2-amino-4-bicycloamino-1,3,5-triazines, herbicide agent based on thereof and method for weeds control

FIELD: organic chemistry, herbicides.

SUBSTANCE: invention describes novel 2-amino-4-bicycloamino-1,3,5-triazines of the general formula (I): wherein R1 and R2 mean independently hydrogen atom, amino-group, (C1-C6)-alkyl, (C1-C4)-alkanoyl, phenylalkyl c 1-6 carbon atoms in alkyl moiety and possibly substituted with halogen atom; or R1 and R2 in common with nitrogen atom to which they are bound form morpholino-group; R3 means hydrogen atom, (C1-C6)-alkyl possibly substituted with halogen atom, hydroxy-, amino-, di-(C1-C4-alkyl)amino-, cyano-group, phenyl, (C1-C4)-alkoxy-, carboxy-group or (C3-C9)-cycloalkyl that can be substituted with halogen atom, phenyl possibly substituted with halogen atom, (C1-C6)-alkyl, hydroxy-group or phenyl, amino-, di-(C1-C4-alkyl)amino-, (C1-C6)-alkoxy-, (C1-C6)-alkylthio-group, or (C2-C6)-alkenyl; R4 and R5 mean independently hydrogen atom, (C1-C4)-alkyl or (C1-C4)-alkanoyl; R6 means independently (C1-C6)-alkyl, (C1-C6)-alkoxy-group or halogen atom; Y1 means a direct bond or -CH2-; Y2 means group -CRaRb wherein Ra and Rb mean independently hydrogen atom or (C1-C6)-alkyl; Y3 means a direct bond, Y2-independent group -CRaRb wherein Ra and Rb mean independently hydrogen atom or (C1-C6)-alkyl, or bivalent group of the formula -O-, -S-; m means 1, 2 or 3; n means 0, 1, 2, 3 or 4, or their salts. Novel compounds possess herbicide activity with the effectiveness 60-100%, for example, in rice plantings and wherein damages of cultivate plants do not exceed 10%.

EFFECT: valuable herbicide properties of compounds.

7 cl, 1 tbl, 4 ex

 

The invention relates to the field of combating weeds, in particular 2-amino-4-bicicletinha-1,3,5-triazine, herbicide tool and method of weed control.

It is known that 2-amino-4-cyclohexylamino-6-perhalocarbon-1,3,5-triazine (U.S. patent No. 3816419 and U.S. patent No. 3932167) or 2-amino-4-alkylamino-6-haloalkyl-1,3,5-triazine (international application WO 90/09378 (European patent application EP-A-411153), the international application WO 88/02368 (European patent application EP-A-283522), the international application WO 94/24086 (European patent application EP-A-509544, European patent application EP-A-492615)) have a weed-killing properties. The use of many well-known derivatives of this type as selective herbicides often leads either to use them in large quantities, or leads to unwanted disastrous consequences for cultivated plants.

The objective of the invention is to expand the range of 2-amino-4-substituted-1,3,5-triazines with herbicide activity.

The problem is solved, we offer 2-amino-4-bicicletinha-1,3,5-triazine General formula (I)

where R1and R2independently of one another denote hydrogen, amino, alkyl with 1-6 carbon atoms, alkanoyl with 1-4 carbon atoms, phenylalkyl with 1-6 carbon atoms in the alkyl part, the possibility is but substituted by halogen,

or

R1and R2together with the nitrogen atom to which they are attached, form morpholinopropan,

R3denotes hydrogen, alkyl with 1-6 carbon atoms, possibly substituted by halogen, hydroxy, amino, di-(C1-4-alkyl)amino, cyano, phenyl, C1-4-alkoxy, carboxypropyl or3-9-cycloalkyl, which, in turn, can be substituted by halogen, phenyl, possibly substituted by halogen, C1-6-alkyl, hydroxy or C1-4-haloalkyl, cycloalkyl with 3-9 carbon atoms, possibly substituted by halogen, C1-6-alkyl, hydroxy or phenyl, amino, di-(C1-4-alkyl)amino, C1-6-alkoxy, C1-6-alkylthio,2-6-alkenylacyl,

R4and R5independently denote hydrogen, alkyl with 1-4 carbon atoms or alkanoyl with 1-4 carbon atoms,

R6is hydrogen, alkyl with 1-6 carbon atoms, alkoxy with 1-6 carbon atoms or halogen, and in the case of n greater than 1, the radicals R6are independent from each other and have the specified values

Y1means a direct bond or divalent group,- CH2-,

Y2means the group of CRaRbwhere Raand Rbindependently mean hydrogen or C1-6-alkyl, and in the case of m=2-4 radicals Y2are independent from each other and have the specified values

Y3means direct St is z, independent Y2group CRaRbwhere Raand Rbindependently mean hydrogen or C1-6-alkyl, or a divalent group of the formula-O-, -S-,

m denotes 1, 2 or 3,

n means 0, 1, 2, 3,or 4

or their salts.

According to the invention preferred compounds of General formula (I) or their salts, where

a) R1and R2independently of one another denote hydrogen or alkanoyl with 1-4 carbon atoms, or its salt,

b) R3denotes hydrogen, alkyl with 1-6 carbon atoms, cianelli with 1-4 carbon atoms, haloalkyl with 1-4 carbon atoms, hydroxyalkyl with 1-4 carbon atoms, alkoxyalkyl with 1-4 carbon atoms in each alkyl group, alkenyl with 2-6 carbon atoms, dialkylaminoalkyl with 1-4 carbon atoms in each alkyl group, cycloalkyl with 3-9 carbon atoms, cycloalkenyl with 3-9 carbon atoms in cycloalkyl group with 1-4 carbon atoms in the alkyl group, phenyl or phenylalkyl with 1-4 carbon atoms in the alkyl group or their salts,

in R3means hydrogen or alkyl with 1-6 carbon atoms, possibly substituted with halogen, and

R4and R5each means hydrogen or salt,

g) Y1means a direct bond or divalent group,- CH2-,

Y2the divalent residue of the formula-CH2-, CH(CH3)-, -C(CH3)2-,

-CH2SN 2-, -CH(CH3)CH2-, -CH2CH(CH3)-, -CH(CH3)CH(CH3)-,

- (CH3)2CH2-, -CH2C(CH3)2-, -CH2CH2CH2-, -CH2CH2CH(CH3)-,

Y3means a direct bond or divalent group,- CH2-,

m is 1, 2 or 3,

n is 0, 1, 2 or 3,

or their salts.

Another object of the invention is the herbicide agent containing compounds of General formula (I) and standard auxiliary forming preparative form supplements.

Another object of the invention is a method of weed control by processing plants, seeds of plants or the planting area compound of General formula (I) or its salt used in effective amounts.

Salts of compounds of formula (I) can be formed by joining the corresponding inorganic or organic acid, for example hydrochloric, Hydrobromic, sulfuric or nitric acid, as well as oxalic acid or sulfonic acids, to a basic group such as amino or alkylamino group.

In the formula (I) and all subsequent formulas, residues of alkyl, alkoxy, haloalkyl, alkylamine, alkylthio, and also the corresponding unsaturated and/or substituted residues in the carbon skeleton may be in the form of straight or branched chain.

Alkylen the e residues in the alkoxy groups, haloalkyl etc. mean, for example, methyl, ethyl, n - or isopropyl, n-, ISO-, tert - or 2-butyl, pentyl, hexyl, such as n-hexyl, isohexyl and 1,3-dimethylbutyl, heptyl, such as n-heptyl, 1-etylhexyl and 1,4-dimethylpentyl; alkenyl matter of the possible unsaturated residues corresponding to residues of alkyl.

Alkenyl means, for example, allyl, 1-methylprop-2-EN-1-yl, 2-methylprop-2-EN-1-yl, but-2-EN-1-yl, but-3-EN-1-yl, 1-methylbut-3-EN-1-yl and 1-methylbut-2-EN-1-yl.

Quinil means, for example, propargyl, but-2-in-1-yl, but-3-in-1-yl, 1-methylbut-3-in-1-yl.

Cycloalkyl are, for example, cyclopropyl, cyclopentyl or cyclohexyl.

Halogen means fluorine, chlorine, bromine or iodine. Haloalkyl means partially or completely replaced by halogen, particularly fluorine, chlorine and/or bromine, in the first place by fluorine or chlorine, alkyl, alkenyl or quinil, for example, monohalides, perhalides, trifluoromethyl, deformity, vermeil, pentafluoroethyl, CH2FCHClCCl3dichloromethyl, CH2CH2Cl.

Depending on conditions phenyl may be substituted one or more times, mainly three-fold, identical or different residues from the group of hydroxy, halogen, alkyl with 1-6 carbon atoms, halogen with 1-4 carbon atoms, such as o-, m - and p-tolyl, dimetilfenil, 2-, 3 - and 4-chlorophenyl, 2-, 3 - and 4-Cryptor and trichlorophenyl, 2,4-, 3,5-, 2,5-and 2,3-dichlorophenyl.

The above General formula (I) also encompasses all stereoisomers and mixtures. Such compounds of formula (I) contain one or more asymmetric carbon atoms or double bonds, which in the General formula (I) are not listed separately. Possible spatial stereoisomers, such as enantiomers, diastereomers, Z - and E-isomers, are included in the formula (I) can be obtained by customary methods from mixtures of the stereoisomers or by stereoselective reactions using stereochemical pure starting materials. Formula (I) also includes more or less stable tautomers, which are formed due to bias one or more double bonds in the triazine ring to aminoven deputies and form hymenopodidae structure when the amino substituent in the formula (I) contains the N-H bond (R1, R2and/or R4=H). For example, the tautomeric structure of formula (I*) and (**) to the formula (I) when R1=N and R4=N.

(where In - bicycl as in the formula (I)).

Compounds of General formula (I) or their salts can be obtained due to the fact that a) compound of formula (II)

where R7- functional group from a carboxy group, such as carboxyethyl, orthocarboxylic, carboxylated, carboxyamide, carboxyanhydride, trichloromethylthio, trichloromethyl,

treated with biguanides formula (III) or its acid salt

or b) the compound of formula (IV)

where R8the residue can react exchange, or a removable group, for example chlorine, trichloromethyl, alkylsulfonyl with 1 to 4 carbon atoms and unsubstituted or substituted phenyl-(C1-C4)alkylsulfonyl or (C1-C4)alkylphenolates,

treated with an amine of formula (V) or its acid salt

or

C) diamino-1,3,5-triazine of the formula (VI)

treated with isocyanate of formula (VII)

moreover, in formulas (II), (III), (IV), (V), (VI) and (VII) residues R1, R2, R3, R4, R5and R6and Y1, Y2, Y3, m and n are specified in the formula (I) value.

The interaction of compounds of formulas (II) and (III) perform primarily in the presence of a basic catalyst in an inert organic solvent, for example tetrahydrofuran(THF), dioxane, acetonitrile, dimethylformamide (DFA), methanol and ethanol, at temperatures between -10°and the boiling point of the solvent, mainly from the 20°C to 60°With; in the case of kislotoupornyh salts of the formula (III), they are used as p is Avila, in situ in the presence of a base. As bases or basic catalysts suitable hydroxides of alkali metals, hydrides of alkali metals, carbonates of alkali metals, the alcoholate of alkali metals, hydroxides of alkaline earth metals, hydrides of alkaline earth metals, carbonates of alkaline earth metals or organic bases, such as triethylamine or 1,8-diazabicyclo[5.4.0.]undec-7-ene (DBU). Depending on the compounds of formula (III) base is used in an amount of from 0.1 to 3 mol equivalents. The compound of formula (II), for example, can be used in equimolar amounts or up to 2-fold mol/equivalent excess relative to the compound of formula (III). Similar methods known from the literature (Comprehensiv Heterocyclic Chemistry, A.R.Katritzky, C.W.Rees, Pergamon Press, Oxford, New York, 1984, vol. 3; part 2B; ISBN 0-08-030703-5, str).

The interaction of compounds of the formula (IV) and (V) carry out mainly with the use of bases as catalysts in an inert organic solvent, for example tetrahydrofuran, dioxane, acetonitrile, dimethylformamide(DFA), methanol and ethanol, at temperatures between -10°and the boiling point of the solvent or solvent mixture, predominantly at 20°C to 60°and in the case of using the compound (V) in the form of acid salts also are in situ in the presence of the basis of the Oia.

As bases or basic catalysts suitable hydroxides of alkali metals, hydrides of alkali metals, carbonates of alkali metals, the alcoholate of alkali metals, hydroxides of alkaline earth metals, hydrides and carbonates of alkaline earth metals or organic bases, such as triethylamine or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

The basis is taken generally in the range from 1 to 3 mol equivalents based on the compound of the formula (IV); a compound of formula (IV) may be used in equimolar with respect to the compound of formula (V) the amount or up to 2-fold mol/equivalent excess. A similar method is in principle known from the literature (Comprehensiv Heterocyclic Chemistry, A.R.Katritzky, C.W.Rees, Pergamon Press, Oxford, New York, 1984, vol. 3; part 2B; ISBN 0-08-030703-5, str).

Interaction diamino-1,3,5-triazines of the formula (VI) with isocyanates of the formula (VII) are carried out using bases as catalysts in an inert organic solvent, for example tetrahydrofuran(THF), dioxane, acetonitrile, dimethylformamide (DFA), at temperatures between -10°and the boiling point of the solvent, mainly from the 20°C to 60°C. as bases or basic catalysts suitable hydroxides, hydrides, carbonates, alcoholate of alkali metals, alkaline earth hydroxides, hydrides, carbonates or organic is a mini-base, such as triethylamine or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The basis for this is taken generally in the range from 0.5 to 3 mol equivalents based on the compound of the formula (VI), the compound of formula (VII) may be used in equimolar with respect to the compound of formula (VI) quantity or slight excess.

Similar methods for acyclic and aromatic derivatives in principle known from the literature (vergl. D.Singh; Heterocycles, 1993, 34, str-935).

Compounds of formula (II), (III), (IV) and (VII) can be obtained either commercially or on the basis of methods known from the literature. The compound can be obtained, for example, using the following method.

Biguanidine formula (III) can be obtained, for example, by the reaction of cyanoguanidine formula

R1R2N-C(=NH)-NH-CN,

where R1and R2as defined in the formula (I), with amines of the formula (V), mostly in the form of hydrohalogenation or other kislotoupornyh salts. Both components are heated to 100-190°in an inert solvent, for example in chlorophenothane, boiling at a higher temperature, such as dichlorobenzene, with the drop down in the form of salts of biguanidine allocate by sucking. A similar method is known, see, for example, L.L.Shapiro, V.A.Parrino, L.Freedmann in JACS 81 (1959) 3728 or H.M.Eisa, A.S.Tantawy and M.M.Kerdawy in Pharmazie 46 (1991) 182 f. The reaction can be accelerated by adding metal salts, such as sulphate of copper (II)chloride, zinc (II) or iron chloride (III) (T.Suyama, T.Soga, .Miauchi in Nippon CALLED KAISHI (1989), (5), 884-887), the reaction in most cases is carried out at a temperature of from 50°C to the boiling point of the solvent. The reaction can be conducted in a large number of solvents, such as tetrahydrofuran (THF), dioxane, alcohols or ethers.

Used for the production of biguanidine formula (III) amines of the formula (V) is used in an alternative method b) for the production of compounds (I) (see below).

The compounds of formula (IV) can be obtained as follows.

1. By reaction of compounds of formula (II) with a derivative of amidinothiourea formula (VIII)

where R9there is alkyl with 1-4 carbon atoms or phenyl-(C1-C4)-alkyl, and R1and R2as in the formula (I), to obtain the compounds of formula (IV)in which R8=-SR9.

2. By reacting cyclic amidine formula (IX) or its kislotoupornoj salt

where R3as indicated in the formula (I),

N-cyanodithioiminocarbonate formula (X),

where R10means alkyl with 1-4 carbon atoms or phenyl-(C1-C4)-alkyl, to obtain the compounds of formula (IV), where R8=-S-R9.

3. The interaction of alkaline dicyanamide with a cyclic derivative of carbonic acid of the formula (II) with a compound of the formula (IV), where R8=NH2.

4. The interaction of trichloroacetonitrile with nitrile carbon dioxide of the formula (XI)

where R3as indicated in the formula (I)receive a first compound of the formula (XII)

where R8=CCl3which is treated with a compound of the formula HNR1R2where R1and R2as indicated in the formula (I), to obtain the compounds of formula (IV), where R8=CCl3.

The above methods 1-4 receive other intermediate products of the formula (XII) with two capable of sharing groups R8[see the formula (IV)] and is able to exchange group consistently replace the corresponding amines or ammonia with getting known methods, the compounds of formula (IV) or formula (I). Similarly, you can improve the compounds of formula (XII)obtained commercially or produced by other methods.

Is obtained analogously to the above methods 1-4 intermediate products of the formula (IV) or (XII), where R8there alkylthio with 1-4 carbon atoms or phenyl-(C1-C4)-alkylthio, can turn into a reactive derivative of formula (IV) or (XII) by oxidation or chlorine is the formation.

The exchange reaction of the derivatives of the carbonic acid of the formula (II) with a derivative of amidinothiourea formula (VIII) is conducted in the presence of bases as catalysts in organic solvent, for example acetone, THF, dioxane, acetonitrile, DFA, methanol, ethanol, at temperatures from -10°C to the boiling point of the solvent, generally at 0°to 20°C.

The exchange reaction can be carried out in water or in a mixture of water with one or more of the aforementioned organic solvents. If the compound (VIII) is used in the form kislotoupornoj salt, it may be released in situ basis. As bases or basic catalysts can be used hydroxides, hydrides, carbonates, alcoholate of alkali metals, alkaline earth hydroxides, hydrides and carbonates or organic bases such as triethylamine or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The basis for this charge in the amount of from 1 to 3 mol equivalents based on the compound of the formula (VIII). The compounds of formula (II) and (VIII) can, for example, be used in equimolar amounts or a slight excess of up to 2 mol equivalents, of the compound of formula (II) by analogy with the method (H.Eilingsfeld, H.Scheuermann, Chem. Ber.; 1997, 100, 1874).

The exchange reaction between amidine formula (IX) and N-cyanodithioiminocarbonate formula (X) occurs mainly in the line is the use of bases as catalysts in an inert organic solvent, such as acetonitrile, DMF, dimethylacetamide(DMA), N-organic (N), methanol and ethanol, at temperatures from -10°C to the boiling point of the solvent, mainly at a temperature of from 20°C to 80°C. If the compound (IX) is used in the form kislotoupornoj salt, it may be released in situ basis. As bases or basic catalysts can be used hydroxides, hydrides, carbonates, alcoholate of alkali metals, alkaline earth hydroxides, hydrides, carbonates or organic bases such as triethylamine or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The basis for this is taken in an amount of from 1 to 3 mol equivalents based on the compound of formula (X). The compounds of formula (IX) and (X) can, for example, be used in equimolar amounts or with 2-fold mol/equivalent excess of the compounds of formula (IX) (similar ways, see T.A.Riley. W.J.Henney, N.K.Dalley, B.E.Wilson, R.K.Robins, J. Heterocyclic Chem., 1986, 23 (6), 1706-1714).

Intermediates of formula (XII), where R8= chlorine, can be obtained by the reaction of alkaline dicyanamide with a derivative of carbonic acid of the formula (II), where R7preferably, the functional group that represents chloride or amide of carbonic acid. The exchange reaction carried out for example with the use of acids as catalysts in an inert organic solvent, for example the EP toluene, chlorobenzene, chlorinated hydrocarbon, at a temperature of from -10°C to the boiling point of the solvent, generally at a temperature of from 20°C to 80°and forming in situ an intermediate connection can gloriouse relevant gloriouse reagent such as phosphorus oxychloride. As acids can be used, for example, halogen acids, for example hydrochloric acid or a Lewis acid such as AlCl3or BF3(U.S. patent No. 5095113).

Intermediates of formula (XII) with R8= trihalomethyl can be obtained by reaction of the corresponding NITRILES trigalogenmetany acid nitrile carbon dioxide of the formula (XI). The exchange reaction is conducted, for example, using an acid catalyst in an inert organic solvent, for example toluene, chlorobenzene, chlorinated hydrocarbon, at a temperature of from -10°C to the boiling point of the solvent, generally at temperatures from -40°C to the boiling point of the solvent, mainly from -10°With 30°C. as the acid used, for example, halogen acids, for example hydrochloric acid or a Lewis acid such as AlCl3or BF3(European patent application EP-A-130939, Ciba Geigy).

Intermediates of formula (IV) or (XII), where R8= (C1-C4) allylmercaptan or unsubstituted or substituted phenyl-(C1With 4)-allylmercaptan, you can gloriavale gloriouse agent, such as elemental chlorine or phosphorus oxychloride in an inert organic solvent, for example toluene, chlorobenzene, chlorinated hydrocarbons or other, at a temperature of from 20°C to 80°obtaining reactive chlorotriazine formula (IV) or (XII), where R14=Cl (J.K.Chakrabarti, D.E.Tupper; Tetrahedron. 1975, 31 (16), 1879-1882).

Intermediates of formula (IV) or (XII), where R8= (C1-C4)allylmercaptan or unsubstituted or substituted phenyl-(C1-C4)-allylmercaptan, or (C1-C4)alkalinity, can be oxidized in an appropriate solvent, such as chlorinated hydrocarbons, acetic acid, water, alcohols, acetone or their mixtures, at temperatures from 0°C to the boiling point of the solvent, mainly on 20°C to 80°S, under the action of an appropriate oxidant such as m-perchlorobenzene acid, hydrogen peroxide, peroxomonosulfate potassium (T.A.Riley. W.J.Henney, N.K.Dalley, B.E.Wilson, R.K.Robins, J.Heterocyclic Chem., 1986, 23 (6), 1706-1714).

The compounds of formula (IV) are obtained by selective nucleophilic substitution of one of the deleted groups of the compound (XII), for example, the group R8consisting of halogen, perhalogenated, alkylsulfonyl with 1-4 carbon atoms, alkylsulfonyl with 1 to 4 carbon atoms or other known what Yu adalemo group, amines of the formula R1R2NH or their salts, and salt can be used in situ, in an appropriate solvent, such as THF, dioxane, alcohol, DFA or acetonitrile or their mixtures, at a temperature of from -10° to the boiling point of the solvent, mainly from -10°to 25°With, in the presence of bases. As the bases used hydroxides, hydrides, carbonates, alcoholate of alkali metals, alkaline earth hydroxides, alkaline earth hydrides, alkaline earth carbonates or organic bases such as triethylamine or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Base charge in relation to the compound of formula (XII) in the range from 1 to 3 mol equivalents; the nucleophile is used usually in an equimolar or excess amount of up to 2 mol equivalents, which may in some circumstances act as a base (V.I.Kaelaev, Dibi Amma, A.F.Lunin; Chemistry of heterocycle. connect., 1985, No. 11, 1557-1563).

Amines of formula (V) can be obtained, for example, by hydrogenation of the corresponding Akimov, which, in turn, can be produced from the corresponding ketones. So A.B.Sen, S.B.Singh in J. Ind.Chem.Soc.43 (1966) 521 describe a similar way as the hydrogen source is used, the reaction conversion of sodium methylate sodium. Next Sarges and others in J.Med.Chem.16 (1973) 1003-1008 describe how the transformation of the ketone to the oxime and its gidrirovanie is using palladium as a catalyst in an appropriate amidohydrolase. There are also known processes for the hydrogenation with Raney Nickel (D.Barby, D.Couturier, N.Abdellatifi, D.Lesieur, C.Lespagnol; J. Heterocycl. Chem. 28 (1991) 449) or hydrogenation using borovodorodam compounds (A.K.Gosh, S.P.McKee, W.M.Sanders. Tetrahedron Lett. 32 (1991) 711-714). In addition, the described and other methods with the corresponding bicyclic derivatives, which can be used for the synthesis of amines of formula (V).

Upon receipt additive acid salts of compounds of formula (I) may be talking about the following acids: halogen acid, such as hydrochloric acid or Hydrobromic acid, and then phosphoric acid, nitric acid, sulfuric acid, mono - or difunctional acid and hydroxycarbonate acid, for example acetic acid, maleic acid, succinic acid, fumaric acid, tartaric acid, citric acid, salicylic acid, sorbic acid or lactic acid, and sulphonic acids, such as p-toluensulfonate or 1.5-naphthalenedisulfonic acid. Additive acidic compounds of formula (I) can be obtained by a simple method with conventional methods of education salts, for example by dissolving the compounds of formula (I) in an appropriate organic solvent, for example methanol, acetone, methylene chloride or benzene, and the addition of an acid at a temperature of from 0°to 100°With posledovaniem salts by filtering and washing with an inert organic solvent.

Additive salts of the bases of the compounds of formula (I) can be obtained mainly in inert polar solvents, such as water, methanol or acetone, at temperatures from 0°to 100°C. as grounds for obtaining salts can be used primarily alkaline carbonates, such as potassium carbonate, alkali and alkaline earth hydroxides, for example NaOH or KOH, alkali and alkaline earth hydrides, for example NaH, alkali and alkaline-earth alcoholate such as sodium methylate, trebuchet potassium, or ammonia or ethanolamine.

In the above embodiments of the method under the "inert solvent" is understood as the solvents in which the respective reaction conditions inert, but this does not mean that they should be inert under any reaction conditions.

Compounds of the invention of formula (I) and their salts, hereinafter referred to as compounds of the invention of formula (I)have a high weed-killing activity against a wide range of industrially important one - and dicotyledonous weeds. Even with hardly destroy perennial weeds growing up from the roots, rhizomes or other vegetative organs, a well-disposed of biologically active substances of the present invention. It does not matter, information on whether a substance before sowing, during the shoots or later.

You can call some p is estavudina one - and dicotyledonous weed flora, not limited to specific kinds, the growth of which can be controlled by the compounds of the invention. From monocotyledonous weeds can be called, for example, Avena, Lolium, Alopecurus, Phalaris, Echinochloa, Digitaria, Setaria, also Cyperusarten from the group of annual and perennial Spezies Agropyron, Cynodon, Imperata and Sorghum and hardy species Cyperusarten.

In dicotyledonous weeds spectrum of action extends to species such as Galium, Viola, Veronica, Lamium, Stellaria, Amaranthus, Sinapis, Ipomoea, Matricaria, Abutilon and Sida, and Convolvulus, Cirsium, Rumex and Artemisia perennial weeds.

Appearing in the specific conditions in rice weeds such as Sagittaria, Alisma, Eleocharis, Scripus and Cyperus are also very well suppressed biologically active substances of the invention.

When making compounds of the invention in the soil before the germ growth of weeds or completely prevented, or they grow before the leaves appear, then the growth stops, and after 3 to 4 weeks, they die.

The use of biologically active substances on the green parts of plants also leads after processing to rapid suspension growth and weed growth is delayed at this stage or they completely die off after a certain time, and thus cultivated plants can be protected from weed competition.

Although compounds of the invention possess high herbicide activity on otnosheniya - and dicotyledonous weeds, cultivated plants and commercially important crops, such as wheat, barley, rye, rice, maize, sugar beet, cotton and soya, are damaged slightly or completely damaged. Therefore, these compounds can be successfully used for the selective suppression of unwanted growth of weeds among crops.

In addition, the substances of the invention possess outstanding properties that regulate the growth of cultivated plants. They regulate metabolism in plants and thereby direct impact on the content of substances in plants and facilitate harvesting, for example, causing desiccation or delay growth. In addition, they can be used for General control and deterrence of undesirable vegetative growth, without destroying the plants themselves. Deterrence vegetative growth plays an important role for many one - and dicotyledonous crops, as constrained or completely eliminated growth during storage in the warehouse.

Compounds of the invention can be applied in the form of a powder sprayer, emulsifying concentrates, solutions in the form of a spray, spray or granules in a conventional compositions.

The compounds of formula (I) can be used in different formulation, depending on what set of biological and/or physicochemical parameters. In ka is este possible forms can be used for example, the powder-spray (WP), water-soluble powder (SP), water-soluble concentrates, emulsifiable concentrates (EC), emulsions (EW)such as emulsion, oil-in-water and water-in-oil, solutions, sprays, concentrated suspensions (SC), dispersions on an oil or water solutions, mixed with oil, capsule suspensions (CS), sprayers (DP), disinfectants, granules for spraying and application in the soil, granules (GR) in the form of microgranulates, granules for spraying, enveloping and adsorption granules, water dispersible granules (WG), water-soluble granules (SG), ULV-form microcapsules and wax forms.

Some types of forms are in principle known and described, for example, in Winnacker-Kuechker, "Chemische Technoljgie", Band 7, .Hauser Verlag Muenchen, 4 Aufl. 1986, Wade van Valkenburg, "Pesticide Formulations", Marcel Dekker, N.Y, 1973* K.Martens, "Spray Drying" Handbook, 3rd Ed. 1979, G.Goodwin Ltd. London.

The tools needed for agricultural preparative forms,such as inert materials, surfactants (surfactant) solvents and other additives are also known and described, for example, in Watkins, "Handbook of Insecticide Dust Diluents and Carriers", 2nd Ed., Darland Books, Caldwell N.J., H.V. Olphen, "Introduction to Clay Colloid Chemistry"* 2nd Ed., J.Wiley & Sons, N.Y.; C.Marsden, "Solvents Guide"; 2nd Ed., Intercience, N.Y. 1963; McCutcheon''s "Detergents and Emulsifiers Annual", MC Publ. Corp., Ringewood N.J.; Sisley and Wood, "Encyclopedia of Surface Active Agents", Chem. Publ. Co. Inc., N.Y. 1964; Schoenfeld, "Grenzflaechenaktive Aethylenoxidaddukte", Wiss. Verlagsgesell., Stuttgart 1976; Winnacker-Kuecher, "Chemische Technologie", Band 7, .Hauser Verlag Mueenchen, 4 Aufl. 1986.

On the basis of these forms can also be found in combination with other pesticides, for example insecticides, acaricides, herbicides, fungicides, and fertilizers, preservatives and/or growth regulators, for example, in the prepared form or in the mixer.

Powder spray it evenly dispersible in water preparations, which, together with the biologically active substance in addition to a diluent or inert substance, also contain detergents (surfactants) ionic and/or nonionic type (wetting means, dispersants), for example polyoxyethylene ALKYLPHENOLS, polyoxyethylene fatty alcohols, polyoxyethylene fatty amines, polyglycolide esters, sulfated fatty alcohols, alkanesulfonyl, alkylbenzenesulfonate, ligninsulfonate sodium 2,2'-dynafilter-6,6'-disulfonate sodium, dibutylaminoethanol sodium or alarmlistener sodium. For the production of powder-spray herbicide biologically active substance is finely pulverized in a conventional machine, for example using a hammer mill, aeration and air-blast mill, and then mixed with auxiliary shaping means.

Emulsifiable concentrates are obtained by dissolving the biologically active substance in an organic solvent, for example, the bout is zero, cyclohexanone, dimethylformamide, xylene, or in an aromatic solvent with a higher boiling point, or in a hydrocarbon compound or mixture of organic solvents with addition of one or more surfactants of ionic and/or nonionic type (emulsifiers). As emulsifiers can be used, for example, kalivia salt alkylarylsulfonates, such as dodecylbenzenesulfonate calcium, or nonionic emulsifiers, such as polyglycolide esters of fatty acids, alkyldiphenylamine esters, polyglycolide ethers of fatty alcohols, condensation products of the propylene oxide-ethylene oxide, polyalkylene esters, sorbitrate esters, as, for example, sorbitrate esters of fatty acids, or polyoxyethylenesorbitan esters, as, for example, polyoxyethylenesorbitan esters of fatty acids.

The spray is produced by grinding the biologically active substance with finely powdered solid substance, for example talc, natural clays like kaolin, bentonite, pyrophillite or diatomaceous earth.

The concentrated suspensions can be water or oil based.

They can be obtained, for example, by wet grinding using a conventional commercially available small mills with the addition, if necessary, detergents, see, for example, higher for other preparative f the RM.

Emulsions such as emulsions oil-in-water (EW), can be obtained by mixing using colloid mills and/or static mixers using aqueous organic solvents and, depending on the circumstances with the addition of surfactants, see, for example, higher for other preparative forms.

The granules can be obtained or by passing a biologically active substance through the nozzle of adsorption, granulated inert material or by applying a concentrate of biologically active substances by means of adhesives, for example polyvinyl alcohol, sodium polyacrylate or mineral oils, to the surface of the material carrier, such as sand, kaolin, or on the surface of granulated inert material. Suitable for use with biologically active substances can also be pelletized in a conventional way, used for the production of fertilizer granules, if desired in a mixture with fertilizers.

Dispersible in water, the granules can be obtained, as a rule, in the usual way, for example drying, spray granulation using a vortex plate and pellet, the mixture using high-speed mixers and extrusion without solid inert material.

The production of pellets using plate is of regulatorv, granulators fluidized bed, extrusion and spray granules, see, for example, the way in "Spray-Drying Handbook" 3rd ed. 1979, G.Goodwin Ltd., London; J.E.Browning, "Agglomeration", Chemical and Engineering 1967, Seiten 147 ff; "Perry's Chemical Engineer''s Handbook", 5th ed., McGraw-Hill, New York 1973, S.8-57.

Learn more about formulation, related to means of protection of plants, see G.C.Kingman, "Weed Control as a Science", John Wiley and Sons, Inc., New York, 1961, Seiten 81-96 und J.D.Freyer, S.A.Evans, "Weed Control Handbook", 5th Ed., Blackwell Scientific Publications, Oxford, 1968, Seiten 101-103.

Preparative compositions contain, as a rule, from 0.1 to 99 wt%, in particular from 0.1 to 95 wt%, biologically active substances of the formula (1).

Powder-spray concentration of the biologically active substance is, for example, about 10-90 wt%, the remainder to 100 wt%. consists of the usual components of forms. In emulsifiable concentrates, the concentration of biologically active substances may be of the order of 1-90, mainly from 5 to 80 wt%. Dust forms contain from 1 to 30 wt%. biologically active substances, mainly in most cases from 5 to 20 wt%. biologically active substance, sprayable solutions contain about 0.05-80, mostly from 2 to 50 wt%. biologically active substances. In dispersible in water the granules, the content of biologically active substances depends in part on what form, liquid or solid, presents active the e connection and any auxiliary means, the fillers were applied to granulation. In granules, dispersible in water, the content of biologically active substances is, for example, from 1 to 95 wt%, mainly between 10 and 80 wt%.

In addition, the named preparative forms depending on the conditions contain common substances, providing adhesion, wetting, dispersing, emulsification, penetration, canning, and also frost-resistant substances, solvents, fillers, carriers and colorants, extinguishers foam, a substance that prevents evaporation, and tools that affect the pH value and viscosity.

As Raman additives for biologically active substances of the invention in agrochemical forms and mixtures can, for example, to use the well-known biologically active substances, which are described, for example, in Weed Research 26, 441-445 (1986), or "The Pesticide Manual", 10th edition, The British Crop Protection Council and the Royal Soc. of Chemistry, 1994. Known from the literature herbicides which can be combined with compounds of formula (I)are, for example, the following biologically active substances (note: the compounds are referred to either as it is accepted in accordance with the International organization for standardization (ISO)or the chemical name, depending on the conditions along with the common code number):

acetochlor; alfthan; klonipin; AK is 7088, ie, [[[1-[5-[2-[chloro-4-(trifluoromethyl)-phenoxy]-2-nitrophenyl]-2-methoxyacridine]-amino]-oxy]-acetic acid ester and acetic acid methyl ester; alachlor; aloxide; ametrine is high; amidosulfuron; amitrole; AMS, i.e. ammoniumsulfate; anilofos; Azul; atrazine; azimsulfuron (DPX-A 8947); isoprotein; Barban; BAS 516 N., ie 5-fluoro-2 phenyl-4H-3,1-benzoxazin-4-he; benazolin; benfluralin; beforeit; enculture-methyl; bensulide; bentazon; benzien; bentover; benzoylpropionic; benzthiazole; bialaphos; bifenox; bromacil; bromobutyl; bromophenoxy; bromoxynil; brauron; buminate; butoxide; butachlor; butamifos; buenaflor; booteasy; butalin; butyl; cafestol (SN-900); carbutamide; Capistrano (ICI-0051); CDAA, i.e. the 2 chloro-N,N-di-2-propylacetamide; CDEC, i.e. the 2-korallovy ether diethyldithiocarbamic acid; chlorotoxin; chloramben; lorazepam-butyl, chlormezanone (ICI-A); chlorbromuron; chlorbutol; chlorgenic; chlorofluro-methyl; ozone chloride; chlorimuron-ethyl; chlornitrofen; chlorotoluron; chloroxuron; chlorpropham; chlorsulfuron; chlorthal-dimethyl; chlorine; cinmetacin; chinaculture; clethodim; clodinafop and its esters (for example, clodinafop-propargyl); clomazone; clomipram; chloroxygen, clopyralid; cumyluron (JC 940); cyanazine; cycloate; cycloaliphatic (AC 104); cycloxydim; cyclotron; cyhalofop and its esters (for example, butyl ether, DE-112); cybercat; ziprin; cobresol; dameron; 2,4-DB; dalapon; desmedipham; desmetryn; Vallat; dicamba; dichlobenil; dichlorprop; diclofop and its ester as diclofop-methyl; diacetyl; Difenoxin; difenzoquat; diflufenican; dimefuron; dimethachlor; deltamethrin; dimethenamid (SAN-582H)* deltason, clomazone; dimethipin; demetracopoulos, dinitramine; dinoseb; dinoterb; diphenamid; DIPROPYLENE; Diquat; dithiopyr; Diuron; DNOC; Eglinton-ethyl; El, i.e. the 5-cyano-1-(1,1-dimethylethyl)-N-methyl-1H-pyrazole-4-carboxamide; endothal; APTS; asbroker; ethalfluralin; atomiculture-methyl; tidiman; idiosyn; ethofumesate; F5231, i.e. N-[2-chloro-4-fluoro-5-[4-(3-forproper)-4.5-dihydro-5-oxo-1H-tetrazol-1-yl]-phenyl]-econsultant; idoxifene and its esters(for example ethyl ester, HN-252); etamesonic (HW 52); fenoprop; phenoxy, fenoxaprop and fenoxaprop-P and their esters, for example fenoxaprop-P-ethyl and fenoxaprop-ethyl; phenoxide; fenuron; femprep-methyl; flazasulfuron; fluazifop and fluazifop-P and their esters, for example fluazifop-butyl and fluazifop-P-butyl; fluchloralin; flumetsulam; flumeturon; flumiclorac and its esters (for example, ventilator, S-23031); flumioxazin (S-482); flubiprofen; flupoxam (KNW-739); foregiven; foreglimpse-ethyl; flourophenyl (UBIC-4243); fluridone; flurochloridone; fluroxypyr; flurtamone; fomesafen; fosamine; voreloxin; glufosinate;glyphosate; galasoft; halosulfuron and its esters (for example, methylether, NC-319); haloxyfop and its esters; haloxyfop-P (=R) and its esters; hexazinone; imazamethabenz-methyl; imazapyr; imazaquin and salt as ammonium salt; imazethapyr; imazethapyr; imazosulfuron; ioxynil; isochrome; isopropylene; Isoproturon; Sauron; isoxaben; isocaporate; carbocylic; lactofen; lentil; linuron; MSRA; SRV; mecoprop; mefenacet; mefluidide; metamitron; metazachlor; methabenzthiazuron; methamphetamine; metasol; methoxyphenol; methyldibromo; metaventure, metaventure; metobromuron; metolachlor; metosulam (DS 511); metoxuron; metribuzin; metsulfuron-methyl; MX; molinet; monolid; monocarbonic dehydrogenative; monolinuron; monuron; MT 128, te-chloro-N-(3-chloro-2-propenyl)-5-methyl-N-phenyl-3-pyridazinone; MT 5950, i.e. N-[3-chloro-4-(1-methylethyl)-phenyl]-2-methylpentane; nitroanilide; napropamide; naptalam; NC 310, i.e. a 4-(2,4-dichlorobenzoyl)-1-methyl-5-benzyloxyethanol; neburon; nicosulfuron; snipercraft; nicraly; nitrogen; nitrophorin; norflurazon; arrancars; oryzalin; oxadiargyl (RP-020630); oxadiazon; oxycontin; paraquat; Babolat; pendimethalin; PERFLUORO; fenazepam; phenmedipham; picloram; piperophos; peribuccal; pirivena-butyl; pretilachlor; primisulfuron-methyl; procesin; prodiamine; propleuron; progenitin-ethyl; prometon; prometryn; PDEC is chlorine; propanil; propaquizafop and its esters; propazine; priem; propisochlor; propyzamide; prosulfuron; prosulfocarb; prosulfuron (MUH-152005); panahar; pyrazoline; person; pyrazosulfuron-ethyl; paradoxien; peridot; pyrithiobac (KIH-2031); pyrexia and its esters (for example, propargilovyh ester); quinclorac; quinmerac; CWinApp and its derivatives of ester, quizalofop and quizalofop-R and its derivatives of ester, for example quizalofop-ethyl; quizalofop-P-tefuryl and-ethyl; renature; rimsulfuron (DP-E 9636); S 275, i.e 2-[4-chloro-2-fluoro-5-(2-propenyloxy)-phenyl]-4,5,6,7-tetrahydro-2H-indazol; sebumeter; sethoxydim; sibron; Simazine; simetryn; SN 106279, i.e 2-[[7-[2-chloro-4-(trifter-methyl)phenoxy]-2-naphthalenyl]-oxy]-propanoic acid methyl ester; sulcotrione, sulfentrazone (FMS-97285, f-6285); colfuturo; sulfometuron-methyl; sulfosate (ISI-A); TCA; tabulam (GSP-5544); abutilon; terbacil; thermocarb; turbuhaler; terbumeton; terbutylazine; terbutryn; TPH 450, i.e. N,N-diethyl-3-[2-ethyl-6-were-sulfonyl]-1H-1,2,4-triazole-1-carboxamide; fenelli (NSC-850); diazafluoren; thiazopyr (Mon-13200); thidiazuron (SN-24085); thifensulfuron-methyl; thiobencarb; thiocarbonyl; tralkoxydim; triallate; triasulfuron; threatened; tribenuron-methyl; triclopyr; tridiphane; triacetin; trifluralin; triflusulfuron and esters (for example, IU the silt ether, DPH-66037); timetron; dicode; vernolate; VL 110547, i.e. a 5-phenoxy-1-[3-(trifluoromethyl)-phenyl]-1H-tetrazol; UBH-509; D-489; LS 82-556; KPP-300; NC-324; NC-330; DPX-N8189; SC-0774; DOWCO-535; DK-8910; V-53482; PP-600; MVN-001; RIH-9201; ET-751; KIH-6127 and KIH-2023.

When using commercial formulations, if necessary, diluted in the usual way with water, for example in the preparation of powder sprays, emulsifiable concentrates, dispersions and water-dispersible granules. Dust compositions, the polymer and loose granules and sprayable solutions are usually not diluted before use inert substances.

Depending on external conditions, namely temperature, humidity, the type of herbicide and so on, changing the quantity of the compounds of formula (I). It can vary, for example, between 0.001 and 10.0 kg/ha or more of active substance, mainly this value is between 0.005 and 5 kg/ha

A. Chemical examples

Example A1 (= example 7 in table 1)

2-amino-4-(2-forfinal)-6-(5,7-dimethyl-1,2,3,4-tetrahydronaphthalen-1-aminol)-1,3,5-triazine.

A. of 27.0 g (0.13 mol) of 1-amino-5,7-dimethyl-1,2,3,4-tetrahydronaphthalen-hydrochloride and 11.5 g (0.13 mol) of cyanoguanidine homogenized and diluted with 60 ml of chlorobenzene. This mixture is heated for 150 min to a temperature of 140-160°; first formed homogeneous mixture, which is then again amalyra the tsya. After cooling and adding 100 ml of toluene is obtained after the extraction of 40.0 g (94%, with a purity of more than 90%) 1-biguanidine-5,7-dimethyl-1,2,3,4-tetrahydronaphthalen-hydrochloride with a melting point of 215-216°C.

b. To 5.9 g (0.02 mol) of 1-biguanidine-5,7-dimethyl-1,2,3,4-tetrahydronaphthalen-hydrochloride in 50 ml of methanol and 6 g of crushed molecular sieves 3 Å add a solution of sodium methylate prepared from 0.96 g (0.04 mol) of sodium and 50 ml of methanol. Then add 4.4 g (0,026 mol) of a compound ethyl ester 2-fermenting acid and stirred for 2 h at a temperature of 25°S, then 4 hours at a temperature of 65°C. the Mixture is filtered, the filtrate concentrated and the residue is dissolved in acetic ether. This solution is washed with water, the organic phase is separated and dried with sodium sulfate. The drying agent is filtered off and evaporated acetic ether. After separation in a chromatographic column on silica gel using a mixture of acetic ether/heptane 7:3) as solvent gain of 3.9 g (54%) of 2-amino-4-(2-forfinal)-6-(5,7-dimethyl-1,2,3,4-tetrahydronaphthalen-1-amino)-1,3,5-triazine with a melting point of 85-88°C.

Example A2 (= example 9 in table 1)

2-Amino-4-(2,3-dimethyl-2,3-epoxypropyl)-6-(5,7-dimethyl-1,2,3,4-tetrahydronaphthalen-1-amino)-1,3,5-triazine.

A. To a cooled to a temperature of 0-2°With a mixture of of 17.4 g (0.3 mol) of acetone and 36.8 g (0.3 mol) of methyl e is the Ira chloropropionic acid is added dropwise a suspension of the 37,1 g (0.3 mol) of trebuchet potassium in 300 ml of THF. After cooled to room temperature, then stirred for 60 minutes. After hydrolysis and extraction with diethyl ether, drying of the organic phase with sodium sulfate and evaporation on a rotary evaporator gain of 34.2 g (75%, with a purity of about 95%) of methyl ester of 2,3-epoxy-2,3-dimethyl-butyric acid. The resulting product can be used without further purification in the next stage.

b. To 5.2 g (0,0175 mol) 1-biguanides-5,7-dimethyl-1,2,3,4 - tetrahydronaphthalen-hydrochloride in 50 ml of methanol and 6 g of crushed molecular sieves 3 Å add a solution of sodium methylate prepared from 0.84 g (0.035 mol) of sodium and 50 ml of methanol. Then add 3.8 g (0,026 mol) methyl ether, 2,3-epoxy-2,3-dimethyl - butyric acid, stirred for 2 h at temeprature 25°S, then 4 h at temperatures of 65°C. the Mixture is filtered, the filtrate concentrated and the residue diluted with acetic ether. This solution is washed with water, the organic phase is separated and dried with sodium sulfate. The drying agent is filtered off and the acetic ether evaporated. After separation in a chromatographic column on silica gel with acetic ether as solvent to obtain 1.4 g (24%) 2-amino-4-(2,3-dimethyl-2,3-epoxypropyl)-6-(5,7-dimethyl-1,2,3,4-tetrahydronaphthalen-1-amino)-1,3,5-triazine with a melting point of 118-119°C.

Example A3 (= example 21 in table 1)

2-Amino-(5,7-dimethylthiochroman-4-amino)-6-(1-methyl-1-hydroxyethyl)-1,3,5-triazine

A. To a suspension of 31.1 g (0,154 mol) of 5,7-dimethylthiochroman-4-it and 18.5 g (0,261 mol) of gidroksiaminopirimidinov in 200 ml of ethanol is added at a temperature of 50-60°suspension of 37.8 g of sodium acetate in water. This mixture is then warm 30 min under reflux. After cooling and extraction of precipitated in the sludge solids gain of 22.2 g of 5,7-dimethylthiochroman-4-onojima (66%, with a purity of 95%) with a melting point 170-174°C.

b. 21,0 g(0,101 mol) of 5,7-dimethylthiochroman-4-noxema suspended in 300 ml of ethanol and added dropwise within a few hours of portions of 22.5 g (0,935 mol) of sodium. This mixture is mixed with water, the aqueous phase is acidified policecontributing hydrochloric acid, precipitated precipitated solid is sucked off and get 11.5g 4-amino-5,7-dimethylthiochroman-hydrochloride (47%, with a purity of 95%), melting point 275-280°C. the resulting product can be used without further purification in the next stage.

C. 9.0 g (0,039 mol) 4-amino-5,7-dimethylthiochroman-hydrochloride and 3.4 g (0,039 mol) of cyanoguanidine homogenized and dissolved in 25 ml of chlorobenzene. The mixture is heated for 150 min to a temperature of 140-160°; first formed homogeneous mixture, which is then again emulsify. After cooling, add 30 ml of toluene and sucking gain of 10.9 g (84%, with a purity of more than 90%) 4-biguanidine-5,7-dimethylthiochroman-hydrochloride t is ccoi melting point 210-211° C.

The resulting product can be used without further purification in the next stage.

d. To of 1.62 g (0,054 mol) of sodium hydride in 40 ml of acetonitrile is added 3.2 g (0,0108 mol) 4-biguanidine-5,7-dimethylthiochroman-hydrochloride and 5 g of crushed molecular sieves 3 Å. Then add 3.8 g (0,027 mol) ethyl ester 2-hydroxyisovaleric acid and stirred for 2 h at a temperature of 25°S, then for 8 hours at a temperature of 65°C. hydrolyzing the Mixture and filtered, the filtrate is diluted with acetic ether, the organic phase is separated and dried with sodium sulfate. The drying agent is filtered off and evaporated acetic ether. After separation through column chromatography using silica gel and acetic ether as solvent to obtain 0.4 g (10%) 2-amino-4-(5,7-dimethylthiochroman-4-amino)-6-(1-methyl-1-hydroxyethyl)-1,3,5-triazine with a melting point 231-232°C.

Example A4 (= example 83 table 1)

2-Amino-4-ethyl-6-(1-indanamine)-1,3,5-triazine

A. In the suspension of 40.3 g (0,164 mol) of 75%toluene solution of 2,4-dichloro-6-ethyl-1,3,5-triazine in 250 ml of toluene was added when the temperature of 10-15°With 45 ml of an approximately 13-molar solution of ammonia in methanol and stirred for about 2 hours the mixture was hydrolized and extracted with acetic ether. The organic phase is dried with sodium sulfate, the drying agent is filtered off and the phase ukusnog the ether evaporated. Gain of 26.5 g (91%, 90% purity) of 2-amino-4-chloro-6-ethyl-1,3,5-triazine with a melting point 125-126°C. This intermediate product can be used without further purification in subsequent reactions.

b. To 3.0 g (of 0.017 mol) at 90% purity) of 2-amino-4-chloro-6-ethyl-1,3,5-triazine and 2.5 g of 1-aminoindane in 30 ml of dimethylformamide added to 5.2 g (of 0.038 mol) of potassium carbonate and the mixture is heated to 100°C for 4 h the Mixture was hydrolized with subsequent extraction of acetic complex ether, then the organic phase is separated and dried with sodium sulfate. The drying agent is filtered off and evaporated phase acetic ether complex. After separation through column chromatography using silica gel with acetic ether/heptane 7:3) as solvent to obtain 3.2 g (70%, 95% purity) of 2-amino-4-ethyl-6-(1-indanamine)-1,3,5-triazine with a melting point 175-178°C.

Table 1 describes the connection receive according to or analogously to the above examples A1-A4. Used in the table of abbreviations below.

Abbreviations in table 1

Nr. = example or example

Fp. = melting point in °or more characteristic compounds (for example, solid foam)

Me = methyl

Et = ethyl

n-Pr = n-propyl

i-Pr = isopropyl

F-i-Pr = corisoprodol or CF(CH3)2and the position of the radical ("Il") is the floor is laid 1

c-Pr = cyclopropyl

C-hexyl = cyclohexyl

1-Me-C-Pr = 1-methyl-cyclopropyl, and the position of the radical ("Il") is position 1

Ac = acetyl

t-Bu = tertbutyl

c-Bu=cyclobutyl

Ph = phenyl

Bz = benzyl

digits = 1. The number in front of the Deputy means the position of the substituent in the aromatic compound

2. The number in front of the substituent R6indicates the position of the substituent in the aromatic compound in accordance with formula (I')

morpholino =

epoxide = 1,2-epoxies-1-yl = oxiranyl

(R6)n= all the substituents R6; case (R6)n= H means that there are no substituents (n=0).

B. Examples of completed forms, compositions

a) Spray means is obtained by mixing 10 weight. parts of the compounds of formula (I) and 90 weight. parts of talc as inert substance and subsequent grinding in an impact mill.

b) Easily dispersible, wettable powder get by mixing 25 parts by weight of the compounds of formula (I), 64 weight. part of the quartz containing kaolin as the inert substance, 10 weight. parts ligninsulfonate potassium and 1 weight. part alarmlistener is the atrium as wetting and spray means and rasmala in a rod mill.

c) a Dispersion concentrate which is easily dispersible in water, get mixing 20 weight. parts of the compounds of formula (I) with 6 weight. parts of alkylphenol ether (* Triton x 207), 3 weight. parts triisobutylaluminum ether (8 EO) and 71 weight. part of paraffinic mineral oil (boiling range for example about 255°s to more than 277° (C)and rasmala it to 5 microns in friction ball mill.

d) Emulsifiable concentrate is obtained from 15 weight. parts of the compounds of formula (I), 75 weight. parts of cyclohexanone as solvent and 10 weight. parts of ethoxylated Nonylphenol as emulsifier.

e) Dispersible in water, the granules are obtained by mixing of the

75 weight. partsthe compounds of formula (I)
10 -"-ligninsulfonate calcium
5 -"-lauryl sodium
3 -"-polyvinyl alcohol :
7 -"-kaolin,

subsequent grinding it in a pin mill and granulating in a vortex granulator, using water as a granulating liquid.

f) Dispersible in water, the granules obtained by homogenizing the pre-crushed

25 weight. partsthe compounds of formula (I)
5 -"-2,2'-dynafilter-6,6'-disulfonate sodium
2 -"-reelectionist sodium
1 weight. partpolyvinyl alcohol :
17 weight. partscalcium carbonate and
50 -"-water

in a colloid mill with subsequent grinding in a pearl mill and subsequent drying with spray.

C. Biological examples

1. Pre-emergence treatment of weeds

Seeds or pieces of rhizomes one - and dicotyledonous weed plants laid out in plastic pots in sandy alumina and covered with earth. Compounds of the invention in the form of wettable powders or emulsion concentrates are used as aqueous suspensions and emulsions for treatment of the upper protective layer of the earth in an amount of from 600 to 800 l/ha

After treatment, the pots are set in greenhouses and maintain favorable conditions for weeds. Perform visual inspection of the damage to the plants after germination compared to the untreated control plants. As shown by the test results, the compounds of the present invention show good herbicide action against a broad spectrum of weed. As follows from the reamers No. 2, 3, 9, 10, 25, 26, 30, 31 (see table 1), the compounds of formula (I) are 60-100%herbicide activity against weeds such as Sinapis alba, Chrysanthemum segetum, Avena sativa, Stellaria media, Echinochloa crus-gali, Lolium Polygonum, Setaria spp., Abutilon theophrasti, amaranthus retroflexus and Panicum miliaceum, when pre-emergence treatment in the amount of 0.5 kg and less of active substance per hectare.

Other compounds falling within General formula (I)also show a similar herbicide activity.

2. Post-harvest processing of weeds

Seeds or pieces of rhizomes one - and dicotyledonous weeds are sown in plastic pots in sandy-clay soil, covered by soil and grown in the greenhouse under optimal conditions for plant growth. Three weeks after sowing the experimental plants are treated at the stage of three sheets. Compounds of the invention prepared in the form of a powder-spray or in the form of an aqueous emulsion concentrates, are sprayed in various dosages on the green parts of the plants from 600-800 l/ha After 3-4 weeks of keeping plants in the greenhouse under optimal conditions, perform visual inspection of the action of drugs on the growth of plants compared to untreated. Tools of the invention have a high weed-killing activity against a broad spectrum of economically important weed in post-harvest processing. As follows from the examples No. 2 3, 9, 10, 25, 26, 30, 31 (see table 1), the compounds exhibit 40-100%herbicide activity against such weeds as Sinapis alba, Echinochloa crus-galli, Lolium Polygonum, Chrysanthemum segetum,Setaria spp., Abutilon theophrasti, Amaranthus retroflexus and Panicum miliaceum, Avena sativa during post-harvest processing using about 0.5 kg and less of active substance per hectare.

Other compounds falling within General formula (I)also show a similar herbicide activity.

3. Effects on weeds in planting rice

Planted and seeded rice, as well as typical weeds of rice grown in the greenhouse in plastic pots to the stage of the third sheet (Echinochloa 1,5-list) (the height of the dam water 2-3 cm). Then spend processing the compounds of the invention. Prepared biologically active substance is suspended in water, dissolve or emuleret and contribute in various dosages with a water podrugu experimental plants. After the processing of experimental plants put in the greenhouse under optimal conditions for growth and maintained under these conditions for the entire period of the experiment. Approximately three weeks after this perform visual inspection of the condition of the plants (degree of damage) compared to the control untreated plants, and connections№2, 3, 9, 10, 25, 26, 30, 31 (see table 1) show 60-100%herbicide activity p is otiv weeds, typical for rice crops, such as Cyperus monti, Echinochloa crus-galli), Eleocharis acicularis and Sagittaria pygmaea.

Other compounds falling within General formula (I)also show a similar herbicide activity.

4. Tolerance of cultivated plants

In subsequent experiments conducted in the greenhouse, sow the seeds of a greater number of cultivated plants and weeds in sandy-clay soil and covered with earth. One part of the pots treated as described in section 1, another part left in the greenhouse until then, until the plant reaches 2-3 leaves, followed by processing in different dosages, as described in section 2, the compounds of the formula (I').

After 4-5 weeks after treatment and incubation in the greenhouse, perform visual inspection, showing that the compounds of the invention - shoots with two leaves of such crops as soybeans, cotton, canola, sugar beets and potatoes, with pre - and post-harvest processing remain intact even at high doses of biologically active substances. Some substances spare, in addition, such crops as barley, wheat, rye, sorghum-millet, maize or rice. The degree of damage to the connections№2, 3, 9, 10, 25, 26, 30, 31 table 1, formula (I'), cultivated plants do not exceed 10%.

1. 2-Amino-4-bicicletinha-1,3,5-triazine General formula (I)

where R1and R2independently of one another denote hydrogen, amino, alkyl with 1-6 carbon atoms, alkanoyl with 1-4 carbon atoms, phenylalkyl with 1-6 carbon atoms in the alkyl part, possibly substituted by halogen, or R1and R2together with the nitrogen atom to which they are attached, form morpholinopropan;

R3denotes hydrogen, alkyl with 1-6 carbon atoms, possibly substituted by halogen, hydroxy, amino, di-(C1-4-alkyl)amino, cyano, phenyl, C1-4-alkoxy, carboxypropyl or3-9-cycloalkyl, which, in turn, can be substituted by halogen, phenyl, possibly substituted by halogen, C1-6-alkyl, hydroxy or1-4-haloalkyl, cycloalkyl with 3-9 carbon atoms, possibly substituted by halogen, C1-6-alkyl, hydroxy or phenyl, amino, di-(C1-4-alkyl)amino, C1-6-alkoxy, C1-6-alkylthio,2-6-alkenylacyl;

R4and R5independently denote hydrogen, alkyl with 1-4 carbon atoms or alkanoyl with 1-4 carbon atoms;

R6is hydrogen, alkyl with 1-6 carbon atoms, alkoxy with 1-6 carbon atoms or halogen, and in the case of n greater than 1, the radicals R6are independent from each other and have the specified values;

Y1means a direct bond or double-shaft is ing group-CH 2-;

Y2means the group of CRaRbwhere Raand Rbindependently mean hydrogen or C1-6-alkyl, and in the case of m=2-4 radicals Y2are independent from each other and have the specified values;

Y3means direct link independent Y2group CRaRbwhere Raand Rbindependently mean hydrogen or C1-6alkyl, or a divalent group of the formula-O-, -S-;

m denotes 1, 2 or 3;

n means 0, 1, 2, 3 or 4

or their salts.

2. 2-Amino-4-bicicletinha-1,3,5-triazine General formula (I) according to claim 1, where

R1and R2independently of one another denote hydrogen or alkanoyl with 1-4 carbon atoms, or their salts.

3. 2-Amino-4-bicicletinha-1,3,5-triazine formula (I) according to claim 1 or 2, where

R3denotes hydrogen, alkyl with 1-6 carbon atoms, cianelli with 1-4 carbon atoms, haloalkyl with 1-4 carbon atoms, hydroxyalkyl with 1-4 carbon atoms, alkoxyalkyl with 1-4 carbon atoms in each alkyl group, alkenyl with 2-6 carbon atoms, dialkylaminoalkyl with 1-4 carbon atoms in each alkyl group, cikalkis with 3-9 carbon atoms, cycloalkenyl with 3-9 carbon atoms in cycloalkyl group with 1-4 carbon atoms in the alkyl group, phenyl or phenylalkyl with 1-4 carbon atoms in the alkyl group, or their salts.

<> 4. 2-Amino-4-bicicletinha-1,3,5-triazine General formula (I) according to one of claims 1 to 3, where

R3means hydrogen or alkyl with 1-6 carbon atoms, possibly substituted with halogen, and R4and R5each means hydrogen, or their salts.

5. 2-Amino-4-bicicletinha-1,3,5-triazine General formula (I) according to one of claims 1 to 3, where

Y1means a direct bond or divalent group,- CH2-;

Y2the divalent residue of the formula-CH2-, CH(CH3)-, -C(CH3)2-, -CH2CH2-, -CH(CH3)CH2-, -CH2CH(CH3)-, -CH(CH3)CH(CH3)-, -C(CH3)2CH2-, -CH2C(CH3)2-, -CH2CH2CH2-, -CH2CH2CH(CH3)-;

Y3means a direct bond or divalent group,- CH2-;

m is 1, 2 or 3;

n is 0, 1, 2 or 3;

or their salts.

6. Herbicide remedy containing the active substance based on the derivatives of 1,3,5-triazines and standard auxiliary forming preparative form, additives, characterized in that the active substance it contains compounds of the formula (I) or its salt according to one of claims 1 to 5.

7. Method of weed control by processing plants, seeds of plants or the planting area with herbicide based on the derivatives of 1,3,5-triazine, wherein clicks the processing are herbicide of the formula (I) or its salt according to one of claims 1 to 5, used in an effective amount.



 

Same patents:

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to N-pyrazinylphenylsulfonamides of the general formula (I) or their pharmaceutically acceptable salts or solvates wherein each R1, R2 and R3 represents independently hydrogen atom, halogen atom, cyano-group, -CF3, -OCF3, -O-(C1-C6)-alkyl or (C1-C6)-alkyl; R4 represents halogen atom, -CO2R12, (C1-C6)-alkoxy-, (C3-C6)-alkenyloxy- or (C3-C6)-alkynyloxy-group, -O-(C1-C6)-alkyl-X-(C1-C6)-alkyl, -O-(C1-C6)-alkyl-R11, -O-(C2-C6)-alkyl-X-R11 or -O-(C1-C6)-alkyl-R16; each R5 and R6 represents independently hydrogen atom, halogen atom, -CO2R12, -CONR14R15, (C1-C6)-alkyl substituted possibly with hydroxy-group, -NR14R15 or 1-3 fluorine atoms; (C1-C6)-alkyl-R11, -XCH(R11)-(C1-C6)-alkyl or -XCH(R16)-(C1-C6)-alkyl, -NR14R15, -N(R11)R11, X-(CH2)qNR14R15, (CH2)nNR14R15, -NHC(O)-(C1-C6)-alkyl substituted possibly with one or more hydroxy-group, (C3-C6)-alkynyl or (C3-C6)-alkenyl possibly branched and, possibly, substituted with 1-3 groups chosen from hydroxy-, cyano-group, halogen atom and =O. Proposed compounds can be used in treatment of chemokine-mediates diseases, for example, inflammatory diseases, such as asthma. Also, invention describes methods for synthesis of compounds of the formula (I), pharmaceutical composition based on thereof, method for preparing pharmaceutical composition and using compounds in producing a medicinal agent.

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

17 cl, 212 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel imidazoline-2-yl-aminophenylamides of the formula (I): wherein R1 means phenyl optionally substituted with one, two or three substitutes chosen independently from group comprising alkyl, alkenyl, alkoxy-group, optionally substituted aryl, optionally substituted aryloxy-, aralkyloxy-group, halogen atom, halogenalkyl, halogenalkoxy-, hydroxy-group, hydroxyalkyl, alkylsulfonyl, alkoxyalkyloxy-, hydroxyalkyloxy-, cyano-, hydroxy-group, cycloalkyl, cycloalkyloxy-, cycloalkylalkoxy-, amino-, alkylamino-, dialkylamino-group, optionally substituted heterocyclyl, optionally substituted heterocyclyloxy-group, optionally substituted heterocyclylsulfonyl, optionally substituted heterocyclylalkyloxy-group, sulfamoyl, alkylsulfamoyl, dialkylsulfamoyl; R2 means hydrogen atom; A means -C(O)-NRa-(CRbRc)n- or -NRa-C(O)-(CRbRc)n-; n = 1-6; each among Ra, Rb and Rc means independently hydrogen atom or alkyl, or their pharmaceutically acceptable salt or solvates, and to compounds of the formula (II): wherein R1, R2, Rb, Rc and A have above given values; each R3 and R4 means independently hydrogen atom or alkoxycarbonyl; Ra means hydrogen atom, alkyl or cycloalkyl. These compounds are effective modulators of IP receptors and firstly antagonists of IP receptors. Except for, invention involves pharmaceutical compositions containing indicated compounds.

EFFECT: valuable biological and medicinal properties of compounds and pharmaceutical composition.

11 cl, 1 tbl, 10 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention describes derivatives of aminotetraline of the formula (I) wherein R1 means (C1-C6)-alkyl; R2 means halogen atom or -OR'; R3 means hydrogen atom (H) or -OR' wherein R' means (C1-C6)-alkyl or -SO2R'' wherein R'' means phenyl, thienyl, isoxazolyl; R4 means (C1-C6)-alkyl, phenyl, piperidinyl, pyrrolidinyl, morpholinyl, piperazinyl, diazepinyl, furanyl, isoxazolyl, imidazolyl and pyrazolyl that can be substituted optionally, and pharmaceutical compositions containing derivatives of aminotetraline. Proposed compounds are selective antagonists of M2/M3 muscarinic receptors and designated for treatment and prophylaxis of diseases associated with smooth muscle disorder.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

23 cl, 1 tbl, 16 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to novel derivatives of nicotinamide of the general formula (I): wherein R1 is chosen from hydrogen atom, unsubstituted or substituted (C1-C6)-alkyl, (C2-C6)-alkenyl, (C3-C7)-cycloalkyl, phenyl or heteroaryl; R2 is chosen from hydrogen atom, (C1-C6)-alkyl and group -(CH2)q-(C3-C7)-cycloalkyl, or -(CH2)mR1 and R2 in common with nitrogen atom to which they are bound form (four-six)-membered heterocyclic ring; R3 represents chlorine atom or methyl group; R4 represents group -NH-CO-R7 or -CO-NH-(CH2)q-R8; R7 is chosen from hydrogen atom, (C1-C6)-alkyl, group -(CH2)q-(C3-C7)-cycloalkyl and others; R8 is chosen from hydrogen atom, (C1-C6)-alkyl, (C3-C7)-cycloalkyl and others; each X and Y is chosen independently from hydrogen atom, methyl group and halogen atom; Z represents halogen atom; m is chosen from 0,1, 2, 3 and 4; n and q are chosen from 0, 1 and 2, and to pharmaceutically acceptable salts or their solvates. Indicated compounds possess inhibitory activity with respect to p38 kinase and can be used in medicine.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

15 cl, 127 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: invention relates to 5-substituted alkylaminopyrazole derivatives of formula I , wherein R1 is CN; W is C-halogen; R1 is halogen; R3 is C1-C3-haloalkyl, C1-C3-haloalkoxy; R4 is hydrogen, C1-C6-alkenyl, C2-C6-alkynyl, C3-C7-cycloalkyl, COR8; A is C1-C12-alkylene; R5 is hydrogen, C3-C6-alkenyl, -(CH )qR7 or NR10R11; R5 is C1-C6-haloalkyl; as well as method for animal exogenous and endogenous pest controlling; pesticide composition and application of said compounds for production of veterinary drug. 5-Substituted alkylaminopyrazole derivatives are useful in pest controlling, including insects, arachnids and helminthes, such as nematodes.

EFFECT: new pesticide derivatives.

9 cl, 12 tbl, 20 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to new amide-type carboxamide derivatives of formula [1] , wherein X represents -N= or -CH= group; R1 represents halogen atom, lower alkyl and a like; R1 represents -CO-R21-R22 (meanings of R21 and R22 are as defined in claim 1); Y1 and Y2 are independently halogen atom, lower alkyl, lower alcoxy group, and a like; ring A represents phenyl and a like; or pharmaceutically acceptable salts thereof. Said derivatives are useful as FXa inhibitors. Also disclosed are pharmaceutical composition based on abovementioned compounds and uses thereof.

EFFECT: new amide-type carboxamide derivatives.

7 cl, 105 ex

FIELD: synthesis of biologically active compounds.

SUBSTANCE: invention relates to hydroxamate derivatives described by general formula I: , in which R1 represents H or linear C1-C6-alkyl; R2 hydrogen, С110-alkyl optionally substituted by 1-5 constituents selected from hydroxy, amino, hydroxyalkyl; C4-C9-cycloalkyl; aryl; C4-C9-heterocycloalkyl, C4-C9-heterocycloalkylalkyl containing 2 heteroatoms (nitrogen and/or oxygen); C4-C9-cycloalkylalkyl; arylalkyl; heteroarylalkyl containing 1-4 nitrogen atoms as heteroatoms; -(CH2)nC(O)R6, -(CH2)nOC(O)R6, -N(R12)C(O)-W; HONH-C(O)-CH=C(R1)arylalkyl, and (CH2)nR7; R3 and R4, identical or different, independently denote hydrogen, optionally OH-substituted C1-C6-alkyl; C(O)-O-W, or -N(R12)C(O)W; or R3 and R4 together with carbon atom, to which they are linked, represent C=O; or R2 together with carbon atom, to which it is linked, and R3 together with carbon atom, to which it is linked, can form C4-C9-heterocycloalkyl containing 2 nitrogen atoms as heteroatoms; or mixed aryl or non-aryl polyheterocyclic ring; R5 is selected from hydrogen; C1-C6-alkyl; C4-C9-cycloalkyl; C(O)-W; aryl optionally substituted by 1-2 constituents selected from halogen and hydroxyalkyl; heteroaryl containing nitrogen as heteroatom; arylalkyl; aromatic polycycle; polyheteroaryl containing 1-2 nitrogen atoms as heteroatoms and optionally substituted by 1-2 substituents selected from hydroxyalkyl, halogen, alkyl, and aryl; mixed aryl-nonaryl polyheterocycle containing nitrogen or oxygen atom as heteroatom and optionally substituted by groups -N-OH, =N-OH; n, n1, n2, and n3, identical or different, are independently selected from within a range of 0-6; X and Y, identical or different, are independently selected from hydrogen, halogen, and nitro group; or pharmaceutically acceptable salt thereof. Invention also relates to a pharmaceutical composition showing inhibitory activity toward hydroxamate derivative of general formula I in combination with one or several pharmaceutically acceptable carriers. Hydroxamate derivative of general formula I are also appropriate for treating proliferative disease and regulating p21 promoter.

EFFECT: enabled use of hydroxamate derivatives as deacetylase inhibitors.

42 cl, 6 tbl, 272 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes novel compounds of the general formula (I) wherein p, R1, R2, R3 and A are determined in the invention description, their individual isomers and their pharmaceutically acceptable salts. Proposed compounds possess antagonistic effect with respect to muscarinic receptors that allows their using in treatment and prophylaxis of diseases yielding to treatment with muscarinic receptor antagonist. Also, invention describes a pharmaceutical composition containing these compounds.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

23 cl, 22 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel substituted derivatives of 4-phenyltetrahydroisoquinoline of the general formula (I): wherein R1, R2, R3 and R4 mean independently of one another hydrogen (H), fluorine (F), chloride (Cl), bromine (Br) atoms, CaH2a+1 wherein one or more atoms H are substituted with F, -NR11R12 or -SOj-R15 wherein a = 1-8; R11 and R12 mean independently of one another H, CeH2e+1 or CrrH2rr-1 wherein e = 1-4; rr = 3, 4, or in common with nitrogen atom to which they are bound form a cycle chosen from group consisting of pyrrolidinyl, piperidinyl, N-methylpiperazinyl, piperazinyl or morpholine; j = 1 or 2; R15 means CkH2k+1 wherein k = 1-8; R5 means CpH2p+1 or CssH2ss-1; p = 1-8; ss = 3-8; R6 means H; R7, R8 and R9 mean independently of one another mean -SOwR23, -NR32COR30, NR32CSR30, -NR32SObbR30, H, F, Cl, Br, -OH, -NH2, CeeH2ee+1, -NR40R41, -CONR40R41 or -COOR42 wherein w = 0, 1 or 2; bb = 2 or 3; R23 means NR25R26 wherein R25 and R26 mean independently of one another H or CzH2z+1, CzzH2zz-1 wherein z = 1-8; zz = 3-8 wherein in CzH2z+1 and CzzH2zz-1 one or more H atoms are substituted with fluorine atom and one or more CH2-groups are substituted with -C(=O) or NR27 wherein R27 means H or CaaH2aa+1 wherein aa = 1-4; or R25 and R26 in common with nitrogen atom to which they are bound form 5-, 6- or 7-membered cycle; R30 means H, CccH2cc+1, CyyH2yy-1, pyrrolydinyl, piperidinyl wherein in their cycles CH2-group can be substituted with oxygen atom (O) or -NR33; R32 and R33 mean independently of one another H or ChH2h+1 wherein cc = 1-8; yy = 3-8; h = 1-8 wherein in the group ChH2h+1 one or more hydrogen atoms are substituted with fluorine atom, and in the groups CccH2cc+1 and CyyH2yy-1 one or more hydrogen atoms can be substituted with fluorine atom, and CH2-group can be substituted with O or -NR31 wherein NR31 means H, methyl, ethyl, acetyl or -SO2CH3; or R30 means 6-membered heteroaryl with 1-4 nitrogen atoms, 0 or 1, S-atoms or 0, or 1 O-atom that represents unsubstituted or substituted with up to three substitutes chosen from group consisting of F, Cl, Br, J, CooH2oo+1 wherein one or more hydrogen atoms can be substituted with fluorine atom, -NO2 or -NR70R71 wherein oo = 1-8; R70 and R71 mean independently of one another H, CuuH2uu+1 or -COR72 wherein uu = 1-8; R72 means H, CvvH2vv+1 wherein vv = 1-8; ee = 1-8; R40 and R41 mean independently of one another H, CttH2tt+1 or -C(NH)NH2 wherein tt = 1-8 and wherein in the group CttH2tt+1 one or more CH2-groups can be substituted with NR44 wherein R44 means CggH2gg+1 wherein gg = 1-8; R42 means H or ChhH2hh+1 wherein hh = 1-8 being, however, two substitutes from group R7, R8 and R9 can't mean -OH simultaneously, and at least one residue from R7, R8 and R9 must be chosen from group consisting of -CONR40R41, -OvSOwR23, -NR32COR30, -NR32CSR30 and -NR32SObbR30. Also, invention relates to using above given compounds for preparing a medicinal agent. Also, invention considers a medicinal agent representing inhibitor of sodium-proton exchange of subtype III (NHE3) based on proposed compounds. Invention provides synthesis of novel compounds, a medicinal agent based on thereof for aims of treatment of such diseases as nervous system ischemia, insult and brain edema, in treatment of snore, shock, impaired respiratory impulse, as purgative agents, as agents against extoparasites, for prophylaxis of gall stones formation, as anti-atherosclerotic agents, agents against diabetes mellitus later complications, cancer diseases, fibrous diseases, endothelial dysfunction, hypertrophies and hyperplasia of organs and others.

EFFECT: valuable medicinal properties of compounds and medicinal agents.

21 cl, 15 tbl, 221 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of quinoline of the formula (I): wherein R1 and R2 are chosen independently from hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, alkylcarbonyl, cycloalkylcarbonyl, phenyl, unsubstituted benzyl or benzyl substituted with halogen atom, cyano-group, trifluoromethyl, alkyl, alkoxy-group, benzylcarbonyl, pyridinyl, furyl, thiophenyl, indanyl, phenyl-SO2-, pyridinyl-SO2-, thiophenyl-SO2; or R1 and R2 in common with atom N to which they are added form piperidino-group, pyrrolidinyl, morpholinyl, azepanyl, 3,4-dihydro-1H-isoquinolinyl, and wherein heterocyclic ring is optionally substituted with one or some substitutes chosen independently from alkyl and alkoxy-group; R3 represents hydrogen atom, alkyl; R4 represents hydrogen atom; A in common with nitrogen atom that is added to quinoline ring represents pyrrolidinyl, azepanyl, and ring A is optionally substituted with one-three substitutes chosen independently from alkoxy-group, hydroxyalkyl, alkoxyalkyl. Also, invention describes methods of synthesis of quinoline derivatives of the formula (I). Proposed compounds can be used as components of pharmaceutical formulations in treatment or prophylaxis of arthritis, cardiovascular diseases, diabetes mellitus, renal insufficiency, disorders in food eating and obesity.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

20 cl, 122 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel imidazoline-2-yl-aminophenylamides of the formula (I): wherein R1 means phenyl optionally substituted with one, two or three substitutes chosen independently from group comprising alkyl, alkenyl, alkoxy-group, optionally substituted aryl, optionally substituted aryloxy-, aralkyloxy-group, halogen atom, halogenalkyl, halogenalkoxy-, hydroxy-group, hydroxyalkyl, alkylsulfonyl, alkoxyalkyloxy-, hydroxyalkyloxy-, cyano-, hydroxy-group, cycloalkyl, cycloalkyloxy-, cycloalkylalkoxy-, amino-, alkylamino-, dialkylamino-group, optionally substituted heterocyclyl, optionally substituted heterocyclyloxy-group, optionally substituted heterocyclylsulfonyl, optionally substituted heterocyclylalkyloxy-group, sulfamoyl, alkylsulfamoyl, dialkylsulfamoyl; R2 means hydrogen atom; A means -C(O)-NRa-(CRbRc)n- or -NRa-C(O)-(CRbRc)n-; n = 1-6; each among Ra, Rb and Rc means independently hydrogen atom or alkyl, or their pharmaceutically acceptable salt or solvates, and to compounds of the formula (II): wherein R1, R2, Rb, Rc and A have above given values; each R3 and R4 means independently hydrogen atom or alkoxycarbonyl; Ra means hydrogen atom, alkyl or cycloalkyl. These compounds are effective modulators of IP receptors and firstly antagonists of IP receptors. Except for, invention involves pharmaceutical compositions containing indicated compounds.

EFFECT: valuable biological and medicinal properties of compounds and pharmaceutical composition.

11 cl, 1 tbl, 10 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to compound of the formula (I): wherein (a) each R1 is chosen independently from hydrogen atom and alkoxy-group; (b) R2 represents hydrogen atom; (c) each R3 and R4 is chosen independently of one another from hydrogen atom, alkyl, alkynyl, heteroalkyl group, aryl; or R3 and R4 in common with nitrogen atom bound with them form heteroaryl or heterocycloaryl substitute optionally substituted with one or more hydroxo-group, carboxyl group, keto-, thioketo-, phenyl group, alkyl, heteroalkyl group, heteroaryl, heterocycloalkyl, spirocycloalkyl and their combinations; (d) each R5 and R6 represents hydrogen atom; or optical isomers, diastereomers and enantiomers represented by above given formula, and their pharmaceutically acceptable salts also. Also, invention describes using compound of the formula (I) for preparing a pharmaceutical composition possessing antibacterial activity and antibacterial pharmaceutical composition containing the safety and effective amount of compound of the formula (I) and a pharmaceutically acceptable carrier. Invention provides synthesis of novel compounds possessing useful biological properties.

EFFECT: valuable properties of compounds and pharmaceutical composition.

7 cl, 37 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): wherein m = 1-4; n = 0-4; A means alkyl, aryl, trifluoromethylfuryl, arylalkyl, arylcycloalkyl, cycloalkylalkyl or aryloxyalkyl; E means -CHOH- or -C(O)-; X means -(CH2)2- or -CH=CH-; Y means -CH2-, arylene, -S-; Z means -COOH; each R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 means independently hydrogen atom or alkyl, or its pharmaceutically acceptable salt or solvate, individual isomer or racemic or nonracemic mixture of isomers. Also, invention relates to a pharmaceutical composition and using compounds based on the formula (I) possessing activity as agonists of prostaglandin. Invention provides preparing novel biologically active compounds and pharmaceutical compositions based on thereof possessing activity as agonists of prostaglandin.

EFFECT: valuable biological property of compounds and pharmaceutical compositions.

24 cl, 1 tbl, 7 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to novel derivatives of nicotinamide of the general formula (I): wherein R1 is chosen from hydrogen atom, unsubstituted or substituted (C1-C6)-alkyl, (C2-C6)-alkenyl, (C3-C7)-cycloalkyl, phenyl or heteroaryl; R2 is chosen from hydrogen atom, (C1-C6)-alkyl and group -(CH2)q-(C3-C7)-cycloalkyl, or -(CH2)mR1 and R2 in common with nitrogen atom to which they are bound form (four-six)-membered heterocyclic ring; R3 represents chlorine atom or methyl group; R4 represents group -NH-CO-R7 or -CO-NH-(CH2)q-R8; R7 is chosen from hydrogen atom, (C1-C6)-alkyl, group -(CH2)q-(C3-C7)-cycloalkyl and others; R8 is chosen from hydrogen atom, (C1-C6)-alkyl, (C3-C7)-cycloalkyl and others; each X and Y is chosen independently from hydrogen atom, methyl group and halogen atom; Z represents halogen atom; m is chosen from 0,1, 2, 3 and 4; n and q are chosen from 0, 1 and 2, and to pharmaceutically acceptable salts or their solvates. Indicated compounds possess inhibitory activity with respect to p38 kinase and can be used in medicine.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

15 cl, 127 ex

FIELD: organic chemistry, medicine, gynecology.

SUBSTANCE: invention relates to novel tetracyclic heterocompounds of the formula (I): wherein X, Y, Z, R1 - R4, n and m has values given in the invention description and used as selective modulating agents for estrogen receptors. Also, invention relates to a method for synthesis of these compounds and pharmaceutical compositions comprising thereof, and their using in treatment and/or prophylaxis of disorders mediated by one or more estrogen receptors. Proposed compounds are useful in treatment and/or prophylaxis of disorders associated with depleting estrogen and comprising such disorders as rush of blood, vaginal dryness, osteopenia and osteoporosis, hormone-dependent cancer and hyperplasia of breast, endometrium, uterus cervix and prostate, endometriosis, uterus fibroma, osteoarthritis that can be used as contraceptive agents both separately and in combination with progestogen or progestogenous antagonist.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

25 cl, 7 tbl, 171 ex

Novel benzodioxols // 2304580

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of benzodioxol of the formula (I): wherein R1, R2, R3, R4, R5, R6, R7 and X are given in the description and the invention claim, and to their pharmaceutically acceptable salts. Also, invention relates to pharmaceutical compositions based on compounds of the formula (I) and their using for preparing medicinal agents used in treatment and/or prophylaxis of diseases associated with modulation of CB1 receptors.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

19 cl, 279 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel crystalline modifications of 1-[4-(5-cyanoindole-3-yl)butyl]-4-(2-carbamoylbenzofuran-5-yl)-piperazine hydrochloride, crystalline modification of 1-[4-(5-cyanoindole-3-yl)butyl]-4-(2-carbamoylbenzofuran-5-yl)-piperazine hydrochloride hydrate (forms V, VI, VIII) and 1-[4-(5-cyanoindole-3-yl)butyl]-4-(2-carbamoylbenzofuran-5-yl)-piperazine hydrochloride anhydrate (forms IV, III, VII, IX). Proposed forms can be used in preparing solid medicinal formulations for treatment of or prophylaxis of depressive states, anxiety disorders, maniacal-depressive disorders, maniacal syndrome, dementia, disorders associated with substrates deficiency, disorder in sexual function, alimentary disorders, obesity, fibromyalgia, insomnia, psychiatric disorders, brain infarction, hypertension, in treatment of adverse effects in treatment of hypogonadism, secondary amenorrhea, premenstrual syndrome and undesirable post-delivery lactation. Also, invention relates to methods for synthesis of forms V and IV and to pharmaceutical compositions and pharmaceutical preparation based on thereof. Invention provides the improved solubility, reduced hygroscopicity and increased storage time of synthesized compounds and the preparation based on thereof.

EFFECT: improved and valuable properties of forms.

13 cl, 46 dwg, 2 tbl, 16 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to pharmaceutical compositions possessing inhibitory effect with respect to MC2R-receptors, for preparing medicinal preparations as tablets, granules, capsules, suspensions, solutions or injections placed into pharmaceutically acceptable package. As active substance the composition comprises azaheterocyclic compound of general formulas (1.1.1) , (1.2.1) or (1.3.1) , wherein R1 in the general formula (1.1.1) represents substituted alkyl, aryl, heteroaryl, heterocyclyl, or R1 in the general formula (1.2.1) represents a substitute of amino-group chosen from hydrogen atom or possibly substituted lower alkyl or lower acyl; each R2, R3 and R4 represents independently of one another a substitute of cyclic system chosen from hydrogen atom, azaheterocyclyl, possibly substituted lower alkyl, possibly substituted hydroxy-group, carboxy-group, cycloalkyl; or R3 and R4 in common with carbon atoms to which they are bound form azaheterocycle, or R1 in common with nitrogen atom to which it is bound, and R3 and R4 in common with carbon atoms to which they are bound form azaheterocycle through R1, R3 and R4; R18 and R19 represent independently of one another substitutes of amino-group chosen from hydrogen atom or lower alkyl substituted with azaheterocycle as their racemates, optically active isomers or their pharmaceutically acceptable salts and/or hydrates; R20 and R21 in common with nitrogen atom to which they are bound form possibly substituted azaheterocycle. Also, invention relates to a method for preparing a pharmaceutical composition and using compounds and compositions for preparing medicinal preparations and for treatment or prophylaxis of diseases associated with enhanced activation of adrenocorticotropic hormone for compounds of general formulas (1.1.1), (1.2.1) and (1.3.1), and for using compounds for experimental investigations of indicated processes in vitro or in vivo also.

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

15 cl, 1 dwg, 4 tbl, 5 ex

FIELD: synthesis of biologically active compounds.

SUBSTANCE: invention relates to hydroxamate derivatives described by general formula I: , in which R1 represents H or linear C1-C6-alkyl; R2 hydrogen, С110-alkyl optionally substituted by 1-5 constituents selected from hydroxy, amino, hydroxyalkyl; C4-C9-cycloalkyl; aryl; C4-C9-heterocycloalkyl, C4-C9-heterocycloalkylalkyl containing 2 heteroatoms (nitrogen and/or oxygen); C4-C9-cycloalkylalkyl; arylalkyl; heteroarylalkyl containing 1-4 nitrogen atoms as heteroatoms; -(CH2)nC(O)R6, -(CH2)nOC(O)R6, -N(R12)C(O)-W; HONH-C(O)-CH=C(R1)arylalkyl, and (CH2)nR7; R3 and R4, identical or different, independently denote hydrogen, optionally OH-substituted C1-C6-alkyl; C(O)-O-W, or -N(R12)C(O)W; or R3 and R4 together with carbon atom, to which they are linked, represent C=O; or R2 together with carbon atom, to which it is linked, and R3 together with carbon atom, to which it is linked, can form C4-C9-heterocycloalkyl containing 2 nitrogen atoms as heteroatoms; or mixed aryl or non-aryl polyheterocyclic ring; R5 is selected from hydrogen; C1-C6-alkyl; C4-C9-cycloalkyl; C(O)-W; aryl optionally substituted by 1-2 constituents selected from halogen and hydroxyalkyl; heteroaryl containing nitrogen as heteroatom; arylalkyl; aromatic polycycle; polyheteroaryl containing 1-2 nitrogen atoms as heteroatoms and optionally substituted by 1-2 substituents selected from hydroxyalkyl, halogen, alkyl, and aryl; mixed aryl-nonaryl polyheterocycle containing nitrogen or oxygen atom as heteroatom and optionally substituted by groups -N-OH, =N-OH; n, n1, n2, and n3, identical or different, are independently selected from within a range of 0-6; X and Y, identical or different, are independently selected from hydrogen, halogen, and nitro group; or pharmaceutically acceptable salt thereof. Invention also relates to a pharmaceutical composition showing inhibitory activity toward hydroxamate derivative of general formula I in combination with one or several pharmaceutically acceptable carriers. Hydroxamate derivative of general formula I are also appropriate for treating proliferative disease and regulating p21 promoter.

EFFECT: enabled use of hydroxamate derivatives as deacetylase inhibitors.

42 cl, 6 tbl, 272 ex

Prucaloprid n-oxide // 2301806

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a novel benzamide derivative of the formula (I) , its stereochemical isomeric forms, its pharmaceutically acceptable acid-additive salts and pharmaceutical compositions containing the indicated novel compound. Also, invention relates to methods for synthesis of indicated compounds, preparing compositions and their using as a medicinal agent use in treatment of digestive tract motor system disorders.

EFFECT: valuable medicinal property of compound and pharmaceutical compositions.

8 cl, 1 tbl, 3 ex

The invention relates to a method for simple macrofire s-triazines bis[4,6-disubstituted)-1,3,5-triazine-2-yl]oxides of the General formula I

where R and R’ are the same or different and mean och3the remainder of the research, piperidine or pyrrolidine
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