Substituted azadioxocycloalkenes, methods for their preparing, intermediate compounds, fungicide agents and method for their preparing, method for control of harmful fungi

FIELD: organic chemistry, chemical technology, agriculture.

SUBSTANCE: invention describes substituted azadioxocycloalkenes of the general formula (I): wherein A means unsubstituted or methyl-substituted dimethylene; Ar means unsubstituted or fluorine-substituted ortho-phenylene, thiophendiyl or pyridindiyl; E means group of the formula: wherein G means oxygen atom, groups -O-CH2-, -CH2-O- or -C(CH3)=N-O-CH2-; Z means unsubstituted or substituted phenyl, pyrimidinyl or thiadiazolyl, or naphthyl. Invention describes 4 methods for preparing compounds of the formula (I), 5 species of intermediate compounds used for preparing compounds of the formula (I), fungicide agents comprising compound of the formula (I) as an active substance, a method for preparing fungicide agents, method for control of harmful fungi using compound of the formula (I). Compounds of the formula (I) show fungicide properties and therefore they can be used in agriculture.

EFFECT: improved preparing methods, valuable properties of compounds.

13 cl, 5 tbl, 18 ex

 

The present invention relates to new substituted dioxazine having fungicidal activity, and more particularly to substituted addictionultram, methods for their production, intermediate products, fungicidal tools and the way they are received.

Known substituted 5,6-dihydro-1,4,2-dioxazine possessing fungicidal activity (see JP-A-02001484 or Chemical Abstracts, vol.113, No. 1, 02.07.1990, abstract No. .6381).

Object of the invention is the expansion of the range of the substituted dioxazine exhibiting fungicidal activity.

The problem is solved proposed substituted azadeoxycytidine General formula (I)

where

A - dimethylene (ethane-1,2-diyl), unsubstituted or substituted stands,

Ar - ortho-phenylene, unsubstituted or substituted by fluorine, theoffender or pyridinyl,

E - a group of the formula

G - oxygen group,- O-CH2-, -CH2-O - or-C(CH3)=N-O-CH2-,

Z - phenyl, pyrimidinyl or thiadiazolyl, unsubstituted or one - or twofold substituted by substituents from the group comprising methyl, ethyl, n - or isopropyl, n-, ISO-, sec - or trebuil, methoxy, ethoxy, trifluoromethyl, triptoreline, deformedarse, fluorine, chlorine, bromine, methylthio, ethylthio, N3C-O-N=CH-, benzyloxy, naphthyloxy, pyridinyl, pyridylthio, pyridine is hydroxy, benzylthio, unsubstituted or substituted by chlorine or stands, thienyl, unsubstituted or substituted stands, phenyl, razmeshanny or substituted by 1 or 2 identical or different substituents from the group comprising methyl, ethyl, methoxy, ethoxy, deformations, trifluoromethyl, fluorine, chlorine and bromine, phenoxy group, unsubstituted or substituted by 1 or 2 identical or different substituents from the group comprising fluorine, chlorine, bromine, cyano, methyl, methoxy, ethyl, deformations, trifluoromethyl, methoxy-carbonyl, and dimethylaminoethanol, and phenylthio group, unsubstituted or substituted once by fluorine, chlorine or bromine, or Z means naphthyl.

Substituted azadeoxycytidine the above General formula (I), where A, Ar, E, G and Z have the above meanings, can be obtained due to the fact that derivatives of carboxylic acids of General formula (II)

where

Ar, E, G and Z have the above values, a R represents a C1-C4-alkyl,

subjected to interaction with hydroxylamine or its kaleidotrope salt, if necessary, in the presence of an acid acceptor and optionally in the presence of a diluent, the resulting product is subjected to interaction with disubstituted alkanes General formula (III)

where

And has the above value is,

X is halogen, alkylsulfonate or phenylsulfonyl; if necessary, in the presence of an acid acceptor and optionally in the presence of a diluent, followed by separation of the target product.

In the following this method is referred to as method a).

Substituted azadeoxycytidine the above General formula (I), where a means dimethylene (ethane-1,2-diyl), Ar is ortho-phenylene, E means a group of the formula

G means oxygen or the group-CH2-O -, and Z denotes phenyl, pyrimidinyl, replaced by stands, ethyl, fluorine, chlorine, bromine, fenoxaprop, substituted cyano, can be obtained due to the fact that hydroxyanisole compounds of General formula (IV)

where A, Ar, and E have the above meanings, is subjected to the interaction with compounds of General formula (V)

where

Z have the above meanings, m is 0 or 1, and X is halogen, optionally in the presence of an acid acceptor and optionally in the presence of a diluent, followed, if necessary, converting the group Z in the desired value and selection of the target product.

In the following this method is referred to as method b).

Substituted azadeoxycytidine the above General formula(I), where a means dimethylene (ethane-1,2-diyl), Ar is ortho-phenylene, E means a group of the formula

G - group-CH2-O-,

Z is phenyl, substituted by stands or ethyl, can be obtained due to the fact that halogenmethyl compounds of General formula (VI)

where

A, Ar and E have the above meanings, and X1means halogen,

subjected to interaction with compounds of General formula (VII)

where Z has the above meaning,

if necessary, in the presence of an acid acceptor and optionally in the presence of a diluent, followed by separation of the target product.

In the following this method is referred to as method b).

Substituted azadeoxycytidine the above General formula (I), where a means dimethylene (ethane-1,2-diyl), Ar is ortho-phenylene, E means a group of the formula

G - group-CH2-O-,

Z is phenyl, substituted by stands or ethyl,

you can get due to the fact that hydroxyalkylated General formula (VIII)

where

A, Ar, E, G and Z have the above values,

subjected to cyclization Volodarsk means, if necessary, in the presence of a diluent, followed by separation of the target product is KTA.

In the following this method is designated as method d).

Carrying out the methods a)to d), representing an additional object of the present invention, are explained by the following data.

If as starting substances are used, for example, methyl ester α-methoxyimino-α-(2-phenoxy-phenyl)-acetic acid, hydroxylamine hydrochloride and 1,2-dibromethane reaction for the proposed method (a) proceeds according to the following reaction scheme:

If as starting substances are used for example 3-methoxyimino-(2-hydroxy-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine and benzylchloride reaction for the proposed method (b) proceeds by the following reaction scheme:

If as starting substances are used for example 3-methoxyimino-(2-chloromethyl-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine and 2-METHYLPHENOL reaction for the proposed method (C) proceeds according to the following reaction scheme:

If as a starting compounds are used, for example, n-(2-hydroxy-ethoxy)-methoxyimino-(2-phenoxy-phenyl)-ndimethylacetamide, the reaction for the proposed method (d) proceeds by the following reaction scheme:

Educt of the formula (II) are known or can be obtained by known methods (see applications 178826, 242081, 382375, 493711).

Educt of the formula (III) are known chemicals for organic synthesis.

Educt of the formula (IV) from the literature are not known. Therefore, a further object of the invention are the compounds of formula (II), where a means dimetilan, Ar - ortho-phenylene, E is a group of the formula

as intermediates for compounds of formula (II).

New hydroxyanisole the compounds of formula (IV) are due to the fact that tetrahydropyranyloxy-compounds of General formula (IX)

where

A, Ar and E have the above values,

subjected to interaction with acid, such as, for example, hydrochloric acid, methanesulfonate acid, benzolsulfonat acid, p-toluensulfonate acid, or acidic ion exchanger, optionally in the presence of a diluent, such as, for example, water, methanol, ethanol or complex ethyl ester acetic acid, at a temperature of 0-100°With (see the following examples).

Tetrahydropyranyloxy-the compounds of formula (IX) from the literature are not known. Therefore, a further object of the invention are the compounds of formula (IX), where a means dimethylene (ethane-1,2-diyl), Ar - ortho-phenylene, E is a group of the formula

as an intermediate is produktov for compounds of formula (I).

New tetrahydropyranyloxy-the compounds of formula (IX) are obtained due to the fact that the esters of General formula (X)

where

Ar, E and R have the above values,

subjected to interaction with hydroxylamine or its hydrochloride, optionally in the presence of an acid acceptor, such as, for example, potassium hydroxide, and, if necessary, in the presence of diluents, such as, for example, methanol and water, and the resulting intermediate product is subjected to in situ interaction with dihalogenoalkane the above General formula (III), optionally in the presence of an acid acceptor, such as, for example, potassium carbonate, at a temperature of 0-100°With (see the description of the proposed method (a) and the following examples).

New esters of the formula (X) from the literature are not known. You can get them due to the fact that esters of tetrahydropyranyloxy-phenyl-acetic acid of General formula (XI)

where

Ar and R have the above values,

subjected to derivatization with conventional methods (see following examples).

New esters of tetrahydropyranyloxy-phenyl-acetic acid of General formula (XI) from the literature are not known. You can get them due to the fact that esters hydroxyphenylarsonic acid on the formula (XII)

where

Ar and R have the above values,

subjected to interaction with dihydropyrano, optionally in the presence of a catalyst, such as, for example, p-toluensulfonate acid, and, if necessary, in the presence of a diluent, such as, for example, Tetra-hydrofuran, at a temperature of 0-100°With (see the following examples).

Educt of the formula (XII) are known chemicals for organic synthesis.

Used in the proposed method, (b) as a further reagent compounds of the formula (V) are known chemicals for organic synthesis.

Used in the proposed method, (C) as the starting material halogenmethyl the compounds of formula (VI) from the literature are not known. Therefore, a further object of the invention are the compounds of formula (VI)

where

A - dimethylene (ethane-1,2-diyl),

Ar - ortho-phenylene,

E - a group of the formula

X1- halogen,

as intermediates for compounds of formula (I).

New halogenmethyl the compounds of formula (VI) are obtained due to the fact that methyl compounds of General formula (XIII)

where

A, Ar and E have the above values,

experience the t interaction with a halogenation agent, such as, for example, N-bromo - or N-chloro-succinimide, optionally in the presence of a catalyst, such as, for example, azoisobutyronitrile, and, if necessary, in the presence of a diluent, such as, for example, carbon tetrachloride, at a temperature of 0-150°With (see the following examples).

Methyl compounds of formula (XIII) from the literature are not known. Therefore, an additional object of the invention are the compounds of formula (XIII),

where

A - dimethylene (ethane-1,2-diyl),

Ar - ortho-phenylene,

E - a group of the formula

as intermediates for compounds of formula (I).

New methylene compounds of the formula (XIII) are obtained due to the fact that the esters of General formula (XIV)

where

where Ar, E and R have the above values,

subjected to sequential interaction with hydroxylamine or its hydrochloride, optionally in the presence of an acid acceptor, such as, for example, hydrooxide potassium, and, if necessary, in the presence of a diluent, such as, for example, methanol, and with disubstituted by alkana the above General formula (III), optionally in the presence of an acid acceptor, such as, for example, potassium carbonate, at a temperature of 0-150°With (see the following examples).

The compounds of formula (XIV) and is known or can be obtained by known methods (see application EP 386561, 498188, the following examples).

Used in the proposed method, (C) as the starting material the compounds of formula (VII) are known chemicals for organic synthesis.

Used in the proposed method, (g) as a starting substance hydroxycarbamide formula (VIII) from the literature are not known. Therefore, another object of the invention are the compounds of formula (VIII), where a means dimethylene (ethane-1,2-diyl), Ar - ortho-phenylene, E is a group of the formula

G - group,- CH2-O-,

Z is phenyl, substituted stands,

as intermediates for compounds of formula (I).

New hydroxycarbamide formula (VIII) are obtained due to the fact that derivatives of General formula (XV)

where

Ar, E, G and Z have the above meanings, and

Y represents halogen, hydroxy or alkoxy,

subjected to interaction with hydroxylamine General formula (XVI)

where

A has the abovementioned meaning,

if necessary, in the presence of an acid acceptor, such as, for example, tri-ethylamine, pyridine or 4-dimethylamino-pyridine, and optionally in the presence of a diluent, such as, for example, methylene chloride, toluene or tetrahydrofuran, at a temperature of 0-150°With (see the home and EP 178826, 242081, 493711).

Derivatives of the formula (XV) are known or can be obtained by known methods (see J. Chem. Soc. Perkin Trans. I 1987, 2829-2823).

The proposed methods (a), (b) and (C) is conducted preferably in the presence of an acid acceptor. As acid acceptors suitable organic or inorganic bases. They belong, for example, hydrides of alkaline earth metals or alkali metals, the alkaline earth metal hydroxide or alkali metal amides, alkaline earth metals or alkali metals, the alkaline earth metal alcoholate or alkali metal acetates, alkaline earth metals or alkali metals, carbonates of alkaline earth metals or alkali metals or hydrogen carbonates of alkaline earth metals or alkali metals, such as, for example, sodium hydride, sodium amide, sodium methylate, sodium ethylate, tert. butyl potassium, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate or ammonium carbonate, and tert. amines, such as, for example, trimethylamine, triethylamine, tributylamine, N,N-dimethylaniline, N,N-dimethyl-benzylamine, pyridine, N-methylpiperidine, N,N-dimethylaminopyridine, diazabicyclo, Diisobutylene or databaseconnect.

As a diluent for carrying out the proposed methods (a), (b) and (C) use water and organic solvents. They belong, in particular, aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons, such as, for example, benzine, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, simple, petroleum ether, hexane, cyclohexane, dichloromethane, chloroform or carbon tetrachloride, ethers, such as, for example, diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran or ethylene glycol-dimethyl or etilenglikolevye ethers; ketones, such as, for example, acetone, butanone or methyl-isobutyl-ketone; NITRILES, such as for example, acetonitrile, propionitrile or benzonitrile; amides, such as, for example, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylformamide, N is an organic or triamide hexamethylphosphoric acid; esters, such as, for example, methyl ester acetic acid or complex ethyl ester of acetic acid; sulfoxidov, as, for example, dimethyl sulfoxide, alcohols, such as, for example, methanol, ethanol, N. - or isopropanol, simple etilenglikolevye ether, simple etilenglikolevye ether, simple diethylene glycol-ether onomatology simple diethylene glycol-monotropy ether, mixtures thereof with water elitista water.

The proposed method (d) is conducted preferably in the presence of means of dehydration. Thus as a means of dehydration particularly suitable conventional Vodolaga chemicals, in particular the acid anhydrides, such as, for example, phosphoric anhydride.

As a diluent for carrying out the proposed method (d) use the conventional inert organic solvents. They belong, in particular, aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons, such as, for example, benzine, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, simple, petroleum ether, hexane, cyclohexane, dichloromethane, chloroform or carbon tetrachloride, ethers, such as, for example, diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran or ethylene glycol-dimethyl or etilenglikolevye ethers; ketones, such as, for example, acetone, butanone or methyl isobutyl ketone; NITRILES, such as, for example, acetonitrile propionitrile or benzonitrile;

amides, such as, for example, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylformamide, N is an organic or triamide hexamethylphosphoric acid; esters, such as, for example, methyl ester acetic acid or complex ethyl ester of acetic acid; sulfoxidov, as, for example, di is ethylsulfonyl.

The reaction temperature when carrying out the proposed methods (a) to (g) may vary within wide limits. Typically operate at a temperature-20-+200°C, preferably at a temperature of 0-150°C.

For the proposed method (a) 1 mol of carboxylic acid derivative of the formula (II) typically use 1-5 mol, preferably 1.0 to 2.5 mol, hydroxylamine or its kaleidotrope salt and usually 1-1 mol, preferably 1.0 to 5.0 mol, disubstituted alkane of the formula (III).

For the proposed method (b) 1 mol hydroxyanisole the compounds of formula (IV) typically use 0.5 to 2.0 mol, preferably 0.9 to 1.2 moles, of the compounds of formula (V).

For the proposed method (b) for 1 mol of the halogenated compounds of formula (VI) is usually used 1-5 mol, preferably 1.5 to 3 mol, of the compound of formula (VII).

For the proposed method (g) 1 mol of hydroxyacetamido formula (VIII) is usually used 1-5 mol, preferably 1.5 to 4 mol, means dehydration.

Reaction processing of reaction mixtures and the selection of target products carried out by known methods (see following examples).

The proposed compounds of the above formula (I) may exist as mixtures of different isomeric forms, in particular, E - and Z-isomers. Use as E-and Z-isomers as well as mixtures of e is their isomers in any form.

The proposed compounds exhibit fungicidal activity. Fungicidal agent that is a further object of the invention is used to control plasma-differeniate, oomycetes, they, zygomycete, records of Ascomycetes, basidomycetes and deuteromycete.

In the following example are some pathogens of fungal diseases belonging to the above families.

The Pythium species, such as, for example, Pythium ultimum, Phytophthora Species, such as, for example, Phytophthora infestans.

Pseudoperonospora species, such as, for example, Pseudoperonospora humuli or

Pseudoperonospora cubense.

The Plasmopara species, such as, for example, Plasmopara viticola.

Species of Peronospora., such as, for example, Peronospora. pisi or Peronospora. brassicae.

The Erysiphe species, such as, for example, Erysiphe graminis.

The Sphaerotheca species, such as, for example, Sphaerotheca fuliginea.

The Podosphaera species, such as, for example, Podosphaera leucotricha.

The Venturia species, such as, for example, Venturia inaequalis.

The Pyrenophora species, such as, for example, Pyrenophora teres or Pyrenophora graminea (conidia form: Cereals, synonym: Helminthosporium).

The Cochliobolus species, such as, for example, Cochliobolus sativus (conidial form: Cereals, synonym: Helminthosporium).

The Uromyces species, such as, for example, Uromyces appendiculatus.

The Puccinia species, such as, for example, Puccinia recondita.

The Tilletia species, such as, for example, Tilletia caries.

The Ustilago species, such as, for example, Ustilago nuda or Ustilago avenae.

The Pellicularia species, such as, for example, Pellicularia sasakii.

The Pyricularia species, such as, for example, Pyricularia oryzae.

The Fusarium species such as, for example, Fusarium culmorum.

The Botrytis species, such as, for example, Botrytis cinerea.

The Septoria species, such as, for example, Septoria nodorum.

The Leptosphaeria species, such as, for example, Leptosphaeria nodorum.

The Cercospora species, such as, for example, Cercospora canescens.

Species of Alternaria, such as, for example, Alternaria brassicae.

The Pseudocercosporella species, such as, for example, Pseudocercosporella herpotrichoides.

Good tolerance of plants active substances necessary to combat plant diseases concentrations allows for the processing of above-ground parts of plants, planting and seeding materials and soil.

Moreover, the active substances can be used particularly successfully for controlling diseases in fruit-growing and vegetable growing, such as, for example, with a pathogen Phytophtora, or for combating diseases of cereals, for example, to combat pathogens Pyrenophora.

In addition, the proposed active substances have a good effect, for example, in the fight against pathogens Erisyphe graminis, Cochliobolus sativus, Leptosphaeria nodorum, Pseudocercosporella herpotrichoides and Fusarium species in cereals, with a pathogen Pyricularia oryzae and Pellicularia sasakii on rice. They also have a wide effect in-vitro.

The active substance can be converted to standard medications, depending on their physical and/or Chi is practical properties, for example, solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols, polymeric microcapsules and shell seed. In addition, they can be the agents for an extremely fine distribution in the form of cool and warm mist.

These drugs get known techniques, for example, by mixing the active substances with extenders, for example with liquid solvents, pressurized liquefied gases and/or solid carriers, optionally with the use of surface-active substances, such as emulsifiers and/or dispersants and/or foam. In the case of using water as a filler can also be used an organic solvent as an auxiliary means. As the organic solvent used in the main: aromatics, such as, for example, xylene, toluene, or alkylnaphthalenes, chlorinated aromatic and aliphatic hydrocarbons, such as chlorobenzene, chloroethylene or methylene chloride, aliphatic hydrocarbons like cyclohexane or paraffins, for example petroleum fractions, alcohols like butanol or glycol and also their ethers and esters, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, strongly polar solvents, such as dimethylformamide or di is ethylsulfonyl, as well as water. Under liquefied gaseous extenders or carriers should be understood such fluid, which at ambient temperature and atmospheric pressure are gaseous, for example, working gases for aerosols, such as, for example, halogenated hydrocarbons as well as butane, propane, nitrogen and carbon dioxide.

As solid carriers used, for example, natural rock flours, such as kaolin, alumina, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, and synthetic rock flours, such as highly dispersed silicic acid, alumina and silicates. As solid carriers for granules are used, for example, crushed and fractionated natural rocks such as calcite, marble, pumice, thick, dolomite, synthetic inorganic and organic flour and organic materials such as sawdust, peel, coconut, corn cobs and stalks of tobacco.

As emulsifiers and/or foaming agent is used, for example, nonionic and anionic emulsifiers, as a complex polyoxyethylene esters of fatty acids, simple polyoxyethylene ethers of fatty alcohols, for example, aklil-aryl-polyglycolic ether, alkyl sulphonates, alkyl sulphates, arylsulfonate, as well as protein hydrolysates. As disperse the ora used for example, exhaust ligninolytic liquor and methylcellulose.

The preparations may also contain a binder, such as, for example, carboxy-methyl cellulose, natural and synthetic powdered, granular or latex polymers, such as gum Arabic, polyvinyl alcohol, polyvinyl acetate, and also natural phospholipids, such as cephalin and lecithins and synthetic phospholipids. Other additives can be mineral and vegetable oils.

In addition, the preparations may contain colouring agents, such as inorganic pigments, for example iron oxide, titanium oxide, ferrocyanide blue, and organic dyes, as alizarin, azo and metalphthalocyanine dyes and micronutrients, such as iron salts, manganese, boron, copper, cobalt and tin.

Preparations usually contain 0.1 to 95 wt.% the active substance, preferably 0.5 to 90 wt.%.

Offer active substances can be applied as such or in the form of their preparations, and also in the form of a mixture with known fungicides, bactericides, acaricides, nematicides or insecticides, for example, in order to increase the spectrum of action of active substances or preventing resistance. In many cases, a synergistic effect is obtained, i.e. the activity of the mixture exceeds the activity of the individual components.

Particularly advantageous for when Catania with the proposed active substances are the following connections:

Fungicides:

2 aminobutane; 2-aniline-4-methyl-6-cyclopropyl-pyrimidine; 2',6'-dibromo-2-methyl-4'-triptoreline-4'-Cryptor-methyl-1,3-thiazole-5-carboxanilide; 2,6-di-chloro-M-(4-trifloromethyl)benzamide; (E)-2-methoxyimino-M-methyl-2-(2-phenoxyphenyl)ndimethylacetamide; 8-hydroxyanisole; methyl(E)-2-{2-[6-(2-CYANOGEN-oxy)pyrimidine-4-yloxy]phenyl}-3-ethoxyacrylate; methyl(E)-methoxyimino[alpha-(o-tolyloxy)-o-tolyl]acetate; 2-phenylphenol (ORR), Aldemar, npropyl-FOS, anilazine, azaconazole, benalaxyl, Benadryl, benomyl, binapacryl, biphenyl, bitertanol, blasticidin-S, bromuconazole, bupirimate, bootybay, calcium polysulfide, captafol, Captan, carbendazim, carboxin, chinomethionat, chloroneb, chloropicrin, CHLOROTHALONIL, chlozolinate, zofrane, having cymoxanil, cyproconazole, zipform, dichlorophen, diclobutrazol, dichlofluanid, declomycin, dicloran, dietphenterm, difenoconazol, dimethirimol, dimethomorph, diniconazole, dinocap, diphenylamine, dipyrithione, datalists, dithianon, dodine, drazoxolon, edifenphos, epoxiconazole, ethirimol, etridiazole, fenarimol, fenbuconazole, fanforum, penetapan, fenpiclonil, fenpropidin, fenpropimorph, pertinacity, fistinginaction, ferbam, Frisoni, fluazinam, fludioxonil, foramide, plugincontrol, flusilazole, flush-amides, flutolanil, flutriafol, folpet, fosetyl-aluminum, phthalide, huberi-Gasol, Furla the forces, pharmacyclics,

guazatine,

hexachlorobenzene, hexaconazole, hymexazol,

imazalil, mebenzadole, iminoctadine, iprobenfos (IBR), iprodion, isoprothiolane,

kasugamycin, preparation of copper such as copper hydroxide, copper naphthenate, chlorosis copper, copper sulfate, copper oxide, copper oxen and Bordeaux mixture,

Maine-copper, MANCOZEB, MANEB, mepanipyrim, mepronil, metalaxyl, metconazole,

metasurfaces, mefenoxam, metiram, metalhawk, myclobutanil,

the Nickel dimethyldithiocarbamate, nitrates-isopropyl, nuarimol,

operacy, oxadixyl, oxamate, oxycarboxin,

peyratout, penconazole, pencycuron, forgiven, pimaricin, piperalin, polyoxin, provenzal, prochloraz, procymidone, propamocarb, propiconazole,

propineb, pyrazophos, pirivenas, Pyrimethanil, pyroxylin, hintzen (PCNB),

Seurat and the making of sulphur,

tebuconazol, telital, tecnazene, tetraconazole, thiabendazol, tilian, thiophanate-methyl, thiram, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, trihemic, tricyclazole, tridemorph, triflumizole, triforine, triticonazole, validamycin And, vinclozolin,

zineb, Zir.

Bactericides:

bronopol, dichlorophen, nitrapyrin, dimethyldithiocarbamate Nickel, kasugamycin, Actelion, francebuy acid, oxytetracycline, provenzal, streptomycin, streaming is ftall, copper sulfate and other preparations of copper.

Insecticides, acaricides, nematicides:

the abamectin, Arafat, acrinathrin, alankar, aldicarb, alphamethrin, amitraz, avermectin, AZ 60541, azadirachtin, azinphos And, azinphos M, azocyclotin, Bacillus thuringiensis, 4-bromo-2-(4-chlorophenyl)-1-(ethoxymethyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile, bendiocarb, benfuracarb, bensultap, betasil-UTRAN, bifenthrin, VRMS, papenbrock, bromophos And, bofenkamp, buprofezin, butocarboxim, butylparaben, cadusafos, carbaryl, carbofuran, carbophenothion, carbosulfan, cartap, caretakers, chlorethoxyfos, chlorethoxyfos, Chlorfenvinphos, chlorfluazuron, chlormephos, N-[(6-chloro-3-pyridinyl)-methyl]-N′-cyano-N-methylethanamine,

the chlorpyrifos, chlorpyrifos M, CIS-resmethrin, claritin, clofentezine, cyanophos, cicloprofen, cyfluthrin, cigalotrin, cyhexatin, cypermethrin, cyromazine,

deltamethrin, demeton M, demeton S, demeton-S-methyl, diafenthiuron, diazinon,

dichlofenthion, dichlorvos, declivous, dicrotophos, diation, diflubenzuron, dimethoate,

dimethylene, dioxathion, disulfoton,

edifenphos, emamectin, esfenvalerate, ethiofencarb, ation, etofenprox,

ethoprophos, etofenprox, etrimfos,

fenamiphos, fenazaquin, fenbutatin, fenitrothion, fenobucarb, fanatical, fenoxycarb, fenpropathrin, feneral, fenpyroximate, fenthion, finaler is you, fipronil, fluazinam, fluazuron, flucycloxuron, flucythrinate, flufenoxuron, flavandiols, fluvalinate, fonofos, formation, fosthiazate, tupfenrock, furathiocarb,

HCH, heptenophos, hexaflumuron, hexythiazox,

Imidacloprid, iprobenfos, isazofos, isofenphos, isoprocarb, isoxathion,

ivemectin,

Lamda-cigalotrin, lufenuron,

Malathion, mecarbam, mevinphos, resolvents, metaldehyde, methacrifos,

methamidophos, methidathion, methiocarb, methomyl, metolcarb, milbemectin,

monocrotophos, moxidectin,

naled, NC 184,nitenpyram,

omethoate, oxamyl, oxydemeton M, oxidation,

parathion And parathion M, permethrin, penhoat, Fort, fosalan, phosmet,

phosphamidon, phoxim, pirimicarb, pirimiphos M, pirimiphos And, profenofos,

profenofos, promecarb, propafol, propoxur, prothiofos, procoat,

pymetrozine, pyraclofos, pyraclofos, pyraclofos, peradventure,

prismatron, feverfew, pyridaben, pyrimidifen, pyriproxifen,

finalpos,

coalition, sabots, silaffin, sulfotep, sulprofos,

tebufenozide, tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin, temephos, terram, terbufos, tetrachlorvinphos, titanox, thiodicarb, thiofanox, thiometon, thionazin, thuringiensis, tralomethrin, triuralin, triazophos, treasure, trichlorfon, triflumuron, trimeter, validation, CMS, killchar, YI 5301 /5302, yamethin.

Offer active substances may be present in the preparations are also in a mixture with other known active substances, such as herbicides, and fertilizers and plant growth regulators.

The active substance can be applied as such, in preparations or received from them working forms, such as, for example, ready-to-use solutions, suspensions, wettable powders, pastes, soluble powders, means for dusting and pellets. They use well-known techniques, for example by watering, spraying, atomization, dispersion, foaming, brush, etc. in Addition, it is possible to apply the active substance according to the method of providing extremely fine distribution or injection means or the active substances in the soil. Possible and processing of seed of useful plants.

When processing parts of the useful plants, the concentration of the active substance used in the preparations can vary within wide limits.

It usually is 1-0,0001 wt.%, preferably 0.5 to 0.001 wt.%.

If the seed treatment is usually applied 0.001 to 50 g of active substance per kg of seed, preferably from 0.01 to 10,

Soil at the application site of the active substance are required concentration of from 0.00001 to 0.1 wt.%, preferably 0.0001 to 0.02 weight..

The invention is illustrated by the following examples.

Example 1

To 1.8 g (25 mmol) of hydroxylamine hydrochloride in 20 ml of methanol at 20°slowly add a solution of 3.3 g of 86%potassium hydroxide in 20 ml of methanol. Then portions add 4.0 g (12.8 mmol) of a compound methyl ester α-methoxyimino-α-[2-(2-methyl-phenoxy-methyl)-phenyl]-acetic acid, after which the reaction mixture is stirred at 40°before the end of the reaction is determined by thin-layer chromatography. Then to the reaction mixture are added first, 1.7 g (12.8 mmol) of potassium carbonate, and then 10.8 g (59 mmol) of 1,2-dibromo-ethane. The mixture is stirred for 12 hours at 65°, then cooled to 20°and filtered. The filtrate is concentrated to obtain by water-jet pump vacuum and the residue is purified by chromatography on a column containing silica gel (eluent: toluene and acetone in a volume ratio 9:1).

Obtain 1.4 g (33% of theory) of 3-{α-methoxyimino-α-[2-(2-methyl-phenoxy-methyl)-phenyl]-methyl}-5,6-dihydro-1,4,3-dioxazine. The refractive index of nD20=1,5705.

The target product of this example is obtained by replacing 1,2-dibromo-ethane 1,2-dimethylsulphoxide and 1,2-diphenylsulfone-ethane.

Analogously to example 1 and in accordance with the General description of the proposed method is you can also get listed in the following table 1 the compounds of formula (I).

1H-NMR spectra are absorbed in CDCl3with tetramethylsilane was as an internal standard. Chemical shift, as a rule, are the values δ (see table 1).

*Nachna log P is defined according to EEC-Directive 79/831 Annex V.A8 by high-performance liquid chromatography on obetovannoi column (18) at a temperature of 43°using as an eluent of 0.1%aqueous phosphoric acid and a linear gradient of acetonitrile (10% to 90%). Calibration was carried out linear alkane-2-areas, the value of log P are known (determination of log P values on the basis of the retention times by linear interpolation between two subsequent alkenone and).

Listed in table 1 as example 22 compound can be obtained, for example, as follows:

To a mixture of 1.5 g (6 mmol) 3-[α-methoxyimino-α-(2-hydroxy-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine, 0.9 g (6 mmol) of 4,6-dichloro-pyrimidine and 30 ml of N.N-dimethylformamide add in an ice bath 0.3 g (6 mmol) of a 60%suspension of sodium hydride in a white-washed oil. After removing the ice bath, the reaction mixture is stirred for 15 hours at 20°C. then condense in the vacuum that is created when using the oil pump, the residue is served in a sophisticated ethyl ester acetic acid, washed with water, dried over sodium sulfate and filtered. From the filtrate the solvent is carefully distilled off in vacuum, obtained using a water-jet pump.

Gain of 1.9 g (86% of theory) of 3-{α-methoxyimino-α-[2-(6-chloro-pyrimidine-4-yl-oxy)-phenyl]-methyl}-5,6-dihydro-1,4,2-dioxazine as an oily residue.

The target product of this example can also be obtained when substituting 4,6-dichloro-pyrimidine and 4-chloro-6-methylsulfonyl-pyrimidine or 4-chloro-6-phenylsulfonyl-pyrimidine.

Listed in table 1 as example 23 compound can be obtained, for example, as follows:

A mixture of 0.3 g (0.9 mmol) of 3-[α-methoxyimino-α-[2-(6-chloro-pyrimidine-4-yl-oxy)-phenyl]-IU the Il}-5,6-dihydro-1,4,2-dioxazine, 0.1 g (0.9 mmol) of 2-hydroxybenzonitrile, 0.1 g (0.9 mmol) of potassium carbonate, copper chloride (I) with the end of a spatula and 5 ml of N,N-dimethylformamide is stirred for 15 hours at 100°C. then condense in the vacuum that is created when using the oil pump, the residue is served in a sophisticated ethyl ester acetic acid, washed with water, dried over sodium sulfate and filtered. The filtrate is concentrated and the residue purified by chromatography on a column containing silica gel (eluent: hexane and acetone in a volume ratio 7:3).

Obtain 0.3 g (81% of theory) of 3-{α-methoxyimino-α-[2-(6-(2-cyano-phenoxy)-pyrimidine-4-yl-oxy)-phenyl]-methyl}-5,6-dihydro-1,4,2-dioxazine with a melting point of 82°C.

Listed in table 1 as example 20 compound can be obtained, for example, as follows:

A mixture of 0.5 g (2 mmol) 3-[(α-methoxyimino-α-(2-hydroxy-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine, 0.3 g (2.2 mmol) of 2-methylbenzylamine, 0.4 g (2.5 mmol) of potassium carbonate and 10 ml of acetonitrile is heated under reflux for 15 hours. Then concentrated, the residue is served in methylene chloride, washed with water, dried over sodium sulfate and filtered. From the filtrate the solvent is carefully distilled off in vacuum, obtained using a water-jet pump.

Obtain 0.4 g (59% of theory) of 3-{α-methoxyimino-α-[2-(2-methyl-benzyloxy)phenyl]-methyl}-5,6-dihydro-1,4,2-dioxazine the melting point 142° C.

Obtained according to example 1, the compound can also be obtained, for example, as follows:

0.75 g (2.4 mmol) of 3-[α-methoxyimino-α-(2-methyl bromide-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine and 0.70 g (6.4 mmol) of 2-METHYLPHENOL dissolved in 15 ml of dimethylformamide, after cooling the mixture to -10°slowly added 0.21 g (7.0 mmol) of 80%sodium hydride. After removal of the cooling bath the reaction mixture is stirred for 14 hours at a temperature of not more than 25°C, after which it is poured on water, taken approx. in two-dimensional quantity. After shaking in a mixture with complex ethyl ester acetic acid, the organic phase is separated, washed with 2-N. sodium liquor, dried over sodium sulfate and filtered. From the filtrate the solvent is carefully distilled off under reduced pressure.

Obtain 0.40 g (49% of theory) of 3-{α-methoxyimino-α-[2-(2-methyl-phenoxy-methyl}-phenyl]-methyl}-5,6-dihydro-1,4,2-dioxazine (refractive index: nD20=1,5705).

Listed in table 1 as example 11 compound can be obtained, for example, as follows:

0.20 g (0,56 mmol) of N-(2-hydroxy-ethoxy)-α-methoxyimino-α-[2-(2,4-dimethyl-phenoxy-methyl)-phenyl]-ndimethylacetamide dissolved in 3 ml of chloroform and mixed at 0°With 0.25 g (1,76 mmol) phosphorus is wow anhydride. The reaction mixture is stirred first for one hour at 20°and then for 4 hours at boiling, then pour it into the water, taken approx. double volume number, and shaken. After separation of the organic phase the aqueous phase three times additionally extracted with chloroform. The combined organic extracts are dried over magnesium sulfate, then concentrated and purified by chromatography on a column containing silica gel (eluent: toluene and acetone in the ratio 10:1).

Get 84 mg (42% of theory) of 3-{α-methoxyimino-α-[2-(2,4-dimethyl-phenoxy-methyl}-phenyl]-methyl}-5,6-dihydro-1,4,2-dioxazine.

1H-NMR (D6-DMSO, δ): 4,87; 3,84; 4,38; 4,10 ppm

Getting starting substances of the formula (IV):

Example (IV-1)

9.0 g (28 mmol) of 3-[(α-methoxyimino-α-[2-tetrahydropyran-2-yl-oxy)-benzyl]-5,6-dihydro-1,4,2-dioxazine and 1.8 g of ion exchanger "Lewatit SPC 108" in 90 ml of methanol is stirred for 15 hours at 20°C. afterwards the mixture is concentrated in vacuum, obtained using a water-jet pump, the remainder served in methylene chloride and filtered. The filtrate is concentrated in vacuum, obtained using a water-jet pump, and the residue is purified by chromatography on a column containing silica gel (eluent: hexane and acetone in a volume ratio 7:3).

As of the 1st faction gain is 0.6 g (9% of theory) of 7-{3-[α -methoxyimino-α-(2-hydroxy-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine} in the form of an amorphous product, and as the 2nd fraction and 3.3 g (50% of theory) of o-{3-[α-methoxyimino-α-(2-hydroxy-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine} with a melting point of 153°C.

Getting starting substances of the formula (IX):

Example (IX-1)

To 6.8 g (98 mmol) of hydroxylamine hydrochloride in 290 ml of methanol add to 13.9 g (211 mmol) of 85%aqueous solution of potassium hydroxide and 17 g (58 mmol) of a compound methyl ester α-methoxyimino-α-(2-Tetra-gidropony-2-yl-hydroxy-phenyl)-acetic acid, whereupon the mixture is stirred for one hour at 40°C. Then added to 7.7 g (56 mmol) of potassium carbonate and drops added 42.5 g (226 mmol) of 1,2-dibromethane. The mixture is heated for 15 hours under reflux and then concentrated in vacuum obtained using a water-jet pump. The remainder served in methylene chloride, washed with water, dried over sodium sulfate and filtered. The filtrate is concentrated and the residue purified by chromatography on a column containing silica gel (eluent: hexane and acetone in a volume ratio 7:3).

Obtain 9.0 g (49% of theory) of 3-[α-methoxyimino-α-(2-tetrahydropyran-2-yl-oxy)-benzyl]-5,6-dihydro-1,4,2-dioxazine as an oily product.

Getting starting substances of the Formula (X):

Example (X-1)

To a solution of 203 g (1,81 mol) of tert. the butyl potassium in 2 l of tert. butanol add drops of 564 g (4,93 mol) of tert. butylnitrite and 411 g (1,64 mol) of a compound methyl ester 2-tetrahydropyranyloxy-phenylacetic acid are dissolved in 500 ml of tert. butanol. After 90 minutes, add drops of 350 g (2,47 mol) of methyliodide, after which the mixture is stirred for 15 hours at 20°C. Then in a vacuum produced by water-jet pump, the residue is served in a simple tert.-butyl ether, dried over sodium sulfate and filtered. The residue is crystallized by thererofre with diethyl ether, and the product produce by sucking.

Get to 69.3 g (15% of theory) of a compound methyl ester α-methoxyimino-α-(2-tetrahydropyran-2-yl-hydroxy-phenyl)-acetic acid with a melting point of 79°C.

Getting starting substances of the formula (XI):

Example (XI-1)

A mixture of 500 g (3.0 mol) of a compound methyl ester of 2-hydroxy-phenyl-acetic acid, 506 g (6.0 mol) of 3,4-dihydro-Piran, p-toluensulfonate with the end of a spatula and 2.5 l of tetrahydrofuran is stirred for 15 hours at 20°C, then mixed under stirring with 10%ice-cold aqueous solution of potassium hydroxide, and then add sodium sulfate and filtered. From the filtrate the solvent is carefully distilled off in vacuum, we obtain the by using water-jet pump.

Receive 698 g (99% of theory) of a compound methyl ester 2-tetrahydropyranyl-hydroxy-phenylacetic acid as an oily residue.

Getting starting substances of the formula (VI):

Example (VI-1)

0.50 g (2,13 mmol) 3-[α-methoxyimino-α-[2-methyl-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine and 0.57 g (3.2 mmol) of N-bromo-succinimide served in 10 ml of Tetra-chloromethane and after adding 200 mg of azoisobutyronitrile heated under reflux for 4 hours. After adding further 0,57 g (3.2 mmol) of N-bromo-succinimide, mix for a further hour and heated under reflux. Then it is cooled and filtered, the filtrate concentrated, and the residue is subjected to chromatography on silica gel (eluent: toluene and acetone in the ratio 10:1).

Receive 20 mg (30% of theory) of 3-[α-methoxyimino-α-[2-methyl bromide-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine.1H-NMR (CDCl3that δ): 4,4 ppm

Getting starting substances of the formula (XIII):

Example (XIII-1)

To 19,6 g (0,283 mol) of hydroxylamine hydrochloride in 150 ml of methanol is added slowly a solution 36,9 g (of 0.565 mol) of 86%potassium hydroxide in 150 ml of methanol. Then add portions 30 g (0,145 mol) of a compound methyl ester α-methoxyimino-α-(2-methyl-phenyl)-acetic acid. The mixture is stirred for 3 hours at 50 C. thereafter at 20°add 20 g (0,145 mol) of potassium carbonate and 122 g (with 0.65 mol) of 1,2-dibromethane. The reaction mixture is stirred for 17 hours at 65°C. After cooling is sucked off, the filtrate concentrated, and the residue is subjected to chromatography on silica gel (eluent: toluene and acetone in the ratio 15:1).

Obtain 15.2 g (45% of theory) of 3-[α-methoxyimino-α-[2-methyl-phenyl)-methyl]-5,6-dihydro-1,4,2-dioxazine.1H-NMR (CDCl3that δ): 2,2 ppm

Getting starting substances of the formula (XIV):

Example (XIV-1)

187.5 g (1,673 mol) of tert. the butyl potassium dissolved in 1875 ml of tert. butanol. To this solution add a solution 471,5 g (of 4.57 mol) of tert. butylnitrite and 250 g (1,525 mol) of a compound methyl ester of 2-methyl-phenylacetic acid in 500 ml of tert. butanol so that the internal temperature does not exceed 50°C. the Mixture is stirred for 90 minutes at 20 - 30°C. then add drops 326,5 g (2.3 mol) of methyliodide. The reaction mixture is stirred for 14 hours at 20°C. the solvent is Then distilled off in vacuum, obtained using a water-jet pump, the residue is served in 2 l of water and extracted three times difficult ethyl ester of acetic acid. The combined organic phases are dried over sodium sulfate and filtered. The filtrate is concentrated, the residue is served in 250 ml of isopropanol and boiling with eshivot with water to the cloud point.

After cooling to 0°and With stirring for 60 minutes, vegascasinoonline product produce by sucking.

Get 84.5 g (27% of theory) of a compound methyl ester α-methoxyimino-α-(2-methyl-phenyl)-acetic acid with a melting point of 53°C.

1H-NMR (CDCl3that δ): 2,19 ppm

Getting starting substances of the formula (VIII):

Example (VIII-1)

0.8 g (2.36 mmol) of the acid chloride α-methoxyimino-α-[2-(2,4-dimethyl-phenoxy-methyl)-phenyl]-acetic acid are dissolved in 10 ml of tetrahydrofuran. To this solution was added 0.26 g (2.6 mmol) of triethylamine. Then at 0°add drops of 0.25 g (2.6 mmol) of O-(2-hydroxy-ethyl)-hydroxylamine dissolved in 10 ml of tetrahydrofuran. The reaction mixture is stirred for 2 hours at 20°C. thereafter, it is poured on water and extracted with complex ethyl ester of acetic acid. The extraction solution is dried over magnesium sulfate, concentrated and subjected to chromatography on silica gel (eluent: toluene and acetone in the ratio 10:1).

Obtain 0.4 g (50% of theory) of N-(2-hydroxy-ethoxy)-α-methoxyimino-α-[2-(2,4-dimethyl-phenoxy-methyl)-phenyl]-ndimethylacetamide.

1H-NMR (CDCl3that δ): 3,65; 3,90; 9,15 ppm

Getting starting substances of the formula (XV):

Example (XV-1)

0,93 g (2,95 mmol) α-methoxyiminoα -[2-(2,4-dimethyl-phenoxy-methyl)-phenyl]-acetic acid mixed with 4.0 g (2.9 mmol) of thionyl chloride and 50 mg of dimethylformamide, and the resulting mixture for 30 minutes, stirred under reflux. Then volatile components carefully distilled off under reduced pressure.

Obtain 0.95 g of the acid chloride α-methoxyimino-α-[2-(2,4-dimethyl-phenoxy-methyl)-phenyl]-acetic acid as an oily residue.

Example (XV-2)

2.0 g (6.1 mmol) of a compound methyl ester α-methoxyimino-α-[2-(2,4-dimethyl-phenoxy-methyl)-phenyl]-acetic acid dissolved in 20 ml of isopropanol. To this solution was added 30 ml of 1 N. sodium lye. Then the mixture is stirred for 14 hours at 40°C, after which it is poured on water. Then 2 N. sodium liquor pH was adjusted to 6, and vegascasinoonline product produce by sucking.

Receive 1.5 g (78% of theory) α-methoxyimino-α-[2-(2,4-dimethyl-phenoxy-methyl)-phenyl]-acetic acid.

1H-NMR (CDCl3that δ): 3,9; 4,85 ppm

Fungicidal activity of substituted audiocassettes formula (I) of the following examples.

Example

Experience with Pyrenophora teres (barley)/protective action

1 weight. part of the active substance is mixed with 10 weight. parts of N-methylpyrrolidone as solvent and 0.6 weight. part II of Otago alkylarylsulphonates ether as an emulsifier, and the resulting concentrate is diluted with water to the desired concentration.

To study the protective effects of young plants are sprayed with the preparation of the active substance to the formation of droplets. After priyanie drug plants are sprayed with a conidial suspension of Pyrenophora teres. Then plants within 48 hours stored in an incubation chamber at a temperature of 20°C and a relative humidity of 100%.

The plants kept in the greenhouse at a temperature of about 20°C and a relative humidity of about 80%.

7 days after inoculation assess.

When it determines that the degree of activity of the compound of example 1 is 100% at a rate of 400 g/ha

The same activity is exhibited by compounds of examples 6, 8, 19, 23, 24, 39, 44, 46, 47, 52, 53, 65, 69, 72, 78, 79.

If you apply the compounds of examples 2, 15, 16, 26 and 29 at the rate of 250 g/ha, the degree of activity of respectively 83, 67, 67, 72, and 68% of the untreated control plants.

Example B

Experience with Phytophthora (tomatoes)/system action

1 weight. part of the compound of example 1 as the active substance is mixed with 4.7 weight. parts of acetone as a solvent and 0.6 weight. part of the simple alkylarylsulphonates ether as an emulsifier, and the resulting concentrate is diluted with water to the desired concentration.

To study systemic properties of the active drug substance is poured on the soil, which is Oh are prepared to conduct the experience of young plants. 3 days after treatment the plants inoculant aqueous spore suspension of Phytophthora infestans.

Then the plants are kept in an incubation chamber at a temperature of about 20°C and a relative humidity of 100%.

3 days after inoculation assess.

When it determines that the degree of activity of the compound of example 1 is 58% at a concentration of 100 h/million

The example In

Experience with Pyricularia (rice) / system action.

1 weight. part of the compound of example 1 as the active substance is mixed with 12.5 weight. parts of acetone as a solvent and 0.3 weight. part of the simple alkylarylsulphonates ether as an emulsifier, and the resulting concentrate is diluted with water to the desired concentration.

For the study of system properties 40 ml of the active substance is poured on the soil in which grew young rice plants. 7 days after treatment the plants inoculant aqueous spore suspension Pyricularia oryzae. After this plant before the assessment is kept in a greenhouse at a temperature of 25°C and a relative humidity of 100%.

4 days after inoculation assessing the damage.

When it determines that the degree of activity of the compound of example 1 is 80% at a flow rate of 100 mg/100 ml

Example D

Experience with Venturia (Apple)/protective

1 weight. part of the active substance is mixed with 4.7 weight. h the amount of acetone as a solvent and 0.3 weight. part alkylarylsulphonates simple ether as an emulsifier, and the resulting concentrate is diluted with water to a concentration equal to 2.5 h/million

To test for protective activity, young plants are sprayed with the composition of biologically active substances. After drying of the deposited plants inoculant with an aqueous suspension of conidia of the pathogen of Apple scab Venturia inaequalis and then leave for one day in an incubation chamber at a temperature of 20°C and 100%relative humidity.

Then the plants are placed in a greenhouse at a temperature of 20°C and a relative humidity of about 70%.

Twelve days after inoculation to determine the percentage of the activity in comparison with untreated control plants. The results of the experiment are summarized in table 2.

Table 2
The active substance of Example No.The degree of activity in % of the untreated control plants
297
3100
1199
12100
1392
15100
17100
1898
3099
8099
9393

Example D

Experience with Sphaerotheca (cucumbers) / protective

1 weight. part of the active substance is mixed with 4.7 weight. parts of acetone as a solvent and 0.3 weight. part alkylarylsulphonates simple ether as an emulsifier, and the resulting concentrate is diluted with water to a concentration equal to 10 h/million

To test for protective activity, young plants are sprayed with the composition of biologically active substances. After drying of the deposited plants are pollinated with conidia of the fungus Sphaerotheca fuliginea. Then the plants are placed in a greenhouse at a temperature of 23-24°C and a relative humidity of about 75%.

Ten days after inoculation to determine the percentage of the activity in comparison with untreated control plants. The results of the experiment are summarized in table 3.

/tr>
Table 3
The active substance of example No.The degree of activity in % of the untreated control plants
11100
1295
1495
3094
3396
5192
80100
93100

Example E Experience with Pseudocercosporella herpotrichoides (wheat) / protective

1 weight. part of the active substance is mixed with 10 weight. parts M-methylpyrrolidone as solvent and 0.6 weight. part alkylarylsulphonates simple ether as an emulsifier, and the resulting concentrate is diluted with water.

To test for protective activity, young plants are sprayed with the composition of biologically active substances, with the biologically active substance is applied in a quantity of 250 g/ha After drying of the deposited plants inoculant at the base of the stem disputes Pseudoercosporella herpotrichoides. Then the plants are placed in a greenhouse at a temperature of about 10°C and a relative humidity of about 80%.

Twenty-one days after inoculation to determine the percentage of the activity in comparison with untreated control plants.

The results of the experiment are summarized in table 4.

/tr>
Table 4
The active substance of example No.The degree of activity in % of the untreated control plants at the rate of consumption of the active substance, equal to 250 g/ha
575
11100
1290
1590
24100
3890

Example G

Experience with Cochliobolus sativus (barley) / protective

1 weight. part of the active substance is mixed with 10 weight. parts of N-methylpyrrolidone as solvent and 0.6 weight. part alkylarylsulphonates simple ether as an emulsifier, and the resulting concentrate is diluted with water.

To test for protective activity, young plants are sprayed with the composition of biologically active substances, with the biologically active substance is applied in a quantity of 250 g/ha

After drying the applied composition of plants is sprayed with a water suspension of conidia of Cochliobolus sativus.

Plants are placed in a greenhouse at a temperature of approximately 20°C and a relative humidity of about 80%.

Twenty-one days after inoculation to determine the percentage of the activity in comparison with untreated control plants at the rate of 250 g/ha

The results of the experiment are summarized in table 5.

Table 5
The active substance of example No.The degree of activity in % of the untreated control plants at the rate of active washes the VA, equal to 250 g/ha
1170
1662
2681

1. Substituted azadeoxycytidine General formula (I)

where a is dimethylene (ethane-1,2-diyl), unsubstituted or substituted stands;

Ar - ortho-phenylene, unsubstituted or substituted by fluorine, theoffender or pyridinyl;

E - a group of the formula

G - oxygen group,- O-CH2-, -CH2-O - or-C(CH3)=N-O-CH2-;

Z - phenyl, pyrimidinyl or thiadiazolyl, unsubstituted or one - or twofold substituted by substituents from the group comprising methyl, ethyl, n - or isopropyl, n-, ISO-, sec - or tert-butyl, methoxy, ethoxy, trifluoromethyl, triptoreline, deformedarse, fluorine, chlorine, bromine, methylthio, ethylthio, H3C-O-N=CH-, benzyloxy, naphthyloxy, pyridinyl, pyridylthio, pyridyloxy, benzylthio, unsubstituted or substituted by chlorine or stands, thienyl, unsubstituted or substituted stands, phenyl, unsubstituted or substituted by 1 or 2 identical or different substituents from the group comprising methyl, ethyl, methoxy, ethoxy, deformations, trifluoromethyl, fluorine, chlorine and bromine, fenoxaprop, unsubstituted or substituted by 1 or 2 identical or different substituents from gr is PPI, comprising fluorine, chlorine, bromine, cyano, methyl, methoxy, ethyl, deformations, trifluoromethyl, methoxycarbonyl and dimethylaminoethanol, and phenylthiourea, unsubstituted or substituted once by fluorine, chlorine or bromine, or Z means naphthyl.

2. The method of obtaining substituted audiocassettes General formula (I)

where a is dimethylene (ethane-1,2-diyl), unsubstituted or substituted stands;

Ar - orthophenylene, unsubstituted or substituted by fluorine, theoffender or pyridinyl;

E - a group of the formula

G - oxygen group,- O-CH2-, -CH2-O - or-C(CH3)=N-O-CH2-,

Z - phenyl, pyrimidinyl or thiadiazolyl, unsubstituted or one - or twofold substituted by substituents from the group comprising methyl, ethyl, n - or isopropyl, n-, ISO-, sec - or tert-butyl, methoxy, ethoxy, trifluoromethyl, triptoreline, deformedarse, fluorine, chlorine, bromine, methylthio, ethylthio, H3C-O-N=CH-, benzyloxy, naphthyloxy, pyridinyl, pyridylthio, pyridyloxy, benzylthio, unsubstituted or substituted by chlorine or stands, thienyl, unsubstituted or substituted stands, phenyl, unsubstituted or substituted by 1 or 2 identical or different substituents from the group comprising methyl, ethyl, methoxy, ethoxy, deformations, cryptomite is, fluorine, chlorine and bromine, fenoxaprop, unsubstituted or substituted by 1 or 2 identical or different substituents from the group comprising fluorine, chlorine, bromine, cyano, methyl, methoxy, ethyl, deformations, trifluoromethyl, methoxycarbonyl and dimethylaminoethanol, and phenylthiourea, unsubstituted or substituted once by fluorine, chlorine or bromine, or Z means naphthyl,

characterized in that the carboxylic acid derivatives of General formula (II)

where Ar, E, G and Z have the above meanings;

R represents a C1-C4-alkyl,

subjected to interaction with hydroxylamine or its kaleidotrope salt optionally in the presence of an acid acceptor and optionally in the presence of a diluent, the resulting product is subjected to interaction with disubstituted alkanes General formula (III)

where a has the above meaning;

X is halogen, alkylsulfonate or phenylsulfonyl,

optionally, in the presence of an acid acceptor and optionally in the presence of a diluent, followed by separation of the target product.

3. The method of obtaining substituted audiocassettes General formula (I)

where a is dimitile the (ethane-1,2-diyl);

Ar - ortho-phenylene;

E - a group of the formula

G is oxygen or the group-CH2-O-;

Z - phenyl, pyrimidinyl, replaced by stands, ethyl, fluorine, chlorine, bromine, fenoxaprop, substituted cyano,

characterized in that hydroxyanisole compounds of General formula (IV)

where A, Ar, and E have the above values,

subjected to interaction with compounds of General formula (V)

where Z has the above meanings;

m denotes 0 or 1;

X means halogen,

optionally, in the presence of an acid acceptor and optionally in the presence of a diluent, followed if necessary by converting the group Z in the desired value and selection of the target product.

4. The method of obtaining substituted audiocassettes General formula (1)

where a is dimethylene (ethane-1,2-diyl);

Ar - orthophenylene;

E - a group of the formula

G - group,- O-CH2-;

Z is phenyl, substituted by stands or ethyl,

characterized in that halogenmethyl compounds of General formula (VI)

p num="450"> where A, Ar, and E have the above meanings;

X1means halogen,

subjected to interaction with compounds of General formula (VII)

where Z has the above meaning,

optionally, in the presence of an acid acceptor and optionally in the presence of a diluent, followed by separation of the target product.

5. The method of obtaining substituted audiocassettes General formula (I)

where a is dimethylene (ethane-1,2-diyl);

Ar - orthophenylene;

E - a group of the formula

G - group-CH2-O-;

Z is phenyl, substituted by stands or ethyl,

characterized in that hydroxyalkylated General formula (VIII)

where

A, Ar, E, G and Z have the above values,

subjected to cyclization Volodarsk means if necessary in the presence of a diluent.

6. The compounds of formula (IV)

where a is dimethylene (ethane-1,2-diyl);

Ar - orthophenylene;

E - a group of the formula

as intermediates for compounds of formula (I).

7. The compounds of formula (IX)

where a is dimethylene (ethane-1,2-diyl);

Ar - orthophenylene;

E - a group of the formula

as intermediates for compounds of formula (I).

8. The compounds of formula (VI)

where

A - dimethylene (ethane-1,2-diyl);

Ar - orthophenylene;

E - a group of the formula

X1- halogen,

as intermediates for compounds of formula (I).

9. The compounds of formula (XIII)

where a is dimethylene (ethane-1,2-diyl);

Ar - orthophenylene;

E - a group of the formula

as intermediates for compounds of formula (I).

10. The compounds of formula (VIII)

where a is dimethylene (ethane-1,2-diyl);

Ar - orthophenylene;

E - a group of the formula

G - group-CH2-O-;

Z is phenyl, substituted stands,

as intermediates for compounds of formula (I).

11. Fungicidal agent, characterized in that they contain a compound of the formula (I) according to claim 1 as an active ingredient.

12. SP is a way to get fungicidal funds according to claim 11, characterized in that compounds of the formula (I) according to claim 1 are mixed with extenders and/or surfactants.

13. The method of combating unwanted fungi, characterized in that compounds of the formula (I) according to claim 1 treated with fungi and/or their habitat.



 

Same patents:

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

SUBSTANCE: invention describes derivatives of benzodiazepine of the general formula (I)

and their pharmaceutically acceptable acid-additive salts wherein X means a ordinary bond or ethynediyl group; when X means ordinary bond then R1 means halogen atom, (lower)-alkyl, (lower)-alkylcarbonyl, (lower)-cycloalkyl, benzoyl, phenyl substituted optionally with halogen atom, hydroxyl, (lower)-alkyl, (lower)-alkoxy-group, halogen-(lower)-alkoxy-group or cyano-group; styryl, phenylethyl, naphthyl, diphenyl, benzofuranyl, or 5- or 6-membered heterocyclic ring representing thiophenyl, furanyl, pyridinyl, dihydropyridinyl, tetrahydropyridinyl which are optionally substituted; when X means ethynediyl group then R1 means hydrogen atom, (lower)-alkyl substituted optionally with oxo-group; (lower)-cycloalkyl substituted with hydroxyl; (lower)-cycloalkenyl substituted optionally with oxo-group; (lower)-alkenyl, optionally substituted phenyl; 5- or 6-membered heterocyclic ring representing thiophenyl, thiazolyl, pyridinyl, dihydropyridinyl, tetrahydropyridinyl or dihydropyranyl and substituted optionally; R3 means phenyl, pyridyl, thiophenyl or thiazolyl which are substituted optionally. These compounds can be used for treatment or prophylaxis of acute and/or chronic neurological diseases, such as psychosis, schizophrenia, Alzheimer's disease, disorder of cognitive ability and memory disorder. Also, invention describes a medicinal agent based on these compounds and a method for preparing compounds of the formula (I).

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

10 cl, 1 tbl, 173 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of aminomethylpyrrolidine of the formula (I) , their salts or hydrates wherein R1 represents aryl with from 6 to 10 carbon atoms or heteroaryl wherein heteroaryl is a five-membered ring or a six-membered ring and comprises from 1 to 2 heteroatoms taken among nitrogen, oxygen and sulfur atom; aryl and heteroaryl can comprise one or more substitutes taken among the group consisting of halogen atom or (C1-C6)-alkoxyl; each radical among R2, R3, R4, R5, R6, R7 and R8 represents hydrogen atom (H) independently; Q represents incomplete structure representing by the following formula: wherein R9 means (C3-C6)-cyclic alkyl that can be substituted with halogen atom; R10 means hydrogen atom (H); R11 means hydrogen atom (H), NH2; X1 means halogen atom; A1 represents incomplete structure representing by the formula (II): wherein X2 means hydrogen atom (H), halogen atom, halogenmethoxyl group, (C1-C6)-alkyl or (C1-C6)-alkoxyl group; X2 and above indicated R9 can be combined to form the ring structure and inclusion part of the main skeleton and such formed ring comprises oxygen, nitrogen or sulfur atom as a component atom of the ring and the ring can comprise (C1-C6)-alkyl as a substitute; Y means hydrogen atom (H). Compounds of the formula (I) elicit an antibacterial effect and can be used for preparing a therapeutic agent.

EFFECT: valuable medicinal properties of compounds.

2 tbl, 61 ex

FIELD: pharmaceutical industry, medicine.

SUBSTANCE: invention relates to 5-membered N-heterocyclic compounds and salts thereof having hypoglycemic and hypolipidemic activity of general formula I , wherein R1 is optionally substituted C1-C8-alkyl, optionally substituted C6-C14-aryl or optionally substituted 5-7-membered heterocyclic group, containing in ring 1-4 heteroatoms selected from oxygen, sulfur and nitrogen; or condensed heterocyclic group obtained by condensation of 5-7-membered monoheterocyclic group with 6-membered ring containing 1-2 nitrogen atoms, benzene ring, or 5-membered ring containing one sulfur atom; { is direct bond or -NR6-, wherein R6 is hydrogen atom or C1-C6-alkyl; m = 0-3, integer; Y is oxygen, -SO-, -SO2- or -NHCO-; A ring is benzene ring, condensed C9-C14-aromatic hydrocarbon ring or 5-6-membered aromatic heterocyclic ring containing 1-3 heteroatoms selected from oxygen and nitrogen, each is optionally substituted with 1-3 substituents selected from C7-C10-aralkyloxy; hydroxyl and C1-C4-alkoxy; n = 1-8, integer; B ring is nitrogen-containing 5-membered heterocycle optionally substituted with C1-C4-alkyl; X1 is bond, oxygen or -O-SO2-; R2 is hydrogen atom, C1-C8-alkyl, C7-C13-aralkyl or C6-C14-aryl or 5-6-membered heterocyclic group containing in ring 1-3 heteroatoms selected from oxygen, sulfur and nitrogen, optionally substituted with 1-3 substituents; W is bond, C1-C20-alkylene or C1-C20-alkenylene; R3 is -OR8 (R8 is hydrogen or C1-C4-alkyl) or -NR9R10 (R9 and R10 are independently hydrogen or C1-C4-alkyl). Compounds of present invention are useful in treatment of diabetes mellitus, hyperlipidemia, reduced glucose tolerance, and controlling of retinoid-associated receptor.

EFFECT: new medicines for treatment of diabetes mellitus, hyperlipidemia, etc.

26 cl, 518 ex, 3 tbl

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to new derivatives of phenylpiperazine of the formula (I): , wherein X represents 1) group of the formula (1): , wherein S1 means hydrogen, halogen atom; S2 and S3 mean independently of one another hydrogen atom, (C1-C6)-alkyl, phenyl or benzyl; S4 means two hydrogen atoms, oxo-group; S5 means hydrogen atom (H), (C1-C4)-alkyl; Y means CH2, oxygen atom (O), sulfur atom (S); or 2) group of the formula (2): , wherein S1 has above given values; R means hydrogen atom (H), (C1-C4)-alkyl, (C2-C6)-alkoxyalkyl, (C2-C4)-alkenyl or (C2-C4)-alkynyl; or 3) group of the formula (3): wherein S1 has above given values; Z means CH2, oxygen atom (O), nitrogen atom (N); or 4) group of the formula (4): , wherein S1 has above given values; or 5) group of the formula (5): , wherein S1 has above given values; A means oxygen atom (O), nitrogen atom (N) linked with piperazine ring at position 5 or 8; or 6) group of the formula (6): , wherein S1 has above given values; S6 and S7 mean hydrogen atom or oxo-group; or 7) group of the formula (7): , wherein one of dotted line can represent a double bond; S1 has above given values; P = T = Q mean nitrogen atom or P = T mean nitrogen atom; Q means CH or CH2; or P = Q mean nitrogen atom; T means CH, CH2, CH-CH3, C-CH3; or P means nitrogen atom; T means CH, CH2; Q represents sulfur atom; m = 2-6; n = 0-2; R5 and R6 mean independently of one another hydrogen atom (H), (C1-C3)-alkyl; or R5 + R6 represent group -(CH2)p- wherein p = 3-5; R7 means (C1-C3)-alkyl, (C1-C3)-alkoxy-, halogen atom, cyano-group; or R6 + R7 (R7 at position 7 of indole ring) mean group -(CH2)q wherein q = 2-4, and their salts. Compound of the formula (I) elicit high affinity both to dopamine D2-receptor and to serotonin reuptake site that allows their applying in treatment of the central nervous system diseases.

EFFECT: valuable medicinal properties of compounds.

5 cl, 3 tbl, 4 sch, 8 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to new derivatives of dihydropyrimidine of the general formula (I):

or its isomeric form of the formula (Ia):

that can be used, for example, for treatment and prophylaxis of hepatitis B. In indicated formulas R1 means unsubstituted phenyl or phenyl substituted once or many times with similar or different substitutes taken among the group including halogen atom, trifluoromethyl group, nitro-, amino-group, hydroxyl and alkyl with 1-6 carbon atoms, or residues of formulas:

, or ; R2 means residue of the formula -XR5 wherein X means a bond or oxygen atom; R5 means alkenyl with 2-4 carbon atoms or alkyl with 1-4 carbon atoms that can be unsubstituted or substituted with phenoxy-group; R3 means amino-group, alkyl with 1-4 carbon atoms or cyclopropyl; R4 means pyridyl that is substituted with up to three times with similar or different substitutes taken among the group including halogen atom, trifluoromethyl group, alkoxy-group with 1-6 carbon atoms and alkyl with 1-6 carbon atoms, and their salts. Also, invention relates to 3,5-difluoro-2-pyridincarboxyimidamide and 3,5-difluoro-2-pyridincarbonitrile that can be sued as intermediates products for preparing compounds of the formula (I) or (Ia) and to a medicinal gent.

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

10 cl, 2 sch, 4 tbl, 9 ex

The invention relates to new derivatives of nitrogen-containing heterocyclic compounds of the formula

or their pharmaceutically acceptable salts, where R1represents H, COCOR2, COOR3or SO2R3, R2is1-6alkyl, C1-6alkenyl,5-7cycloalkyl, 2-thienyl, 3-thienyl, phenyl or substituted phenyl, R3is phenylalkyl,represents a saturated five-membered nitrogen-containing heterocyclic ring with one nitrogen atom or benzododecinium saturated six-membered nitrogen-containing heterocyclic ring;is oxazol, oxadiazole or thiazole, And is associated with carbon atom of the five-membered heteroaromatic rings and represents COO(CH2)mAr,where R1has the values listed above or is CONR4(CH2)mAr or (CH2)mO(CH2)nAr and R1cannot be COCOR2or SO2R3, R4represents H or<

The invention relates to new N-heterocyclic derivatives of the formula (I):

where: A means-OR1-C(O)N(R1R2or-N(R1R21; each X, Y and Z independently represents N or C(R19); each U represents N or C(R5), provided that U is N only when X represents N, and Z and Y denote CR19; each W represents N or CH; V denotes: (1) N(R4); (2) C(R4)H; or (3) the groupdirectly related to the group -(C(R14R20)n-A,denotes a 5-6-membered N-heterocyclyl, optionally containing 6-membered ring additional heteroatom selected from oxygen, sulfur and NR6where R6denotes hydrogen, optionally substituted phenyl, 6-membered heterocyclyl containing 1-2 nitrogen atom, optionally substituted 5-membered heterocyclyl containing 1-2 nitrogen atom, aminosulfonyl, monoalkylammonium, dialkylaminoalkyl,1-6alkoxycarbonyl, acetyl, etc

The invention relates to organic chemistry, in particular, optionally N-oxidized compounds represented by the formula:

in which R1represents a hydrogen atom, a C1-6alkyl group, phenyl group, optionally substituted by a halogen atom, a C1-6alkylthio or C1-6alkylsulfonyl, or amino group, optionally substituted (i) C1-6alkyl group, or (ii) acyl group(C=O)-R5where R5represents C1-6alkyl group, phenyl or pyridyl; R2is6-14aryl group, optionally substituted by a halogen atom or C1-6alkoxy, or 5 - or 6-membered aromatic heterocyclic group containing one sulfur atom or one nitrogen atom; R3represents a phenyl group, optionally substituted by one or two C1-6alkyl groups or C1-6alkoxy; X represents a sulfur atom; Y represents O, S, SO2or NR4where R4represents a hydrogen atom or a C1-6alkyl group; and Z represents a bond, C1-6alkylenes group, optional zameshannuu oxo or C1-6alkyl group

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

FIELD: organic chemistry.

SUBSTANCE: method relates to new method for production of 5-chloro-4-[(2-imidazoline-2-yl)amino]-2,1,3-benzothiadiazole hydrochloride of formula I . Claimed compound is high effective drug and is used in medicine as myorelaxant of central action. Claimed method includes condensation of N,N-dimethyldichloromethyleneammonium chloride with 5-chloro-4-amino-1,1,3-benzothiadiazole in organic solvent followed by treatment of formed alpha-chloroformamidine of formula R-N=C(Cl)N(CH3)2, wherein R is 5-chloro-2,1,3-benzothiazol-4-yl, with ethylenediamine. Formed intermediate of formula R-N=C(NH-CH2-CH2-NH2)N(CH3)2 is treated with hydrochloric acid, heated in organic solvent and 5-chloro-4-[(2-imidazoline-2-yl)amino]-2,1,3-benzothiadiazole hydrochloride of formula I is isolated.

EFFECT: simplified method for preparation of target compound directly in hydrochloride form.

FIELD: pharmaceutical industry, medicine.

SUBSTANCE: invention relates to 5-membered N-heterocyclic compounds and salts thereof having hypoglycemic and hypolipidemic activity of general formula I , wherein R1 is optionally substituted C1-C8-alkyl, optionally substituted C6-C14-aryl or optionally substituted 5-7-membered heterocyclic group, containing in ring 1-4 heteroatoms selected from oxygen, sulfur and nitrogen; or condensed heterocyclic group obtained by condensation of 5-7-membered monoheterocyclic group with 6-membered ring containing 1-2 nitrogen atoms, benzene ring, or 5-membered ring containing one sulfur atom; { is direct bond or -NR6-, wherein R6 is hydrogen atom or C1-C6-alkyl; m = 0-3, integer; Y is oxygen, -SO-, -SO2- or -NHCO-; A ring is benzene ring, condensed C9-C14-aromatic hydrocarbon ring or 5-6-membered aromatic heterocyclic ring containing 1-3 heteroatoms selected from oxygen and nitrogen, each is optionally substituted with 1-3 substituents selected from C7-C10-aralkyloxy; hydroxyl and C1-C4-alkoxy; n = 1-8, integer; B ring is nitrogen-containing 5-membered heterocycle optionally substituted with C1-C4-alkyl; X1 is bond, oxygen or -O-SO2-; R2 is hydrogen atom, C1-C8-alkyl, C7-C13-aralkyl or C6-C14-aryl or 5-6-membered heterocyclic group containing in ring 1-3 heteroatoms selected from oxygen, sulfur and nitrogen, optionally substituted with 1-3 substituents; W is bond, C1-C20-alkylene or C1-C20-alkenylene; R3 is -OR8 (R8 is hydrogen or C1-C4-alkyl) or -NR9R10 (R9 and R10 are independently hydrogen or C1-C4-alkyl). Compounds of present invention are useful in treatment of diabetes mellitus, hyperlipidemia, reduced glucose tolerance, and controlling of retinoid-associated receptor.

EFFECT: new medicines for treatment of diabetes mellitus, hyperlipidemia, etc.

26 cl, 518 ex, 3 tbl

FIELD: organic chemistry, pharmaceutical composition.

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

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

23 cl, 3 dwg, 43 ex

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

SUBSTANCE: invention relates to derivatives of heteroarylalkylpiperazine of the general formula (I):

wherein m = 1, 2 or 3; q means NH or oxygen atom (O); R1, R2, R3, R4 and R5 are taken independently among the group including hydrogen atom, (C1-C15)-alkyl, OR20 wherein R20 represents hydrogen atom; R6, R7 and R8 represent hydrogen atom; R9, R10, R11, R12, R13, R14, R15 and R16 are taken independently among the group including hydrogen atom, (C1-C4)-alkyl; or R9 and R10 in common with carbon atom to which they are joined form carbonyl group; R17 means heteroaryl that is taken among the group including indolyl, benzoxazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, pyridyl, benzopyrazinyl substituted optionally with 1-2 substitutes taken among the group including hydrogen atom, CF3 group, (C1-C8)-alkyl, phenyl, CON(R20)2. Compounds elicit property as a partial inhibitor of oxidation of fatty acids and can be used in therapy for protection of skeletal muscles against results of muscular or systemic diseases. Also, invention describes a pharmaceutical composition based on the claimed compounds.

EFFECT: valuable medicinal properties of compounds.

39 cl, 3 tbl, 25 ex

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

The invention relates to new derivatives of nitrogen-containing heterocyclic compounds of the formula

or their pharmaceutically acceptable salts, where R1represents H, COCOR2, COOR3or SO2R3, R2is1-6alkyl, C1-6alkenyl,5-7cycloalkyl, 2-thienyl, 3-thienyl, phenyl or substituted phenyl, R3is phenylalkyl,represents a saturated five-membered nitrogen-containing heterocyclic ring with one nitrogen atom or benzododecinium saturated six-membered nitrogen-containing heterocyclic ring;is oxazol, oxadiazole or thiazole, And is associated with carbon atom of the five-membered heteroaromatic rings and represents COO(CH2)mAr,where R1has the values listed above or is CONR4(CH2)mAr or (CH2)mO(CH2)nAr and R1cannot be COCOR2or SO2R3, R4represents H or<

The invention relates to sulfhemoglobinemia heterocyclic compound represented by formula (I), its pharmaceutically acceptable salts and their hydrates

where the values of A, B, K, T, W, X, Y, U, V, Z, R1specified in paragraph 1 of the claims

The invention relates to new and nitrate salts of compounds of formulas (I) to(VI), which can be used in medicine for the treatment of bone disorders such as abnormalities in bone and joints
The invention relates to a method for producing 5-chloro-4-/(2-imidazolin-2-yl)amino/-2,1,3-benzothiadiazole the hydrochloride by hydrochlorination 5-chloro-4-/(2-imidazolin-2-yl)amino/-2,1,3-benzothiadiazole of concentrated hydrochloric acid in the environment of ethyl alcohol at 20-35With target product is separated from the reaction mixture by dilution with water, heating to 75-80With that clarification of the resulting solution activated carbon, cooling the clarified solution to 0-2With, then the selected product is filtered, washed with alcohol and dried at 70C in vacuum (120 mm RT.CT.) get 5-chloro-4-/(2-imidazolin-2-yl)amino/-2,1,3-benzothiadiazole hydrochloride with a melting point 292-294C (with decomposition) and mass fractions of the main substance of at least 99.8%, the product yield is 80% on the original basis

The invention relates to compounds of formula (I)

in which f represents phenylenebis radical, a represents the radical

in which Rl, R2, R3, R4, R5represent independently a hydrogen atom, IT is a group or an unbranched or branched alkyl or alkoxyalkyl having from 1 to 6 carbon atoms; R11represents a hydrogen atom, an unbranched or branched alkyl radical having from 1 to 6 carbon atoms, or the radical

in which Rl, R2, R3, R4, R5represent independently a hydrogen atom, IT is a group or an unbranched or branched alkyl or alkoxyalkyl having from 1 to 6 carbon atoms; b is a thiophene; W is absent or represents an Association or S; X represents a bond or a radical -(CH2)k-NR16-, -O-, -CO-, -NR16-CO-, and so forth, and k is 0 or 1; Y represents a bond or a radical selected from the radicals -(CH2)m-, -(CH2)m-O-(CH2)n, -(CH-Q-(CH2)n; and Q represents pieperazinove radical, m and n are equal to integers from 0 to 6; R16, R17, R18represent independently a hydrogen atom, or a salt of the compounds

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of cyclic amide of the formula (I)

or its salt, or hydrate, or solvate wherein X represents (C1-C6)-alkyl, (C1-C6)-alkyl substituted with phenyl, (C2-C6)-alkenyl substituted with phenyl or halogenphenyl, (C2-C6)-alkynyl substituted with phenyl, phenyl that can be substituted with (C1-C6)-alkyl; one or more halogen atom, nitro-group, phenyl, (C1-C6)-alkoxy-group, halogen-(C1-C6)-alkyl, halogen-(C1-C6)-alkoxy-group, phenyl-(C1-C6)-alkyl, (C1-C6)-alkoxyphenyl-(C1-C6)-alkyl, amino-group, optionally substituted with (C1-C6)-alkyl, acetyl, (C1-C6)-alkoxy-group, substituted with phenyl, phenylcarbonyl, furanyl; 1- or 2-naphthyl, monocyclic (C3-C8)-cycloalkyl, amino-group substituted with one or more substitutes taken among phenyl, halogenphenyl, (C1-C6)-alkoxyphenyl, (C1-C6)-alkyl, halogen-(C1-C6)-alkyl, phenyl-(C1-C6)-alkyl; 5- or 6-membered monocyclic heterocyclic group comprising 1 or 2 heteroatoms, such as nitrogen (N), oxygen (O), sulfur (S) atom optionally substituted with halogenphenyl, halogen atom, benzyl, (C1-C6)-alkyl, phenyl; 8-10-membered bicyclic heteroaryl group comprising 1 or 2 heteroatoms taken among N, O and optionally substituted with halogen atom; 8-10-membered polycyclic cycloalkyl group; Q means -CH2-, -CO-, -O-, -S-, -CH(OR7)- or -C(=NR8)- wherein R7 means hydrogen atom (H), (C1-C6)-alkyl; R8 means OH, (C1-C)-alkoxy-group, acylamino-group, (C1-C6)-alkoxycarbonylamino-group, phenyl-(C1-C6)-alkoxy-group; n = 0-5; B represents group or wherein each among R3, R4, R5 and R6 represents independently substitute taken among group consisting of hydrogen atom (H), halogen atom, NO2 (nitro-group), (C1-C6)-alkoxy-group, CN (cyano-group); m = 1 or 2; ring represents 5- or 6-membered aromatic heterocyclic ring comprising one or two heteroatoms taken among O, S, N. Compound of the formula (I) elicit activity inhibiting binding sigma-receptors that allows their using as component of medicinal agent.

EFFECT: valuable medicinal properties of compounds.

21 cl, 2 sch, 4 tbl, 183 ex

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