Method of producing piperazinophenols

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing piperazinophenols, involving reaction of piperazine, N-(β-aminoethyl)piperazine, N-(β-benzylaminoethyl)piperazine or N,N1-bis-(piperazinoethyl)ethylenediamine with a Mannich base in an aqueous medium at temperature 90-110°C in molar ratio of piperazine, N-(β-aminoethyl)piperazine, N-(β-benzylaminoethyl)piperzine:Mannich base equal to 1:0,8-2, N,N1-bis-(piperazinoethyl)ethylenediamine:Mannich base equal to 1:2 or 1:4 until release of dimethylamine stops; as well as aminomethylation of piperazine or N-(β-aminoethyl) piperazine with diphenylol propane (DPP) in the presence of formaldehyde (FA) in an aqueous medium with molar ratio piperazine: FA: DPP equal to 1:1:1 or 1:2:2 at temperature 50-90°C for 4-10 hours. Reactants react in the presence of a surfactant in amount of 2-6% of the weight of the starting piperazine, and the surfactant used is neonol, OP-7, OP-10.

EFFECT: ensuring fire safety of the process, high output of the end product which can be used as antioxidant phenol stabilisers.

1 cl, 13 ex

 

The invention relates to the field of organic synthesis, particularly to a method of obtaining on the basis of piperazine, N-(β-amino-ethyl)piperazine (AEP) and N,N1bis-(piperidinoethyl)Ethylenediamine (PEEDA) mono-, di - and tetrahedron that can be used as antioxidant phenolic stabilizers.

Know the use of N-(3,5-di-tertbutyl-oxybenzyl)-piperazine as stabilizers for unsaturated hydrocarbons and their derivatives [A.S. No. 1098935, CL C07D 241/04, SC 15/20, publ. Bull. No. 23, 1984]. Obtaining a derivative of piperazine carry out interaction piperazine and 3,5-di-tert-butyl-4-hydroxy-N1N1-dimethylbenzylamine - Mannich bases (Ω) in the environment of the polar organic solvent is isopropyl alcohol for 3 hours at 90°C. the Molar ratio of piperazine to Ω is 2:1.

The disadvantages of the method of obtaining the derivative of piperazine are the complexity of the technological process due to the use of isopropyl alcohol is flammable compounds, as well as the relatively low yield (62%).

Know the use of derivatives PEADA as stabilizers for unsaturated hydrocarbons or chlorinated [A.S. No. 1118638, CL C07D 241/04, C07C 7/20, C07C 17/42, publ. in bull. No. 38, 1982]. Derivatives PEED get in a known manner in two stages: the interaction of AEP with dichloroethane in with the food of the polar organic solvent by heating and subsequent condensation of the intermediate N,N 1bis-(piperidinoethyl)Ethylenediamine with OM when the molar ratio of piperazine to Ω equal to 1:1 for 4 hours at 100-130°C, and the solvent used isopropyl alcohol.

The disadvantage of this method of obtaining piperazineethanol is the complexity of the technological process due to the use of isopropyl alcohol is flammable compounds.

A known method of producing piperazineethanol, including interaction piperazine, AEP or PEED the founding of manniche in the environment of the polar solvent at a temperature of 90-110°C to stop shedding dimethylamine, and as the polar solvent used dioxane or isopropyl alcohol. The molar ratio of piperazine and AEP to Ω is 1:0.8 to 2, and PEED:OM is 1:2 or 1:4 [Zagidullin R.N. N-(β-amino-ethyl)piperazine and its derivatives in the reaction of aminomethylpyridine. Journal of General chemistry, 1991, vol 61, issue 1, s-251].

A disadvantage of the known method of producing piperazineethanol is a fire hazard process due to the use of flammable solvents (isopropyl alcohol, dioxane).

The closest in technical essence and the achieved result is a method of producing piperazineethanol, including interaction piperazine, AEP, N-(β-benzylamino)piperazine (BAP) or PEED the founding of manniche in the environment of the polar dissolve the El when the molar ratio of piperazine, AEP or BAAP:OM=1:0.8 to 2, and PEED:OM=1:2 or 1:4 at a temperature of 90-110°C to stop shedding dimethylamine; and aminomethylpyridine piperazine or AEP-diphenylolpropane (Suite) in the presence of formaldehyde (FA) in a polar solvent at a molar with a ratio of piperazine:FA:sequential function=1:1:1 or 1:2:2 at a temperature of 50-90°C for 4-10 hours, where as the polar solvent used boiling alcohols. The product yield is 60-78% [Zagidullin R.N. Piperazineethanol as stabilizers for unsaturated compounds and their chlorinated. Journal of heterocyclic compounds, 1990, No. 10, s-1369].

The disadvantages of the known method of producing piperazineethanol are the complexity of the technological process due to the use of flammable solvents - alcohols, as well as the relatively low yield of product.

The task of the invention is to simplify and security of the process of obtaining piperazineethanol, increasing product yield.

This goal is achieved by the fact that in the proposed method of obtaining piperazineethanol, including interaction piperazine, AEP, BAAP or PEED the founding of manniche in the environment of the polar solvent at a molar ratio of piperazine and AEP or BAP:M is 1:0.8 to 2, and PEED:Ω equal to 1:2 or 1:4 at a temperature of 90-110°C until the termination highlighted what I dimethylamine; aminomethylpyridine piperazine or AEP-diphenylolpropane (Suite) in the presence of formaldehyde (FA) in a polar solvent at a molar ratio of piperazine:FA:sequential function=1:1:1 or 1:2:2 at a temperature of 50-90°C for 4-10 hours, and the solvent used water. The interaction between the reagents is carried out in the presence of surface active substances (surfactants) in an amount of 2-6% by weight of the original piperazine, as a surfactant use neonol, OP 7, OP-10.

The method consists in carrying out the process of obtaining piperazineethanol in the aquatic environment that ensures the safety of the process. The use of surfactants ensures the homogeneity of the reaction mass, input neonols, OP 7, OP-10) as a surfactant in the amount of 2-6% by weight of the original piperazine, AEP or PEED provides a high yield of the target product. Enter surfactants less than 2% by weight of piperazine does not provide a higher yield of the target product, and the introduction of surfactant more than 6% leads to excess of this reagent.

The technical result in the use of the invention is expressed in ensuring the fire safety of the technological process of obtaining piperazineethanol, which is achieved by using water as a solvent, as well as increasing the yield of the target product through the interaction of the reactants in the presence of surfactants.

Pic is b is illustrated by the following examples.

Example 1. In a reactor provided with a mechanical stirring device, a thermometer, load 86 g (1.0 mol) of piperazine, 300 ml of distilled water, 1.7 g OP 7 (2% by weight of piperazine) as a surfactant, 7210 g (0.8 mol) of Mannich bases. The molar ratio of piperazine:OM=1:1. The reaction mixture is heated at a temperature of 95-100°C for 3-4 hours before the termination of the allocation of gaseous dimethylamine. At the same time produce a distillate of water and amine from the reaction mass. After drying receive 208 g of N1-(3,5-di-tertbutyl-4-oxybenzyl)piperazine (compound 1), yield 79%. The melting temperature (TPL) 231-232°C. Found, %: C 75,43; H 10,23; N 9,04 [C19H32N2O3. Calculated, %: C 75,0; H 10,52; N Of 9.21.

Example 2. In the conditions of example 1 was charged to the reactor 86 g of piperazine, 300 g of water, 1.7 g OP 7 (2% by weight of piperazine) as a surfactant, 526 g of the Mannich bases. The molar ratio of piperazine:OM=1:2. Get the 411 g of N1N1bis(3,5-di-tertbutyl-4-oxybenzyl)piperazine (compound 2), yield 80%. Melting point 220-222°C. Found, %: C 78,57; H 10,37; N 5,02 [C34H54N2O2]. Calculated, %: C 78,16; H 10,34; N Are 5.36.

Example 3. In a reactor provided with a mechanical stirring device, a thermometer, load 86 g (1.0 mol) of piperazine, 100 ml of distilled water, 228 g (1.0 mol) Suite, and 83.3 g of 36%aqueous formaldehyde solution (in terms of n the dry matter 30 g, to 1.0 mole) and 2.58 g of OP-10 (3% of the original weight of piperazine). The molar ratio of piperazine:FA:sequential function=1:1:1. The reaction mixture is heated at a temperature of 55-60C for 6.5 hours. Then the reaction mixture is distilled water and boiling components. After drying receive 241,2 g of 2-(4-oxybenzyl)-2-[3-piperidinomethyl-4-oxyfuel]propane (compound 3), melting point 263°C. Yield 80%.

Example 4. In the conditions of example 3 was charged to the reactor 86 g (1.0 mol) of piperazine, 100 ml of distilled water, 456 g (2.0 mol) Suite, 166,6 g of 36%aqueous solution of formaldehyde (calculated on the dry matter 60 g, 2.0 mol) and 5,16 g neonols (6% of the original weight of piperazine). The molar ratio of piperazine:FA:sequential function=1:2:2. The reaction mixture is heated at a temperature of 55-60C for 6 hours. Then the reaction mixture is distilled water and boiling components. After drying receive 475 g of N1N1bis[2,2-di(4 oksifenil)propane]piperazine (compound 4), melting point 126°C. the product Yield 84%.

Example 5. In the conditions of example 1 was charged to the reactor of 12.9 g AEP (0.1 mol), 50 g of water, 0.26 g of neonols (2% by weight AEP) as a surfactant, to 26.3 g of the Mannich bases (0.1 mol). The molar ratio of AEP:OM=1:1. Get to 28.9 g of N-3,5-di-tertbutyl-4-hydroxybenzyl-N1-(β-amino-ethyl)piperazine (compound 5), the yield of 83.5 per cent. TPL 162°C. Found, %: C 72,99; H 11,07; N 11,68 [C21H37N3O]. Calculated, %: C 72,62; H 10,66;N 12,10.

Example 6. In the conditions of example 1 was charged to the reactor of 12.9 g AEP (0.1 mol), 50 g of water, of 0.77 g of neonols (6% by weight AEP) as a surfactant, for 52.6 g of the Mannich bases (0.2 mol). The molar ratio of AEP:OM=1:2. The formation of the target product is given by equation 4. Get to 47.46 g of N-3,5-di-tertbutyl-4-hydroxybenzyl-N1-(β-3,5-di-tertbutyl-4-hydroxyethylaminomethyl)piperazine (compound 6), yield 84%. TPL 111-112°C. Found, %: C 76.86 euros; H 10,12; N 7,02 [C36H59N3O2]. Calculated, %: C 76,46; H 10,44; N 7,43.

Example 7. In the conditions of example 3 was charged to the reactor 129 g (1.0 mol) of N-(β-amino-ethyl)piperazine (AEP), 250 ml of distilled water, 228 g (1.0 mol) Suite, and 83.3 g of 36%aqueous solution of formaldehyde (calculated on the dry matter 30 g, 1.0 mol) and 3.9 g of OP-10 (3% of the original weight of piperazine). The molar ratio of piperazine:FA:sequential function=1:1:1. The reaction mixture is heated at a temperature of 70-75°C for 6 hours. Then the reaction mixture is distilled water and boiling components. After drying receive 273,8 g of 2-(4-oxybenzyl)-2-[3-ethylenediaminetetra-4-oxyfuel]propane (compound 7), melting point 109°C. the product Yield 79%. Found, %: C 71,70; H cent to 8.85; N 11,02 [C22H32N3O2]. Calculated, %: C 71,35; H 8,64; N 11,35.

Example 8. In the conditions of example 3 was charged to the reactor 129 g (1.0 mol) AEP, 250 ml of distilled water, 456 g (1.0 mol) Suite, 166,6 g of 36%aqueous solution of formaldehyde (PE is eschete dry matter 60 g 2.0 mol) and 7,74 g neonols (6% of the original weight of piperazine). The molar ratio of piperazine:FA:sequential function=1:2:2. The reaction mixture is heated at a temperature of 75-80C for 8 hours. Then the reaction mixture is distilled water and boiling components. After drying, the residue receive 468,9 g N1N1bis[2,2-di(4 oksifenil)propane]N-(-amino-ethyl)piperazine (compound 8), melting point 195°C. Yield 80%.

Example 9. In the conditions of example 1 was charged to the reactor of 21.9 g BAP, 30 g of water, 0.87 g OP 7 (4% of the weight of BAEP), 26,3 g Mannich bases. Get a 33.2 g of N-(β-benzylamino)piperazine-N1-(4-hydroxy-3,5-di-tert-butylbenzyl)piperazine (compound 9). Boiling point : 154-156°C at 23-24 mm Hg Yield of 80%. Found, %: C 77,27; H 10,15; N to 9.32 [C28H43N3O]. Calculated, %: C A 76.88; H 9,83; N 9,60.

Example 10. In the conditions of example 1 was charged to the reactor 28.4 g PEEDA (0.1 mol), 80 ml of water, 0.56 g of neonols (2% by weight PEEDA) and 52.6 g of the Mannich bases (0.2 mol). The molar ratio of PEEDA:OM=1:2. The reaction mixture is heated to 90-95°C and stirred for 6 hours until the termination of allocation of dimethylamine. After distillation, volatile impurities and drying receive 51.8 g of N1N1bis[N-(4-hydroxy-3,5-di-tertbutylphenyl)piperazinyl]Ethylenediamine (compound 10), yield 81%. TPL product 262-263°C. Found, %: C 66,95; H becomes 9.97; N 10,24 [C44H76N6O2 ]. Calculated, %: C 66,58; H 9,58; N 10,59.

Example 11. In the conditions of experiment 1 was charged to the reactor 28.4 g PEEDA (0.1 mol), 100 g of water, 1.7 g of neonols (6% by weight PEEDA) and of 105.2 g of the Mannich bases (0.4 mol). The molar ratio of PEEDA:OM=1:4. The reaction mixture is heated to 95°C and stirred for 6 hours until the termination of allocation of dimethylamine. After distillation, volatile impurities and drying get to 75.7 g of N1N1N1N1-Tetra (3,5-di-tertbutylphenyl-4-hydroxybenzyl)-N1N1bis[piperidinoethyl]Ethylenediamine (compound 11). Yield 80%. TPL product 158-160°C. Found, %: C 79,19; H 10,53; N? 7.04 baby mortality [C74H120N6O4]. Calculated, %: C 76,81; H 10,38; N 7,26.

Example 12. In the conditions of example 1 was charged to the reactor 86 g of piperazine, 300 g of water, 0,86 g OP 7 (1% by weight of piperazine) as a surfactant, 526 g of the Mannich bases. The molar ratio of piperazine:OM=1:2. Get 360 g of N1N1bis(3,5-di-tertbutyl-4-oxybenzyl)piperazine (compound 2), yield 70%.

Example 13. In the conditions of example 1 was charged to the reactor 86 g of piperazine, 300 g of water and 6.9 g OP 7 (1% by weight of piperazine) as a surfactant, 526 g of the Mannich bases. The molar ratio of piperazine:OM=1:2. Get the 411 g of N1N1bis(3,5-di-tertbutyl-4-oxybenzyl)piperazine (compound 2), yield 80%.

Below is a chemical structural formula of the obtained piperazineethanol:

p> The General formula

Connection 1

Connection 2

Connection 3

Connection 4

Connection 5

Connection 6

Connection 7

Compound 8

Connection 9

The General formula

Connection 10

Connection 11

where

The resulting piperazineethanol tested as stabilizers of unsaturated compounds, the test results presented in the table.

For testing in the flask is charged with the subject of unsaturated hydrocarbons (40-100 g), the required number of piperazineethanol (in the range of 0.05-25% by weight of an unsaturated compound) as a stabilizer and incubated at 60°C under atmospheric pressure for 2 days. Similarly spend idling experience without the use of stabilizers. The resinification product is determined by the ratio of the weight of the resin remaining after the distillation of hydrocarbon, minus weight widen the first stabilizer, to the weight of the original unsaturated hydrocarbon.

The test results of piperazineethanol as stabilizers unsaturated hydrocarbons are presented in the table.

Piperazineethanol, No. of connectionsThe amount of stabilizer, % by weight of the hydrocarbonName of unsaturated hydrocarbonsThe resinification, %Colour of product
Without stabilizer-2-chloro-pentan-36,9yellow liquid
Connection 10,12-chloro-pentan-31,8transparent
Connection 20,082-chloro-pentan-31,6transparent
Connection 30,122-chloro-pentan-32,2transparent
Without stabilizer -1,2,3-trichlorpropane7,2yellow liquid
Connection 30,051,2,3-trichlorpropane3,1transparent
Connection 40,051,2,3-trichlorpropane2,8transparent
Connection 50,051,2,3-trichlorpropane2,7transparent
Without stabilizer-piperidin1,25yellowish fluid.
Connection 60,25piperidin0,25transparent
Connection 70,25piperidin0,27transparent
Compound 80,25 piperidin0,30transparent
Connection 90,25piperidin0,35transparent
Without stabilizer-1,1,2,3-tetrachloropropane10,6yellow liquid
Connection 100,11,1,2,3-tetrachloropropane6,3transparent
Connection 110,11,1,2,3-tetrachloropropane6,1transparent

Piperazineethanol have a stabilizing ability for unsaturated hydrocarbons and chlorohydrocarbons.

The method of producing piperazineethanol, including interaction piperazine, N-(β-amino-ethyl)piperazine, N-(β-benzylamino)piperazine or N,N1bis-(piperidinoethyl)Ethylenediamine with the base of manniche in the environment of the polar solvent at a temperature of 90-110°C at a molar ratio of piperazine, N-(β-amino-ethyl)piperazine, N-(β-benzylamino)Pipa is asin: the basis of manniche, equal to 1:0.8 to 2, N,N1bis-(piperidinoethyl)Ethylenediamine: the basis of manniche equal to 1:2 or 1:4 to stop shedding dimethylamine; and aminomethylpyridine piperazine or N-(β-amino-ethyl)piperazine-diphenylolpropane (Suite) in the presence of formaldehyde (FA) in a polar solvent at a molar ratio of piperazine: FA: sequential function equal to 1:1:1 or 1:2:2 at a temperature of 50-90°C for 4-10 h, characterized in that the polar solvent used water, the interaction of the reagents is carried out in the presence of surface the active substance in an amount of 2-6% by weight of the original piperazine, and as surface-active substances are used neonol, OP 7, OP-10.



 

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FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel acid-additive salts of pyrrolopyrimidinone derivative, represented by formula (1) which is selected from gentisate, maleate, citrate, fumarate and semitartrate salts, which possess improved properties in their application, in particular higher stability.

EFFECT: invention also relates to method of obtaining acid-additive salts of pyrrolopyrimidinone derivative, represented by formula (1) and to pharmaceutical composition, containing them, for treatment and prevention of erectile dysfunction, pulmonary arterial hypertension, chronic obstructive lung disease, benign prostate gland hypertrophy and diseases of lower urinary tract.

11 cl, 30 ex, 7 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to synthesis of novel 4-(azacycloalkyl)phthalonitriles. Novel 4-(azacycloalkyl)phthalonitriles of general formula

are obtained. The method of obtaining said compounds involves nucleophilic substitution of the bromine atom in 4-bromophthalonitrile (BPN) with N,N-cycloalkyleneamines.

.

The reaction takes place in the presence of a deprotonation agent K2CO3 and a catalytic complex Cul/dipyridyl formed in situ at temperature 90-95°C for 12 hours. Molar ratio of reactants BPN: amine: Cul: dipyridyl: K2CO3=1:1.2:0.1:0.1:1.5. After the reaction, the mixture is cooled and filtered. The filtered residue is washed with water and recrystallised.

EFFECT: obtaining novel 4-(azacycloalkyl)phthalonitriles using a method which is safe for this class of compounds.

2 cl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula in which Q together with carbon and nitrogen atoms whereto attached forms a 9-10-member bicyclic heterocycle, and R1 and R2, R3, R4, R5 and R6 are as specified in cl.1 of the patent claim, or to its enantiomers, or a mixture of its enantiomers, or to its pharmaceutically acceptable salt. Also, an invention refers to a method for activation of glucokinase activity in mammals, by introduction of the compound described above, to a method of treating the pathological conditions associated with glucokinase activity and impaired glucose tolerance by means of introduction of the compound of formula I, to a pharmaceutical composition on the basis of the presented compounds, and also to application of the compounds of formula I for preparing the pharmaceutical composition.

EFFECT: there are produced and described new compounds which are activators of glucokinase activity and can be used as therapeutic agents for preventing and treating impaired glucose tolerance, insulin-independent diabetes and obesity.

14 cl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: compound of formula pharmaceutically acceptable salt or solvate of a compound or salt (I), ring Q represents optionally substituted monocyclic or condensed (C6-C12)aryl or optionally substituted monocyclic or condensed heteroaryl where said substitutes are chosen from: halogen; (C1-C6)alkyl optionally substituted by 1-3 halogen atoms; (C1-C6)alkylsulphonyl; phenyl optionally substituted by 1 or 2 substitutes chosen from halogen, (C1-C6)alkyl which can be substituted by 1-3 halogen atoms, groups (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and (C1-C6)alkylthio; monocyclic or condensed heteroaryl optionally substituted by halogen; or oxo; Y1 represents a bond or -NR6-CO-, where R6 represents hydrogen, ring A represents optionally substituted a nonaromatic heterocyclyldiyl where said substitutes are chosen from (C1-C6)alkyl optionally substituted by groups hydroxy, (C1-C6)alkylamino, di(C1-C6)alkylamino, morpholino, (C1-C6)alkylaminocarbonyl, di(C1-C6)alkylaminocarbonyl; cyano; (C3-C6)cycloalkyl; (C1-C6)alkoxy; (C1-C6)alkoxy(C1-C6)alkyl; phenyl; benzyl; benzyloxymethyl; thienyl; 4-8-members monocyclic nonaromatic heterocycle having 1 or 2 heteroatoms chosen from N or O, and optionally substituted by 1 or 2 substitutes chosen from (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and oxo; (C1-C6)alkylamino; di(C1-C6)alkylamino; a group of formula: -Y2Z'- represents a group of formula: [Formula 2] each R7 independently represents hydrogen, (C1-C6)alkyl or (C3-C6)cycloalkyl, each of R8 and R9 independently represents hydrogen or (C1-C6)alkyl, n is equal to an integer 0 to 3, Z1 represents a bond, -O-, -S- or-NR9 - where R9 represents hydrogen, (C1-C6)alkyl, acyl or (C1-C6)alkylsulphonyl, ring B represents optionally substituted aromatic carbocyclediyl or optionally substituted aromatic heterocyclediyl where said substitutes are chosen from (C1-C6)alkyl, halogen, (C1-C6)alkoxy and oxo; Y3 represents a bond optionally substituted (C1-C6)alkylene or (C3-C6)cycloalylene, optionally interrupted -O- or optionally substituted (C2-C6)alkenylene where said substitutes are chosen from (C1-C6)alkyl, (C3-C6)cycloalkyl, halogen and (C1-C6)alkoxycarbonyl; Z2 represents COOR3; R3 represents hydrogen or (C1-C6)alkyl.

EFFECT: preparation of new compounds.

30 cl, 9 tbl, 944 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula [I-D1] or pharmaceutically acceptable salt thereof,

,

where each symbol is defined in the claim. The invention also relates to pharmaceutical compositions containing said compound and having HCV polymerase inhibiting activity.

EFFECT: disclosed compound exhibits anti-HCV activity, based on HCV polymerase inhibiting activity and is useful as an agent for preventing and treating hepatitis C.

32 cl, 497 tbl, 1129 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of benzene sulphonamide of formula (I), tautomeric and stereoisomeric forms and physiologically acceptable salts thereof: where X is O, S; R1 is H, halogen; R2 is H, halogen; halogen; R3 is NO2, CN; R4 is: ,

where R71 is H; R72 is H; Z1 is -[CH2]P-, where p = 2.

EFFECT: compounds have antagonistic activity towards CCR3, which enables for their use in making medicinal agents.

13 cl, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to the new compounds of formula (I): whereat R1 is -SO2NR102R103, -NR101SO2R104 or -COOR105 whereat R101 is hydrogen atom, R102 and R103 each independently represents hydrogen atom or C1-4 alkyl, R104 is C1-4 alkyl and R105 is hydrogen atom or C1-4 alkyl ; X is bond, -CH2- or -O-; Y is -CH2-; ring A and ring B, which are same or different, each independently is benzene, pyridine, pyrazol or piperidine which can have the following substituents: C1-4 alkyl or halogen; ring D is piperidine; R2 is whereat the arrow shows the position of the bond with the ring D; R51 is (1) hydrogen atom a, (2) C1-6alkyl, which can have the following substituents: (a) hydroxy, (b) methoxy, (c) cyano, (d) carboxy, (e) halogen, (f) methyl sulphonylamino, (g) C3-8cycloalkyl or phenyl, which can have the following substituents: methyl, halogen, hydroxy or methoxy, (h) thienyl, pyrazolyl, tetrahydropyranyl, thiazolyl, isooxalyl, imidazolyl, tetraazolyl, pyridyl, pyrimidinyl which can have the following substituents: methyl, trifluoromethyl or hydroxy, (3) C2-10alkenyl, (4) C2-10alkynyl, (5) phenyl which can have the following substituents: C1-4alkyl or halogen, or (6) pyridine or tetrahydropyran; R52 is (1) hydrogen atom a, (2) C1-6alkyl which can have the following substituents: (a) hydroxy, (b) methoxy, (c) carboxy, (d) C3-8cycloalkyl, (e) phenyl or (f) oxo, (3) C3-8cycloalkyl or phenyl which can have the following substituents: C1-4alkyl, hydroxy, cyano, oxo, carbamoyl, N-methyl aminocarbonyl, carboxy, halogen, methoxy, trifluoromethoxy, methythio, methylsulphonyl, acetylamino, dimethylamino, acetyl, tetraazolyl, trifluoromethyl or methylsulphonylamino (4) C3-10cycloalkenyl, (5) adamantyl, (6) thienyl, pyrazolyl, tetrahydropyranyl, isoxaazolyl, isothiazolyl, thiadiazolyl, piperidinyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, indolyl, benzothiazolyl, benzoisothiazolyl, benzotriazolyl, dioxaindanyl, benzodioxaindanyl which can have the following substituents: C1-4alkyl, hydroxy, oxo, halogen, azido or trifluoromethyl or (7) benzyloxy groups; and R53 is hydrogen atom or C1-6alkyl; to its salts or its solvates. The invention refers also to the regulator CCR5, to the agent of prevention and/or treatment of HIV infection, immunological or inflammatory diseases, to the pharmaceutical composition, to the medicinal preparation, to the method of disease treatment or prevention as well as to the application of compound as in claim 1.

EFFECT: obtaining of new bioactive compounds possessing anti CCR5 receptor activity.

23 cl, 41 ex

FIELD: chemistry.

SUBSTANCE: inventive subject matter is compouns and their pharmaceutically acceptable salts which can be applied in prevention and treatment of diseases caused by HCV infection. Structural formulae of the compounds are presented in the claim.

EFFECT: obtaining anti-HCV medicine including the claimed compound or its pharmaceutically acceptable salt as active component.

2 cl, 100 ex

FIELD: medicine; cosmetology.

SUBSTANCE: invention contains antiperspirant, continuous phase and structure-forming agent containing cyclic depeptide derivative, method of production thereof, method of hidropoiesis prevention or reduction, derivative of cyclic depeptide and gel base for antiperspirant.

EFFECT: compositions have higher activity.

46 cl, 10 tbl, 6 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compositions and methods for treatment of depressive disorder in subject using the therapeutically effective dose of agonist(s) of delta-receptors of the general formula: wherein Ar1 represents a 6-membered carbocyclic aromatic ring with a substitute Y at its carbon atom wherein Y represents carboxamide of the formula: CONR9R10 wherein both R9 and R10 represent ethyl group; Z is chosen from group consisting of hydrogen atom (H), -OH and alkoxy-group; Ar2 represents a 6-membered carbocyclic aromatic ring with a substitute X at its carbon atom wherein X represents H, or pharmaceutically acceptable ester or salt of such compound. Invention provides antidepressant effect in a patient in using indicated compounds in lower doses as compared with the known agonists of delta-receptors showing the related chemical structure with compounds proposed.

EFFECT: improved method of treatment, enhanced and valuable medicinal properties of compounds.

17 cl, 1 tbl, 21 ex

FIELD: organic chemistry, medicine, ophthalmology, pharmacy.

SUBSTANCE: invention relates to new derivatives of nitrogen-containing heterocyclic compounds of the general formula (I): wherein X1, X2, X3, X4 and X5 mean -CH2 or one of them represents -NH and another X1-X5 represent -CH2; k = 0, 1 or 2; when t = 2, then radicals R1 are similar or different; R1 represents direct or branched (C1-C8)-alkyl or (C1-C8)-alkoxy-group; A means phenyl or pyridinyl; R2 means hydrogen atom (H), hydroxyl, halogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-group; n = 0, 1-4; radicals R2 are similar or different, when n > 1; p = 0 or 1-5; Y means -OC(O); Z means -CH, or to their pharmaceutically acceptable salts. Compounds of the formula (I) possess agonistic activity with respect to muscarinic receptors and can be used in medicine as medicinal preparations for treatment of neurodegenerative diseases or diseases associated with increased intraocular pressure.

EFFECT: valuable medicinal properties of derivatives.

6 cl, 1 tbl, 2 dwg, 16 ex

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