Substituted thienocycloalk(ene)ylamino-1,3,5-triazines

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention relates to substituted thienocycloalk(ene)ylamino-1,3,5-triazines of the general formula (I): wherein R1 means hydrogen atom; R2 means hydrogen atom, formyl or alkylcarbonyl, group N(R1R2) denoting dialkylaminoalkylideneamine; R3 means unsubstituted or halogen-substituted alkyl; Z means one of the following thienocycloalkyl groups: and wherein A1, A2 and A3 mean alkylene. Also, invention describes a method for synthesis of indicated compounds and intermediate compounds used in the synthesis. Compounds can be used as herbicides.

EFFECT: improved method for synthesis, valuable agricultural properties of compounds.

8 cl, 4 tbl, 5 ex

 

The invention relates to new substituted teenieclub(EN)ylamino-1,3,5-triazine, the way they are received, including new intermediate products, and their use as herbicides.

The number is replaced by taylorkillian-1,3,5-triazines are already known from the (patent) literature (see international application WO-A-98/15537, WO-A-98/15539, the application for a German patent DE-A-19744232). These compounds, however, still did not have any special value.

In U.S. patent US 4740230 and European patent application EP 283522 described taylorkillian-1,3,5-triazine that can be used as herbicides. However, herbicide activity is not high enough.

Substituted teenieclub(EN)ylamino-1,3,5-triazine still not known.

Now received new substituted teenieclub(EN)ylamino-1,3,5-triazine General formula (I)

in which

R1denotes hydrogen,

R2denotes hydrogen, formyl or alkylsulphonyl, or the group N(R1R2also designates dialkylaminoalkyl,

R3denotes unsubstituted or substituted with halogen alkyl,

Z denotes one of the following cyanocyclohexyl groups

where

m denotes the number 0, 1 or 2,

n denotes the number 0, 1 or 2,

And1means alkane is PII (alkylen),

And2means alcander (alkylen),

And3means alcander (alkylen),

R4denotes alkyl,

R5denotes halogen or alkyl.

Saturated or unsaturated hydrocarbon group such as alkyl, alcander are in General possible, as needed, a linear or branched.

Preferred substituents or values present residues above and in further formulas, defined below.

And1means preferably alcander (alkylen) with 1-3 carbon atoms,

And2means preferably alcander (alkylen) with 1-3 carbon atoms,

And3means preferably alcander (alkylen) with 1-3 carbon atoms,

R2represents preferably hydrogen, formyl or alkylaryl containing from 1 to 6 carbon atoms in the alkyl group, or the group N(R1R2) denotes preferably dialkylaminoalkyl group with the number of carbon atoms up to 4 alkyl group or alkylidene group, respectively,

R3means are preferably unsubstituted or substituted by halogen alkyl with 1-6 carbon atoms,

R4means is preferably alkyl containing from 1 to 6 carbon atoms,

R5means are preferably halogen or alkyl containing from 1 to 6 atoms in the of Lerida,

And1refers particularly preferably methylene, dimethylene or trimethylene,

And2refers particularly preferably methylene, dimethylene or trimethylene,

And3refers particularly preferably methylene, dimethylene or trimethylene,

R2refers particularly preferably hydrogen, formyl or acetyl, propionyl, n - or Isobutanol, or

the group N(R1R2) denotes dimethylaminomethylphenol or diethylaminoethylamine,

R3refers particularly preferably unsubstituted or substituted by fluorine, chlorine or bromine, methyl, ethyl, n - or isopropyl, n-, ISO - or sec-butyl,

R4refers particularly preferably methyl, ethyl, n - or isopropyl,

R5refers particularly preferably fluorine, chlorine, bromine, methyl, ethyl, n - or isopropyl,

And1indicates most preferably methylene or dimethylene,

And2indicates most preferably methylene or dimethylene,

And3indicates most preferably methylene or dimethylene,

R2means are most preferably hydrogen, formyl or acetyl, propionyl, n - or Isobutanol, or

the group N(R1R2refers most preferably dimethylamino-methylaminopropyl,

R4means are most preferably methyl or the Tyl,

R5indicates most preferably fluorine, chlorine, bromine, methyl or ethyl.

In the General formula (I) Z means, most preferably,

and

p denotes 2, 3 or 4, a n, m, R4and R5defined as above.

Above in General or the above preferred values the determination of residues apply both to the end products of the formula (I)and, respectively, to those that are possible to obtain a desired initial or intermediate products. These definitions residues can be combined among themselves, and also between the preferred values in any combination.

Preferred in accordance with the invention are those compounds of formula (I), in which the combination mentioned above as preferred values.

Particularly preferred in accordance with the invention are those compounds of formula (I), in which the combination mentioned above as particularly preferred values.

Most preferred in accordance with the invention are those compounds of formula (I), which is a combination of the above is given as the very most preferred values.

Most of predpochtitel is generated in accordance with the invention are those compounds of formula (I), in which Z has the meaning indicated above as preferred.

In accordance with the invention compounds of General formula (I) contain, if necessary, one asymmetric substituted carbon atom and can therefore exist in different enantiomeric (forms R and S configuratie) or diastereomeric forms. The invention applies to various possible individual enantiomeric or stereoisomeric forms of the compounds of General formula (I), and mixtures of these isomers.

New substituted teenieclub(EN)ylamino-1,3,5-triazine General formula (I) show interesting biological properties. They differ, in particular, a strong herbicide activity.

Get new substituted teenieclub(EN)ylamino-1,3,5-triazine General formula (I), when the biguanides of the General formula (II)

in which

R1, R2and Z have the above values,

and/or adducts join acid compounds of General formula (II) is subjected to interaction with alkoxycarbonyl compounds of General formula (III)

R3-CO-OR'(III)

in which

R3have the above significance and

R' denotes alkyl,

if necessary, in the presence of an auxiliary reagent is, if necessary, in the presence of a diluent

and, if necessary, the thus obtained compounds of General formula (I) under certain deputies conduct further transformation of conventional methods.

Compounds of General formula (I) can be converted by conventional methods into other compounds of General formula (I) in accordance with the above definition of the substituents, for example, by the interaction of the compounds of formula (I)in which R2denotes hydrogen, allermuir agent such as, for example, acetylchloride, acetic anhydride, propionate, propionic anhydride, methyl ether of Harborview acid or ethyl ester of Harborview acid (when administered as R2for example, formyl groups or alkylaryl instead of a hydrogen atom).

If you use, for example, 1-(4,5,6,7-tetrahydrobenzo(b)thiophene-4-yl)-biguanide and methyl ether triperoxonane acid as starting materials, can be present during the reaction in the method in accordance with the invention, the following exemplary scheme:

Used in the method of obtaining, in accordance with the invention compounds of General formula (I) as starting compounds, biguanides defined General formula (II). In the General formula (II) R1, R2and Z are mainly suitable for the NGOs, first of all, the values that described above in connection with the description of the compounds according to the invention of General formula (I), mainly, respectively, as particularly preferred for R1, R2and Z.

Suitable adducts with acid compounds of the formula (II) are their addition products with proton acids such as, for example, hydrogen chloride (hydrochloric acid), hydrogen bromide (Hydrobromic acid), sulfuric acid, methanesulfonate, benzosulfimide and p-toluensulfonate.

The original substance of General formula (II) are not yet known from the literature; they are as new substances is also an object of this application.

Get new biguanides of the General formula (II), when the amine compounds of General formula (IV)

Z-NH2(IV)

in which Z has the meaning indicated above,

and/or adducts with acids of compounds of General formula (IV), as, for example, hydrochloride - subject interaction with cyanoguanidine ("dicyandiamide") of the formula (V),

if necessary, in the presence of an auxiliary reagent, such as hydrogen chloride, and optionally in the presence of a diluent, such as n-decane or 1,2-dichlorobenzene, when temperature is round between 100° With 200°With (see examples receipt).

The biguanides of the General formula (II) can be sent after receiving them without pre-allocation to obtain the compounds of General formula (I) according to the method in accordance with the invention (see examples receipt).

Required as intermediate products of these amino compounds of General formula (IV) are known and/or can be obtained by known methods (see J. Org. Chem. 18 (1953), 1511-1515; the application of Japan JP-A-03223277 - cited in Chem. Abstracts 1992:128652 or 116:128652).

Get the amino compounds of General formula (IV), when the corresponding cyclic ketones (one of the residues And1And2or And3refers to then-CO-) is subjected to interaction with formamide at temperatures between 140°and 190°and received formylamino connection then hydrolized by heating with aqueous hydrochloric acid (see J. Org. Chem. 18 (1953), 1511-1515), or when the corresponding cyclic ketones first interaction with hydroxylamine hydrochloride, optionally in the presence of a diluent, such as, for example, pyridine at temperatures between 0°s and 50°converted into the corresponding oximes, and they interact with a reducing agent such as sodium borohydride, in the presence of an auxiliary reagent, such as, for example, tetravalent titanium chloride and in the presence of razbaby the El, as, for example, 1,2-dimethoxyethane, at temperatures between -20°C and +50°With (see examples receipt).

The corresponding cyclic ketones are known and/or can be obtained by known methods (see J. Chem. Soc. 1953, 1837-1842; J. Heterocycl. Chem. 2 (1965), 4448; ibid 17 (1980), 87-92; ibid 29 (1992), 1213-1217; J. Pharm. Sci. 52 (1963), 898-901; application U.S. And 3301874).

Hereinafter, used in the method of obtaining, in accordance with the invention compounds of General formula (I) as starting compounds, alkoxycarbonyl connection defined General formula (III). In the General formula (III), R3has, mainly or primarily, the value of which is indicated above in connection with the description of the compounds according to the invention of General formula (I), principally or as particularly preferred for R3; R' preferably denotes alkyl with 1-4 carbon atoms, in particular methyl or ethyl.

The original substance of General formula (III) are known synthesis chemicals.

The method of obtaining, in accordance with the invention compounds of formula (I) are, if necessary, with the use of an auxiliary reagent. As an auxiliary reagent consider, in General, the usual inorganic or organic bases or acid acceptors. These include, preferably acetates, amides, carbonates, bicarbonates, hydrides, guide the oxides or alcoholate of alkali metals or alkaline earth metals, as, for example, sodium acetate, potassium or calcium, lithium amide, sodium, potassium or calcium, sodium carbonate, potassium or calcium, bicarbonate of sodium, potassium or calcium, lithium hydride, sodium, potassium or calcium hydroxide of lithium, sodium, potassium or calcium, methanolate, ethanolate, n - or ISO-propanol, n-, ISO-, sec - or tert-butanolate sodium or potassium; also referred to as basic organic nitrogen compounds, such as trimethylamine, triethylamine, Tripropylamine, tributylamine, ethyldiethanolamine, N,N-dimethylcyclohexylamine, dicyclohexylamine, ethyldiglycol, N,N-dimethylaniline, N,N-dimethylbenzylamine, pyridine, 2-methyl-, 3-methyl-, 4-methyl-, 2,4-dimethyl-, 2,6-dimethyl-, 3,4-dimethyl - and 3,5-dimethylpyridine, 5-ethyl-2-methylpyridine, 4-dimethylaminopyridine, N-methylpiperidine, 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

The method of obtaining, in accordance with the invention compounds of General formula (I) are, if necessary, with diluent. As diluent consider, first of all inert organic solvent. This includes, in particular, aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons, such as, for example, benzine, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, petroleum ether, hexane, Ziklag is Xan, methylene chloride, chloroform, carbon tetrachloride; ethers, such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, or dimethyl or diethyl ethers of ethylene glycol; ketones, such as acetone, butanone or methyl isobutyl ketone; NITRILES, such as acetonitrile, propionitrile or butyronitrile; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylformamide, N is an organic or hexamethylphosphorotriamide; esters such as methyl acetate or ethyl acetate, sulfoxidov, such as dimethyl sulfoxide, alcohols, such as methanol, ethanol, n- or isopropanol, onomatology ether of ethylene glycol, monotropy ether of ethylene glycol, onomatology ether of diethylene glycol, monotropy ether of diethylene glycol, mixtures thereof with water or pure water.

The reaction temperature may vary when carrying out the method in accordance with the invention in a wide area. In General, operate at temperatures between 0°150°C, preferably between 10°120°C.

The method in accordance with the invention is carried out usually under normal pressure. However, it is also possible to carry out the method in accordance with the invention at elevated or reduced pressure -- in General between 0.1 bar and 10 bar.

For carrying out the method in accordance with the invention is administered initial matter, in General, in PR is approximately equimolecular quantities. However, it is also possible to use one component in a large excess. The interaction is conducted typically in a suitable diluent in the presence of an auxiliary reagent, and the reaction mixture is stirred generally for several hours at the required temperature. Processing then spend the usual methods (see examples receipt).

The active substance in accordance with the invention can be used as defoliants (substances that promote the falling leaves), desiccant (substances that promote drying plants), oppressive weeds, and in particular as herbicides. Under the weeds in the broadest sense must be understood all plants in areas of cultivated plants, where they are unwanted. Are there substances in accordance with the invention as total or selective herbicides depends essentially on the quantities used.

The active substance in accordance with the invention can for example be used for the following plants:

Dicotyledonous weed species: mustard, peppergrass, bedstraw, starwort, chamomile, Popovka, syt, chenopodii, nettles, Ragwort, amaranth, purslane, cocklebur, bindweed, morning glory, Highlander, Sesbania, Kotelnik, Thistle, Thistle, sow Thistle, nightshade, Rorippa, Rotala, Lindernia, dead-nettle, Veronica, gradnika, Emex, dope, violet, peak is inik, poppy, cornflower, clover, Buttercup, dandelion.

Dicotyledonous crops: cotton, soybeans, beets, carrots, beans, peas, potatoes, flax, sweet potatoes, Vic, tobacco, tomato, peanuts, cabbage, lettuce, cucumber, pumpkin.

Monocotyledonous weeds: barnyard grass, spickle, millet, digitalis, Timothy, bluegrass, fescue, Eieusine, Brachiaria, ryegrass, brome, wild oats, papyrus, sorghum, wheat grass, cynodon, Monochoria, Fimbristylis, arrowheads, bolotnitsa, reed, paspalum, Ischaemum, Sphenoclea, hedgehog, bent grass, Alopecurus, meliza, agiles, reed Canary grass.

Monocotyledonous crops: rice, maize, wheat, barley, oats, rye, sorghum, millet, sugarcane, pineapple, asparagus, onions.

The use of active substances in accordance with the invention, however, in no case is not limited to these types, but applies equally well to other plants.

The active substance in accordance with the invention are suitable, depending on the concentration, for herbicides universal steps, for example for industrial and roadside landings and roads and squares with wood pests without them. It is also possible active substances in accordance with the invention to use as herbicides in crops of long-term growth, for example in the forest, planting parks, fruits, grapes, citrus fruits, nuts, bananas, coffee, tea, rubber, oil palm, cocoa, berry is hops, the Park and sports lawns and pastures, as well as selective herbicides in annual crops.

Compounds in accordance with the invention of the formula (I) demonstrate a strong herbicide action and a broad spectrum of action when used on the soil and aboveground parts of plants. They fit in a certain amount for the selective combating of monocotyledonous and dicotyledonous weeds in monocotyledonous and dicotyledonous crops, as for predicaciones and paleoglaciology processing.

The active substance can be used in conventional compositions, such as solutions, emulsions, wettable powders, suspensions, powders, tools for pollination, pastes, soluble powders, granules, concentrated suspensions and emulsions, impregnated active substances of natural and synthetic materials, and microencapsulated in a polymeric material.

These songs get by known methods, for example by mixing the active substances with filling additives, that is liquid solvents and/or solid fillers, if necessary, with the use of surfactants, that is emulsifiers and/or dispersing agents, and/or foaming agents.

In the case of using water as the filling of the additive can, for example, also use organic dissolve the ate as auxiliary solvents. As liquid solvents are considering mainly aromatics, such as xylene, toluene or alkylnaphthalenes, chlorinated aromatics and chlorinated aliphatic hydrocarbons, such as chlorobenzene, chloroethylene or methylene chloride, aliphatic hydrocarbons, such as cyclohexane or paraffins, for example petroleum fractions, mineral and vegetable oils, alcohols, such as butanol or glycol and its ethers and esters, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, strongly polar solvents, such as dimethylformamide and dimethylsulfoxide, and water.

As solid fillers consider: for example ammonium salts and powders of natural rocks, such as kaolin, alumina, talc, chalk, quartz, attapulgite, montmorillonite or diatomites, and powders of synthetic rocks, such as highly dispersed silicic acid, alumina and silicates, as solid fillers for granules consider: for example, crushed and fractionated natural rocks such as calcite, marble, pumice, thick, dolomite, and also synthetic granules of inorganic and organic powders, and granules of organic material such as sawdust, coconut husks, cobs is okorusu and stems of tobacco; as emulsifying and/or foam-forming means consider: for example nonionic and anionic emulsifiers, such as esters of polyethylene oxide with fatty acids, ethers of polyethylene oxide with fatty alcohols, for example alkylacrylate esters of poliatilenglikola, alkyl sulphonates, alkyl sulphates, arylsulfonate, and also protein hydrolysates; as dispersing substances considered: for example, sulfite liquor lignin and methylcellulose.

Can be used in the compositions of substances that enhance the adhesion, such as carboxymethylcellulose, natural and synthetic powdered, granular, or forming 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.

It is possible to use colorants such as inorganic pigments, for example iron oxide, titanium oxide, ferrocyanide blue, and organic dyestuffs, such as alizarin, azo and metallophthalocyanine dyes, and trace elements such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.

The compositions usually contain between 0.1 and 95% of the mass. the active substance, preferably between 0.5 and 90%.

The active substance in soo is according to the invention can be used as such or in formulations as well as in mixtures with known herbicides for weed control, and possible ready-to-use formulations or finished packaged mixture.

For the mixtures considered are known herbicides, for example:

Acetochlor, acifluorfen(-sodium), klonipin, alachlor, aloxide(-sodium), ametrine is high, amithlon, amidosulfuron, anilofos, Azul, atrazine, azafenidin, azimsulfuron, benazolin(-ethyl), benporath, encultured (-methyl), bentazon, benzamycin, benzefoam, benzoylperoxy(-ethyl), bialaphos, bifenox, bispyribac(-sodium), bromated, bromophenoxy, bromoxynil, butachlor, butoxide, butyl, cafestol, galaxidi, carbetamide, carfentrazone(-ethyl), chlorotoxin, chloramben, ozone chloride, chlorimuron(-ethyl), chlornitrofen, chlorsulfuron, chlortoluron, cinidon(-ethyl), cinmetacin, chinaculture, clefoxydim, clethodim, clodinafop(-propargyl), clomazone, clomipram, clopyralid, cloperastine(-methyl), karasulu(-methyl), cumyluron, cyanazine, cybotron, cycloate, cycloaliphatic, cycloxydim, cyhalofop(-butyl), 2,4-D, 2,4-DB, 2,4-DP, desmedipham, diallate, dicamba, diclofop(-methyl), dicloflam, diacetyl(-ethyl), difenzoquat, diflufenican, diflubenzuron, dimefuron, delpeyrat, dimethachlor, deltamethrin, dimethenamid, Dimexidum, dinitramine, diphenamid, Diquat, dithiopyr, Diuron, damron, aprobada, EPTC, espoir, ethalfluralin, this is Malfurion(-methyl), ethofumesate, idoxifene, ethoxysulfuron, atalented, fenoxaprop(-P-ethyl), phentramin, planrep(-isopropyl), Flam-prop(-isopropyl-L), planrep(-methyl), flazasulfuron, florasulam, flue-ifop (-P-butyl), flatlet, flucarbazone, flufenacet, flumetsulam, flumiclorac(pencil), flumioxazin, flubiprofen, flumetsulam, fluometuron, perchloride, verglichen(-ethyl), flupoxam, flourophenyl, flurried(-methyl-sodium), flurenol(-butyl), fluridone, fluroxypyr(-methyl), flurried, flurtamone, fluthiacet(-methyl), flutamide, fomesafen, glufosinate(-ammonium), GLOBOSAT(-isopropylammonium), galasoft, haloxyfop(-ethoxyethyl), haloxyfop(P-methyl), hexazinone, imazamethabenz(-methyl), imazamethabenz, imazamox, imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, iodosulfuron(-methyl-sodium), ioxynil, isopropylene, Isoproturon, Sauron, isoxaben, isoxaflutole, isoxaflutole, isocaporate, lactofen, lenacil, linuron, PA, manual gearbox, mefenacet, mesotrione, metamitron, metazachlor, methabenzthiazuron, metaventure, metobromuron, (alpha)metolachlor, metosulam, metoxuron, metribuzin, metsulfuron(-methyl), molinet, monolinuron, nitroanilide, napropamide, neburon, nicosulfuron, norflurazon, arrancars, oryzalin, oxadiargyl, oxadiazon, oxasulfuron, oxacyclobutane, oxilorphan, paraquat, pelargonia acid, pendimethalin, pend the'alene, pentoxide, phenmedipham, piperophos, pretilachlor, primisulfuron(-methyl), prometryn, propachlor, propanil, propaquizafop, propisochlor, propyzamide, prosulfocarb, prosulfuron, pyraflufen(-ethyl), pyrazole, pyrazosulfuron(-ethyl), paradoxien, pirenoxine, perimutter, peridot, Perminova(methyl), pyrithiobac(-sodium), quinchlorac, quinmerac, quinoclamine, quizalofop(-P-ethyl), quizalofop(-R-tefuryl), rimsulfuron, sethoxydim, simensen, simetryn, sulcotrione, sulfentrazone, sulfometuron(-methyl), sulfosate, sulfosulfuron, tabulam, tebuthiuron, tepraloxydim, terbutylazine, terbutryn, trichlor, tefloned, thiazopyr, thidiazuron, thifensulfuron(-methyl), thiobencarb, thiocarbonyl, tralkoxydim, triallate, triasulfuron, tribenuron(-methyl), triclopyr, tridiphane, trifluralin and triflusulfuron.

It is also possible mixture with other known active compounds such as fungicides, insecticides, acaricides, nematicides, protective substances used for feeding birds feeding on plants and improving soil structure,

The active substance can be used as such, in the form of compositions containing them or derived from them by further dilution ready to use forms, such as ready-to-use solutions, suspensions, emulsions, powders, pastes and granulates. Making conduct regular and ways, for example by watering, spraying, spraying, sprinkling.

The active substance in accordance with the invention can be used both before and after germination of the plants. They can be made before planting in the soil.

Used quantity of active substances can vary within a wide range. They depend mainly on the type of desired effects. Usually the quantities used are between 1 g and 10 kg of active substance per hectare of sown area, preferably between 5 g and 5 kg per hectare

The receipt and use of active substances in accordance with the invention follows from the following examples.

Examples:

Example 1

(The method with the joint acquisition of the initial substances of the formula (II))

A mixture of 3.5 g (an 18.4 mmole) of the hydrochloride 4,5,6,7-tetrahydrobenzo[b]thiophene-4-yl-amine and 1.6 g (an 18.4 mmole) of cyanoguanidine heated for two hours at 150°C, then cooled rapidly in a bath of acetone and dry ice and stirred with diethyl ether. The resulting crystalline solid is separated by filtration and dissolved in 50 ml of methanol. To the solution was added 6.6 g (46,7 mmole) of sodium sulfate, and then immediately added at room temperature (about 20° (C) in turn 1.4 g (13.3 mmole) of methyl ether 2-forproposal acid and 2.1 g (12.1 mmol who) of sodium methylate. The reaction mixture is stirred for 20 hours at room temperature, and then immediately vacuum on a water-jet pump. The residue is distributed between water and methylene chloride, the organic phase is separated, dried over sodium sulfate and filtered. The filtrate is vacuum on the water pump and the residue purified by chromatography on a column (silica gel, ethyl acetate/hexane, 20:80 by volume).

Obtain 0.84 g (16% of theory) of 2-amino-4-(1-foradil)-6-(4,5,6,7-tetrahydrobenzo[b]thiophene-4-yl-amino)-1,3,5-triazine as a pale yellow oil.

LogP=4.26 deathsa)

Analogously to example 1 and in accordance with the General description of the methods of obtaining, in accordance with the invention can also be obtained as the examples shown in the following table 1 compounds of General formula (I).

Table 1

Examples of compounds of formula (I).
Example No.R1R2R3ZPhysical data
2-NR1R2:

CHFCH3
3N-The o-CH 3CHFCH3
4N-CO-C2H5CHFCH3
5NNCF(CH3)2LogP=1,75a)

Example No.R1R2R3ZPhysical data
6-NR1R2:

CF(CH3)2logP=2,67b)
7N-CO-CH3CF(CH3)2logP=2,66a)
8N-CO-C2H5CF(CH3)2logP=2,93a)
9NNCHCl2
10NNCF2CllogP=3,01a)
11NNC2F5
12NNCH2OCH3

Example No.R1R2R3ZPhysical data
13NNn-C3H7logP=1,61a)
14NNi-C3H7
15NNCF3
16NNCF3logP=3,27a)
17NNCHFCH3 logP=1,97a)
18NNCF(CH3)2logP=2,03a)

Example No.R1R2R3ZPhysical data
19NNCF3
20NNCHFCH3
21NNCF(CH3)2
22NNCF3
23NNCHFCH3
24NNCF(CH3)2
25NNCF3

Example No.R1R2R3ZPhysical data
26NNCHFCH3logP=2,21a)
27NNCF(CH3)2
28NNCF3
29NNCHFCH3
30NNCF(CH3)2
31NNCF3
32NNCHFCH3

Example No.R1R2R3ZPhysical data
33NNCF(CH3)2
34NNCF3
35NNCHFCH3
36NNCF(CH3)2
37NHCF3
38NNCHFCH3
39NNCF(CH3)2

Example No.R1R2R3ZF. the physical data
40NNCF3
41NNCHFCH3
42NNCF(CH3)2
43NNCF3logP=3,47a)
44NNCHFCH3logP=2,16a)
45NNCF(CH3)2

Example No.R1R2R3ZPhysical data
46NNCF3
47NNCHFCH3
48NNCF(CH3)2
49NNCF3
50NNCHFCH3
51NHCF(CH3)2LogP=2,05a)
52NNCF3
53NNCHFCH3

Example No.R1R2R3ZPhysical data
54NNCF(CH3)2
55NNCF3
56NNCHFCH3logP=2,47a)
57NNCF(CH3)2
58NNCF3
59NNCHFCH3
60NNCF(CH3)2

Example No.R1R2R3ZPhysical data
61NNCF3
62NNCHFCH3
63NNCF(the N 3)2
64NNCF3
65NNCHFCH3
66NNCF(CH3)2
67N-CHOCHFCH3LogP=2,93a)

Example No.R1R2R3ZPhysical data
68NNCHFCH2CH3colorless oil1H-NMR (400 MHz, CDCl3):δ=0.97 (t, 3H), 1.58-2.00 (m, 5H), 2.10 (mc, 1H), 2.53 (mc, 2H), 4.82-5.62 (m, br, 4H), 6.68 (d, 1H), 7.08 (d,1H)
69NNCH(CH3)2colorless oil

1H-NMR(400 MHz, CDCl3):δ=1.18 (ept, br, 6H), 6.66 (d, 1H), 7.06 (d, 1H)
70NNCH3colorless oil

1H-NMR (300 MHz, CDClC):δ=1.82(s, br, 3H), 6.66 (d, 1H), 7.06 (d, 1H), 1.72-2.36 (m, 4H), 2.62 (mc, 2H), 5.08-5.63 (m, 4H)
71NNCF(CH3)2< / br>
(R)-configuration
colorless oil

[a]20D=19,9° (C=1, CHCl3)

Example No.R1R2R3ZPhysical data
72NNCF(CH3)2< / br>
(S)-configuration
colorless oil

[a]20D=21,0° (C=1, CHCl3)
73NNCHFCH3< / br>
(R)-configuration
oil

[a]20D=19,2° (C=1, CHCl3)
74NNCHFCH3< / br>
(S)-configuration
a colourless oil is

[a]20D=20,8° (C=1, CHCl3)
75NNCHFCH2CH3colorless oil

1H - NMR (400 MHz, CDCl3):δ=1.02(t, 3H), 1.83-2.10 (m, 2H), 2.22 (mc, 1H), 2.66-3.02 (m, 3H), 4.80-5.75 (m, br, 4H), 6.78 (d, 1H), 7.23 (d, 1H)
76NNCH(CH3)2colorless oil

1H-NMR (400 MHz, CDCl3): δ=1.20 (mc, br, 6H), 2.72 (mc, br,1H)

Example No.R1R2R3ZPhysical data
77NNCH3colorless oil

1H-NMR (300 MHz, CDCl3): δ=1.78(s, br, 3H), 2.65-3.03 (m, 3H)
78NNCF(CH3)2< / br>
(R)-configuration
colorless oil

[a]20D=19,9° (C=1, CHCl3)
79NNCF(CH3)2
(S)-configuration
colorless oil

[a]20D=6,9° (C=1, CHCl3)
80NNCHFCH3< / br>
(R)-configuration
colorless oil

[a]20D=23,0°(C=1, CHCl3)
81NNCHFCH3< / br>
(S)-configuration
colorless oil

[a]20D=19,3° (C=1, CHCl3)

Shown in example 1 and in table 1 determination of logP values was performed in accordance with the Directive of EEC 79/831 application V.A8 by using GHWA (high performance liquid chromatography) on a column with a reversible phase (18). Temperature: 43°C.

(a) Eluent for the determination in the acidic region: 0.1% aqueous phosphoric acid, acetonitrile; linear gradient from 10% acetonitrile to 90% acetonitrile - the corresponding results in table 1 are markeda).

(b) Eluent to determine the neutral region: from 0.01 molar aqueous phosphate buffer solution, acetonitrile; linear gradient from 10% acetonitrile to 90% acetonitrile - the corresponding results in table 1 are markedb).

The calibration was made with unbranched Alkan-2-areas (3 is about 16 carbon atoms), for which the logP values are known (determination of the logP values by the retention times by linear interpolation between the two following each other by alkenone).

Value λmaxwas determined using UV spectra from 200 nm to 400 nm in the maxima of the chromatographic signals.

Educt of the formula (II):

Example II-1

A mixture of 24,9 g (0,122 mol) of the hydrochloride of 2-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-4-yl-amine and 10.3 g (0,122 mol) of cyanoguanidine heated one hour at 150°and immediately thereafter rapidly cooled in a bath of acetone and dry ice. The reaction mixture was stirred at -78°With acetone, and the resulting solid is filtered at room temperature is stirred with diethyl ether and again filtered.

Get 27,3 g (78% of theory) of the hydrochloride of 2-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-4-yl-biguanide in the form of a dark brown solid (logP=1,12a)).

Analogously to example II-1 can, for example, also get listed in the following table 2 compounds of General formula (II).

Table 2

Examples of compounds of the formula (II), R1and R2if necessary, are hydrogen
Example No. ZPhysical. data
II-2logP=0,73a.)
II-3
II-4
II-5

Educt of the formula (IV):

Example IV-1

Stage 1

for 77.3 g (of 0.51 mole) of 6,7-dihydro-benzo[b]thiophene-4(5H)-it mix with 69,5 g (1.0 mole) of hydroxylamine hydrochloride in 600 ml of pyridine for two hours at room temperature (about 20°). Immediately thereafter the reaction mixture is poured into 1 liter of water, conc. hydrochloric acid to establish a pH of 1 and extracted with ethyl acetate. The organic extraction solution is dried over sodium sulfate and filtered. The filtrate is vacuum on a water-jet pump, obtained as solid residue is stirred with petroleum ether and produce suction.

Get to 74.5 g (88% of theory) of 6,7-dihydrobenzo[b]thiophene-4(5H)-oxime as a mixture of isomers E and Z 1:1.

Stage 2

A solution of 8.4 g (50 mmol) of 6,7-dihydrobenzo[b]thiophene-4(5H)oxime in 50 ml of 1,2-dimethoxyethane tell is to see to the mixture of 20.0 g (105 mmol) of tetravalent titanium chloride and 8.0 g (210 mmol) of sodium borohydride in 200 ml of 1,2-dimethoxyethane at 0° C. the Reaction mixture was placed in an ice bath and stirred for about 20 hours. Then to the mixture poured the water and set the pH value 9 25%ammonia solution. Dropped the precipitate was separated by filtration through celite and the filtrate is extracted with methylene chloride. The organic extraction solution is dried over sodium sulfate and filtered. The filtrate is vacuum on a water-jet pump.

Obtain 4.5 g (59% of theory) of 4,5,6,7-tetrahydrobenzo[b]thiophene-4-yl-amine as a colourless oil.

Hydrochporide compounds obtained in accordance with example IV-1, can be obtained, for example, as follows:

Stirred mixture of 4.1 g (27 mmol) of 4,5,6,7-tetrahydrobenzo[b]thiophene-4-yl-amine, 4 ml conc. hydrochloric acid and 50 ml of methanol hour at room temperature (about 20° (C) and immediately after this, the vacuum on the water-jet pump. The residue is stirred with diethyl ether and was isolated by suction obtained crystalline product.

Obtain 3.8 g (75% of theory) of the hydrochloride 4,5,6,7-tetrahydrobenzo[b]thiophene-4-yl-amine as a brown solid.

Examples of usage:

Example A.

Test up germination.

Solvent: 5 parts by weight of acetone.

Emulsifier: 1 weight part alkylsilanes ether polyglycol.

To get the target workpiece active substances plumage is eshivot 1 weight part of the active substance with the specified amount of solvent, add the specified amount of emulsifier concentrate and diluted with water to the desired concentration.

Seeds of tested plants are sown in normal field. In about 24 hours field sprinkle cooked preparation of the active substance so as to receive, respectively, a desired amount of active ingredient per unit area. The concentration of the solution for spraying choose to get in 1000 litres of water per hectare, respectively, a desired amount of the active substance.

After three weeks, assess the degree of damage to the plants in % damage in comparison with the development of the untreated control.

Mean:

0% = no action (as untreated control).

100% = total destruction.

In this test the compound in accordance with example get 1 shows, for example, a strong action against weeds.

Table And

Test pre-germination/sprouting
The active ingredientUsed the number of grams of active ingredient per hectareAlopecurusSpickleGrudniaAmaranthBedstraw
(1)5001001009510090

Example B.

Test after germination.

Solvent: 5 parts by weight of acetone.

Emulsifier: 1 weight part alkylsilanes ether polyglycol.

To get the target workpiece active substance is stirred for 1 weight part of the active substance with the specified amount of solvent, add the specified amount of emulsifier concentrate and diluted with water to the desired concentration.

Preparation of the active substance is sprayed with the subjects of the plants when they have a height of from 5 to 15 cm to obtain, respectively, a desired amount of active ingredient per unit area. The concentration of the solution for spraying choose to get in 1000 litres of water per hectare, respectively, a desired amount of the active substance.

After three weeks, assess the degree of damage to the plants in % damage in comparison with the development of the untreated control. Mean:

0% = no action (as untreated control).

100% = total destruction.

In this test the compound in accordance with example get 1 shows, for example, a strong action against sorne the Cove.

Table B

Test after germination/sprouting
The active ingredientUsed the number of grams of active ingredient per hectareAlopecurusSpickleAmaranthMustardCocklebur
(1)50095100100100100

1. Compounds of General formula (I)

in which R1denotes hydrogen;

R2denotes hydrogen, formyl or alkylsulphonyl, or the group N(R1R2also designates dialkylaminoalkyl;

R3denotes unsubstituted or substituted with halogen alkyl;

Z denotes one of the following cyanocyclohexyl groups

where m denotes the number 0, 1 or 2;

n denotes the number 0, 1 or 2;

And1means alcander (alkylen);

And2means alcander (alkylen);

And3oboznachaet alcander (alkylen);

R4denotes alkyl;

R5denotes halogen or alkyl.

2. Compounds according to claim 1, characterized in that

And1means alcander (alkylen) with 1-3 carbon atoms;

And2means alcander (alkylen) with 1-3 carbon atoms;

And3means alcander (alkylen) with 1-3 carbon atoms;

R2denotes hydrogen, formyl or alkylaryl containing from 1 to 6 carbon atoms in the alkyl group, or

the group N(R1R2refers dialkylaminoalkyl group with the number of carbon atoms up to 4 alkyl group or alkylidene group, respectively;

R3denotes unsubstituted or substituted with halogen alkyl with 1-6 carbon atoms;

R4represents alkyl containing from 1 to 6 carbon atoms;

R5denotes halogen or alkyl containing from 1 to 6 carbon atoms,

and the remaining residues have the above values.

3. Compounds according to claim 1 or 2, characterized in that

And1denotes methylene, dimethylene or trimethylene;

And2denotes methylene, dimethylene or trimethylene;

And3denotes methylene, dimethylene or trimethylene;

R2denotes hydrogen, formyl or acetyl, propionyl, n - or Isobutanol, or

the group N(R 1R2) denotes dimethylaminomethylphenol or diethylaminoethylamine;

R3denotes unsubstituted or substituted by fluorine, chlorine or bromine, methyl, ethyl, n - or isopropyl, n-, ISO - or sec-butyl;

R4denotes methyl, ethyl, n - or isopropyl;

R5denotes fluorine, chlorine, bromine, methyl, ethyl, n - or isopropyl;

and the remaining residues have the above values.

4. Compounds according to claims 1 to 3, characterized in that

And1denotes methylene or dimethylene;

And2denotes methylene or dimethylene;

And3denotes methylene or dimethylene;

R2denotes hydrogen, formyl or acetyl, propionyl, n - or Isobutanol, or

the group N(R1R2) denotes dimethylaminomethylphenol;

R4denotes methyl or ethyl;

R5denotes fluorine, chlorine, bromine, methyl or ethyl,

and the remaining residues have the above values.

5. Compounds according to claims 1 to 4, characterized in that Z represents

and p denotes 2, 3 or 4, and the remaining residues have the meanings indicated in claims 1 to 4.

6. The method of obtaining substituted triazines according to claims 1 to 5, characterized in that the biguanides of the General formula (II)

in which R1, R2and Z have the meanings indicated in claims 1 to 5,

and/or adducts join acid compounds of General formula (II) is subjected to interaction with alkoxycarbonyl compounds of General formula (III)

R3-CO-OR' (III)

in which R3has the meaning indicated in claims 1 to 4, and

R' represents an alkyl,

optionally, in the presence of an auxiliary reagent, and optionally in the presence of a diluent and optionally in the thus obtained compounds of General formula (I) under certain deputies conduct further transformation of conventional methods.

7. The compounds of formula (II)

in which R1, R2and Z have the meanings indicated in claims 1 to 5,

as well as adducts join acid compounds of General formula (II).

8. Herbicide agent, characterized in that it contains a compound according to one of claims 1 to 5, and conventional additives and/or surfactants.



 

Same patents:

New compounds // 2261245

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new compounds of the formula (I): wherein m = 0, 1, 2 or 3; each R1 represents independently halogen atom, cyano-group, hydroxyl, (C3-C6)-cycloalkyl, (C1-C6)-alkoxy-group, (C1-C6)-halogenalkyl, (C1-C6)-halogenalkoxy-group, -NR9R10, (C3-C6)-cycloalkylamino-, (C1-C6)-alkylthio-, (C1-C6)-alkylcarbonylamino-group or (C1-C6)-alkyl; X represents -O- or CH2-, OCH2-, CH2O-, CH2NH-, NH-; Y represents nitrogen atom (N) or group CH under condition that when X represents -O- or CH2O-, CH2NH- or NH-group then Y represents group CH; Z1 represents a bond or group (CH2)q wherein q = 1 or 2; Z2 represents a bond or group CH2 under condition that both Z1 and Z2 can't represent a bond simultaneously; Q represents -O- or sulfur atom (S) or group CH2 or NH; R2 represents group of the formula: n = 0; each R4, R5, R6 and R7 represents independently hydrogen atom (H), (C1-C6)-alkyl either R4, R5, R6 and R7 represent in common (C1-C4)-alkylene chain joining two carbon atoms to which they are bound to form 4-7-membered saturated carbon ring, either each R5, R6 and R7 represents hydrogen atom, and R4 and R8 in common with carbon atoms to which they are bound form 5-6-membered saturated carbon ring; R8 represents hydrogen atom (H), (C1-C6)-alkyl or it is bound with R4 as determined above; each R9 and R10 represents independently hydrogen atom (H), (C1-C6)-alkyl; R15 represents (C2-C6)-alkyl, (C2-C6)-alkenyl, (C3-C6)-cycloalkyl, (C5-C6)-cycloalkenyl, adamantyl, phenyl or saturated or unsaturated 5-10-membered heterocyclic ring system comprising at least one heteroatom taken among nitrogen, oxygen and sulfur atoms wherein each group can be substituted with one or more substitute taken independently among nitro-group, hydroxyl, oxo-group, halogen atom, carboxyl, (C1-C6)-alkyl, (C1-C6)-alkoxy-, (C1-C6)-alkylthio-group, (C1-C6)-alkylcarbonyl, (C1-C6)-alkoxycarbonyl, phenyl and -NHC(O)-R17 under condition that R15 doesn't represent unsubstituted 1-pyrrolidinyl, unsubstituted 1-piperidinyl or unsubstituted 1-hexamethyleneiminyl group; t = 0, 1, 2 or 3; each R16 represents independently halogen atom, cyano-group, hydroxyl, (C3-C6)-cycloalkyl, (C1-C6)-alkoxy-group, (C1-C6)-halogenalkyl, (C1-C)-halogenalkoxy-group, -NR18R19, (C1-C6)-cycloalkylamino-, (C1-C6)-alkylthio-, (C1-C6)-alkylcarbonylamino-group, (C1-C6)-alkyl; R17 means (C1-C6)-alkykl, amino-group, phenyl; each R18 and R19 means independently hydrogen atom (H), (C1-C6)-alkyl, or its pharmaceutically acceptable salt or solvate. Compounds of the formula (I) elicit activity of a modulating agent with respect to activity of chemokine MIP-1α receptors that allows their using in pharmaceutical composition in treatment of inflammatory diseases.

EFFECT: valuable medicinal properties of new compounds.

14 cl, 98 ex

FIELD: pharmaceutical chemistry.

SUBSTANCE: invention relates to new amide derivatives of general formula I

1, as well as to pharmaceutical acceptable salts or cleaving in vivo esters thereof. Claimed compounds are capable to inhibit cytokine production due to inhibition of p38 kinase action and are useful in treatment of various diseases such as inflammation or allergic disorders. Also are disclosed methods for production the same, pharmaceutical composition and method for inhibition of TNFα cytokine production. In formula I X is -NHCO- or -CONH-; m = 0-3; R1 is halogen, C1-C6-alkoxy, N-(C1-C6)-alkyl-di{(C1-C6)-alkyl]-amino-(C2-C6)-alkylamino, or heterocyclyl, heterocyclyl-(C1-C6)-alkyl, heterocyclyloxy, heterocyclyl-(C1-C6)-alkoxy, heterocyclylamino, N-(C1-C6)-alkylheterocyclylamino, heterocyclyl-(C1-C6)-alkylamino, N-(C1-C6)-alkylheterocyclyl-(C1-C6)-alkylamino, heterocyclylcarbonylamino, heterocyclylsulfonylamino, N-heterocyclylsulfamoyl, heterocyclyl-(C2-C6)-alkanoylamino, heterocyclyl-(C1-C6)-alkoxy-(C1-C6)-alkyl, heterocyclyl-(C1-C6)-alkylamino-(C1-C6)-alkyl, or N-(C1-C6)-alkylheterocyclyl-(C1-C6)-alkylamino-(C1-C6)-alkyl, wherein any of heterocylyl in R1 optionally may contain 1 or 2 substituents selected from oxo- or thioxogroup; n = 0-2; R2 is hydrogen or C1-C6-alkyl; R2 is hydrogen, C1-C6-alkyl or C1-C6-alkoxy; q = 0-4; Q is aryl, aryloxy, etc.

EFFECT: new inhibitors of cytokine production.

13 cl, 8 tbl, 20 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to a method for preparing derivatives of indole of the general formula (I):

wherein R1 represents hydroxy-group; R2 represents hydrogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, (C2-C6)-alkoxyalkyl or 4-methoxybenzyl; R3 represents hydrogen atom or (C1-C6)-alkyl; each among R4 and R represents independently hydrogen atom, (C1-C6)-alkyl or (C1-C6)-alkoxy-group; D represents an ordinary bond, (C1-C6)-alkylene, (C2-C6)-alkenylene or (C1-C6)-oxyalkylene; in the group-G-R6 wherein G represents an ordinary bond, (C1-C6)-alkylene; R represents saturated or unsaturated carbocyclic ring (C3-C15) or 4-15-membered heterocyclic ring comprising 1-5 atoms of nitrogen, sulfur and/or oxygen wherein this ring can be substituted. Also, invention describes a method for preparing derivatives of indole and DP-receptor antagonist comprising derivative of the formula (I) as an active component. As far as compounds of the formula (I) bind with DP-receptors and they are antagonists of DP-receptors then they can be useful for prophylaxis and/or treatment of diseases, for example, allergic diseases.

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

11 cl, 7 tbl, 353 ex

FIELD: organic chemistry, medicine, pharmacy.

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

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

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

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

13 cl, 7 sch, 8 tbl, 41 ex

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: pharmaceutical industry, in particular new bioactive chalcones.

SUBSTANCE: invention relates to new chalcones of formula I

, pharmaceutically acceptable salts or solvates thereof, wherein Ar is optionally substituted C5-C10-carbocycle group or 5- or 6-membered heterocycle group having sulfur atom in cycle, and Ar substituents are selected independently from Cl, Br, F, CN, SCH3 and OR10, wherein R10 is linear or branched C1-C6-hydrocarbon; R is OH or R10; R2 and R3 are independently phenyl, saturated linear or branched C1-C6-hydrocarbon, or R2 and R3 together with carbon atom attached thereto form 5- or 6-membered carbocycle group with the proviso, that in compounds where R is OH and both R2 and R3 are methyl, Ar is not phenyl, 4-chlorophenyl, 4-chlorophenyl, 4-methylphenyl, 2-chlorophenyl, 3,4-dimethoxyphenyl, or 4-methoxyphenyl. Also disclosed are drug component for treatment or prophylaxis of neoplasm and pharmaceutical compositions with antiproliferation effect based on compounds of formula I.

EFFECT: new chalcone derivatives with value bioactive action.

26 cl, 2 tbl, 22 ex

FIELD: organic chemistry, pharmaceutical industry, medicine.

SUBSTANCE: invention relates to new derivatives of S-substituted N-1-[(hetero)aryl]alkyl-N'-1-[(hetero)aryl]alkylisothioureas of general formula I

in form of free base and salts with pharmaceutically accepted acids, as well as racemate, individual optical isomers or mixture thereof. In formula R1, R2, R3, R4, Y and Z are as described in specification. Compounds of present invention are capable to potentiate (positively modulate) AMPA/KA glutamate receptors and simultaneously to block transmembrane currents induced by activation of NMDA glutamate receptors. Also disclosed are method for production of said compounds, including optical isomers; pharmaceutical composition; method for investigation of glutamatergic system, and method for Alzheimer's disease, treatment; as well as method for extreme retentiveness of memory by administering of effective amount of claimed compounds.

EFFECT: new pharmaceutically active compounds for Alzheimer's disease treatment.

23 cl, 1 tbl, 11 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: invention relates to new substituted thienyl(amino)sulfonylureas of formula I ,

wherein A represents nitrogen or methane; Q represents direct bond or imino; R1 represents fluorine, chlorine, bromine, unsubstituted C1-C4-alkyl, C1-C4-alkoxyl optionally substituted with halogen, unsubstituted C1-C4-alkylthio, or di(C1-C4-alkyl)amino; R2 represents hydrogen or C1-C4-alkyl. Compounds of present invention are useful as herbicide agents.

EFFECT: new compounds with herbicide activity.

5 cl, 11 tbl, 5 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: invention relates to new substituted thien-3-yl-sulfonylamino(thio)carbonyl-triazolin(thi)ons of general formula I

(wherein Q represents oxygen or sulfur; R1 represents unsubstituted alkyl; R2 represents hydrogen, halogen, unsubstituted alkyl; R3 represents hydrogen, halogen, alkyl optionally substituted with alkoxy, alkoxy or arylthio, optionally substituted with alkoxy or halogen, unsubstituted cycloalkyl or cycloalkyloxy, or unsubstituted arylalkoxy or aryloxy; R4 represents unsubstituted alkyl, alkoxy, dialkylamino, cycloalkyl) and their salts. Compounds of present invention are useful as herbicide agents. Also disclosed is herbicide composition and new synthetic intermediates for compounds of formula I.

EFFECT: new compounds and intermediates thereof with herbicide activity.

16 cl, 13 tbl, 67 ex

FIELD: organic chemistry, medicine, pharmacy.

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

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

20 cl, 6 tbl, 192 ex

FIELD: pharmaceutical chemistry, medicine.

SUBSTANCE: invention relates to substituted pyridines and pyridazines with angiogenesis inhibition activity of general formula I

(I)1, wherein ring containing A, B, D, E, and L represents phenyl or nitrogen-containing heterocycle; X and Y are various linkage groups; R1 and R2 are identical or different and represent specific substituents or together form linkage ring; ring J represents aryl, pyridyl or cycloalkyl; and G's represent various specific substituents. Also disclosed are pharmaceutical composition containing claimed compounds, as well as method for treating of mammalian with abnormal angiogenesis or treating of increased penetrability using the same.

EFFECT: new pyridine and pyridazine derivatives with angiogenesis inhibition activity.

26 cl, 6 tbl, 114 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for preparing benzo[b]thiophenes of the formula (I):

wherein X represents sulfur atom (S); R1 represents CN or COOA; each among R2 and R3 represents hydrogen atom; A represents (C1-C6)-alkyl. Method involves the dehydrogenation reaction of tetrahydrobenzothiophene of the formula (II):

wherein R1-R3 and X have values given above; Ac represents (C1-C6)-acyl in the presence of a catalyst taken in the catalytic amount based on precious metal and hydrogen acceptor followed by deacylation reaction of acylated amino-group by amine effect. Compounds of the formula (I) are intermediate substances in producing dyes, agents for plants protection and in manufacture of drugs.

EFFECT: improved preparing method.

7 cl, 3 ex

FIELD: organic chemistry, medicine, pharmacy.

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

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

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

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

13 cl, 7 sch, 8 tbl, 41 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new N-(2-arylpropionyl)-sulfonamides of the formula (1): wherein R2 means phenyl, thiophenyl optionally substituted with 1-3 substitutes taken independently among halogen atom, (C1-C4)-alkyl, phenyl, phenoxy-group, benzyl, benzoyl, (C1-C7)-acyloxy-group, 2-thienoyl or 1-oxo-2-isoindolyl; R means linear or branched (C1-C16)-alkyl, trifluoromethyl, cyclohexyl, o-tolyl, 3-pyridyl, p-cyanophenylmethyl, p-aminomethylphenylmethyl, 2-cyano-1-propyl, alkoxyethylene group CH3-(CH2)ni-(OCH2CH2)mi- wherein ni and mi mean a whole number from 1 to 3, or the group P1P2N-CH2-CH2- wherein P1 and P2 represent independently hydrogen atom (H), (C1-C3)-alkyl, benzyloxycarbonyl, α-, β- or γ-pyridocarbonyl, carboxycarbonyl or carbalkoxycarbonyl; or R1 and P2 in common with nitrogen atom to which they are bound form morpholino-group; R' means hydrogen atom (H) or linear or branched (C1-C3)-alkyl, or their salts with strong or mean bases. Compounds of the formula (1) show inhibitory activity with respect to chemotaxis and degranulation of neutrophiles induced with interleukin-8 and can be used in pharmaceutical composition used for prophylaxis and treatment of tissue injures.

EFFECT: valuable medicinal properties of compounds.

13 cl, 2 dwg, 2 tbl, 18 ex

FIELD: organic chemistry, pharmaceutical industry, medicine.

SUBSTANCE: invention relates to new derivatives of S-substituted N-1-[(hetero)aryl]alkyl-N'-1-[(hetero)aryl]alkylisothioureas of general formula I

in form of free base and salts with pharmaceutically accepted acids, as well as racemate, individual optical isomers or mixture thereof. In formula R1, R2, R3, R4, Y and Z are as described in specification. Compounds of present invention are capable to potentiate (positively modulate) AMPA/KA glutamate receptors and simultaneously to block transmembrane currents induced by activation of NMDA glutamate receptors. Also disclosed are method for production of said compounds, including optical isomers; pharmaceutical composition; method for investigation of glutamatergic system, and method for Alzheimer's disease, treatment; as well as method for extreme retentiveness of memory by administering of effective amount of claimed compounds.

EFFECT: new pharmaceutically active compounds for Alzheimer's disease treatment.

23 cl, 1 tbl, 11 ex

FIELD: pharmaceutical chemistry, medicine.

SUBSTANCE: invention relates to new compounds of formula I ,

solvates or pharmaceutically acceptable salts having antiarrhythmic activity, including ventrical fibrillation, as well as pharmaceutical compositions containing the same. Compounds of present invention are useful in treatment or prevention of arrhythmia, modulation of ion channel activity, for topic or local anesthesia, etc. In formula I X is direct bond, -C(R6,R14)-Y- and C(R13)=CH-; Y is direct bond, O, S, and C1-C4-alkylene; R13 is hydrogen, C1-C6-alkyl, C3-C8-cycloalkyl, unsubstituted aryl or benzyl; R1 and R2 are independently C3-C8-alkoxyalkyl, C1-C8-hydroxyalkyl and C7-C12-aralkyl; or R1 and R2 together with nitrogen atom directly attached thereto form ring of formula II ,

wherein said ring is formed by nitrogen and 3-9 ring atoms selected independently from carbon, sulfur, nitrogen and oxygen, etc; R3 and R4 are independently attached to cyclohexane ring in 3-, 4-, 5-, or 6-position and represent independently hydrogen, hydroxyl, C1-C6-alkyl and C1-C6-alkoxy; and when R3 and R4 are bound with the same atom of cyclohexane ring they may form together 5- or 6-membered spiroheterocycle ring containing one or two heteroatoms selected from oxygen and sulfur; A is C5-C12-alkyl, C3-C13-carbocyclic ring, or ring structure as defined herein.

EFFECT: new antiarrhythmic drugs.

30 cl, 12 dwg, 34 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: invention relates to new substituted thien-3-yl-sulfonylamino(thio)carbonyl-triazolin(thi)ons of general formula I

(wherein Q represents oxygen or sulfur; R1 represents unsubstituted alkyl; R2 represents hydrogen, halogen, unsubstituted alkyl; R3 represents hydrogen, halogen, alkyl optionally substituted with alkoxy, alkoxy or arylthio, optionally substituted with alkoxy or halogen, unsubstituted cycloalkyl or cycloalkyloxy, or unsubstituted arylalkoxy or aryloxy; R4 represents unsubstituted alkyl, alkoxy, dialkylamino, cycloalkyl) and their salts. Compounds of present invention are useful as herbicide agents. Also disclosed is herbicide composition and new synthetic intermediates for compounds of formula I.

EFFECT: new compounds and intermediates thereof with herbicide activity.

16 cl, 13 tbl, 67 ex

FIELD: organic chemistry, pharmacology.

SUBSTANCE: invention relates to compounds of formula I ,

where R(1), R(2), R(3), R(4), R(5), R(6), R(7), R(8), R(30), and R(31) are disclosed in claims. Compound of present invention are particularly useful as new antiarrythmia bioactive substances, in particular for treatment and prophylaxis of atrial arrhythmia (e.g., atrial fibrillation or auricular flutter).

EFFECT: higher efficiency.

13 cl, 18 ex, 1 tbl

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to a new derivative of bicyclic heteroaromatic compound of the general formula (I) or its pharmaceutically acceptable salt eliciting agonistic activity with respect to luteinizing hormone (LH). Compounds can be used for preparing medicinal agents for control ability for conception. In compounds of the general formula (I) R1 represents R7 wherein R7 represents (C6-C10)-aryl optionally substituted with halogen atom at ortho- and/or meta-position; NHR8, OR8 wherein R8 means (C1-C8)-alkyl that can be substituted with halogen atom, (C1-C8)-alkylcarbonyl, (C1-C8)-alkylcarbonyloxy-group, phenyl, (C6-C10)-arylcarbonylamino-group, 5-methyl-2-phenylimidazol-4-yl, (C6)-heterocycloalkyl wherein 1-2 heteroatoms are taken among nitrogen and oxygen atoms, ethyloxycarbonylmethylthio-(C1-C4)-alkoxy-group, amino-group, (C6-C7)-heteroaryl; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R2 represents (C1-C8)-alkyl or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R3 represents (C1-C8)-alkyl possibly substituted with (C6-C14)-aryl possibly substituted with halogen atom, (C1-C4)-alkoxy-group, (C1-C4)-alkoxycarbonyl, mono- or tri-(C6-C10)-cycloalkyl, (C6-C10)-aryl, (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; (C5-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; (C3-C8)-cycloalkyl, (C2-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; X represents sulfur atom (S) or N(R4); Y represents nitrogen atom (N); R4 represents (C1-C8)-alkyl, phenyl-(C1-C8)-alkyl; or X represents sulfur atom (S), and Y represents CH; Z represents NH2 or OH; A represents sulfur (S), oxygen atom (O) or a bond. Also, invention relates to a pharmaceutical composition.

EFFECT: valuable properties of compounds and composition.

14 cl, 1 tbl, 119 ex

FIELD: organic chemistry, medicine, pharmacology.

SUBSTANCE: invention relates to new derivatives of carbamic acid esters of the general formula (I):

and their pharmaceutically acceptable salts eliciting activity with respect to metabotropic glutamate receptors mGlu of group I that can be used for treatment of acute and/or chronic neurological disorders. In the general formula (I) R1 means hydrogen atom or (C1-C7)-alkyl; R2 and R2' mean independently of one another hydrogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-group, halogen atom or trifluoromethyl; X means oxygen (O), sulfur (S) atom or two hydrogen atoms not forming a bridge; A1/A2 mean independently of one another phenyl or 6-membered heterocycle comprising 1 or 2 nitrogen atom; B represents group of the formula:

wherein R3 means (C1-C7)-alkyl and others; Y means -O-, -S- or a bond; Z means -O- or -S-; or B means 5-membered heterocyclic group of formulae: (a) , (b) , (c) or (d) . Also, invention relates to methods for preparing compounds and to a medicinal agent based on thereof.

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

22 cl, 1 tbl, 2 sch, 78 ex

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention describes derivatives of 2-amino-1,3,5-triaziene of the formula (I): wherein R1 means phenyl or alkyl with from 1 to 6 carbon atoms that can be substituted with one or some radicals taken among halogen atom and cyano-group; R2 means unsubstituted cyclopropyl, cyclobutyl or cyclopentyl groups or substituted that with radical taken among halogen atom and alkyl with from 1 to 4 carbon atoms, or furyl, or tetrahydrofuryl; R3 means radical of the formula -N(B1-D1)(B2-D2); R4 means radical of the formula -B3-D3; A1 means direct alkylene with 1-5 carbon atoms or direct alkenylene with 2-5 carbon atoms; A2 means a direct bond or direct alkylene with 1-4 carbon atoms; B1, B2 and B3 mean a direct bond; D1, D2 and D3 mean hydrogen atom; (X)n means a number of X substitutes wherein X means independently halogen atom, nitro-group or unsubstituted alkyl with 1-6 carbon atoms or substituted that with one or some radicals taken among halogen atom and alkoxy-group with 1-6 carbon atoms; n = 0, 1 or 2 and wherein the total sum of carbon atoms in radicals A1 and A2-R2 is at least 6 carbon atoms. Also, invention describes the herbicide agent containing compound of the formula (I) and additives used usually for plants protection and a method for control of hazard plants and using the effective dose of compound of the formula (I) for treatment of plants or planting surface. Invention provides preparing effective herbicides.

EFFECT: valuable properties of compounds.

7 cl, 45 tbl, 4 ex

Up!