1-C3-alkyl; Ar denotes a radical of formula

and

where: Ra denotes halogen, C1-C6-alkyl, fluorinated C1-C6-alkyl, C1-C6-alkoxy, fluorinated C1-C6-alkoxy, phenyl sulphonyl, CN, -NR6R7, where R6 and R7, together with an N atom, form a 5- or 6-member saturated ring or denotes a 5-member saturated or unsaturated aromatic or non-aromatic heterocyclic ring containing, as ring members, 1, 2 or 3 heteroatoms selected from N, O and S, and where the heterocyclic ring can carry 1, 2 or 3 substitutes selected from halogen and C1-C6-alkyl, or denotes a 6-member saturated heterocyclic ring containing, as ring members, one N and one O atom; Rb and Rc independently denote H, halogen, CH3, OCH3, CH2F, OCH2F, CHF2, OCHF2, CF3, OCF3, CH2CH2F, OCH2CH2F, CH2CHF2, OCH2CHF2, CH2CF3 or OCH2CF3; Rd denotes Ra or a 5- or 6-member heteroaromatic ring containing, as ring members, 1, 2 or 3 heteroatoms selected from N, O and S, and where the heteroaromatic ring can carry 1 substitute selected from C1-C6-alkyl and C1-C6-alkylthio; Re denotes H or is defined as Ra; Rf is defined as Ra; k equals 0, 1, 2, 3; j equals 0, 1, 2, 3, 4; provided that Ra does not denote F, CH2F, CHF2, CF3, OCF3, if A denotes 1,4-Ph, Ar denotes a radical of formula (A) and Rb and Rc denote H, halogen; except compounds, where R1 denotes propyl, G denotes CH2, n equals 1, A denotes 1,4- Ph, E denotes NH, Ar denotes a radical of formula (F) and Rd denotes halogen, C1-C6-alkyl, C2-C6-alkenyl or a 5-member heteroaromatic ring; and physiologically acceptable acid addition salts thereof.

EFFECT: compounds exhibit 5HT6 receptor simulating activity, which allows for their use in a pharmaceutical composition.

25 cl, 6 tbl, 107 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds specified in cl. 1, and also to a pharmaceutical composition possessing binding activity with respect to Bcl proteins, to applying the declared compounds for preparing a drug for treating cancer and for treating a bcl-mediated disorder.

EFFECT: use of the compounds as Bcl protein inhibitors.

18 cl, 2 tbl, 41 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula where R1, R2 and R3 are independently selected from a group consisting of hydrogen, halogen and lower alkyl containing 1-6 carbon atoms; R4 denotes a residue given in the claim; R5 denotes hydrogen or methyl; R10 is selected from a group consisting of: (i) hydrogen; (ii) (C1-C10) alkyl; (iii) (C1-C10)alkyl, substituted with one or more substitutes independently selected from a group consisting of -N(CH3)2, morpholinyl, (C1-C4) alkoxy, hydroxyl, -CON(CH3)2 and halogen; (iv) monocyclic (C3-C8) cycloalkyl containing one N heteroatom; (v) 9-methyl-9-azabicyclo[3.3.1]nonane; (vi) phenyl; (vii) phenyl substituted with one or more (C1-C4)alkoxy; R11 is selected from a group consisting of hydrogen and (C1-C10)alkyl; or R10, R11 and a nitrogen atom with which they are bonded, together, form a nitric heterocycle or a substituted nitric heterocycle, such as given in the claim. The invention also relates to a pharmaceutical composition, having serotonin type 3 receptor modulating capacity and a method of treating a disorder which depends on serotonin type 3 receptor modulation.

EFFECT: compounds of formula II as serotonin type 3 receptor modulators.

18 cl, 1 tbl, 159 ex

FIELD: chemistry.

SUBSTANCE: invention describes a compound of formula (I): or pharmaceutically acceptable salt thereof, or stereoisomer, in which: n equals 0 or 1; X denotes CH2, C=O; R1 denotes a) -(CH2)mR3 or -CO(CH2)mR3, where m equals 0, 1; and R3 denotes a 5-10-member aryl or heteroaryl, where the heteroaryl denotes a mono- or bicyclic aromatic ring containing 5-10 ring atoms, from which at least one or two atoms are heteroatoms selected oxygen, nitrogen or sulphur, optionally substituted with one or more halogens; b) -C=YR4, where Y denotes O; and R4 denotes: (C1-C10)alkyl; (C1-C10)alkoxy; (C0-C10)alkyl-(5-10-member heteroaryl), where "heteroaryl" denotes a mono- or bicyclic aromatic ring containing 5-10 ring atoms, from which at least one or two atoms are heteroatoms selected from oxygen, nitrogen or sulphur, said heteroaryl is optionally substituted with one or more substitutes selected from halogen, oxo or 2-(C1-C6)alkyl, where Z denotes S; (C0-C10)alkyl-(5-10-member aryl), said aryl is optionally substituted with one or more substitutes selected from halogen; (C1-C6)alkoxy, which itself is optionally substituted with one or more halogens; (C1-C6)alkyl, which itself is optionally substituted with one or more halogens; or -Z-(C1-C6)alkyl, where Z denotes S or SO2, and where said (C1-C6)alkyl can be optionally substituted with one or more halogens; or (C1-C6)alkyl-CO-O-R12, where R12 denotes H or (C1-C6)alkyl; or c) -C=ZNHR6, where Z denotes O or S; and R6 denotes: (C1-C10)alkyl; (C1-C10)alkoxy; 5-10-member aryl or heteroaryl, where "heteroaryl" denotes a bicyclic aromatic ring containing 9 ring atoms, from which at least one or two atoms are oxygen atoms; optionally substituted with one or more substitutes selected from halogen; cyano; (C1-C6)alkoxy, which itself is optionally substituted with one or more halogens; (C1-C6)alkyl, which itself is optionally substituted with one or more halogens; and R2 denotes H or (C1-C6)alkyl. Also described is a pharmaceutical composition for inhibiting TNFα, based on the compound of formula I.

EFFECT: novel compounds which can regulate production of certain cytokines, including TNF-α, are obtained and described.

27 cl, 81 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (IB) or to their pharmaceutically acceptable salts:

, wherein R means formula: R1 means -C(O)NR3R4, -C(O)R3 and -C(O)OR3; each R3 and R4 independently means H, C1-10 alkyl, wherein alkyl is optionally substituted by one -OH; R3 and R4 are bound together with N atoms to form a 5-6-member heterocyclic ring which additionally contains one O heteroatom; R5 means H; R6 means CN; R7 means H; W means C. What is described is a method for producing both them and intermediate compounds of formula (1-1c): , wherein: R1 means -C(O)NR3R4; R3 and R4 are specified above.

EFFECT: compounds (IB) shows DPP-IV inhibitory activity that allows them being used in a pharmaceutical composition.

9 cl, 12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of general formula (I) or its pharmaceutically acceptable salts which have action of mTOR inhibitors. What is also declared is preparing a pharmaceutical composition containing a therapeutically effective amount of the compound of formula (I) and a pharmaceutically acceptable carrier or diluent; besides, what is declared is the use of the compound of formula (I) or its pharmaceutically acceptable salts for preparing the drug for ensuring anticancer action.

EFFECT: preparing the pharmaceutically acceptable salts for preparing the drug for ensuring anticancer action.

11 cl, 25 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula I wherein the substitutes A, B, B', Q and R1-R5 in formula I are specified as follows: A and B' are one of the following groups: (i) (R6)N(CH2)n, wherein n is 0 or 1; (ii) (CH2)n, wherein n is 0, 1 or 2; (iii) C(O)(CH2)n, wherein n is 0 or 1; or provided each of A and B' represents nitrogen, together they can form a bivalent radical of formula: -(CH2)s-X1-(CH2)t- (a), wherein each s and t is independently 1 or 2, and X1 represents (CH2)n, wherein n is 0 or 1; B is one of the following groups: (i) (R6)N; (ii) oxygen; (iii) C=δ, wherein δ represents oxygen or sulphur; (iv) C(R6)=C(R7); each R6 and R7 independently represent hydrogen, C1-4-alkyl; R1 is specified in the following groups: (i) phenyl group substituted by one or more substitute such as: - halogen specified in F, CI, Br or I, or alkyl1 group; aryl1 or heteroaryl group1; cyano, NH-alkyl1, N(alkyl1)(alkyl1) and amino; - NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl group, or (ii) pyridinyl group which can be substituted by one substitute, such as halogen specified in I, F, Cl or Br; alkyl1 group; aryl1 group; cyano, NH-alkyl1, N(alkyl1)(alkyl1), and amino; -NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl1 group; each R2, R3, R4 and R5 are independently specified in hydrogen or linear or branched alkyl group containing 1 to 10 carbon atoms; Q is specified in the following groups: (i) alkyl1; (ii) aryl1; (iii) heteroaryl1. The compounds of formula (I) are used for preparing a drug showing the c-kit inhibitor properties and aiming at treating a disease specified in neoplastic, allergic, inflammatory and autoimmune diseases.

EFFECT: use of oxazole derivatives as tyrosine kinase inhibitors.

13 cl, 1 tbl, 31 ex

FIELD: chemistry.

SUBSTANCE: described are novel diaminotriazole compounds of general formula

(values of radicals are given in the claim), pharmaceutically acceptable salts thereof, a pharmaceutical composition containing said compounds, a method of inhibiting JAK2 and JAK3 kinase activity and use of the novel compounds to produce a medicinal agent for treating several diseases.

EFFECT: high efficiency of the compounds.

19 cl, 3 tbl, 26 ex

FIELD: chemistry.

SUBSTANCE: invention relates to use of 1,2,4-triazole derivatives of formula I:

, where R1, R2 and R3 independently denote hydrogen or halogen; R4 denotes C1-C6 alkyl; R5 and R6 independently denote C1-C6 alkyl or, together with a nitrogen atom to which they are bonded, form a 5-7-member heterocyclyl group, in which the 6-member heterocyclyl can further contain one oxygen or nitrogen atom and can be substituted with acetyl, C1-C6 alkyl or phyenyl; X-S-, -SO-, -SO2- or O; and n is a whole number selected from 1-8; or pharmaceutically acceptable salts, stereoisomers or solvates thereof, when producing a drug for treating or preventing sigma-1 receptor-mediated diseases or conditions, methods of producing said compounds, intermediate compounds and pharmaceutical compositions which contain compounds of formula 1.

EFFECT: improved compounds.

19 cl, 49 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds specified in cl. 1, and also to a pharmaceutical composition possessing binding activity with respect to Bcl proteins, to applying the declared compounds for preparing a drug for treating cancer and for treating a bcl-mediated disorder.

EFFECT: use of the compounds as Bcl protein inhibitors.

18 cl, 2 tbl, 41 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed compound relates to novel biaryl-meta-pyrimidine, corresponding to structure (A) and their pharmaceutically acceptable salts. In structure (A): X is selected from group consisting of bond O, and CH2, and Y represents bond; or X and Y together can represent bond; each R1 and R2 independent on each other are selected from group consisting of H and unsubstituted C1-C6alkyl; each of p, q, r, n, m independent on each other represents integer number 0 or 1; G0 is selected from group consisting from N and CH; each G represents independently CH, N, CR6 or C, when bound with X, on condition that not more than two groups of G represent N, and each R6 does not depend on another R6; R5 represents methyl, Values of other radicals are given in the invention formula.

EFFECT: compounds possess inhibiting activity with respect to family of JAK kinases, in particular JAK2 kinases, and can be used in treatment of myeloproliferative disease, which results from genetic or protein fusions, as a result of increase of function of kinase from family of JAK kinases in cell signal transmission, as well as in treatment of true polycythemia, primary thrombocytopenia, myeloid fibrosis with myeloid metaplasia, proliferative diabetic retinopathy, cancer or eye diseases.

66 cl, 2 tbl, 246 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula where R1, R2 and R3 are independently selected from a group consisting of hydrogen, halogen and lower alkyl containing 1-6 carbon atoms; R4 denotes a residue given in the claim; R5 denotes hydrogen or methyl; R10 is selected from a group consisting of: (i) hydrogen; (ii) (C1-C10) alkyl; (iii) (C1-C10)alkyl, substituted with one or more substitutes independently selected from a group consisting of -N(CH3)2, morpholinyl, (C1-C4) alkoxy, hydroxyl, -CON(CH3)2 and halogen; (iv) monocyclic (C3-C8) cycloalkyl containing one N heteroatom; (v) 9-methyl-9-azabicyclo[3.3.1]nonane; (vi) phenyl; (vii) phenyl substituted with one or more (C1-C4)alkoxy; R11 is selected from a group consisting of hydrogen and (C1-C10)alkyl; or R10, R11 and a nitrogen atom with which they are bonded, together, form a nitric heterocycle or a substituted nitric heterocycle, such as given in the claim. The invention also relates to a pharmaceutical composition, having serotonin type 3 receptor modulating capacity and a method of treating a disorder which depends on serotonin type 3 receptor modulation.

EFFECT: compounds of formula II as serotonin type 3 receptor modulators.

18 cl, 1 tbl, 159 ex

FIELD: chemistry.

SUBSTANCE: invention relates to specific derivatives of bicyclic amides disclosed in the claim, as well as a pharmaceutical composition.

EFFECT: compounds having protein kinase inhibiting activity, meant for use in treating protein kinase-dependant diseases, preferably proliferative diseases such as tumorous diseases.

13 cl, 115 ex

FIELD: chemistry.

SUBSTANCE: described are novel 7-member heterocyclic compounds of general formula (values of radicals are given in the claim) or salts thereof or solvates thereof having chymase inhibiting activity and suitable for preventing or treating different diseases in which chymase is involved, a method of producing said compounds, intermediate compounds and a pharmaceutical composition for preventing or treating diseases in which chymase is involved, including compounds of formula (I) or pharmaceutically acceptable salts or solvates thereof.

EFFECT: improved properties of the compound.

23 cl, 12 tbl, 308 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula I wherein the substitutes A, B, B', Q and R1-R5 in formula I are specified as follows: A and B' are one of the following groups: (i) (R6)N(CH2)n, wherein n is 0 or 1; (ii) (CH2)n, wherein n is 0, 1 or 2; (iii) C(O)(CH2)n, wherein n is 0 or 1; or provided each of A and B' represents nitrogen, together they can form a bivalent radical of formula: -(CH2)s-X1-(CH2)t- (a), wherein each s and t is independently 1 or 2, and X1 represents (CH2)n, wherein n is 0 or 1; B is one of the following groups: (i) (R6)N; (ii) oxygen; (iii) C=δ, wherein δ represents oxygen or sulphur; (iv) C(R6)=C(R7); each R6 and R7 independently represent hydrogen, C1-4-alkyl; R1 is specified in the following groups: (i) phenyl group substituted by one or more substitute such as: - halogen specified in F, CI, Br or I, or alkyl1 group; aryl1 or heteroaryl group1; cyano, NH-alkyl1, N(alkyl1)(alkyl1) and amino; - NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl group, or (ii) pyridinyl group which can be substituted by one substitute, such as halogen specified in I, F, Cl or Br; alkyl1 group; aryl1 group; cyano, NH-alkyl1, N(alkyl1)(alkyl1), and amino; -NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl1 group; each R2, R3, R4 and R5 are independently specified in hydrogen or linear or branched alkyl group containing 1 to 10 carbon atoms; Q is specified in the following groups: (i) alkyl1; (ii) aryl1; (iii) heteroaryl1. The compounds of formula (I) are used for preparing a drug showing the c-kit inhibitor properties and aiming at treating a disease specified in neoplastic, allergic, inflammatory and autoimmune diseases.

EFFECT: use of oxazole derivatives as tyrosine kinase inhibitors.

13 cl, 1 tbl, 31 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula

and ,

where the ring X represents benzole or pyridine; R1 represents substituted alkyl; R2 represents optionally substituted aryl or optionally substituted 4-7-member monocyclic heterocyclic group or optionally substituted condensed group of heterocyclic group with the benzole ring where the substitutes of optionally substituted aryl, optionally substituted 4-7-member monocyclic heterocyclic group and optionally substituted condensed group of heterocyclic group with the benzole ring are selected from a group consisting of; (1) alkyl optionally substituted by a group selected from halogen and alkoxycarbonyl, (2) alkoxy optionally substituted by halogen, (3) halogen, (4) 4-7-member monocyclic heterocyclic group or (5) amino, optionally mono- or disubstituted alkyl, and (6) hydroxyl, R3 represents hydrogen or alkyl: R4 represents hydrogen, halogen or alkyl; R5 represents hydrogen or alkyl; R6 and R7 are identical or different, and each represents hydrogen or halogen; or pharmaceutically acceptable salt. Also, the invention refers to a IKur blocker containing the compounds described above as an active ingredient, and also to a preventive and therapeutic agent for cardiac arrhythmia and atrial fibrillation.

EFFECT: there are produced and described new compounds applicable as a IKur blocker effective for preventing or treating cardiac arrhythmia, such as atrial fibrillation.

12 cl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

,

and pharmaceutically acceptable salts and solvates thereof, in which R1 is an optionally substituted alkyl or similar, R2 is a group of formula: -Y-R5, where Y is -O- or S; R5 is a substituted alkyl (the substitute is an optionally substituted cycloalkyl or similar), a branched alkyl or similar; R4 is hydrogen or C1-10 alkyl; R3 is a group of formula: -C(=O)-Z-R6, where Z is -NR7- or -NR7-W-; R6 is an optionally substituted cycloalkyl or similar; R7 is hydrogen or C1-10 alkyl, W is C1-10 alkylene; X is =N- provided that a compound in which R2 is 2-(4-morpholino)ethoxy, 2-, 3- or 4-pyridylmethoxy, 1-methylpiperidinyl-2-methoxy, benzyloxy or 4-substituted benzyloxy is excluded; and R3 is N-(1-adamantyl)carbamoyl, N-(2-adamantyl)carbamoyl and N-(3-noradamantyl)carbamoyl. Said compound is an 11β-hydroxysteroid dehydrogenase type 1 inhibitor. The invention also relates to a pharmaceutical composition containing said compound as an active ingredient.

EFFECT: improved properties of the compound.

23 cl, 72 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound of general formula I

,

and a pharmaceutically acceptable salt thereof, where X denotes CH2, CHF or S, Y denotes CN, R1, R2, R3 and R4 denotes hydrogen, n equals 1, m equals 0 or 1, R denotes R11, R12 or R13, where R11 includes at least one group selected from the following b) or c), where optionally substituted heterocyclic and heteroaryl groups are bonded with a noradamantyl part either directly or through a methylene adjacent group or a C-C bond or C-N bond; b) the substituted 5-member heteroaryl group, in which the heteroaryl ring is a monocyclic aromatic ring system, includes two or more heteroatoms selected from nitrogen and oxygen; c) the heterocyclic group is optionally substituted with a C1-C3 alkyl or oxo group, where the heterocyclic ring system is a 5-9-member mono- or bicyclic ring system with one or more heteroatoms selected from a group consisting of nitrogen and sulphur, where heteroatoms can also be present as functional groups, where the heterocyclic ring system can contain one or two double bonds, and where the monocyclic heterocyclic ring can be condensed with a phenyl ring, R12 is selected from hydrogen, halogen, hydroxy, amino and C1-C4 alkoxy; R13 is a substituted phenyl, where the substitutes, which can be identical or different, include at least one group selected from a) hydrogen; b) nitro, amino; c) the saturated or unsaturated monocyclic heterocyclic ring system is optionally substituted with one or more groups selected from C1-C3 alkyl and oxo, where the heterocyclic ring system is a 5-member ring with one or more heteroatoms selected from a group consisting of nitrogen and sulphur, where the heteroatoms can also be present as functional groups. The present invention also relates to a pharmaceutical composition having dipeptidyl peptidase IV inhibiting activity, methods of obtaining the novel compound of formula I and use in treating type II diabetes and diabetic complications as well as for treating dyslipidaemia, hypercholesteremia, obesity and hyperglycaemia.

EFFECT: novel dipeptidyl peptidase IV inhibitors.

10 cl, 1 tbl, 43 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula

, where the dotted line in the 6-member nitrogen-containing ring Z of formula (I) (said ring Z consists of ring atoms numbered 1 to 6) indicates that a double bond is either present in the 3,4-position of the ring Z of formula (I), or a double bond is absent in ring Z of formula (I); and where the double bond may be present in the 3,4-position of the ring Z of formula (I); or: the double may be absent in ring Z of formula (I) if: i) X denotes N or N+-O-, or ii) V denotes -O-CH2-Q-, or iii) W denotes para-substituted phenyl or para-substituted pyridinyl, and V denotes pyrrolidinyl of formula:

X denotes CH, N, or N+-O-; W denotes para-substituted phenyl or para-substituted pyridinyl; V denotes -O-CH2-Q-, where Q is bonded with a group U of formula (I), or V denotes pyrrolidinyl of formula:

U denotes mono-, di-, tri- or tetra-substituted aryl, where the substitutes are independently selected from C1-7-alkyl and halogen; Q denotes a five-member heteroaryl with two or three heteroatoms independently selected from O and N; R1 denotes C1-7-alkyl or cycloalky; R2 denotes halogen or C1-7-alkyl; R3 denotes halogen or hydrogen; R4 denotes C1-7-alkyl-O-(CH2)0-4-CH2-; R'R"N-(CH2)0-4-CH2-, where R' and R" are independently selected from a group consisting of hydrogen, C1-7-alkyl (optionally substituted with one-three fluorine atoms), cyclopropyl (optionally substituted with one-three fluorine atoms), cyclopropyl- C1-7-alkyl (optionally substituted with one-three fluorine atoms) and -C(=O)-R"', where R'" denotes C1-4-alkyl, C1-4-alkoxy, -CH2-CF3, or cyclopropyl; or R12NH-C(=O)·(O)0-1-(CH2)0-4-, where R12 denotes C1-4-alkyl or cyclopropyl; and n equals 0; and salts thereof. The invention also relates to a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds having inhibiting effect on renin.

21 cl, 112 ex

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