Method of obtaining derivatives of n-piperidino-1,5-diphenylpyrazole-3-carboxamide

FIELD: chemistry.

SUBSTANCE: aim of the invention is to create a method of obtaining a compound with general formula I , in which R1 represents a hydrogen atom or halogen or (C1-C4)alkene group; R2, R3, R4, R5, R6, R7 each independently represents a hydrogen atom or halogen or (C1-C4)alkene, (C1-C4)alkoxy, trifluoromethyl group as well as its salts. The proposed method involves reaction of a pentane derivative with formula X-(CH2)5-X'(II), in which each of X and X' independently represent a halogen atom or YSO2O- group, in which Y represents (C1-C4)alkene, (C1-C4)perfluoroalkene, phenyl group, unsubstituted or substituted with methyl, chloro- or a nitro- group, and the corresponding derivative of pyrazole-3-carbohydrazide. The invention also pertains to the method of obtaining N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (rimonabant) and its salts.

EFFECT: development of an alternative method of obtaining formula I compounds and, in particular, pure rimonabant, which shows activity in clinic in obesity and smoking addiction.

11 cl, 1 ex

 

The object of the present invention is a method for obtaining compounds of the formula:

in which

R1denotes a hydrogen atom or halogen or (C1-C4)alkyl group;

R2, R3, R4, R5, R6, R7denote each independently a hydrogen atom or halogen or (C1-C4)alkyl, (C1-C4)CNS, triptorelin group;

and its salts.

The compounds of formula (I) described in several patents and patent applications EP 0656354 IN, ER 1150961 as receptor antagonists ST1cannabinoids. More specifically N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide or rimonabant showed activity in the clinic for obesity and dependence on tobacco.

The prior art known to produce the compounds of formula (I) by reacting N-aminopiperidine and the functional derivative of the acid:

This method of synthesis is described in particular in patent EP 0656354 IN when receiving rimonabant. As a functional derivative use, for example, a complex alkilany ester or acid chloride.

According to the present invention obtain the connection formula (I), characterized in that enter into interaction derived the pentane formula X-(CH 2)5-X'(II)in which each X and X' independently denotes a halogen atom or a group YSO2O-, in which Y denotes a (C1-C4)alkyl, (C1-C4)performanceline, phenyl group, unsubstituted or substituted by methyl, chloro - or nitro-group, and derived pyrazole-3-carbohydrazide formula:

in which R1,R2, R3, R4, R5, R6, R7have the same values as defined above for (I).

The reaction is carried out in the presence of a base in a solvent and at a temperature of from room temperature to the temperature of heating under reflux of the solvent.

More specifically, in the method according to the invention is used as a compound of the formula (II), in which each X and X' independently denotes a halogen atom.

Also more specifically used as a compound of the formula (II), in which each X and X' independently denotes a group YSO2O-, in which Y has the above meaning.

A particular implementation of the present invention differs in that get rimonabant by reacting the compounds of formula (II) and 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbohydrazide formula:

According to a particular variant implementation is injected into the interaction 1,5-IDAC is ogeneity formula (II) and 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbohydrazide (IIIa).

More specifically enter into interaction 1,5-dibromethane and 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbohydrazide (IIIa).

The reaction is carried out in the presence of organic bases, such as tertiary amine, such as triethylamine, or inorganic bases, such as NaOH, KOH, K2CO3, Na2CO3Cs2CO3.

The reaction is carried out in an aromatic solvent such as toluene or chlorobenzene, in the ether solvent, for example tetrahydrofuran or dimethoxyethane or dioxane, or in a nitrile solvent such as acetonitrile or propionitrile.

Preferably the reaction is carried out in acetonitrile in the presence of triethylamine or Na2CO3or K2CO3.

More preferably the reaction is carried out in acetonitrile at reflux in the presence of Na2CO3.

More specifically, an object of the present invention is a method of obtaining N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide, its salts, characterized in that enter into interaction 1,5-dibromethane and the compound of formula (IIIa) in the presence of Na2CO3in acetonitrile at reflux.

Under the halogen atom understand the atom of bromine, chlorine or iodine.

The compounds of formula (III), and receipt of them known from pre the striding level of technology: Canadian J. Chem. 1963, 41 (7), 1813-1818; J.Chem.Engineering Data, 1977, 22(1), 104-110; J.Med.Chem., 2002, 45, 2708-2719.

In the publication J.Med.Chem., 2002 described, in particular, 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbohydrazide and obtain from the appropriate acid chloride.

The following examples illustrate the invention without limiting it.

In these examples and in the description uses the following abbreviations:

DCM: dichloromethane.

Mass spectra were measured by the method of ionization, called Electrospray (ES).

The spectra of nuclear magnetic resonance of the proton (NMR1H) were recorded at 200 MHz or 300 MHz in DSMO-d6or in CDCl3. Chemical shifts δ expressed in ppm (ppm).

The signals observed in NMR have the following legend: s: singlet, su: broadened singlet; d: doublet; DD: unleashed doublet; t: triplet; dt: unleashed triplet; to: quadruplet; m: array; MT: multiplet.

The preparation stage 1

5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbohydrazide.

In a stream of nitrogen was placed 20 g of the chloride of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxylic acid in 100 ml of ethanol and heated under reflux for 2 hours. Cooled to 20-25°With, then give 50 g of hydrazine hydrate is added and again heated under reflux for 3 hours 30 minutes. The reaction medium is filtered in the hot state, then evaporated E. anal. The reaction medium is concentrated and then treated with 150 ml of DCM and defend. The aqueous phase is removed, the organic phase is twice washed with 100 ml of water, then DCM is evaporated. After drying in vacuum gain of 16.9 g of the target product.

ES+: [M+Na]+=417,419,421, 423

ES-: [M-H]-=393, 395, 397, 399

NMR (CDCl31H at 300 MHz): 2,35 ppm: s: 3H; 4,0 ppm: d: 2H;? 7.04 baby mortality ppm: m: 2H; to 7.25 ppm: bm: 4H; 7,41 ppm: d: 1H; 8,04 ppm: m: 1H.

Example 1

N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide.

In a stream of nitrogen was placed 10 g of the compound obtained in preparation 1, and 5.3 g of sodium carbonate in 100 ml of acetonitrile. The reaction medium is heated under reflux acetonitrile and injected 6.9 ml of 1,5-dibromethane, then continue to heat for 45 hours. Wednesday hydrolyzing by adding 50 ml of water, defend, then remove the aqueous phase. The organic phase is washed with 2 times 50 ml saturated aqueous NaCl. The acetonitrile is evaporated to dryness and the gain of 18.4 g of crude product. The resulting crude product is subjected to chromatography on silica gel (eluent cyclohexane/acetone: 75/25 V/V). The resulting product is treated with 100 ml of methylcyclohexane and recrystallized. Obtain 5.7 g of pure desired product.

NMR (DMSO-d61H at 200 MHz): 1,31 ppm: bm: 2H ; of 1.55 ppm: bm: 4H; 2,22 ppm: s: 3H; 4,0 ppm: d: 2H; 7,22 ppm: d: 2H; 7,43 ppm: d: 2H; 7,56 ppm: DD 1H; 7,71 ppm: d: 1H; 7,76 ppm: d: 1H; 9,02 ppm: s: 1H.

1. The method of obtaining the compounds of formula

in which R1denotes a hydrogen atom or halogen or (C1-C4)alkyl group;

R2, R3, R4, R5, R6, R7denote each independently a hydrogen atom or halogen or (C1-C4)alkyl, (C1-C4)CNS, triptorelin group,

and its salts, characterized in that

enter into interaction derived pentane formula

in which each X and X' independently denotes a halogen atom or a group YSO2O-, in which Y denotes a (C1-C4)alkyl, (C1-C4)performanceline, phenyl group, unsubstituted or substituted by methyl, chloro - or nitro-group,

and derived pyrazole-3-carbohydrazide formula

in which R1, R2, R3, R4, R5, R6, R7have the same values as defined above for (1), in the presence of a base in a solvent and at a temperature of from room temperature to the temperature of heating under reflux of the solvent.

2. The method according to claim 1, characterized in that the compound of formula (II) ka is every X and X' independently denotes a halogen atom.

3. The method according to claim 1, characterized in that the compound of formula (II) each X and X' independently denotes a group Y-SO2-O-, in which Y has the meaning given in claim 1.

4. The method according to claim 1 obtain the N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide, its salts, characterized in that:

enter in the interaction of the compound of formula (II) and 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbohydrazide formula

5. The method according to claim 4, characterized in that enter into interaction 1,5-dehalogenation and the compound of formula (IIIa).

6. The method according to claim 5, characterized in that enter into interaction 1,5-dibromethane and the compound of formula (IIIa).

7. The method according to claim 1, wherein the base is selected from triethylamine, NaOH, KOH, K2CO3, Na2CO3Cs2CO3.

8. The method according to claim 1, characterized in that the solvent is selected from toluene, chlorobenzene, tetrahydrofuran, dimethoxyethane, dioxane, acetonitrile or propionitrile.

9. The method according to claim 1, characterized in that the interaction is carried out in the presence of triethylamine, Na2CO3or2CO3in acetonitrile.

10. The method according to claim 1, characterized in that the interaction is carried out in the presence of Na2CO3in acetonitrile at reflux.

p> 11. The method of obtaining N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide, its salts, characterized in that enter into interaction 1,5-dibromethane and the compound of the formula

in the presence of Na2CO3in acetonitrile at reflux.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention refers to the method of preparation of 3-halogen-4.5-dihydro-1H-pyrasol compound of the formula , it includes interreaction with HX1of other 4.5-dihydro-1H-pyrasol compound of the formula , in which X1 is halogen and R3, R4, Z, n and X2 have values given in the description. The invention also describes preparation of the compounds of the formula , in which X1, R3, R6, R7, R8a, R8b and n have values, which are indicated in the description, in terms of the formula (Ia) of the compound, prepared according to p.1 of the invention formula.

EFFECT: development of the alternative method of preparation of the compounds with using reagent of relatively low price.

9 cl, 1 tbl, 4 ex, 9 dwg

FIELD: chemistry.

SUBSTANCE: the said invention relates to о-cyclopropylcarboxanilides of general formula (I) , where Het stands for pyrrolyl, pyrazolyl or thiazolyl, each being substituted with R4, R5 and R6 groups; R1, RЗ stand for hydrogen or halogen; R3 stands for С2-12 alkyl, С3-12 cycloalkyl, С3-12 cycloalkyl substituted with С1-3 alkyl, phenyl or halogen-substituted phenyl; and R4, R5 and R6 are independently selected from hydrogen, halogen, С1-4 alkyl or С1-4 haloalkyl, provided that at least one of R4, R5 and R6 is other than hydrogen. Intermediates used in synthesis of I, as well as antimicrobial composition and methods for control and prevention of cultivated plants' infection with phytopathogenic microorganisms are described.

EFFECT: compounds can be used to protect plants from being infected with phytopathogenic microorganisms.

8 cl, 7 tbl, 12 ex

FIELD: organic chemistry, fungicides.

SUBSTANCE: invention describes pyrazolylcarboxanilides of the formula (I) wherein R means difluoromethyl or trifluoromethyl group; R1 and R2 mean independently of one another halogen atom or (C1-C6)-alkyl; R3 means fluorine atom, and agent and method for control of undesirable fungi using compounds of the formula (I), and novel intermediate substances - derivatives of aniline and halogenpyrazolcarboxanilides. Compounds of the formula (I) elicit fungicide properties and can be used in protection of plants.

EFFECT: valuable properties of compounds and agent.

15 cl, 8 tbl, 10 ex

FIELD: organic chemistry, insecticides.

SUBSTANCE: invention relates to compounds of the formula (1) , their N-oxides and salts that can be used in agriculture wherein values A, B, J, R1, R3, R4 and n are given in the invention claim. Also, invention describes a method for control of arthropoda pests to provides high productivity that comprises applying the effective dose of compound of the formula (1) on arthropoda pests and in medium of their habitation, and a the composition with arthropocide activity comprising compounds of the formula (1).

EFFECT: valuable properties of compounds and composition.

23 cl, 34 tbl, 759 ex

FIELD: organic chemistry, agriculture, insecticides.

SUBSTANCE: invention relates to a substituted anilide derivative of the formula (I): wherein R1 represents hydrogen atom, (C1-C6)-alkyl group; R2 represents hydrogen atom, halogen atom or halogen-(C1-C6)-alkyl group; R3 represents hydrogen atom, halogen atom, (C1-C6)-alkyl group, hydroxyl group or (C1-C6)-alkoxy-group; t = 1; m = 0; each among X that can be similar or different represents (C2-C8)-alkyl group, hydroxy-(C1-C6)-alkyl group or (C3-C6)-cycloalkyl-(C1-C6)-alkyl group; n = 1 or 2; Z represents oxygen atom; Q means a substitute represented by any of the following formulae: Q1-Q3, Q6, Q8-Q12, Q14-Q19, Q21 and Q23 (wherein each among Y1 that can be similar or different represents halogen atom, (C1-C6)-alkyl group, and so on); Y2 represents (C1-C6)-alkyl group or halogen-(C1-C6)-alkyl group; Y3 represents (C1-C6)-alkyl group, halogen-(C1-C6)-alkyl group or substituted phenyl group; p represents a whole number from 1 to 2; q represents a whole number from 0 or 2; r represents a whole number from 0 to 2. Also, invention proposes a chemical for control of pests of agricultural and fruit crops. The chemical comprises substituted anilide derivative of the formula (I) as an active component and represents insecticide, fungicide or acaricide. Also, invention proposes a method for addition of the chemical for control of pests of agricultural and fruits crops. Also, invention proposes aniline derivative represented by the general formula (II): wherein R1 represents hydrogen atom, (C1-C6)-alkyl group; R2 represents hydrogen atom, halogen atom or halogen-(C1-C6)-alkyl group; R3 represents hydrogen atom, halogen atom, (C1-C6)-alkyl group, hydroxyl group or (C1-C6)-alkoxy-group; t = 1; m = 0; each among X that can be similar or different represents (C2-C8)-alkyl group, hydroxy-(C1-C6)-alkyl group or (C3-C6)-cycloalkyl-(C1-C6)-alkyl group; n = 1 or 2. Invention provides the development of anilide derivative as insecticide, fungicide and acaricide against pests of agricultural and fruit crops.

EFFECT: valuable properties of compound.

5 cl, 6 tbl, 27 ex

FIELD: organic chemistry, fungicides, agriculture.

SUBSTANCE: invention describes pyrazolcarboxamide of the formula (I) wherein if X means oxygen atom (O) then R1 represents (C1-C3)-alkoxy-(C1-C3)-alkyl; R2 means (C1-C3)-halogenalkyl; R3 means fluorine (F), chlorine (Cl) or bromine atom (Br), and if X means sulfur atom (S) then R1 means (C1-C3)-alkyl; R2 means (C1-C3)-halogenalkyl; R3 means halogen atom. Also, invention describes a method for preparing compounds of the formula (I), a composition for control of microorganisms and prevention for their attack and damage of plants, and a method for control of phytopathogen organisms, and compound of the formula (V) wherein X means sulfur atom (S); R1 means (C1-C3)-alkyl; R2 means (C1-C3)-halogenalkyl; R3 means chlorine, bromide or iodine atom. Invention provides control and prevention in infection of plants with phytopathogenic microorganisms - fungi in agriculture and horticulture.

EFFECT: valuable agricultural properties of compounds.

9 cl, 4 tbl, 12 ex

The invention relates to N-piperidino-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-aripirazole-3-carboxamide, its pharmaceutically acceptable salt and solvate, which are strong antagonists of cannabinoid ST1receptors

The invention relates to substituted 1-phenylpyrazol-3-carboxamide formula (Ia) in which R1xis in position 4 or 5 and denotes the group-T-CONRaRbin which T represents a direct bond or (C1-C7-alkylen; NRaRbdenotes a group selected from (a), (b), (C); R5and R6denote, independently of one another, hydrogen, (C1-C6)-alkyl, (C3-C8)-alkenyl or R5and R6together with the nitrogen atom to which they are linked, represent a heterocycle selected from pyrrolidine, piperidine, research, piperazine, substituted in position 4 by Deputy R9; R7denotes hydrogen, (C1-C4)-alkyl or benzyl; R8denotes hydrogen, (C1-C4)-alkyl, or R7and R8together with the carbon atom to which they are attached, form a (C3-C5-cycloalkyl; R9denotes hydrogen, (C1-C4)-alkyl, benzyl or a group-X-NR'5R'6in which R'5and R'6represent, independently from each other, (C1-C6)-alkyl; R10denotes hydrogen, (C1-C4)-alkyl; s= 0-3; t=0-3, provided that (s+t) in the same group greater than or equal to 1; the divalent radicals a and E together with the atom is which in addition, may be substituted by one or more (C1-C4-alkilani; R2xand R3xdenote, independently of one another, hydrogen, (C1-C6)-alkyl, (C3-C8-cycloalkyl, (C3-C8-cyclooctylmethyl provided that R2xand R3xdo not simultaneously denote hydrogen or R2xand R3xtogether form tetramethylene group; and their pharmaceutically acceptable salts

The invention relates to new compounds for combating pests, in particular derivatives carbanilide and fungicide-insecticidal tool based on them

The invention relates to pyrazole derivative of the formula I, where1means the group - NRR1R2or group-OR2, g2- g6the same or different and independently of one another denote hydrogen, halogen, C1-4alkyl, C1-4alkoxyl, trifluoromethyl, or C1-4allylthiourea; w2-w6the same or different and independently of one another denote hydrogen, halogen, C1-4alkyl, C1-4alkoxy or trifluoromethyl, provided that at least one of the substituents g2-g6and one of the substituents w2-w6different from hydrogen; R1means hydrogen or C1-4alkyl; R2- nah3-15-carbocyclic radical, unsubstituted or mono - or multiply substituted WITH1-4by alkyl; R3is hydrogen or the group CH2-R6; R4and R5each independently of one another denote hydrogen or C1-4alkyl; or R4means hydrogen and R5and w6together form an ethylene radical; R6means hydrogen, or when the deputies of the g2g3, g4, g5and/or g6different from1-4of alkyl, R6means hydrogen, C1-4alkyl or C1-5alkoxyl, and their salts

FIELD: organic chemistry, fungicides, agriculture.

SUBSTANCE: invention describes pyrazolcarboxamide of the formula (I) wherein if X means oxygen atom (O) then R1 represents (C1-C3)-alkoxy-(C1-C3)-alkyl; R2 means (C1-C3)-halogenalkyl; R3 means fluorine (F), chlorine (Cl) or bromine atom (Br), and if X means sulfur atom (S) then R1 means (C1-C3)-alkyl; R2 means (C1-C3)-halogenalkyl; R3 means halogen atom. Also, invention describes a method for preparing compounds of the formula (I), a composition for control of microorganisms and prevention for their attack and damage of plants, and a method for control of phytopathogen organisms, and compound of the formula (V) wherein X means sulfur atom (S); R1 means (C1-C3)-alkyl; R2 means (C1-C3)-halogenalkyl; R3 means chlorine, bromide or iodine atom. Invention provides control and prevention in infection of plants with phytopathogenic microorganisms - fungi in agriculture and horticulture.

EFFECT: valuable agricultural properties of compounds.

9 cl, 4 tbl, 12 ex

FIELD: organic chemistry, agriculture, insecticides.

SUBSTANCE: invention relates to a substituted anilide derivative of the formula (I): wherein R1 represents hydrogen atom, (C1-C6)-alkyl group; R2 represents hydrogen atom, halogen atom or halogen-(C1-C6)-alkyl group; R3 represents hydrogen atom, halogen atom, (C1-C6)-alkyl group, hydroxyl group or (C1-C6)-alkoxy-group; t = 1; m = 0; each among X that can be similar or different represents (C2-C8)-alkyl group, hydroxy-(C1-C6)-alkyl group or (C3-C6)-cycloalkyl-(C1-C6)-alkyl group; n = 1 or 2; Z represents oxygen atom; Q means a substitute represented by any of the following formulae: Q1-Q3, Q6, Q8-Q12, Q14-Q19, Q21 and Q23 (wherein each among Y1 that can be similar or different represents halogen atom, (C1-C6)-alkyl group, and so on); Y2 represents (C1-C6)-alkyl group or halogen-(C1-C6)-alkyl group; Y3 represents (C1-C6)-alkyl group, halogen-(C1-C6)-alkyl group or substituted phenyl group; p represents a whole number from 1 to 2; q represents a whole number from 0 or 2; r represents a whole number from 0 to 2. Also, invention proposes a chemical for control of pests of agricultural and fruit crops. The chemical comprises substituted anilide derivative of the formula (I) as an active component and represents insecticide, fungicide or acaricide. Also, invention proposes a method for addition of the chemical for control of pests of agricultural and fruits crops. Also, invention proposes aniline derivative represented by the general formula (II): wherein R1 represents hydrogen atom, (C1-C6)-alkyl group; R2 represents hydrogen atom, halogen atom or halogen-(C1-C6)-alkyl group; R3 represents hydrogen atom, halogen atom, (C1-C6)-alkyl group, hydroxyl group or (C1-C6)-alkoxy-group; t = 1; m = 0; each among X that can be similar or different represents (C2-C8)-alkyl group, hydroxy-(C1-C6)-alkyl group or (C3-C6)-cycloalkyl-(C1-C6)-alkyl group; n = 1 or 2. Invention provides the development of anilide derivative as insecticide, fungicide and acaricide against pests of agricultural and fruit crops.

EFFECT: valuable properties of compound.

5 cl, 6 tbl, 27 ex

FIELD: organic chemistry, insecticides.

SUBSTANCE: invention relates to compounds of the formula (1) , their N-oxides and salts that can be used in agriculture wherein values A, B, J, R1, R3, R4 and n are given in the invention claim. Also, invention describes a method for control of arthropoda pests to provides high productivity that comprises applying the effective dose of compound of the formula (1) on arthropoda pests and in medium of their habitation, and a the composition with arthropocide activity comprising compounds of the formula (1).

EFFECT: valuable properties of compounds and composition.

23 cl, 34 tbl, 759 ex

FIELD: organic chemistry, fungicides.

SUBSTANCE: invention describes pyrazolylcarboxanilides of the formula (I) wherein R means difluoromethyl or trifluoromethyl group; R1 and R2 mean independently of one another halogen atom or (C1-C6)-alkyl; R3 means fluorine atom, and agent and method for control of undesirable fungi using compounds of the formula (I), and novel intermediate substances - derivatives of aniline and halogenpyrazolcarboxanilides. Compounds of the formula (I) elicit fungicide properties and can be used in protection of plants.

EFFECT: valuable properties of compounds and agent.

15 cl, 8 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: the said invention relates to о-cyclopropylcarboxanilides of general formula (I) , where Het stands for pyrrolyl, pyrazolyl or thiazolyl, each being substituted with R4, R5 and R6 groups; R1, RЗ stand for hydrogen or halogen; R3 stands for С2-12 alkyl, С3-12 cycloalkyl, С3-12 cycloalkyl substituted with С1-3 alkyl, phenyl or halogen-substituted phenyl; and R4, R5 and R6 are independently selected from hydrogen, halogen, С1-4 alkyl or С1-4 haloalkyl, provided that at least one of R4, R5 and R6 is other than hydrogen. Intermediates used in synthesis of I, as well as antimicrobial composition and methods for control and prevention of cultivated plants' infection with phytopathogenic microorganisms are described.

EFFECT: compounds can be used to protect plants from being infected with phytopathogenic microorganisms.

8 cl, 7 tbl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention refers to the method of preparation of 3-halogen-4.5-dihydro-1H-pyrasol compound of the formula , it includes interreaction with HX1of other 4.5-dihydro-1H-pyrasol compound of the formula , in which X1 is halogen and R3, R4, Z, n and X2 have values given in the description. The invention also describes preparation of the compounds of the formula , in which X1, R3, R6, R7, R8a, R8b and n have values, which are indicated in the description, in terms of the formula (Ia) of the compound, prepared according to p.1 of the invention formula.

EFFECT: development of the alternative method of preparation of the compounds with using reagent of relatively low price.

9 cl, 1 tbl, 4 ex, 9 dwg

FIELD: chemistry.

SUBSTANCE: aim of the invention is to create a method of obtaining a compound with general formula I , in which R1 represents a hydrogen atom or halogen or (C1-C4)alkene group; R2, R3, R4, R5, R6, R7 each independently represents a hydrogen atom or halogen or (C1-C4)alkene, (C1-C4)alkoxy, trifluoromethyl group as well as its salts. The proposed method involves reaction of a pentane derivative with formula X-(CH2)5-X'(II), in which each of X and X' independently represent a halogen atom or YSO2O- group, in which Y represents (C1-C4)alkene, (C1-C4)perfluoroalkene, phenyl group, unsubstituted or substituted with methyl, chloro- or a nitro- group, and the corresponding derivative of pyrazole-3-carbohydrazide. The invention also pertains to the method of obtaining N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (rimonabant) and its salts.

EFFECT: development of an alternative method of obtaining formula I compounds and, in particular, pure rimonabant, which shows activity in clinic in obesity and smoking addiction.

11 cl, 1 ex

FIELD: chemistry, pharmacology.

SUBSTANCE: invention relates to novel compounds -acidified arylcycloalkylamins of formula I in any of their stereoisomeric forms or in form of their mixture in any ratio, or their pharmaceutically acceptable salts, where in formula I : R1 represents aryl, not obligatory substituted with one or two similar or different substitutes, selected from group that includes C1-C6-alkyl and halogen; R2 represents aryl or heteroaryl, which represents residue of 5-6-member aromatic monocyclic heterocycle, containing 1-2 nitrogen atoms as heteroatom and/or 1 sulfur atom or oxygen atom, or residue of 9-10-member aromatic bicyclic heterocycle, containing 1-2 nitrogen atoms as heteroatom, each of which is unsubstituted or contains 1-3 similar or different substitutes, selected from group, consisting of halogens, NH2, unsubstituted C1-C10-alkyl, C1-C10 -alcoxy, C1-C10-alkylamino and di(C1-C10-alkyl)amino, and at least monosubstituted C1-C10-alkyl, etc., n represents 1, 2, 3 or 4. Invention relates to pharmaceutical composition, stimulating expression of endothelial NO synthase, based on said compounds, as well as application of compounds of formula I for production of medication for stimulating expression of endothelial NO-synthase and for treatment of such cardiovascular diseases as atherosclerosis, thrombosis, coronary artery disease, hypertension and impaired cardiac function.

EFFECT: invention ensures enhancing composition and treatment method efficiency.

9 cl, 2 tbl, 41 ex

FIELD: chemistry, pharmacology.

SUBSTANCE: claimed invention relates to compounds of formula (I) or their pharmaceutically acceptable salts, where Q represents optionally substituted with 1-3 substituents, determined in formula, phenyl or pyridyl or pyrodazinyl; R2 represents C1-6alkyl or aminogroup, determined in item 1 of formula or C1-6alkyl, substituted with said aminogroup; bond between oxygen atom O* and adjacent carbon atom C1 or (i) is double bond, which determines carbonyl group [C(=O)], where R6 represents C1-6alkyl or cyclopropyl; or (ii) represents simple bond, where, in case of simple bond, said oxygen atom O*, is in addition bound to group R6 and, taken together with R6 and with adjacent nitrogen atom, determines optionally substituted with C1-6alkyl, oxadiazolyl ring, bond between C1 and adjacent nitrogen atom being double bond.

EFFECT: obtaining medications which are useful in obtaining medications for treatment of conditions connected with p38 kinase and/or in obtaining medications for treatment of inflammatory diseases or conditions in patient.

8 cl, 6 tbl, 88 ex

FIELD: chemistry.

SUBSTANCE: described are 2,4,6-phenyl-substituted cyclic ketoenols of formula (I, in which W, X, Y and CKE are given in invention formula. Also described are esters of acylamino acids of formula (II), substituted derivatives of phenylacetic acid of formula (XXIX), (XXVII), (XXXI), which are intermediate compounds for obtaining formula (I) compound.

EFFECT: obtaining herbicidal preparation containing combinations of biologically active substances, including (a), formula (I) compound and (b') improving compatibility with cultural plants mefenpyr-diethyl, with weight ratio 5-1:1-7.7.

9 cl, 46 tbl, 36 ex

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