Application of pyrimidine compounds for making antiparasitic agents

FIELD: medicine.

SUBSTANCE: method of mite controlling in warm-blooded animals includes introduction to the specified mammal of compound of formula I wherein R1 means hydrogen; R2 and R3 independently mean hydrogen or formyl; R4, R5, R6, R7, R8, R9, R10, R11, R12 and R13 independently mean hydrogen, halogen, nitrogroup, C1-C2alkyl or halogenC1-C2alkyl; both X1 and X2 mean O.

EFFECT: improvement of the method.

5 cl, 4 tbl, 6 ex

 

The present invention relates to the use of 4,6-disubstituted 5-aminopyrimidine compounds of the formula

in which

R1denotes hydrogen, halogen, cyano, HE, SH, NO2, COOH, COOR2, CONH2, CONR2R3, SO3N, SO2NR2R3C1-C6alkyl, halo,-C1-C6alkyl, C1-C6alkoxygroup, halo,-C1-C6alkoxygroup,2-C6alkenyl, halo,-C2-C6alkenyl,2-C6quinil,3-C6cycloalkyl, halo,-C3-C6cycloalkyl,3-C6cycloalkylation,3-C6cycloalkylation,2-C6alkenylacyl, halo,-C2-C6alkenylacyl, C1-C6allylthiourea, halo,-C1-C6allylthiourea, C1-C6alkylsulfonates, halo,-C1-C6alkylsulfonates, C1-C6alkylsulfonyl, halo,-C1-C6alkylsulfonyl, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C2-C6altertekhnogrupp, halo,-C2-C6altertekhnogrupp,2-C6alkanesulfonyl, halo,-C2-C6alkanesulfonyl,2-C6alkanesulfonyl, halo,-C2-C6alkanesulfonyl, NR2R3, nezam the seal or one-Patsany aryl or unsubstituted or substituted hetaryl, however substituents selected from the group comprising halogen, cyano, HE, SH, NO2, COOH, COOR2, CONH2, CONR2R3, SO3N, SO2NR2R3C1-C6alkyl, halo,-C1-C6alkyl, C1-C6alkoxygroup, halo,-C1-C6alkoxygroup,2-C6alkenyl,

halo-C2-C6alkenyl,2-C6quinil,3-C6cycloalkyl, halo,-C3-C6cycloalkyl,3-C6cycloalkylation,3-C6cycloalkylation,2-C6alkenylacyl, halo,-C2-C6alkenylacyl, C1-C6allylthiourea, halo,-C1-C6allylthiourea, C1-C6alkylsulfonates, halo,-C1-C6alkylsulfonates, C1-C6alkylsulfonyl, halo,-C1-C6alkylsulfonyl, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C2-C6altertekhnogrupp, halo,-C2-C6altertekhnogrupp,2-C6alkanesulfonyl, halo,-C2-C6alkanesulfonyl,2-C6alkanesulfonyl, halo,-C2-C6alkanesulfonyl and NR2R3,

R2and R3independently of one another denote hydrogen, C1-C6alkyl, halo,-C1-C6alkyl, formyl, C1-C 6alkylsulphonyl, halo,-C1-C6alkylsulphonyl, C1-C6alkoxycarbonyl, halo,-C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl, di-C1-C6alkylaminocarbonyl or unsubstituted or one-Patsany benzyl, the substituents of which, when it is substituted, selected from the group comprising halogen, cyano, HE, SH, NO2, COOH, COOR2, CONH2, CONR2R3, SO3H, SO2NR2R3C1-C6alkyl, halo,-C1-C6alkyl, C1-C6alkoxygroup, halo,-C1-C6alkoxygroup,2-C6alkenyl, halo,-C2-C6alkenyl,2-C6quinil,3-C6cycloalkyl, halo,-C3-C6cycloalkyl,3-C6cycloalkylation,3-C6cycloalkylation,2-C6alkenylacyl, halo,-C2-C6alkenylacyl, C1-C6allylthiourea, halo,-C1-C6allylthiourea, C1-C6alkylsulfonates, halo,-C1-C6alkylsulfonates, C1-C6alkylsulfonyl, halo,-C1-C6alkylsulfonyl, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C2-C2altertekhnogrupp, halo,-C2-C6altertekhnogrupp,2-C6alkenylacyl the Nile, halo-C2-C6alkanesulfonyl,2-C6alkanesulfonyl and halo-C2-C6alkanesulfonyl,

R4, R5, R6, R7, R8, R9, R10, R11, R12and R13independently of one another denote hydrogen, halogen, a cyano, a nitro-group, HE, SH, NO2, COOH, COOR2, CONH2, CONR2R3, SO3N, SO2NR2R3C1-C6alkyl, halo,-C1-C6alkyl, C1-C6alkoxygroup, halo,-C1-C6alkoxygroup,2-C6alkenyl, halo,-C2-C6alkenyl,2-C6quinil,3-C6cycloalkyl,2-C6alkenylacyl, halo,-C2-C6alkenylacyl, C1-C6allylthiourea, halo,-C1-C6allylthiourea, C1-C6alkylsulfonates, halo,-C1-C6alkylsulfonates, C1-C6alkylsulfonyl, halo,-C1-C6alkylsulfonyl, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C2-C6altertekhnogrupp, halo,-C2-C6altertekhnogrupp,2-C6alkanesulfonyl, halo,-C2-C6alkanesulfonyl,2-C6alkanesulfonyl, halo,-C2-C6alkanesulfonyl, C1-C6alkylamino, di-C1-C alkylamino, C1-C6alkylsulfonamides, halo,-C1-C6alkylsulfonamides, C1-C6alkylsulphonyl, halo,-C1-C6alkylsulphonyl, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl, di-C1-C6alkylaminocarbonyl, unsubstituted or one-Patsany aryl or unsubstituted or substituted hetaryl, with substituents selected from the group comprising halogen, cyano, HE, SH, NO2, COOH, COOR2, CONH2, CONR2R3, SO3H, SO2NR2R3C1-C6alkyl, halo,-C1-C6alkyl, C1-C6alkoxygroup, halo,-C1-C6alkoxygroup,2-C6alkenyl, halo,-C2-C6alkenyl,2-C6quinil,3-C6cycloalkyl, halo,-C3-C6cycloalkyl,3-C6cycloalkylation,3-C6cycloalkylation,2-C6alkenylacyl, halo,-C2-C6alkenylacyl, C1-C6allylthiourea, halo,-C1-C6allylthiourea, C1-C6alkylsulfonates, halo,-C1-C6alkylsulfonates, C1-C6alkylsulfonyl, halo,-C1-C6alkylsulfonyl, C1-C6alkylsulfonyl, halo-C1-C6alkylsulfonyl, C2-C6altertekhnogrupp, halo-C2-C6altertekhnogrupp,2-C6alkanesulfonyl, halo,-C2-C6alkanesulfonyl,2-C6alkanesulfonyl, halo,-C2-C6alkanesulfonyl and NR2R3,

X1and X2independently of one another denote C(R14)(R15), NR14, O, S, SO or SO2and

R14and R15independently of one another denote hydrogen, C1-C6alkyl, formyl, C1-C6alkylsulphonyl or halo-C1-C6alkylsulphonyl,

to combat parasites, especially ticks, animals, primarily in productive livestock and domestic animals, and also relates to pesticidal compositions containing at least one of these compounds.

From the literature, for example from WO 98/54154, WO 00/49001, WO 02/24663 or US 6342499, various known compounds that have been proposed for use as active substances with pesticidal properties. However, such active substances not fully satisfy their biological properties, all demands in the field of pest control, and therefore in this area, there remains a need in active substances with pesticidal properties, especially for combating ectoparasites. According to the invention this problem can be solved through application of the above compounds of formula I.

In the above values of the substituents alkyl as individual groups and as structural element of other groups and compounds, such as halogenated, alkylamino, alkoxygroup, allylthiourea, alkylsulfonyl and alkylsulfonyl, is in each case based on the number of carbon atoms in a particular group or a particular connection or remotemachine, for example, represents methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl or octyl, or branched, for example, represents isopropyl, isobutyl, sec-botep, tert-butyl, isopentyl, neopentyl or isohexyl.

Cycloalkyl as individual groups and as structural element of other groups and compounds, such as halachically, cycloalkanes and cycloalkylation, represents in each case based on the number of carbon atoms in a particular group or a particular connection cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl.

Alkenyl as individual groups and as structural element of other groups and compounds-is, in each case based on the number of carbon atoms in a particular group or a particular connection and conjugated or isolated double bonds or remotemachine, for example, represents allyl, 2-b, the Tennille, 3-pentenyl, 1-hexenyl, 1-heptenyl, 1,3-hexadienyl or 1,3-octadiene, or branched, for example, is Isopropenyl, Isobutanol, isoprenyl, tert-pentenyl, isohexanol, isoheptane or isooctanol.

Quinil as individual groups and as structural element of other groups and compounds-is, in each case based on the number of carbon atoms in a particular group or a particular connection and conjugated or isolated double bonds or remotemachine, for example, represents propargyl, 2-butynyl, 3-pentenyl, 1-hexenyl, 1-heptenyl, 3-HEXEN-1-inyl or 1.5-heptadien-3-inyl, or branched, for example, is a 3-methylbut-1-inyl, 4-ethylpent-1-inyl, 4-metrex-2-inyl or 2-methylhept-3-inyl.

Aryl represents phenyl or naphthyl.

Hetaryl represents pyridyl, pyrimidyl, s-triazinyl, 1,2,4-triazinyl, thienyl, furanyl, peril, pyrazolyl, imidazolyl, thiazolyl, triazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, benzothiazyl, benzofuranyl, benzothiazolyl, indolyl or indazole, preferably pyridyl, pyrimidyl, peril, imidazolyl or furanyl primarily pyridyl or pyrimidyl.

Halogen (respectively, the "halo") generally represents fluorine, chlorine, bromine or iodine. The same applies to the halogen component of other groups, such as Gal is alkyl.

Halogen-substituted carbon-containing groups and compounds may be partially halogenated or perhalogenated, with halogen substituents in the case of polygalacturonase may be identical or different. Examples of haloalkyl as individual groups and as structural element of other groups and compounds, such as haloalkoxy or haloalkylthio, are methyl, which as substituents contains from one to three fluorine atoms, chlorine and/or bromine, for example F2or CF3, ethyl, which as substituents contains from one to five fluorine atoms, chlorine and/or bromine, such as CH2CF3, CF2CF3, CF2CCl3, CF2CHCl2, CF2CHF2, CF2CFCl2, CF2ADHD2, CF2CHClF, CF2CHBrF or CClFCHClF, propyl or isopropyl, each of which as substituents contains from one to seven fluorine atoms, chlorine and/or bromine, such as CH2CHBrCH2Br, CF2CHFCF3CH2CF2CF3or CH(CF3)2, butyl or one of its isomers, each of which as substituents contains from one to nine atoms of fluorine, chlorine and/or bromine, such as CF(CF3)FF3or CH2(CF2)2CF3pencil or one of its isomers, each of which is diversified as substituents contains from one to eleven fluorine atoms, chlorine and/or bromine, such as CF(CF3)(F)2CF3or CH2(CF2)3CF3and hexyl or one of its isomers, each of which as substituents contains from one to thirteen fluorine atoms, chlorine and/or bromine, for example (CH2)4Snugs2Br, CF2(F)4CF3CH2(CF2)4CF3or(CF3)2(F)2CF3.

Alkoxygroup preferably have a chain length of from 1 to 6 carbon atoms. As examples of alkoxygroup can be called methoxy-, ethoxy-, propoxy-, isopropoxy, h-butoxy, isobutoxy-, second -, butoxy - and tert-butoxypropyl, as well as the isomers of pentyloxy and hexyloxy, preferable at this methoxy - and ethoxypropan. Haloalkoxy preferably have a chain length of from 1 to 6 carbon atoms. As examples of haloalkoxy can be called formatosi, deformedarse, triptoreline-, 2,2,2-triptoreline-, 1,1,2,2-tetrafluoroethoxy-, 2-floratone-, 2-chloroethoxy-, 2,2-diflorasone - and 2,2,2-trichlorethene, the preferred of which deformedarse-, 2-chloroethoxy and tripterocarpa.

Preferred according to the invention compounds are the following:

(1) compound of formula I, in which R1denotes hydrogen, halogen, NO2C1-C6alkyl, halo,-C1-C 6alkyl, C1-C6alkoxygroup, halo,-C1-C6alkoxygroup,3-C6cycloalkyl, halo,-C3-C6cycloalkyl,3-C6cycloalkylation,3-C6cycloalkylation, C1-C6allylthiourea, halo,-C1-C6allylthiourea, unsubstituted or one-Patsany aryl or unsubstituted or substituted hetaryl, more preferably denotes hydrogen, halogen, NO2C1-C6alkyl, halo,-C1-C6alkyl, C1-C6alkoxygroup or halo-C1-C6alkoxygroup, particularly preferably hydrogen, C1-C6alkyl or C1-C6alkoxygroup;

(2) the compound of the formula I, in which R2and R3independently of one another denote hydrogen, C1-C6alkyl, formyl, C1-C6alkylsulphonyl, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl, di-C1-C6alkylaminocarbonyl or unsubstituted or one-Patsany benzyl, more preferably independently of one another denote hydrogen, C1-C4alkyl, formyl, C1-C4alkylsulphonyl or benzyl, particularly preferably independently of one another denote hydrogen, C1-C2alkyl, formyl or benzyl;

(3) the compound of the formula I, in which R4, R5, R6/sub> , R7, R8, R9, R10, R11, R12and R13independently of one another denote hydrogen, halogen, a cyano, a nitro-group, C1-C6alkyl, halo,-C1-C6alkyl, C1-C6alkoxygroup, halo,-C1-C6alkoxygroup,3-C6cycloalkyl, C1-C6allylthiourea, halo,-C1-C6allylthiourea, unsubstituted or one-Patsany aryl or unsubstituted or substituted hetaryl, more preferably independently of one another denote hydrogen, halogen, a nitro-group, C1-C4alkyl, halo,-C1-C4alkyl, C1-C4alkoxygroup or halo-C1-C4alkoxygroup, particularly preferably independently of one another denote hydrogen, halogen, a nitro-group, C1-C2alkyl or halo-C1-C2alkyl, most preferably independently of one another denote hydrogen, halogen, the nitro-group or CF3;

(4) the compound of the formula I, in which X1and X2independently of one another denote NR14, O or S, more preferably independently of one another denote NH, O or S, particularly preferably About;

(5) the compound of the formula I, in which R14and R15independently of one another denote hydrogen, C1-C4alkyl, formyl, C1-C4alkylsulphonyl, bol is e preferably independently of one another denote hydrogen or C 1-C4alkyl, particularly preferably hydrogen;

(6) the compound of the formula I, in which R1denotes hydrogen, halogen, C1-C6alkyl, halo,-C1-C6alkyl, C1-C6alkoxygroup, halo,-C1-C6alkoxygroup,3-C6cycloalkyl, halo,-C3-C6cycloalkyl,3-C6cycloalkylation,3-C6cycloalkylation, C1-C6allylthiourea or halo-C1-C6allylthiourea, R2and R3independently of one another denote hydrogen, C1-C6alkyl, formyl, C1-C6alkylsulphonyl, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl, di-C1-C6alkylaminocarbonyl or benzyl, R4, R5, R6, R7, R8, R9, R10, R11, R12and R13independently of one another denote hydrogen, halogen, a cyano, a nitro-group, C1-C6alkyl, halo,-C1-C6alkyl, C1-C6alkoxygroup, halo,-C1-C6alkoxygroup,3-C6cycloalkyl, C1-C6allylthiourea, halo,-C1-C6allylthiourea, unsubstituted or one-Patsany aryl or unsubstituted or substituted hetaryl, X1and X2independently of one another denote NR14, O or S and R14indicates bodoro is, C1-C4alkyl, formyl, C1-C4alkylsulphonyl;

(7) the compound of the formula I, in which R1denotes hydrogen, halogen, NO2C1-C6alkyl, halo,-C1-C6alkyl, C1-C6alkoxygroup or halo-C1-C6alkoxygroup, R2and R3independently of one another denote hydrogen, C1-C4alkyl, formyl, C1-C4alkylsulphonyl or unsubstituted or one-Patsany benzyl, R4, R5, R6, R7, R8, R9, R10, R11, Rl2and R13independently of one another denote hydrogen, halogen, C1-C4alkyl, halo,-C1-C4alkyl, C1-C4alkoxygroup or halo-C1-C4alkoxygroup and X1and X2independently of one another denote NH, O or S;

(8) the compound of the formula I, in which R1denotes hydrogen, C1-C6alkyl or C1-C6alkoxygroup, R2and R3independently of one another denote hydrogen, C1-C2alkyl or formyl, R4, R5, R6, R7, R8, R9, R10, R11, Rl2and R13independently of one another denote hydrogen, halogen, NO2C1-C2alkyl or halo-C1-C2alkyl and X1and X2indicate On;

(9) the compound of the formula I, in which 1denotes hydrogen, C1-C6alkyl or C1-C6alkoxygroup, R2and R3independently of one another denote hydrogen, C1-C2alkyl or formyl, R4, R5, R6, R7, R8, R9, R10, R11, Rl2and R13independently of one another denote hydrogen, fluorine or CF3and X1and X2denote O.

According to the invention particularly preferred compounds of formula I listed below in table 1, and first of all compounds described below in the examples of synthesis.

Proposed in the invention the compounds of formula I, in each case in free form or in salt form, you can get way than, for example, the fact that the compound of the formula

which is a known compound or can be obtained analogously to corresponding known compounds and in which R1, R2and R3are indicated for the formula I values and Q1and Q2represent leaving groups, is subjected to the interaction with the compound of the formula

which is a known compound or can be obtained analogously to corresponding known compounds and in which R4, R5, R6, R7, R8and X2have you specified for the formula Znaczenia, and then the obtained intermediate compound in the future, i.e. after it has been pre-allocated, or directly, i.e. without isolation, is subjected to the interaction with the compound of the formula

which is a known compound or can be obtained analogously to corresponding known compounds and in which R9, R10, R11, R12, R13and X1are indicated for the formula I, values, and if necessary, the compound of formula I obtained in this way or that way, in each case in free form or in salt form is converted into another compound of formula I, share the resulting mixture of isomers and allocate the target isomer and/or a free compound of formula I, obtained as described above, transferred to salt or salt of the compounds of formula I, obtained as described above was transferred into the free compound of formula I or into another salt.

The above explanations about the salts of the compounds of formula I similarly apply to the salts of the parent compounds, the above and subsequent description.

Upon receipt of the proposed in the invention compounds discussed above reagents can be interaction between them as such, i.e. without addition of a solvent or diluent, e.g. the measures in the molten state. However, in most cases it may be appropriate to add to the reaction mixture an inert solvent or diluent or a mixture thereof. As examples of such solvents or diluents can be called aromatic, aliphatic and alicyclic hydrocarbons and halogenated hydrocarbons, such as benzene, toluene, xylene, mesitylene, tetralin, chlorobenzene, dichlorobenzene, Brabanthal, petroleum ether, hexane, cyclohexane, dichloromethane, trichloromethane, carbon tetrachloride, dichloroethane, trichloride or tetrachloride, ethers, such as diethyl ether, DIPROPYLENE ether, diisopropyl ether, disutility ether, tert-butyl methyl ether, onomatology ether of ethylene glycol, monotropy ether of ethylene glycol, dimethyl ether of ethylene glycol, dimethoxyethane ether, tetrahydrofuran or dioxane, ketones, such as acetone, methyl ethyl ketone or methyl isobutyl ketone, amides such as N,N-dimethylformamide, N,N-diethylformamide, N,N-dimethylacetamide, N is an organic or triamide hexamethylphosphoric acids, NITRILES, such as acetonitrile or propionitrile, and sulfoxidov, such as dimethylsulfoxide. It is preferable to use N,N-dimethylformamide, N is an organic or tetrahydrofuran.

Preferred leaving groups Q include halogen, mainly chlorine.

As an example, the OS is Avani, suitable for catalysis carried out in accordance with the proposed invention by way of the reaction include hydroxides, hydrides, amides, alkanoate, acetates, carbonates, dialkylamides or alkylsilane alkaline or alkaline earth metals, bonds alkylamines, alkylenediamines, optionally N-alkylated, optionally unsaturated cyclooctylamine, heterocyclic bases, ammonium hydroxides and carbocyclic amines. Specific examples of such bases include hydroxide, hydride, amide, methanolate, acetate and sodium carbonate, tert-butanolate, hydroxide, carbonate and potassium hydride, diisopropylamide lithium bis(trimethylsilyl)amide, potassium, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, Hinkley, N-methylmorpholine, hydroxide designed, and 1,5-diazabicyclo[5.4.0]undec-5-ene (DBU). Preferred among the above grounds sodium hydride or potassium carbonate.

The reaction is expediently carried out at a temperature of from about 60 to about 120°C., preferably from about 80 to about 100°C.

Salts of compounds of formula I can be obtained by a known method. So, for example, acid additive salts of compounds of the formula I get them treatment acceptable acid sludge is acceptable ion exchange reagent, and salts with bases - processing acceptable base or acceptable ion exchange reagent.

Salts of compounds of the formula I can in the usual way to turn into the free compounds of formula I, for which the acid-salt additive can, for example, to process acceptable ó agent or suitable ion exchange reagent, and salts with bases, for example, to process acceptable acid or suitable ion exchange reagent.

Salts of compounds of the formula I can in a known manner to transform into other salts of compounds of the formula I, with an acid additive salt can, for example, be converted into other acid additive salts, for example, treatment with a salt of an inorganic acid such as hydrochloride, acceptable metal salt such as a sodium, barium or silver salt, of an acid, for example with silver acetate, in an acceptable solvent in which the resulting inorganic salt, for example silver chloride, is insoluble and in the precipitates from the reaction mixture.

Depending on the specific methods and/or reaction conditions, the compounds of formula I having salt-forming properties can be obtained in free form or in the form of salts.

The compounds of formula I can also be obtained in the form of their hydrates and/or they may also contain other molecules solvent is th, who, for example, may optionally be used for the crystallization of compounds represented in solid form.

The compounds of formula I under certain conditions can be represented in the form of their possible optical and/or geometric isomers or as mixtures thereof. In accordance with this present invention relates to the pure isomers and to all possible mixtures of isomers, which means above and in the following description, even if in each individual case and not given specific details regarding the stereochemical structure of the compounds.

A mixture of diastereoisomeric compounds of the formula I obtained offered in the invention method, or otherwise, on the basis of differences in physico-chemical properties of the components of such mixtures to separate the known way, for example fractionated crystallization, distillation and/or chromatography, on a clean diastereoisomer.

Formed under appropriate conditions, a mixture of enantiomers can be divided into pure isomers known methods, for example by recrystallisation from an optically active solvent, by chromatography on chiral adsorbents, for example, liquid chromatography high pressure (ghvd) on the cellulose acetate, using suitable for this purpose microorganisms, by cleavage with specific immobilienangebote or formation of compounds include, for example using chiral crown ethers, in which case only one enantiomer forms a complex.

In addition to the separation of corresponding mixtures of isomers according to the invention, there is also the opportunity to get well-known methods of diastereoselective or enantioselective synthesis of pure diastereoisomers or enantiomers, for example by inclusion in the proposed invention, a method of starting materials (doctow) with the corresponding stereochemical structure.

In any case, it is preferable to select or synthesize biologically more active isomer, for example enantiomer, if the individual isomeric components have different biological activity.

In the implementation proposed in the invention method, it is preferable to use those starting materials and intermediate products, which allow to obtain the compounds of formula I, which are presented in the beginning of the description as the most preferred.

The present invention relates, in particular, those variants of the method of obtaining the proposed invention compounds, which are described below in the examples.

The present invention relates also to novel starting materials and intermediate products used according to the invention for receiving the Oia compounds of the formula I, to the use of these raw materials and intermediate products and the way they are received.

Proposed in the invention the compounds of formula I are particularly broad spectrum of activity and are valuable active ingredients that allow for the control of pests and parasites. Proposed in the invention compounds are most suitable for combating ectoparasites and to some extent also for combating endoparasites of animals, and in the hygiene sector, and yet have a good tolerance of warm-blooded animals.

According to the present invention under the ectoparasites refers, in particular, insects, mites (including Parasitiformes ticks) and crustaceans (sea lice). Such parasites include Lepidoptera, Coleoptera, Homoptera, Hemiptera, Heteroptera, Diptera, Dictyoptera, Thysanoptera, Orthoptera, Anoplura, Siphonaptera, Mallophaga, Thysanura, Isoptera, Psocoptera and Hymenoptera. However, it should be noted those ectoparasites that "annoy" people or animals and which are carriers of pathogens, for example flies such as Musca domestica, Musca vetustissima, Musca autumnalis, Fannia canicularis, Sarcophaga carnaria, Lucilia cuprina, Lucilia sericata, Hypoderma bovis, Hypoderma lineatum, Chrysomyia chloropyga, Dermatobia hominis, Cochliomyia hominivorax, Gasterophilus intestinalis, Oestrus ovis, biting flies such as Haematobia irritans irritans, Haematobia irritans exigua, Stomoxys calcitrans, horse-flies of the subfamily Tabanidae such as Haematoota spp.(for example, Haematopota pluvialis) and Tabanus spp.(e.g., Tabanus nigrovittatus), and the subfamily Chrysopsinae, such as Chrysops spp.(e.g., Chrysops caecutiens), Keds, such as Melophagus ovinus (sheep flies), flies TSE-TSE, such as Glossinia spp., other biting insects with small two-winged insects such as Ceratopogonidae (biting midges), Simuliidae (blackflies), Psychodidae (baboonery), and blood-sucking insects, such as blood-sucking mosquitoes, such as Anopheles spp., Aedes spp. Culex spp., fleas, such as Ctenocephalides felis and Ctenocephalides canis (cat fleas and dog, respectively), Xenopsylla cheopis, Pulex irritans, Ceratophylllus gallinae, Dermatophilus penetrans, lice (Anoplura), such as Linognathus spp., Haematopinus spp., Solenopotes spp., Pediculus humanis, and hematophagous biting (Mallophaga), such as Bovicola (Damalinia) ovis, Bovicola (Damalinia) bovis and other genera Bovicola spp. The ectoparasites are also the representatives of the order Acarina (mites)such as Chorioptes bovis, Cheyletiella spp., Dermanyssus gallinae, Demodex canis, Sarcoptes scabiei, Psoroptes ovis and Psorergates spp., including Parasitiformes ticks. As an example, well-known representatives of Parasitiformes mites can be called Boophilus, Amblyomma, Anocentor, Dermacentor, Haemaphysalis, Hyalomma, Ixodes, Rhipicentor, Margaropus, Rhipicephalus, Argas, Otobius, Ornithodoros, etc. that mainly infect warm-blooded animals, including farm animals, in particular cattle, horses, pigs, sheep and goats, poultry, in particular chickens, turkeys, Guinea fowls and geese, farmed fur-bearing animals such as mink, Lisi is, chinchillas, rabbits and the like, as well as room and Pets, such as cats and dogs, and humans.

Proposed in the invention the compounds of formula I are also effective on all or individual stages of development, not only with the normal sensitivity of pests and parasites, but also resistant to widely used parasiticides pests and parasites. This refers primarily to resistant parasiticides insects and representatives of the order Acarina. Insecticidal, ovicide and/or acaricidal action proposed in the invention of active substances can manifest itself directly, i.e. manifest in the destruction of pests and parasites, coming immediately after treatment or only after a certain period of time, for example during moulting, or destruction of their eggs, or indirectly, for example, be manifested in the reduction of the number of deposited eggs and/or the number of hatching from eggs of individuals, with good activity corresponds death (mortality) of at least 50-60% of pests and parasites.

The compounds of formula I can also be used for combating pests and parasites in the hygiene sector, especially to fight with representatives from the order of Diptera of the families Muscidae, Sarcophagidae, Anophilidae and Culicidae, from the order Orthoptera, from the order Dictyoptera (e.g., family Blattidae (cockroaches), such as Blatella germanica, Blatta orientalis, Periplaneta americana) and from the order Hymenoptera (e.g., families Formicidae (ants) and Vespidae (wasps)).

With the invention it has been unexpectedly found that its proposed compounds of formula I are also effective in combating ectoparasites of fish, primarily parasites of the subclass Copepoda (for example, from the group Siphonostognatoidae (sea lice), and at the same time is well tolerated by the fish.

Some compounds of formula I can also be active in the fight against certain types of worms. Combating helminths is economically important because they can cause serious diseases in mammals and poultry, such as sheep, pigs, goats, cattle, horses, donkeys, camels, dogs, cats, rabbits, Guinea pigs, hamsters, chickens, turkeys, Guinea fowls and other poultry bred in farms birds, as well as in ornamental birds. Typical representatives of nematodes are At, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostonum, Oesophagostonum, Charbertia, Trichuris, Strongylus, Trichonema, Dictyocaulus, Capillaria, Heterakis, Toxocara, Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxascaris and Parascaris. As an example of trematodes can, in particular, to refer to the members of the family Fasciolideae primarily Fasciola hepatica.

High pesticidal activity proposed in the invention compounds of formula I is manifested in the destruction (death the property) at least 50-60%, more preferably more than 90%, most preferably up to 95-100%, the above-mentioned parasites and pests of their total number. The compounds of formula I preferably apply inward and outward in an unmodified form or, preferably, together with auxiliary substances commonly used in cooking techniques preparative forms, and therefore, such compounds can be processed by known techniques to obtain, for example, liquid preparations (for example, drugs for point or drip treatment, samarasekara drugs for treatment of bulk drugs for aerosol spray or sprays, emulsions, suspensions, solutions, mulgirigala concentrates, concentrates, solutions), semi-solid drugs (e.g., creams, ointments, pastes, gels, liposomal preparations) and solid preparations (for example, feed additives, tablets, including, in particular, tablets, capsules, powders, including soluble powders, granules, preparations in which the active substance embedded in a polymer substance (matrix), in particular implants and microparticles). The type of drug, as well as methods of treatment are chosen in accordance with the objectives and the prevailing circumstances.

Preparative form, i.e. the preparations containing the active substance of the formula I or p is such active substances in combination with other active substances and, if necessary, solid, semi-solid or liquid excipient, get a known method, for example by homogeneous mixing and/or grinding the active substances with extenders, which, when clicked should take into account their physiological compatibility.

As solvents can be used, for example, alcohols (aliphatic and aromatic), such as benzyl alcohol, ethanol, propanol, isopropanol or butanol, fatty alcohols, such as alerby alcohol, glycols and their ethers and esters, such as glycerol, propylene glycol, dipropyleneglycol ether, ethylene glycol, onomatology or ethyl ether of ethylene glycol and buildinstall, ketones, such as propylene carbonate, cyclohexanone, isophorone or diacetolol alcohol, and glycols such as PEG 300. In addition to this formulation may contain strong polar solvents, such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide, or water, esters of fatty acids, such as etiloleat or isopropyl, vegetable oils, such as rapeseed, castor, coconut or soya oil, synthetic mono-, di - and triglycerides, such as glycerylmonostearate and triglycerides of medium chain length, and, when appropriate, silicone oils. The above substances may also serve as carriers for active is exist in a particular formulation.

As ointment bases, respectively, structure-forming ingredients you can use the following fillers: substances oil-based, such as petrolatum or waxes, fundamentals of wool waxes, such as lanolin or lanolin alcohols, glycols, such as macrogol, lipid basis, such as phospholipids, and triglycerides, such as hydrogensource vegetable oil.

In some cases, may also require the use of emulsifiers, wetting and conducive to the spread of drug through skin or wool cover animal agents, usually lecithins such as soybean lecithin, salts of fatty acids with alkaline earth and alkali metals, alkyl sulphates, such as cetylstearyl sodium, Khalatov, fatty alcohols such as cetyl alcohol, Sterol, such as cholesterol, esters of fatty acids, sorbitan and polyoxyethylene, such as Polysorbate 20, esters of fatty acids and sorbitan, such as sorbitanoleat, esters of fatty acids and ethers of fatty alcohols and polyoxyethylene such as simple proximally ether, block copolymers of polyoxypropylene and polyoxyethylene, such as PluronicTM, esters of sucrose, such as distearate sucrose esters of fatty acids and polyglycerol such to the to polyricinoleate, and esters of fatty acids, such as etiloleat or isopropylmyristate.

Formulation may also contain geleobrazovanie and thickeners, such as, for example, derivatives of polyacrylic acid, ethers of cellulose, polyvinyl alcohols, polyvinylpyrrolidone and highly dispersed silicon dioxide.

As a polymeric substances that provide a controlled release of active substances, it is possible to use derivatives, for example, polylactic acid, copolymer of lactic and glycolic acids, polyarteritis, polietilensorbit, polyanhydrides and starch, as well as matrix-based PVC.

In some cases, you may want to add activators percutaneous absorption (promoting skin penetration substances, such as ketones, sulfoxidov, amides, esters of fatty acids and fatty alcohols.

In addition, you can also add preservatives, such as sorbic acid, benzyl alcohol and parabens, and antioxidants, such as α-tocopherol.

The active ingredient or combination of active substances can also enter the body in the form of capsules, for example terdoslavich capsules or soft capsules.

As a binder in the manufacture of tablets and pills can be used chemically modified natural polymer substances which, soluble in water or alcohol, such as starch, cellulose or derivatives of proteins (for example, methylcellulose, carboxymethylcellulose, metilgidroxiatilzelllozu such proteins, as Zein, gelatin and the like), as well as synthetic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, etc. Tablets also contain fillers (e.g. starch, microcrystalline cellulose, sugar, lactose, etc.), lubricants (e.g. magnesium stearate) and leavening agents (e.g. cellulose derivatives) and is equipped with an acid-resistant coating, for example, acrylates.

Proposed in the invention the compounds of formula I can be used individually or in combination with other biocides. So, for example, to increase the effectiveness of these compounds can be combined with pesticides, have the same effect, or, for example, to broaden the spectrum of action of these compounds can be combined with substances that have a different action. In some cases, it may be advisable to add repellent substances, so-called repellents. Since the compounds of formula I are adulticide", i.e. the effective mainly in the fight against parasites, fully reached the adult stage of development (adult stage), it may be appropriate to add them to the pesticides that more is effective for combating parasites in the earlier stages of their development. This way you can fight with most of the population of parasites that cause significant economic damage. In addition, the combined effect would greatly impede the development of such parasites resistance to the active substances. Some combination of drugs can also show a synergistic effect, so it is possible to reduce the overall consumption rate of the active substance, that it is appropriate from an environmental point of view. A preferred group of active substances, and particularly preferred active substances, one or more of which may be used in combination with the compound of the formula I, described below.

Active ingredients suitable for use in a mixture with the proposed in the invention compounds are biocides such as insecticides and acaricides with different mechanism of action, which are listed below and are already quite well-known experts in this field, in particular chitin synthesis inhibitors, growth regulators, current-type juvenile hormone substances acting type adulticidal substances insecticide with a broad spectrum of action, acaricides with a wide range of actions and nematicides and well-known helminthology and insect repellent is x and/or mites substances, i.e. the aforementioned repellents or drugs, providing smoothcriminal parasites from the skin of the host.

As not limiting the scope of invention examples suitable for use in combination with the proposed invention the compounds of insecticides and acaricides include the following:

1. the abamectin11. AZ 6054122. BFMC
2. AC 30363012. azinphos And23. papenbrock
3. Arafat13. azinphos M24. bromophos And
4. acrinathrin14. azinphos-methyl25. bofenkamp
5. alankar15. azocyclotin26. buprofezin
6. aldicarb16. the toxin of Bacillus subtil.27. butocarboxim
7. α-cypermethrin17. bendiocarbTid
8. alphamethrin18. benfuracarb 29. cadusafos
9. amitraz19. bensultap30. carbaryl
10. avermectin B120. β-cyfluthrin31. the carbofuran
21. bifenthrin32. carbophenothion

33. cartap67. ethoprophos100. insecticide
34. cloethocarb68. etrimfosactive nematodes
35. chlorethoxyfos69. fenamiphos101. insecticide
36. chlorfenapyr70. fenamiphosactive viruses
37. chlorfluazuron71. finishin102. iprobenfos
38. chlormephos72. fenbutatin103. isofenphos
39. the chlorpyrifos73. penetration104. isoprobe the b
40. CIS-resmethrin74. fenobucarb105. isoxathion
41. claritin75. fanatical106. ivermectin
42. clofentezine76. fenoxycarb107. λ-cigalotrin
43. cyanophos77. fenpropathrin108. lufenuron
44. cicloprofen78. feneral109. Malathion
45. cyfluthrin79. fenpyroximate110. mecarbam
46. cyhexatin80. fenthion111. resolvents
47. D-234181. fenvalerate112. metaldehyde
48. deltamethrin82. fipronil113. methamidophos
49. demeton M83. fluazinam114. methiocarb
50. demeton S84. flu is suron 115. methomyl
51. demeton-S-methyl85. flucycloxuron116. methoprene
52. dichlofenthion86. flucythrinate117. metolcarb
53. declivous87. flufenoksuron118. mevinphos
54. dition88. plutopress119. milbemectin
55. diflubenzuron89. fonofos120. moxidectin
56. timeout90. formation121. naled
57. dimethylene91. fosthiazate122. NC 184
58. dioxathion92. tupfenrock123. NI-25, acetamiprid
59. DPX-MP06293. NSN124. nitenpyram
60. edifenphos94. heptenophos125. omethoate
61. emamectin 95. hexaflumuron126. oxamyl
62. endosulfan96. hexythiazox127. oxydemeton M
63. esfenvalerate97. the hydropreneCat
64. ethiofencarb98. Imidacloprid129. parathion
65. ation99. insecticide130. parathion-methyl
66. etofenproxactive mushrooms131. permethrin

132. pintout151. pyriproxifen170. thiodicarb
133. port152. RH-5992171. thiofanox
134. fosalan153. RH-2485172. thionazin
135. phosmet154. coalition173. thuringiensis
136. phoxim155. sabots 174. tralomethrin
137. pirimicarb156. selflove175. triuralin
138. pirimiphos And157. spinosad176. triazamate
139. pirimiphos M158. sulfotep177. triazophos
140. promecarb159. sulprofos178. treasure
141. propafol160. tebufenozide179. trichlorfon
142. propoxur161. tebufenpyrad180. triflumuron
143. prothiofos162. tebupirimfos181. timetaken
144. procoat163. teflubenzuron182. validation
145. pyraclofos164. tefluthrin183. KMK (3,5-
146. predatation165. temephosxylylenediisocyanate)
147. Pires is Erin 166. terramCar
148. feverfew167. terbufos185. YI 5301/5302
149. pyridaben168. tetrachlorvinphos186. ζ-cypermethrin
150. pyrimidifen169. titanox187. decamethrin

Below are not limiting the scope of invention examples suitable for use according to the invention of helminthoides, some members of which in addition to helminthoides action also possess insecticidal and acaricidal action and so partly mentioned in the above list:

(A1) praziquantel: 2-cyclohexylcarbonyl-4-oxo-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-α]isoquinoline;

(A2) closantel: 3,5-diid-N-[5-chloro-2-methyl-4-(a-cyano-4-Chlorobenzyl)phenyl]salicylamide;

(A3) triclabendazole: 5-chloro-6-(2,3-dichlorophenoxy)-2-methylthio-1H-benzimidazole;

(A4) levamisol: L-(-)-2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b]thiazole;

(A5) mebendazole: methyl ester (5-benzoyl-1H-benzimidazole-2-yl)carbamino acids;

(A6) omphalitis: macrocyclic enzymatic product of fungus Omphalotus olearius, described in WO 97/20857;

(A7) abamectin: avermectin B 1;

(A8) ivermectin: 22,23-dihydroavermectin B1;

(A9) moxidectin: 5-O-demethyl-28-deoxy-25-(1,3-dimethyl-1-butenyl)-6,28-epoxy-23-(methoxyimino)milbemycin;

(A10) doramectin: 25-cyclohexyl-5-O-demethyl-25-de(1-methylpropyl " avermectin A1a;

(A11) milbemectin: mixture milbemycin And3and milbemycin And4;

(A12) milbemycin: 5-oxime milbemectin.

Below are not limiting the scope of invention examples suitable for use according to the invention repellent substances (repellents and substances providing smoothcriminal parasites from the skin of the host):

(R1) DEET N,N-diethyl-m-toluamide;

(R2) KBR 3023: N-butyl-2-oxycarbonyl(2-hydroxy)piperidine;

(R3) Zemiata: N-2,3-dihydro-3-methyl-1,3-thiazol-2-ilidene-2,4-xylidene.

The above active substances that can be used in a mixture with the proposed in the invention compounds, the most well-known specialists in this field. Most of them are described in various publications Pesticide Manual, published by The British Crop Protection Council, London, a other is described in various editions of The Merck Index, published by Merck & Co., Inc., Rahway, New Jersey, USA, or in the patent literature. With this in mind, the list below is limited to some publications, which in the example described above active ingredients:

(I) O-methylcarbamoyl the m 2-methyl-2-(methylthio)propionic aldehyde (aldicarb) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., p.26;

(II) S-(3,4-dihydro-4-oksobenzo[d]-[1,2,3]triazine-3-ylmethyl)-O,O-dimethylphosphorodithioate (azinphos-methyl) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., p.67;

(III) ethyl-N-[2,3-dihydro-2,2-dimethylbenzofuran-7-jocstarbunny(methyl)aminothio]-N-isopropyl-β-alaninate (benfuracarb) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., pp.96;

(IV) 2-methylbiphenyl-3-ylmethyl-(Z)-(1RS)-CIS-3-(2-chloro-3,3,3-Cryptocom-1-enyl)-2,2-dimethylcyclopropanecarboxylate (bifenthrin) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., pp.118;

(V) 2-tert-Butylimino-3-isopropyl-5-phenyl-1,3,5-thiadiazine-4-one (buprofezin) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(VI) 2,3-dihydro-2,2-dimethylbenzofuran-7-illecillewaet (carbofuran) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(VII) 2,3-dihydro-2,2-dimethylbenzofuran-7-yl(dibutylamino)methyl-carbamate (carbosulfan) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(VIII) S,S'-(2-dimethylaminomethylene)-bis(THIOCARBAMATE) (cartap) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(IX) 1-[3,5-dichloro-4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenyl]-3-(2,6-differentail)urea (chlorfluazuron) is known from The Pesticide Manual, published by The British Crop Protection Concil, London 1997, 11th ed., s;

(X) O,O-diethyl-O-3,5,6-trichloro-2-pyridylacetate (chlorpyrifos) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XI) (RS)-α-cyano-4-fluoro-3-phenoxybenzyl-(1RS,3RS;1RS,3RS)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (cyfluthrin) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s.293;

(XII) mixture of (S)-α-cyano-3-phenoxybenzyl-(Z)-(1R,3R)-3-(2-chloro-3,3,3-tryptophanyl)-2,2-dimethylcyclopropanecarboxylate and (R)-α-cyano-3-phenoxybenzyl-(Z)-(1R,3R)-3-(2-chloro-3,3,3-tryptophanyl)-2,2-dimethylcyclopropanecarboxylate (λ-cigalotrin) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XIII) the racemate comprising (S)-α-cyano-3-phenoxybenzyl-(1R,3R)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate and (R)-α-cyano-3-phenoxybenzyl-(1S,3S)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (α-cypermethrin), known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XIV) a mixture of the stereoisomers of (S)-α-cyano-3-phenoxybenzyl-(1RS,3RS,1RS,3RS)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (ζ-cypermethrin) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XV) (S)-α-cyano-3-phenoxybenzyl-(1R,3R)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (deltamethrin) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XVI) (4-chlorophenyl)-3-(2,6-is iptorrents)urea (diflubenzuron) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XVII) (1,4,5,6,7,7-hexachloro-8,9,10-trinorborn-5-ene-2,3-rebismart)sulfite (endosulfan) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XVIII) α-ethylthio-o-trimethylarsine (ethiofencarb) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XIX) O,O-dimethyl-O-4-nitro-m-tolypocladium (fenitrothion) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XX) 2-second-butylphenylmethyl (fenobucarb) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXI) (RS)-α-cyano-3-phenoxybenzyl-(RS)-2-(4-chlorophenyl)-3-methylbutyrate (fenvalerate) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXII) S-[formyl(methyl)carbamoylmethyl]-O,O-dimethylphosphorodithioate (formation) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXIII) 4-methylthio-3,5-xylylenediisocyanate (methiocarb) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., p.813;

(XXIV) 7-chlorobicyclo[3.2.0]hepta-2,6-Dien-6-endimetriosis (heptenophos) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXV) 1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-imagenames (Imidacloprid) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXVI) 2-isopropylphenyl arbamate (isoprocarb) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXVII) O,S-dimethylphosphorodithioate (methamidophos) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXVIII) of S-methyl-N-(methylcarbamoyl)thioacetimidate (methomyl) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXIX) methyl-3-(diethoxyphosphoryloxy)but-2-ENOAT (mevinphos) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXX) O,O-diethyl-O-4-nitrophenylphosphate (parathion) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXXI) O,O-dimethyl-O-4-nitrophenylphosphate (parathion-methyl) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXXII) S-6-chloro-2,3-dihydro-2-oxo-1,3-benzoxazol-3-ylmethyl-O,O-diethylphosphonate (vocalon) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXXIII) 2-dimethylamino-5,6-dimethylpyrimidin-4-ultimatecarpage (pirimicarb) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXXIV) 2-isopropoxybenzonitrile (propoxur) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXXV) 1-(3,5-dichloro-2,4-differenl)-3-(2,6-differentail)urea (diflubenzuron) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXXVI) S-tert-butylthioethyl-O,O-dimethylphosphorodithioate(terbufos) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXXVII) ethyl(3-tert-butyl-1-dimethylcarbamoyl-1H-1,2,4-triazole-5-ylthio)acetate (triazamate) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XXXVIII) abamectin is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., p.3;

(XXXIX) 2-second-butylphenylmethyl (fenobucarb) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XL) N-tert-butyl-N'-(4-ethylbenzoyl)for 3,5-dimethylbenzophenone (tebufenozide) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XLI) (±)-5-amino-1-(2,b-dichloro-α,α,α-Cryptor-n-tolyl)-4-triftormetilfullerenov-3-carbonitrile (fipronil) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XLII) (RS)-α-cyano-4-fluoro-3-phenoxybenzyl-(1RS,3RS;1RS,3RS)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (β-cyfluthrin) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XLIII) (4-ethoxyphenyl)-[3-(4-fluoro-3-phenoxyphenyl)propyl](dimethyl)silane (selfloader) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XLIV) of tert-butyl(E)-α-(1,3-dimethyl-5-Phenoxyethanol-4-ylmethylamino)-n-toluate (fenpyroximate) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XLV) 2-tert-butyl-5-(4-tert-butylbenzyl)-4-chloropyridin-3(2H)-he (Piri is Aben) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XLVI) 4-[[4-(1,1-dimetilfenil)phenyl]ethoxy]hinzelin (fenazaquin) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XLVII) 4-phenoxyphenyl-(RS)-2-(pyridyloxy)propyl ether (pyriproxyfen) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XLVIII) 5-chloro-N-{2-[4-(2-ethoxyethyl)-2,3-dimethylphenoxy]ethyl}-6-ethylpyrimidine-4-amine (pyrimidifen) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(XLIX) (E)-N-(6-chloro-3-pyridylmethyl)-N-ethyl-N'-methyl-2-nitropyridinium (nitenpyram) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(L) (E)-N1-[(6-chloro-3-pyridyl)methyl]-N2-cyano-N-methylacetamide (NI-25, acetamiprid) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., p.9;

(LI) avermectin b1known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., p.3;

(LII) insecticide active plant extract, especially (2R,6S,12S)-1,2,6,6A,12,12A-hexahydro-2-Isopropenyl-8,9-dimethoxypropane[3,4-b]furo[2,3-h]chromen-6-he (rotenone), known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s, and extract from Azadirachta indica, primarily azadirachtin known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., p.59;

(LIII) a preparation containing insecticide active nemato is s, preferably, the preparation containing Heterorhabditis bacteriophora and Heterorhabditis megidis, known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s, the preparation containing Steinernema feltiae, known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s, and the drug containing Steinernema scapterisci, known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(LIV) preparation derived from Bacillus subtilis, known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., p.72, or a preparation derived from a strain of Bacillus thuringiensis, with the exception of the compounds selected from the strain GC91 or strain NCTC11821 known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(LV) product containing insecticide active mushrooms, preferably a preparation containing Verticillium lecanii is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s, the preparation containing Beauveria brogniartii known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., p.85, and the drug containing Beauveria bassiana, is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(LVI) preparation containing insecticide active viruses, preferably a preparation containing virus Neodipridon Sertifer NPV known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s, the preparation containing the virus Mamestra brassicae NPV known from The Pesticide Manual, published by The British Crop Protection Coucil, London 1997, 11th ed., s, and a drug containing the virus of Cydia pomonella granulosis known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(LVII) of 7-chloro-2,3,4A,5-tetrahydro-2-[methoxycarbonyl(4-trifloromethyl)carbarnoyl] indole [1,2E]oxazoline-4-carboxylate (DPX-MP062, indoxacarb) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(LVIII) N'-tert-butyl-N'-(3,5-dimethylbenzoyl)-3-methoxy-2-methylbenzoate (RH-2485, methoxyfenozide) is known from The Pesticide Manual, published by The British Crop Protection Council, London 1997, 11th ed., s;

(LIX) isopropyl ether (N'-[4-methoxybiphenyl-3-yl]hydrazinecarboxamide acid (D 2341) is known from Brighton Crop Protection Conference, 1996, s-493.

Connection (R2) we know from the Book of Abstracts, 212th ACS National Meeting, Orlando, FL, 25-29 August 1996, AGRO-020, publisher: American Chemical Society, Washington, D.C.CONEN: 63BFAF.

In accordance with this another important object of the present invention are a combination of drugs to control parasites of warm-blooded animals, characterized in that they are in addition to the compounds of formula I contain at least one active ingredient having the same or a different action, and at least one physiologically compatible carrier. It should be noted that the present invention is not limited to two combined drugs, i.e. drugs, containing only two active substances.

About the commonly proposed in the invention insecticidal and acaricidal compositions contain from 0.1 to 99 wt.%, especially from 0.1 to 95 wt.%, the active substance of the formula I or mixtures of active substances of the formula I and from about 99.9 to 1 wt.%, first of all from and 99.8 to 5 wt.%, solid or liquid additives, including from 0 to 25 wt.%, first of all, from 0.1 to 25 wt.%, Surfactant.

Proposed in the invention compositions for the treatment of animals can be applied locally, orally, parenterally or subcutaneously, for which such compositions may be presented in the form of solutions, emulsions, suspensions (drugs for infusion into the oral cavity of the animal), powders, tablets, pills, capsules, collars, earrings and samarasekara drugs to handle the loading.

For the preferred medications for local external application includes ready-to-use liquid preparations intended for point or drip processing, for processing bulk or aerosol spray and usually represents the variance or suspoemulsions or a combination of the active substance and excipients conducive to the spread of drug along the body of the animal. The method consisting in applying samarasekara preparations for handling bulk or point (drip) processing involves the local application of ready-to-use concentrate on the animal. This kind of drug is intended for direct grease is on a relatively small area of the skin or coat of the animal, mostly on the back and buttocks of the animal, or in one or several points on the back and buttocks of the animal along his spine. This preparation should be applied in small doses constituting from about 0.05 to 1 ml per kg, preferably about 0.1 ml per kg, while the total cost for processing one animal, equal to from 1 to 100 ml, preferably a maximum of about 50 ml. Clear, however, that the total consumption of the drug depends on the specific processed animal and will be different, for example, for young cats and cattle. Similar drugs to handle bulk or point (drip) processing in the application are automatically distributed throughout the body of the animal and thus have a protective prophylactic or therapeutic effect on almost all body parts of the animal. However, even when applying samarasekera product for processing bulk or spot treatment with a swab or spraying or dripping in a relatively small area of coat of the animal is active ingredient begins essentially automatically spread ("spread") over a large area along the skin or coat due to the presence of the drug components, promoting such distribution of the active substance, and this process of "Samaras the importance of" active substance is more intense due to the committed animal movements.

These samarasekara preparations for processing of bulk and point (drip) processing mainly contain media that provide rapid diffusion of the active substance on the skin or wool cover an animal host and are usually referred to as distributing oils. As an example, suitable for use in these purposes carriers can be called oil solutions, alcohol and isopropanol solutions, in particular solutions of 2-octyldodecanol or olejowego alcohol, solutions of esters of monocarboxylic acids, such as isopropylmyristate, isopropyl, lurileksua, aerolef, decillia, exellent and esters of Caproic acid and saturated fatty alcohols with a chain length of C12-C18the solutions of esters of dicarboxylic acids, such as dibutyl phthalate, diisopropylnaphthalene, diisopropylamide and di-n-butylacetat, or solutions of esters of aliphatic acids, such as glycols. In the composition of these drugs may be useful to include also known dispersant used, for example, in the pharmaceutical or cosmetic industry. As an example, this can be called 2-pyrrolidone, 2-(N-alkyl)pyrrolidone, acetone, polyethylene glycol and its ethers and esters, propylene glycol or synthetic triglycerides.

Oil the solutions contain, for example, vegetable oils such as olive oil, peanut oil, sesame oil, pine oil, linseed oil or castor oil. Vegetable oil can also be present in epoxydecane. In addition, you can also use paraffin and silicone oils.

Usually samarasekara preparations for processing of bulk and for point (drip) processing contain from 1 to 20 wt.% the compounds of formula I, from 0.1 to 50 wt.% dispersant and 45 to the 98.9 wt.% the solvent.

The method consisting in applying samarasekara preparations for handling bulk or point (drip) processing, it is preferable to use primarily for herd animals such as cattle, horses, sheep or pigs, when oral administration of the drug or its introduction by injection each animal is a time-consuming procedure that is associated with a high expenditure of time. This method, which due to its simplicity can, obviously, be applied to all other animals, including individual home and Pets, has found widespread among pet owners because it allows frequent use without expert help of a veterinarian.

As provided in the sale of products is generally preferable compounds or compositions in the form of concentrates, that is how the end user, as a rule uses dilute drugs. However, the form of release of the drug depends on the method of its use, thus the way of its introduction into the body. Products for oral administration are most often produced in the form of concentrates which must be diluted or add to the stern, then how supplied on sale samarasekara preparations for processing of bulk or point (drip) processing is usually produced in the form ready for use concentrate.

Such preparations may also contain additional additives, such as stabilizers, antispyware, viscosity regulators, binders or adhesives, and other active substances that achieve special effects.

Insecticidal and acaricidal compositions of this type used by the end consumer, is also included in the scope of the present invention.

The active substances of the formula I, their use for combating pests and parasites of any of the proposed in the invention methods or in part of any intended for these purposes proposed in the invention compositions can be used in all their spatial isomers or mixtures thereof.

In the present invention it is also proposed a method of prevention for the protection of animals, especially productive livestock, domestic, and to Mytnyk animals from parasitic helminths, namely, that the active substances of formula I or obtained on the basis thereof and compositions containing them orally, by injection or parenterally administered to the animals as an additive to food or drink or in solid or liquid form. The present invention relates further to offer it to the compounds of formula I, intended for use in one of these methods.

Below the invention is illustrated in the examples, not limiting its scope, under the active substance refers to one of the compounds listed below in table 1. Thus, in particular, the following composition is preferred compositions (preparative forms) (data in % correspond wt.%).

Examples of compositions (preparative forms)

1. The granulatea)b)
the active ingredient5%10%
kaolin94%-
highly dispersed silicic acid1%-
attapulgite- 90%

The active ingredient is dissolved in methylene chloride and the resulting solution was spray applied to the carrier, after which the solvent is evaporated in vacuum. Such granules can be added to the feed for the animals.

2. The granulate

the active ingredient3%
polyethylene glycol (200 MM)3%
kaolin94%

(MM denotes the molecular weight)

Finely ground active ingredient is uniformly served in the mixer to kaolin, oblastnomu polyethylene glycol. In this way receive a dust free granules coated.

3. Tablets or pills

I.the active ingredient33,00%
the methylcellulose0,80%
highly dispersed silicic acid0,80%
corn starch8,40%
II.crystalline lactose22,50%
corn starch17,00%
microcrystalline cellulose16,50%
magnesium stearate1.00%

I. Methylcellulose stir in the water. After swelling material admixed silicic acid and the resulting mixture is suspended until homogeneity. The active substance is mixed with corn starch. Then to this mixture add the above aqueous suspension and knead until pasty state. The resulting mass granularit by pushing through a sieve 12 mesh and dried.

II. Thoroughly mix between all 4 auxiliary substances.

III. The mixture previously obtained at stages I and II are mixed among themselves and pressed into tablets or pills.

4. Preparations for injection

A. Oil filler (slow release)

td align="center"> to 100 ml
1.the active ingredient0.1 to 1.0 g
peanut butter
2.the active ingredient0.1 to 1.0 g
sesame oilto 100 ml

Receiving: Active substance with stirring and, if necessary, with moderate heating is dissolved in part from just provided the recipe amount of oil and after cooling the solution volume was adjusted to the desired, and then sterilized by filtration through a suitable membrane filter with a pore size of 0.22 μm.

B. mixing with the water solvent (average speed release)

1.the active ingredient0.1 to 1.0 g
4-hydroxymethyl-1,3-dioxolane (nominally glycerol)40 g
1,2-propandiolto 100 ml
2.the active ingredient0.1 to 1.0 g
glyceryltrinitrate40 g
1,2-propandiolto 100 ml

Receiving: the Active substance is dissolved under stirring in part from just provided the recipe the amount of the solvent, after which the volume of the solution was adjusted to the desired and then sterilized by filtration through a suitable membrane filter with a pore size of 0.22 μm.

Century Water solubilized (quick release)

1.the active ingredient0.1 to 1.0 g
polyethoxysiloxane castor oil (40 ethylenoxide links)10 g
1,2-propandiol20 g
benzyl alcohol : 1 g
water for injectionto 100 ml
2.the active ingredient0.1 to 1.0 g
polyethoxysiloxane servicemanual (20 ethylenoxide links) 8 g
4-hydroxymethyl-1,3-dioxolane (nominally glycerol)20 g
benzyl alcohol : 1 g
water for injectionto 100 ml

Receiving: the Active substance is dissolved in a solvent and a surfactant, then the volume of the solution was adjusted to the required addition of water. Then, the solution is sterilized by filtration through a suitable membrane filter with a pore size of 0.22 μm.

5. Samarasekera preparation for processing bulk

A.the active ingredient5 g
isopropylmyristate10 g
isopropanolto 100 ml
B.the active ingredient2 g
exellent5 g
triglycerides medium chain length 15 g
ethanolto 100 ml
Centurythe active ingredient2 g
aerolef5 g
N-organic40 g
isopropanolto 100 ml

6. Samarasekera drug for point (drip) processing

A.the active ingredient10-15 g
monotropy ether of diethylene glycolto 100 ml
B.the active ingredient10-15 g
ektralite10 g
isopropanolto 100 ml
Centurydei is adequate substance 10-15 g
isopropanol20 g
benzyl alcohol : to 100 ml

7. Spray

A.the active ingredient1 g
isopropanol40 g
propylene carbonateto 100 ml
B.the active ingredient1 g
propylene glycol10 g
isopropanolto 100 ml

Such water system preferably also be used for oral administration and/or for insertion into the rumen (intraluminal).

Such compositions may also contain further auxiliary substances and additives, such as stabilizers, for example, optional epoxydecane vegetable oils (in particular, oksidirovanie coconut, rapeseed or soybean oil), antispyware, for example silicone oil, preservatives, viscosity regulators, binders, adhesives, as well as fertilizers or other active substances that achieve special effects.

In the composition described above compositions can also include other biologically active substances or additives, which has a neutral properties with respect to compounds of formula I and do not have undesirable effects on being treated animal host, as well as mineral salts or vitamins.

Below the invention is illustrated in the examples. These examples do not limit the scope of the invention. The abbreviation "h" indicates the time in hours. Used in the examples of starting compound can be obtained by the literature methods or are commercially available products.

Examples retrieve

Example 1: 4,6-bis-(4-fluoro-3-methylphenoxy)pyrimidine-5-ylamine

In 1 ml of dimethylformamide (DMF) was dissolved 154 mg of 4-fluoro-3-METHYLPHENOL and slowly add 30 mg of sodium hydride. The reaction mixture was stirred for 1 h at room temperature, and then one portion add 0.5 ml of stock solution of 66 mg of 4,6-dichloro-5-aminopyrimidine in DMF. The resulting reaction mixture is stirred, then heated to 100°C with a dwell time at this temperature for 2 h, and the ATEM incubated for 18 h at 80°C. Next, the reaction mixture is allowed to cool to room temperature. The precipitation is filtered off using filter cartridges made of PE, and washed with 2 ml of acetonitrile. The crude mixture was finally purified by preparative chromatography with reversed phase column Daisogel C18-ODS AR by gradient elution, which originally used a mixture of water/formic acid (in the ratio of 10000:1) gradually replaced by a mixture of acetonitrile/formic acid (in the ratio of 10000:1). After removal of the solvent receive specified in the header of the connection.

Example 2: 4,6-bis-(3-pertenece)pyrimidine-5-ylamine

171 mg of 3-terfenol mix 1.38 g of potassium carbonate, and then add 1 ml of stock solution of 84 mg of 4,6-dichloro-5-aminopyrimidine in DMF, and then optionally add 1 ml of DMF. The resulting reaction mixture is stirred for 18 h at 80°C. Then the reaction mixture is allowed to cool to room temperature. The precipitation is filtered off using filter cartridges made of PE, and washed with 2 ml of acetonitrile. The crude residue is purified by preparative chromatography with reversed phase column Daisogel C18-ODS AR by gradient elution, which originally used a mixture of water/formic acid (in the ratio of 10000:1) gradually replaced by a mixture of acetonitrile/formic acid (aspect] is to 10000:1). After removal of the solvent receive specified in the header of the connection.

Example 3: 4,6-bis-(4-fluoro-3-(trifluoromethyl)phenoxy)pyrimidine-5-ylamine

A solution of 40.8 g of 4-fluoro-3-(trifluoromethyl)phenol in 70 ml of DMF is stirred in an atmosphere of inert gas and cooled to 10°C. Next, with vigorous stirring, slowly add 5.8 g of sodium hydride. The mixture is allowed to cool to room temperature and stirred for 1 h then added dropwise a solution of 19.9 g of 4,6-dichloro-5-aminopyrimidine in 50 ml of DMF and the reaction mixture is heated up to 80°C with a dwell time at this temperature for 24 hours After stopping the reaction by addition of water and concentration under reduced pressure the crude mixture was extracted twice with ethyl acetate. The combined organic phases are washed with water and saturated sodium chloride solution and then dried over magnesium sulfate and charcoal. Dark brown oily residue is dissolved in 100 ml diethyl ether and treated with 100 ml of hexane. Received specified in the title compound crystallized with the formation of a colourless solid with a melting point 104-105°C.

Example 4: [4,6-bis-(4-fluoro-3-(trifluoromethyl)phenoxy)]pyrimidine-5-ylacetamide

In 2 ml of dichloromethane is dissolved 57 mg ethyldiethanolamine and 100 mg of 4,6-bis-(4-fluoro-3-(trifluoromethyl)phenoxy)]-5-aminopyrimidine and treated with 3.2 mg di is ethylaminomethyl and 41 mg of acetic anhydride. Next, the reaction mixture was stirred at room temperature for 72 h, after which the solvent is evaporated, the residue is dissolved in ethyl acetate, extracted with 2 ml of 1N. hydrochloric acid, saturated sodium bicarbonate solution and brine and then dried over magnesium sulfate. The organic layer is evaporated and the resulting solid is purified column chromatography (eluent: dichloromethane, ethyl acetate). After removal of the solvent receive specified in the header of the connection.

Example 5: Ethyl ester of 4,6-[bis-(4-fluoro-3-(trifluoromethyl)phenoxy)]pyrimidine-5-ylcarbamate acid

In 2 ml of pyridine was dissolved 100 mg of 4,6-[bis-(4-fluoro-3-(trifluoromethyl)phenoxy)]-5-aminopyrimidine and handle 44 mg ethylchloride. Next, the reaction mixture was stirred at room temperature for 18 hours then add 2 ml of 2n. hydrochloric acid and the mixture is extracted three times with diethyl ether. The combined organic layers are washed with saturated sodium bicarbonate solution and brine and then dried over magnesium sulfate. After removal of solvent the crude residue purified preparative GHUR with normal phase, receiving specified in the header of the connection.

Example 6: 4,6-[bis-(3-(trifluoromethyl)phenylamino)]pyrimidine-5-ylamine

In 10 ml of a mixture of tetrahydrofuran/water (ratio 1:1) add 1.0 g of 3-(trifluoromethyl)aniline and 0.5 g of 5-neither the ro-4,6-dichloropyrimidine, and then 2 drops of concentrated hydrochloric acid. Next, the reaction mixture was stirred for 18 h at boiling under reflux, cooled to room temperature and then add 2.5 g of tin dichloride. After that, the mixture is stirred for 18 h at boiling under reflux and evaporated under reduced pressure and add ethyl acetate. The organic phase is washed with saturated sodium bicarbonate solution and brine and then dried over magnesium sulfate. After removal of solvent the residue is purified by preparative chromatography with reversed phase column Daisogel C18-ODS AR by gradient elution, which originally used a mixture of water/formic acid (in the ratio of 10000:1) gradually replaced by a mixture of acetonitrile/formic acid (in the ratio of 10000:1). After removal of the solvent receive specified in the title compound in the form of solids.

Similarly, the above methods can also obtain the compounds listed in the following tables.

Table 1
No.Xl/2R1 R2R3R5/10R6/11R7/12R8/13tPL(°C)
1.1OHHHHFClH164-165
1.2OHHHCF3HHF112-115
1.3OHHHHFFH155-156
1.4OHHHHH/td> FH110-112
1.5OHHHHHCF3H81-83
1.6OHHHHClHH140-141
1.7OHHHFFHF128-129
1.8OHHHHHHCl179-182
1.9O/td> HHHHFCF3H104-105
1.10OHHHHFHH164-166
1.11OHHHHClClH177-179
1.12OHHHHClFH151-152
1.13OHHHHNO2 HH
1.14OHHHHHClH115-116
1.15OHHHHCF3HH130-132
1.16OOEtHHHFCF3H96-98
1.17OHHHHHHH145-146
1.18 OHHHHMeHH170-171
1.19OHHHHCNHCl
1.20OHHHHFMeH155-156
1.21OHHHHClNO2H198-200
1.22OHHHHH F3Hoil
1.23OHHHHHBrH121-123
1.24OHHHHHOMeH148-149

No.Xl/2R1R2R3R5/10R6/11R7/12R8/13tPL(C)
1.26OHHHHCNH N241-242
1.27OHHHHOMeHN189-191
1.28OHHC(O)OEtHFCF3N114-115
1.29OHHC(O)MeHFCF3N122-124
1.30OHC(O)OEtC(O)OEtHFCF3N167-169
1.31NH HHHHFCF3N199-201
1.32NHHHCHOHFCF3N223-228
1.33NHHHHHClClN222-226
1.34NHHHHHCF3HN207-212
1.35NHHHHHF HCF3156-159
1.36OHHCHOHFCF3N182-186
1.37NHHHHHHCF3N171-175
1.38OHHCHOHFClN128-133
1.39OHHHHClCF3N130-132
1.40 NHHHHHClCF3N230-234
1.41NHHHHHHF3N133-140
1.42OHHBnHFCF3Noil
1.43OHHC(O)NHEtHFCF3N
1.44OHHMeFCF3N80-81
1.45OHHHHHNO2N206-208
1.46OHMeMeHFCF3N
1.47OHHHHHHOMe187-188
1.50OHBnBnHFCF3N
1.51OHHC(O)MeHFClN107-115
1.52OHHCHOHHCF3N177-184
1.53OMeHHHFCF3N116-125
1.54OHHHHFNCl167-168
1.55OHH HHFNOMe157-158
1.56OHHHHFNMe140-142
1.57OOMeHHHFCF3N113-115
1.58OHHHHBrCF3N139-144
1.59OOiPrHHHFCF3N 122-124
1.60OHHHHMeClN129-132
1.61OHHHHFNF146-148
1.62OHHHHClNMe165-167
1.63OHHC(O)NMe2HFCF3N
1.64OHH C(O)OCH2ClHFCF3N
1.65OHHHHHClMe167-170
1.66OHHHFHFF139-141
1.67OHHHHPhNN207-208
1.69OHHHHMeNMe 204-205
1.70OHHHFHFN137-138
1.71OHHHFHNBr154-155

No.Xl/2R1R2R3R5/10R6/11R7/12R8/13tPL(°C)
1.72OHHHClHClH185-186
1.73OHHHHBrHF198-199
1.74OHHHClClHCl164-165
1.75OHHHHClHOMe167-168
1.76OHHHHClHCl185-186
1.77OHHHH HCF3Cl
1.78OHHHHHCF3F
1.79OHHHFHCF3H101-102
1.80OHHHHFHBr101-102
1.81OHHHHBrHH181-183
1.82 OHHHHClMeH172-174
1.83OHHHHCNClH206-209
1.84OHHCHOHClCF3H188-189
1.85OHHHCF3HCF3H103-104
1.86OHHHH MeCF3H110-111
1.87OHHHHBrBrH103-106
1.88OHHHHHCNH201-203
1.89OHHHHOMeCF3H135-136
1.90OHHHHCNCNH210-212
1.92 OHHC(O)CH2ClHFCF3H169-171
1.93OHHHHFFF139-144
1.94OHHHFFHBr182-185
1.95OHHHHCNCF3H163-165
1.96CH2HHHH FFH
1.97OHHHCF3HHCl125-127
1.98OHHHHHClCl190-192
1.99OHHHClHClCl189-191
1.100OHHHHClClCl217-219
1.101 OHHHClClClH225-226
1.102OHHHHFPhHoil
1.103OHBnCHOHFCF3Hoil
1.104OHHC(O)CF3HFCF3H126-128
1.105OHHHH HC(O)MeH120-124
1.106SO2HHHHClCF3H222-224
1.107OHHHHMeNO2H167-169
1.108OPhHHHFCF3H98-101
1.109OHHHBrFBrH221-223
1.110OSMeHHHFCF3H131-133
1.111OSO2MeHHHFCF3H172-176
1.112OSOMeHHHFCF3H135-139
1.113OCF3HHHFCF3H154-155

tr>
Table 2
No.R5R6R7R8tPL(°C)
2.1HFC1H132-135
2.2HFFH101-103
2.3HMeHMe153 to 155
2.5HFHH97-98
2.6HFMeH109-110
2.7HHHH83-85
2.8CF3HHFoil
2.9HHCF3Hoil
2.10HClCF3H84-85
2.11HHHCF3oil
2.12HCF3HH107-109
2.13HHFH91-92
2.14HC1MeH111-112
2.15HOMeHH126-127
2.16HHHF3oil
2.17HClC1H102-103
2.18HMeHH118-119
2.19HHHOMe85-86
2.20HFHF103-105
2.21FHHF122-124
2.22H PhHH111-113
2.23HFHC1111-112
2.24FFHF92-94
2.26FHFH116-117
2.27HFHOMe111-113
2.28HClFH84-86
2.29HHF3Hoil
2.30HHOMe H84-86
2.31CF3HCF3Hoil
2.32HFHBr116-118
2.33HFHMeoil
2.34HHC1Hoil
2.35C1HC1Hoil
2.36HMeC1H91-93
2.37FFHBr117-119
2.38HClHF98-100
2.39HClHH86-88

No.R5R6R7R8tPL(°C)
2.40HClHOMeoil
2.41ClNHCl151-153
2.42 HBrHF97-100
2.43HClHMe114-117
2.44HHHF121-122
2.45HFFF95-97
2.46FFFH97-100
2.47CF3 NHCl105-107
2.48NBrCF3H86-87
2.50NOMeCF3H103-105
2.51NCLHCl105-107
2.52NCLNO2H136-137
2.53 FHCF3H50-54
2.54NBrBrH110-115
2.55NNCNH96-98
2.56NMeCF3H68-70
2.57NBrHH65-67
2.58 NCNCF3Hoil
2.60NCNClH145-147
2.61ClHClCl150-152
2.62HClClCl
2.63HCNFH120-122
2.64HClCl127-128
2.65ClClClH127-129
2.66HHC(O)MeH103-106
2.67BrFBrH138-140
2.68HMeNO2H119-121
2.69 FHClH47-49
2.70NHSO2MeH130-132
2.71NO2HCF3H100-101
2.73BrMeBrH131-133
Table 3
No.R4/R9R5/R10R6 /R11R7/R12R8/R13tPL(°C)
3.1FHFHF
3.2FFFFF133-136

Table 4
No.X1R3R6R9R10R11R12R13tPL(°C)
4.1 NHHFHCF3FHH141-146
4.2NMeHFHCF3FHH100-101
4.3NHHFHHCF3HH44-49
4.4NHC(O)MeFHHCF3HH197-199
4.5SO2HFH CF3ClHH95-97
4.6NHC(O)IUFHCF3FHH210-212
4.7NC(O)MeC(O)IUFHCF3FHH173-175
4.8OHClHClHClH126-128
4.9OHClHFFHH112-11
4.10OHClHMeFHHoil
4.11OCHOFHCF3ClHH167-169
4.12OCHOFHNO2ClHH142-145
4.13OHFFHFHF136-138
4.14OHF FFFFFoil

Biological examples

1. Action in vitro against Dermanyssus gallinae (avian blood-sucking mite)

On properly prepared 96-well plate with the test substances for evaluation of their antiparasitic activity is placed consisting only of females in the population of ticks. Each connection to determine the minimum effective dose (MFA) test method serial dilution. Ticks left in contact with the test compound for 10 min, and then incubated at 25°C and 60%relative humidity for 5 days, during which control the action of the tested compounds on ticks. Test the connection manifests acaricidal activity if the mites are killed, not laying eggs. During the experience to identify possible growth activity of the tested compounds are registered for the conduct of an egg-laying and hatching from them tick.

2. Action in vitro against Rhipicephalus sanguineus (dog tick)

On properly prepared 96-well plate with the test substances for evaluation of their antiparasitic activity is placed consisting only of adults persons who nd the population of mites. Each connection to determine his MFA tested by serial dilution method. Ticks left in contact with the test compound for 10 min, and then incubated at 28°C and 80%relative humidity for 7 days, during which control the action of the tested compounds on ticks. Test the connection manifests acaricidal activity if the mites are killed.

3. Action in vitro against Ctenocephalides felis (cat flea)

On properly prepared 96-well plate is placed a mixed population of adult fleas that have access to the processed test substances in the blood supplied through a system of artificial feeding. Each connection to determine his MFA tested by serial dilution method. Fleas feed processed the test substances with the blood within 24 h, and then register the effect of test compounds on fleas. Insecticidal activity was determined on the basis of the number of dead fleas retrieved from a system of artificial feeding.

Insecticidal or acaricidal efficacy of compounds No. 1.2, 1.3, 1.7, 1.9, 1.22, 1.36, 2.1, 2.2, 2.5, 2.11, 2.13, 2.14 and 2.17 in HTS exceeds 80%. Thus, in particular, the effectiveness of the compounds No. 1.7, 1.9, 1.22 when used at a concentration of 100 ppm million in the fight against Ctenocephalides felis exceeds 80%.

1. Way of dealing with CL the soup in warm-blooded animals, includes introduction to the specified mammal the compounds of formula

in which R1denotes hydrogen;
R2and R3independently of one another denote hydrogen or formyl;
R4, R5, R6, R7, R8, R9, R10, R11, R12and R13independently of one another denote hydrogen, halogen, a nitro-group, With1-C2alkyl or Halogens1-C2alkyl; and X1and X2denote O.

2. The method according to claim 1, where R2and R3denote hydrogen.

3. The method according to claim 1 or 2, where R4, R5, R6, R7, R8, R9, R10, R11, R12and R13independently of one another denote hydrogen, fluorine or CF3and X1and X2denote O.

4. The method according to claim 1, where the compound of formula I is a 4,6-bis-(4-fluoro-3-triptoreline)pyrimidine-5-ylamine.

5. The method according to any one of claims 1 to 4, in which the compound of formula I is introduced warm-blooded animal in the form of a product for spot treatment.



 

Same patents:

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

The invention relates to a new crystalline modification D dicyclanil (2 cyclopropylamino-4,6-diaminopirimidina-5-carbonitrile) of formula I

FIELD: chemistry; pharmacology.

SUBSTANCE: invention refers to new pyrimidine compounds of formula (I) with selective inhibition of "КДР" and "ФРФР" kinase. These compounds and their pharmaceutically acceptable salts are antiproliferative agents. In formula (I) , where R1 is chosen from series including -H, -(CH2)n -5-6-merous heterocycle containing 1-2 heteroatoms chosen from nitrogen, sulphur oxygen or dioxide, (C1-C6)alkyl, (C3-C6)cycloalkyl where n stands for 0, and each groups including heterocycle, alkyl, cycloalkyl is independently optionally substituted to three groups chosen from: -OR9, -COR10, -CO2R10, -CONR10R11 and -CN; R2 stands for -H or -OCH3; R3 stands for -H, -F or -OCH3; R4, R5 and R7 stand for -H, R6 means (C1-C6)alkyl or OR12; R8 stands for -H or -F; R9 stands for -H and (C1-C6)alkyl, (C1-C6)alkoxide R10 and R11 independently are chosen from -H and (C1-C6)alkyl, (C1-C6)alkoxy, and R12 stands for -H and (C1-C6)alkyl.

EFFECT: can be used for treating and preventing solid cancers, specifically breast, rectum, lung and prostate cancer.

FIELD: chemistry.

SUBSTANCE: there is disclosed compounds of formula II , where each R2 independently stands for H, halogen, cyano, NO2, OR5, NR6R7, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo, arylalkyl, substituted arylalkyl, heterocycloalkyl or substituted heterocycloalkyl; B represents O, S, SO or SO2; each W and X independently represents C or N; n is within 0 to 4 if both W and X represent C, 0 to 3, if either X or W represent N, and 0 to 2 if both X and W represent N; R3, R5, R6, R7 are independently chosen from H, alkyl, substituted alkyl, alkenyl, alkinyl, substituted alkinyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo; R4 represents optionally substituted 5-6-merous heteroaryl containing nitrogen atom provided (a) if R4 stands for pyridyl, R4 is not substituted with both hydroxy and methoxy groups; and (b) R4 stands for pyrimidinyl, it is n-substituted =O; A is chosen from following compounds of formula: , where D stands for S or O; m is within 0 to 6; R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26 and R27 are independently chosen from H, halogen, NR30R31, OR32, CO2R33, SO2R36, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkinyl, substituted alkinyl, -CN, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl or substituted heterocycloalkyl; R28 and R29 are independently chosen from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl or together they form carbocyclic or heterocyclic ring consisting of 3 to 8 atoms; and R30, R31, R32, R33 and R36 are independently chosen from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkinyl, substituted alkinyl, cycloalkyl, substituted cycloalkyl, alkoxycarbonyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo, heterocycloalkyl or substituted heterocycloalkyl as pharmaceutical composition for cancer treatment containing compound of formula II.

EFFECT: production of new compounds and based pharmaceutical composition applied for cancer treatment.

18 cl, 147 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): their pharmaceutically acceptable salts or solvates, or stereoisomers possessing properties of agonists of β2-adrenoreceptors, to pharmaceutical composition based on thereof, using the claimed compounds in manufacturing a medicinal agent, and to a method for modulation of β2-adrenergic receptors. In the formula (I) each among R1-R5 is chosen independently from group comprising hydrogen atom, (C1-C4)-alkyl and Ra wherein alkyl is substituted optionally with substituted chosen from Rb; or R4 and R5 are combined to form group of the formula: -NRdC(=O)C(Rd)=C(Rd)-; R6, R7 and R8 represent hydrogen atom; R9 represents (C1-C4)-alkyl; R10 represents hydrogen atom or (C1-C4)-alkyl; each among R11, R12 and R13 is chosen independently from group including hydrogen atom, (C1-C4)-alkyl, vinyl, cyclohexyl, phenyl, halogen atom, -CO2Rd, -ORd, -S(O)mRd, -N(NRdRe)Rd or -S(O)2NRdRe, 5-6-membered monocyclic heteroaryl comprising 1 or 2 heteroatoms chosen from nitrogen (N), sulfur (S) atoms, 9-membered bicyclic heteroaryl comprising N as a heteroatom and 5-membered heterocycle comprising N as a heteroatom; or R11 and R12 in common with atoms to which they are bound form 6- or 7-membered heterocyclic ring comprising oxygen (O) atom as a heteroatom and wherein for R11-R13 each phenyl or heteroaryl is substituted optionally with 1 or 2 substitutes chosen independently from Rc, and each heterocyclyl is substituted optionally with 1 or 2 substitutes chosen from Rb and Rc; alkyl is substituted optionally with substitute chosen from Rb, and vinyl is substituted optionally with substitute chosen from Rm; w = 0, 1, 2, 3 or 4. Values Ra, Rb, Rc, Rd, Rm and m are given in the invention claim.

EFFECT: improved method for modulation, valuable medicinal properties of compounds and pharmaceutical composition.

22 cl, 225 ex

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

SUBSTANCE: invention relates to derivatives of pyrimidine of the general formula (I) and their pharmaceutically acceptable acid-additive salts possessing properties of neurokinin-1 (NK) receptors antagonists. In the general formula (I): R1 means lower alkyl, lower alkoxyl, pyridinyl, pyrimidinyl, phenyl, -S-lower alkyl, -S(O2)-lower alkyl, -N(R)-(CH2)n-N(R)2, -O-(CH)n-N(R)2, -N(R)2 or cyclic tertiary amine as a group of the formula: R1 means lower alkyl, lower alkoxyl, pyridinyl, pyrimidinyl, phenyl, -S-lower alkyl, -S(O2)-lower alkyl, -N(R)-(CH2)n-N(R)2, -O-(CH)-N(R)2, -N(R)2 or cyclic tertiary amine of the formula: that can comprise additional heteroatom chosen from atoms N, O or S, and wherein this group can be bound with pyrimidine ring by bridge -O-(CH2)n-; R2 means hydrogen atom, lower alkyl, lower alkoxyl, halogen atom or trifluoromethyl group; R3/R3' mean independently of one another hydrogen atom or lower alkyl; R4 means independently of one another halogen atom, trifluoromethyl group or lower alkoxyl; R means hydrogen atom or lower alkyl; R means independently of one another hydrogen atom or lower alkyl; X means -C(OH)N(R)- or -N(R)C(O)-; Y means -O-; n = 1, 2, 3 or 4; m means 0, 1 or 2. Also, invention relates to a pharmaceutical composition comprising one or some compounds by any claim among claims 1-19 and pharmaceutically acceptable excipients. Proposed compounds can be used in treatment, for example, inflammatory diseases, rheumatic arthritis, asthma, benign prostate hyperplasia, Alzheimer's diseases and others.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

21 cl, 1 tbl, 76 ex

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention elates to novel derivatives of uracil of the formula [I] possessing herbicide activity, a herbicide composition based on thereof and to a method for control of weeds. In derivatives of uracil of the formula [I] the group Q-R3 represents a substituted group taken among:

wherein a heterocyclic ring can be substituted with at least a substitute of a single species taken among the group involving halogen atom, (C1-C6)-alkyl-(C1-C6)-alkoxy; Y represents oxygen, sulfur atom, imino-group or (C1-C3)-alkylimino-group; R1 represents (C1-C3)-halogenalkyl; R2 represents (C1-C3)-alkyl; R3 represents OR7, SR8 or N(R9)R10; X1 represents halogen atom, cyano-group, thiocarbamoyl or nitro-group; X2 represents hydrogen or halogen atom wherein each among R7, R8 and R10 represents independently carboxy-(C1-C6)-alkyl and other substitutes given in the invention claim; R9 represents hydrogen atom or (C1-C6)-alkyl. Also, invention relates to intermediate compounds used in preparing uracil derivatives.

EFFECT: improved preparing method, valuable properties of compounds.

40 cl, 16 sch, 12 tbl, 65 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of cyanoaryl (or cyanoheteroaryl)-carbonylpiperazinyl-pyrimidines of the general formula and their physiologically acceptable salts that elicit the broad spectrum of biological activity exceeding activity of structurally related known compounds. In the general formula (I) R1 represents radical OR3 wherein R3 represents saturated hydrocarbon radical with linear or branched chain and comprising from 1 to 4 carbon atoms; R2 represents phenyl radical substituted with cyano-radical (-C≡N) or radical representing 5- or 6-membered heteroaromatic ring wherein heteroatom is taken among oxygen (O), nitrogen (N) or sulfur (S) atom and substituted with cyano-radical (-C≡N). Also, invention relates to methods for preparing compounds of the general formula (I) that involve incorporation of group of the formula:

into piperazinyl-pyrimidine compound or by the condensation reaction of corresponding pyrimidine with piperazine comprising group of the formula:

. Also, invention relates to pharmaceutical composition and applying these compounds. Compounds can be used for preparing medicinal agents useful in human therapy and/or for therapeutic applying in veterinary science as agents eliciting ant-convulsive and soporific effect or for the general anesthesia.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

13 cl, 7 sch, 8 tbl, 41 ex

The invention relates to new derivatives of arylpiperazines General formula I, where X Is O or S1- C1-C4alkoxy, CF3, R2- C1-C6alkyl, saturated WITH3-C6cycloalkyl; heteroseksualci of 3-6 ring atoms, heteroatom of which is O, S or N, optionally N-substituted WITH1-C6by alkyl; phenyl, optionally substituted by F, Cl, Br, NH2CH3CF3or OCH3; 5-6-membered heteroaryl, the heteroatom of which is O, S or N, possibly substituted, or condensed heteroaromatic system containing 9 atoms

The invention relates to new arylpyrimidines compounds of formula I having the effect of antagonist 5HT2B-receptor, and pharmaceutical compositions

The invention relates to a new method of production (its variants) aminophenylalanine formula I, having the properties of plant growth regulators or herbicides, as well as intermediate products for their production

The invention relates to novel acylated to aminophenylacetylene General formula I which possess herbicide action and selectivity of action in comparison with the previously known compounds of this series

FIELD: medicine.

SUBSTANCE: invention refers to veterinary medicine and namely to pharmacy and deals with development of veterinary remedy in the form of ointment intended for animal arachnoses treatment. Ointment consists of chlorophos, sea-buckthorn oil, dimexyde, castor oil and low-molecular polyethylene (NMPE-2) at certain ratio of components.

EFFECT: invention allows increasing depth of penetration and duration of ointment action, decreasing its toxicity and increasing immunological status of diseased animals.

2 ex

FIELD: agriculture.

SUBSTANCE: invention provides new compositions for local application containing, at least, one derivative of 1-N-aryl-pyrosol and formamidines, such as amitraz, and methods of treatment, monitoring, or prevention of invasion by parasites on mammal or birds. Compositions of invention includes compositions spot-on (on withers), pour-on (detergent) or compositions in the form of spray and able to include, furthermore, ectoparasitic, such as IGR composition, derivative of avermektyne or milbemycins, or perythroid insecticide, and/or antihelminthic, such as benzimidazoles or imidazo-thiazol. Composition of invention more long-term duration of parasitic monitoring, at high monitoring rate, remaining effective during up to three months from the first use, prevent ticks attachment to animal, thereby, providing protection against disease, transferring by ticks. Ectoparasit, which can be monitored, subject to treatment or prevention by means of particular invention include ixodic ticks, fleas, ticks, mange, louses, mosquitoes, fly and grubs of cattle.

EFFECT: providing of more long-term duration of parasitic monitoring at high monitoring rate, remaining effective during up to three months from the first use, prevent ixodic attachment to animal, thereby, providing protection against disease, transferring by ixodics.

20 cl, 7 ex

FIELD: veterinary.

SUBSTANCE: invention relates to field of veterinary parasitology, in particular, to compositions for treatment and protection of vertebrate animals from sarcoptoidoses. Claimed composition includes (wt %): S-phenvalerate - 0.003 - 3 Glycerin - 0.008 - 5 Dymethyl sulphoxide - 0.008 - 5 Isopropyl alcohol - 0.015 - 12 Polyethylene glycol-400 - 0.086 - 41 Phenoxyethanol - 0.1 - 34 Water the remaining part.

EFFECT: claimed composition ensures 100% death of imago of sarcoptoid mites, their eggs, as well as possesses long residual action on skin, is convenient in application, does not produce negative effect on animal organism.

1 tbl, 4 ex

FIELD: agriculture; veterinary.

SUBSTANCE: composition consists of alphametrin, surface active compound, alcohol and solvent, chloracetophos, in certain ratio of components. Isopropyl alcohol is used as alcohol and neonole is used as surface active compound; mixed petroleum solvent for rubber industry with end point of 80-120°C or mixed petroleum solvent with end point of 50-170°C is used as solvent.

EFFECT: improved efficiency, versatility and reduced toxicity of composition.

2 cl, 3 tbl, 7 ex

FIELD: agriculture; veterinary.

SUBSTANCE: composition for treatment of animal arachnid myiasis consists of S-phenvalerate, surface active substance, isopropyl alcohol and solvent, chloracetophos, in specific ratio of components. Neonole AF 9-10 is used as surface active substance; mixed petroleum solvent for rubber industry with end point of 80-120°C or mixed petroleum solvent with end point of 50-170°C is used as solvent.

EFFECT: improved efficiency, versatility and reduced toxicity of insectoacaricide composition.

2 cl, 3 tbl, 7 ex

FIELD: animal science.

SUBSTANCE: the innovation deals with applying high-activity composition of synergistic action for controlling parasitic acarids on animals that contains the combination of pyrethroid and nicotinyl compounds and, also, the method for treating animals infected with parasitic acarids in the course of which it is necessary to treat animals with the above-mentioned composition.

EFFECT: higher efficiency of control.

6 cl, 9 ex, 4 tbl

FIELD: synthesis of biologically active compounds.

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

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

10 cl, 10 dwg, 9 tbl, 14 ex

FIELD: medicine, veterinary parasitology.

SUBSTANCE: one should apply biologically active preparation onto animal's body, it contains, weight%: cipermetrin 2.25 - 2.74, dimethylsulfoxide 10.0 - 30, polyethylene glycol - 400 10.0 -40.0, isopropyl alcohol - the rest. This preparation should be applied with thin stream in October-November along both sides of animal's vertebral column at the dosage of about 0.08 - 0.1 ml/kg body weight. The innovation provides efficient therapy due to applying curative composition of simple content, steady application onto animal's hair and skin, gradual penetration into subcutaneous fatty layer, tight and prolonged retaining at the surface. The composition is not washed with water and, also, provides simplicity in application, cheapness of therapy and absence of side effects.

EFFECT: higher efficiency of therapy.

2 ex

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