The way to obtain 6-fluoro-1,2-benzisothiazole, orthotamine peacelove derivative and its production method

 

(57) Abstract:

Use: as intermediate products to obtain pharmaceutically active compounds. The inventive product 1 - 6-fluoro-1,2-benzisothiazole f-ly 1, where R is hydrogen, lower alkyl or a group of f-crystals of 2 or 3, where R1CHO, or-CN. Reagent 1: compound f-ly 4, where R above; R3-benzyl Reagent 2: halogenation agent, better sulfurylchloride. Reagents 1 and 2 interaction give compound f-crystals 5, which is subjected to interaction with ammonia, better at room temperature. Connection f-crystals 4 is produced from compound f-crystals 6 and benzylmercaptan environment aprotic organic solvent. 3C. and 2 C.p. f-crystals. The structure of formulas 1, 2, 3, 4, 5 and 6 (see Fig.).

The invention relates to a method for producing 6-fluoro-1,2-benzisothiazole formula

(I) where R is a hydrogen atom, a lower alkyl or a group of the formula

orwhere R1means-Cho or - CN, namely, that on-halogenoalkane derivative of the formula:

where R has the above meanings, is subjected to the interaction with R3SH, where R3- benzyl, environment aprotic organic solvent, with the formation of the compounds of formula

(III)where R and R3impulsivo of sulfanilamide formula

(IV)Subjected to interaction obtained sulfanilamide with ammonia in the compounds of the formula

(I)

The resulting 1,2-benzisothiazole formula I can be used as intermediates to obtain pharmaceutically active compounds that can be used, for example, as antipsychotic agents and as inhibitors of reuptake of serotonin.

The present invention also relates to compounds of the formula

(III)where R and R3have the above values,

which can be used as intermediates for producing compounds of the formula IV.

Unless otherwise indicated, the term "lower alkyl" is meant straight or branched alkyl with 1-6 carbon atoms. Examples of alkyl are methyl, ethyl, n-propyl, isobutyl, pentyl and hexyl.

Unless otherwise indicated, the term "halogen" are due to the atoms fluorine, chlorine, bromine or iodine.

Known methods for producing 1,2-benzisothiazoles, based on on-halogenoalkane compounds. An example of one of these methods is the handling of o-ha the BOM cannot however, to obtain 6-fluoro-1,2-benzisothiazole with high output.

Proposed in accordance with the present invention, the method makes it possible to obtain 6-fluoro-1,2-benzisothiazole of on-halogenoalkane compounds with high yield without resorting to high temperatures and without the use of an autoclave.

It was found that when applying the above reaction with the formation of compound III substitution nucleophilic group, R3SH occurs selectively at the fluorine atom adjacent to the carbonyl functional group of the phenyl ring. The reaction is usually carried out in a medium of an organic solvent, such as tetrahydrofuran, in the presence of a base such as tert-butoxide potassium, at a temperature of 0-150aboutWith, preferably with 10-100aboutS, most preferably 15-80aboutC. Preferred R3SH - compounds include benzylmercaptan.

To obtain sulphonylchloride IV compound III is subjected to interaction with a halogenation agent, such as sulfurylchloride, sulfanilamide, bromine or chlorine, most preferably sulfurylchloride. The reaction is usually carried out in a medium of an organic solvent, such as dichloroethane or dichloromethane separated from the reaction mixture without additional purification is subjected to interaction with ammonia, receiving the target benzisothiazol. The reaction is usually carried out in a medium of an organic solvent, such as tetrahydrofuran, at a temperature of 0-100aboutC, preferably at 15-80aboutMost preferably at ambient temperature.

Source divorcethe, in which R means heteroseksualci, such as piperidinyl receive, for example, by acylation of 1,3-diferently by the reaction of the Friedel-known manner, using the appropriate galoyanized.

Source divorcethe, in which R means a hydrogen atom, lower alkyl, get known methods.

Source divorcethe, in which R means bicycleretailer, such as troparil receive from dialkylated 2,4-diferentialglea, which is subjected to interaction with fosforiliruyusciye agent, such as triethylphosphite and mortification, in the presence of a suitable solvent, for example dichloromethane, with the formation of the compounds of the formula

(V) where R4means lower alkyl. This reaction is usually carried out at temperatures from -25aboutWith up to room temperature for 10-30 hours

The resulting compound V is then subjected entries batch
with the formation of the compounds of the formula

The reaction is usually conducted in the environment of a suitable solvent, such as tetrahydrofuran, at temperatures from -78aboutWith up to room temperature for 10-30 hours

Compound VI is then subjected to contact with an aqueous HCl solution in the environment of acetone at boiling point, within 2-8 h with education in the connection

< / BR>
The obtained compound VII was transferred to compound II, where R1means CN or CO2R2by known methods, for example by reacting with bromine cyan or chloroformate, in the presence of a base, for example potassium carbonate, with the formation of the resulting compound (II), where R1means CN, respectively CO2R2.

The following examples are given solely to illustrate the invention and should not be considered as limiting the scope of its protection. All temperature, unless otherwise indicated, are given in degrees Celsius.

P R I m e R 1. 4-fluoro-2-(feniletilic)benzaldehyde

Benzylmercaptan (1,74 g) in 10 ml of tetrahydrofuran (THF) was added dropwise to a solution of tert-butoxide potassium (1,58 g) in 60 ml THF. The resulting suspension was stirred at ambient temperature nie half an hour at room temperature. After this there was added thereto a saturated solution of ammonium chloride and subjected to extraction with ethyl acetate (EtOAc). The combined organic layers were washed with brine, dried over MgSO4, was filtered and was evaporated, getting 3.11 g of crude product. After crystallization from methanol has been solid with so pl. 81-82aboutC.

Calculated, %: C 68,27; N 14,50

WITH14H11FOS

Found, %: C 68,31; N 4,37

Century 6-Fluoro-1,2-benzisothiazol

Sulfurylchloride (1.04 g) was added dropwise to a suspension of 4-fluoro-2-(feniletilic)benzaldehyde (2.0 g) in 23 ml of dichloroethane at room temperature. The resulting solution was stirred for 0.5 h, after which the solvent was removed in vacuum and the residue is suspended in 10 ml of THF and treated at room temperature with 10 ml of ethanol (EtOH), saturated with ammonia (NH3). The resulting mixture was stirred for half an hour, was added to her water and the resulting product extraction EtOAc. The combined organic layers were washed with brine, dried over MgSO4, was filtered and was evaporated, resulting in the 1.0 g of crude product. In the treatment using a rapid preparative thin-layer chromatography (elution with a mixture of ethyl acetate and hexane) pointillart (1,59 g) in 10 ml THF was added dropwise to a solution of tertbutoxide potassium (1.4 g) in 55 ml of THF. The resulting suspension was stirred for 5 min at ambient temperature, then added to her 2,4-defloration (2.0 g). The reaction mixture was stirred for half an hour at room temperature, was added a saturated solution of ammonium chloride, and then was subjected to extraction with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, was filtered and was evaporated, resulting in the 3.2 g of crude product. After recrystallization from methanol was obtained 2.1 g (63%) of product as a solid substance with so pl. 111-112aboutC.

Calculated, %: C 69,21; N 5,03

C15H13FOS

Found, %: C 69,42; N 5,11

Century 6-Fluoro-3-methyl-1,2-benzisothiazol

Sulfurylchloride (0.52 g) was added dropwise to a suspension of 4-fluoro-2-(feniletilic)acetophenone (1.0 g) in 12 ml of dichloroethane at room temperature. The resulting solution was stirred for half an hour, after which the solvent was removed in vacuum and the residue is suspended in 12 ml of THF and treated at room temperature, 12 ml tOH saturated with NH3. The resulting mixture was stirred for half an hour, then added to it water and the resulting product was extracted with EtOAc. The combined organic layers washed the result of treatment with accelerated preparative thin-layer chromatography (elution with a mixture of ethyl acetate and hexane) received 0,37 g (58%) solid pale yellow color with tons of dps 50-57aboutC.

P R I m e R 3. A. 4-[4-fluoro-2-(feniletilic)benzoyl]-1-piperidinecarboxylic-Devid

To a stirred solution of tert-butoxide potassium (4.6 g) in THF (125 ml) was added dropwise benzylmercaptan (5,1 g) in THF (60 ml). After stirring for half an hour at ambient temperature was added in portions with 4-(2,4-di-perbenzoic)-1-piperidinecarboxylate (10.3 g). Present in the reaction mixture a white flocculent solid is passed into the solution and stirring at ambient temperature was continued for 2 h the Reaction was then stopped, pouring the reaction mixture into water and the aqueous suspension was subjected to extraction with EtOAc. The organic extract was washed (water), dried (MgSO4) and the solvent drove receiving 14.0 g of a viscous oily liquid. The obtained oily liquid was mixed with a portion of another party (14,7 g) and the whole product was ground EtO2receiving the result of 20.4 g (63%) solids with temperature. melting 96-98aboutC. After recrystallization from a mixture of toluene and hexane were obtained off-white solid product with the pace. plvl. 101-103aboutC.

Calculated, %: C 67,20; N 5,64; N 3,92

C20H20FNO2S

Found, %: C 67,42; N 5,96; N 3,90

Century 4-the thio)]-1-piperidinyl - localdevice (40 g) in methylene chloride (CH2CL2) (400 ml) was added dropwise sulfurylchloride (8,9 ml) in CH2CL2(28 ml). After the addition was finished the reaction mixture was stirred for 1 h at ambient temperature. After that it was filtered to remove small amounts of nerastvorimogo material and evaporated, receiving the result of 40.7 g of sulphonylchloride in the form of a thick oily liquid, which was aterials when standing. This crude sulphonylchloride was dissolved in THF (500 ml) and the resulting solution was added dropwise a saturated solution of NH3in tOH (180 ml). The reaction mixture was stirred for 2 h at room temperature and then left to stand at this temperature for 16 hours then poured into water and the aqueous suspension was subjected to extraction with EtOAc. The organic extract was washed (water), dried (MgSO4) and the solvent drove, receiving the result of 29.6 g of a thick oily liquid, which was subjected to purification using preparative high performance liquid chromatography filled with silica gel column by elution with 3% Et2NH - EtOAc. The yield of the target compounds, representing an oily liquid was 12.2 g (42%). By rubbing with isoprop the and. The melting point of the obtained solid product was equal 104-106aboutC.

Calculated, %: 59,07; N 4,96; N OR 10.60

C13H13FN2OS

Found, %: C 59,17; N 5,07; N 10,48

P R I m e R 4. A. Diethyl-1-(2,4-differenl)-1-methoxymetopon

Portreporter (86 g) was added dropwise to a solution of dimethylacetal 2,4-diferentialglea (114 g) and triethylphosphite (101 g) in 1.2 l of CH2Cl2at -25aboutC. the resulting solution was allowed to warm to room temperature and stirred it for 20 hours then to it was added water and vigorously stirred mixture within 10 minutes the Organic layer was separated, washed with brine, dried over MgSO4was filtered and concentrated, obtaining as the residual liquid substance. In the treatment using high-performance liquid chromatography on a column of silica gel (elution CH2Cl2and then 5% EtOAc - CH2CL2) received 136 g of diethyl-1-(2,4-differenl)-1-methoxymethamphetamine in liquid form.

Century (2,4-differenl)(8-methyl-8-azabicyclo-[3.2.1]-Octan-3-yl)methanomicrobia-ri d

Diethyl-1-(2,4-differenl)-1-methoxy - metaphosphate (76 g) was dissolved in THF (1600 ml). The solution was cooled to -78aboutWith E. rose above -65aboutC. the resulting solution was stirred for 1 h, then added to the reaction mixture slowly dropwise tropinone (32,7 g) dissolved in THF (100 ml). At the end of the addition the mixture was slowly allowed to warm to room temperature and was stirred overnight. Then thereto was added a saturated solution of NaCl (1.5 l), the layers were separated, the organic layers were collected and dried over MgSO4and the solvent drove away, getting in the oily liquid (73 g). This oily liquid (38 g) was dissolved in acetone (2 l) was slowly added to the resulting solution, water (35 ml) and concentrated Hcl (182 ml) and boiled the mixture for 3 h under reflux. After that, acetone and drove the remainder in the form of an aqueous solution was subjected to extraction with EtOAc, podslushannyy TO2CO3then the extraction of CH2Cl2and dried over MgSO4. After removal of the solvent was received 31,3 g oily liquid, which was aterials. A portion of this solid (3 g) was dissolved in EtOH (75 ml), the resulting solution was acidified with ethanolic Hcl was added ethyl ether (75 ml), resulting from the solution fell precipitate the product as a salt (2.65 g), so pl. 224-225aboutC.

Calculated, %: C becycle[3.2.1]-octane-8-carbonitrile

Brazian (4.0 g) in one step was added to the suspension (2,4-difluorophenyl)8-methyl-8-azabicyclo[3.2.1] Oxton-3-yl/-methanone (5.0 g) and potassium carbonate (5.2 g) in 80 ml of dimethylformamide at room temperature. The mixture was stirred for 2 h and then was diluted with water and EtOAc. The layers were separated and the aqueous phase was subjected to extraction with EtOAc. The combined organic layers were washed with water and brine, dried over MgSO4, filtered and concentrated, resulting in the 3.5 g of solid, which was recrystallized from a mixture of EtOAc and heptane. Melting point 162-164aboutC.

Calculated, %: C 65,21; N 5,11; N 10,14

WITH15H14F2N2O

Found, %: C 65,16; N 5,10; N 10,08

d. 3-[4-fluoro-2(feniletilic)benzyl]-8-azabicyclo[3.2.1]octane-8-carbonitrile

Benzylmercaptan (0,67 g) in 5 ml of THF was added dropwise to a solution of tertbutoxide potassium (0.6 g) in 15 ml THF. The resulting suspension was stirred at ambient temperature for 5 min, then added to it (2,4-differentail)-8-azabicyclo[3.2.1] octane-8-carbonitrile (1.5 g). The reaction mixture was stirred for half an hour at room temperature, then was added a saturated solution of ammonium chloride and the resulting product was extracted with EtO, deliver 1.7 g of crude product. After recrystallization from methanol was obtained 0.87 g of product in the form of a solid substance with so pl. 166-167aboutC.

Calculated, %: C 69,45; N TO 5.56; N OF 7.36

C22H21FN2OS

Found, %: C 69,37; N 5,69; N 7,15.

E. 3-(6-Fluoro-1,2-benzisothiazol-3-yl)-8-azabicyclo[3.2.1] octane-8-carbonitrile

Sulfurylchloride (5,33 g) was added dropwise at room temperature to a suspension of 3-[4-fluoro-2-(feniletilic)benzoyl] -8-azabicyclo-[3.2.1] octane-8-carbonitrile (15 g) in 160 ml of dichloroethane. The resulting solution was stirred for 1.25 h, then the solvent is kept in vacuum and the residue suspended in 160 ml of THF and treated at room temperature with 160 ml of ethanol saturated with ammonia. The resulting mixture was stirred for 1.5 h, after which the solvent was removed in vacuum and the residue was distributed between water and CH2Cl2. The combined organic layers were washed with brine, dried over MgSO4, was filtered and was evaporated, resulting in the 10.7 g of solid, which was filtered through silica gel (elution CH2CL2). The solid obtained after evaporation of the filtrate (6,82 g) precrystallization of EtOAc, obtaining 4.1 g of white isS

Found, %: 62,63; N. OF 4.90; N 14,73

It should be noted that changes are possible and different ways within the scope of the invention defined by the attached claims.

THE WAY TO OBTAIN 6-FLUORO-1,2-BENZISOTHIAZOLE, ORTHOTAMINE PEACELOVE DERIVED AND HOW TO OBTAIN IT.

1. The way to obtain 6-fluoro-1,2-benzisothiazole General formula I

< / BR>
where R is hydrogen, lower alkyl or a group of the formula

< / BR>
where R1- CHO or - CN,

based on orthotamine ventilago derivative, characterized in that as orthotamine ventilago derived using the compound of General formula III

< / BR>
where R has the above meanings;

R3- benzyl,

which is subjected to interaction with a halogenation agent with the formation of compounds of General formula IV

< / BR>
where R has the above meanings;

Hal is halogen,

with the subsequent interaction of the compounds of formula IV with ammonia to obtain the compounds of formula I.

2. The method according to p. 1, characterized in that the compound of formula III is subjected to interaction with sulfurylchloride as the halogenation agent at room temperature.

3. The method according to claim what.

4. Orthotamine peacelove derivative of General formula III

< / BR>
where R is hydrogen, lower alkyl, piperidinecarboxylate or 8-azabicyclo [3,2,1]Octan-8-carbonitrile;

R3- benzyl.

5. The method of obtaining orthotamine ventilago derivative of General formula III

< / BR>
where R is hydrogen, lower alkyl, piperidinecarboxylate or 8-azabicyclo [3,2,1]Octan-8-carbonitrile;

R3- benzyl,

wherein the 2,4-differencirovke compound of General formula II

< / BR>
where R has the above meaning,

subjected to interaction with the compound of General formula

R3SH,

where R3has the specified value in the environment aprotic organic solvent.

 

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29 cl, 1 tbl, 94 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: medicine.

SUBSTANCE: invention refers to an acid addition dopenzil salt [()-2-[(1-benzyl-4-piperidinyl)mathyl]-5,6-dimehoxy-1-indanone] of general formula (II), where X stands for a radical of fumaric acid prepared by reaction of dopenzil base and fumaric acid in ethanol or 2-propanol as a solvent, separation of dopenzil salt produced thereby and optionally washings with an organic solvent. The invention also concerns a pharmaceutical composition, the method of preparing the pharmaceutical compositions, application of acid addition dopenzil salt, and also the method for prevention or treatment of the diseases.

EFFECT: preparation of new acid addition dopenzil salt which is applicable for prevention or treatment of the diseases associated with acetylcholine lack in brain, Alzheimer's disease or senile psychosis.

8 cl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel anthranilic acid derivatives having inhibitory effect on production of matrix metalloprotease 13 of formula 1 , where R1 is a hydrogen atom or carboxy protective group selected from C1-3alkyl; R2 is phenyl, C3-6cycloalkyl, saturated or unsaturated 5-6-member heterocyclic group containing 1-3 heteroatoms selected from N, O, S, which can be condensed with phenyl, which can be optionally substituted with C1-6alkyl, C1-6alkoxy, acetyl, acetoxy, halogen, halogenC1-6alkyl, nitro group, hydroxyl group, CN, amino group, phenyl, saturated or unsaturated 5-6-member heterocyclic group containing 1-4 heteroatoms selected from N, O, S, which can be disubstituted with C1-6alkyl; R3 is phenyl, C3-6cycloalkyl, C5cycloalkenyl, saturated or unsaturated 5-6-member heterocyclic group containing 1-3 heteroatoms selected from N, O, S, which can be condensed with phenyl (except benzoxazole), which can be optionally substituted with C1-6alkyl, C1-6alkoxy, phenyl, acetyl, halogen, halogenC1-6alkyl, halogenC1-6alkoxy, nitro group, hydroxyl group, hydroxyC1-6alkyl, CN, acetylamino, ketone, phenoxy, benzoyl, benzyl, amino group, which can be disubstituted with C1-6alkyl, carboxy group, C1-6alkylsufonyl group or pyrrolyl; X1 is a carbonyl group or sulfonyl group; X2 is a C1-3alkylene, C2-3alkenylene or C2-3alkynylene group which can be optionally substituted with C1-3alkyl, or a bond; provided that when X1 is a sulfonyl group and X4 is a bond, X2 is a C1-3alkylene, C2-3alkenylene or C2-3alkynylene group which can be optionally substituted with C1-3alkyl; X3 is an oxygen atom or a bond; and X4 is a group with general formula -X5-X6- or -X6-X5-, where the bond on the left side of each formula is bonded to R3; and X5 is an oxygen atom, a sulphur atom, an imino group which can be optionally protected or a bond; X6 is a C1-4alkylene, C2-3alkenylene or C2-3alkynylene group or a bond, as well as to their pharmaceutically acceptable salts. The invention also relates to a matrix metalloprotease 13 production inhibitor and a therapeutic agent for making a medicinal agent for treating rheumatoid arthritis.

EFFECT: possibility of making a medicinal agent for treating rheumatoid arthritis.

8 cl, 7 tbl, 633 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) or pharmaceutically acceptable salts thereof where R1 and R2 together denote a group selected form groups of formula (III-1): , where R9 denotes 1) a lower alkyl group, optionally substituted with a halogen atom or lower alkoxy group, 2) an aryl group, 3) an aralkyl group, 4) a heteroarylalkyl group, 5) a heteroaryl group, where the aryl, aralkyl, heteroarylalkyl and heteroaryl groups can be substituted with a halogen atom, lower alkyl group, optionally substituted with a lower alkoxy group or 1-3 halogen atoms, lower alkoxy group, optionally substituted with 1-3 halogen atoms, cyano group, hydroxy group, alkylsulphonyl group, cycloalkylsulphonyl group, aryl group, heteroaryl group, alkylaminocarbonyl group, alkanoyl amino group, alkyl amino group or dialkylamino group; R10 denotes a lower alkyl group, optionally substituted with 1-3 halogen atoms, or a lower alkylsulphonyl group; X9-X12 denotes a carbon atom or a nitrogen atom, where the carbon atom can be independently substituted with a lower alkyl group, optionally substituted with a halogen atom or a lower alkoxy group, lower alkoxy group, optionally substituted with a halogen atom, or a cyano group or a halogen atom; R3 denotes a) a group of formula (II-1): (ii-U where R4 and R5, taken together with a nitrogen atom, form a 5- or 6-member monocyclic ring, where the monocyclic ring may contain a substitute in form of a lower alkyl group, m1 equals 3; or b) a group of formula (II-2): , where R6 denotes a lower alkyl group or cycloalkyl group; m2 equals 1 or 2; X1-X4 all denote carbon atoms, or one of X1-X4 denotes a nitrogen atom and the rest denote carbon atoms; and where "heteroaryl" in each case relates to a 5- or 6-member aromatic ring containing 1-3 heteroatoms selected from a nitrogen atom, oxygen atom and a sulphur atom. The invention also relates to a histamine H3 receptor antagonist or inverse agonist, as well as a preventive or medicinal agent.

EFFECT: obtaining novel biologically active compounds, having histamine H3 receptor antagonist or inverse agonist activity.

11 cl, 8 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel method for obtaining ()N-[1-(4-fluorophenyl)-2-(1-ethylpiperidin-4-yl)ethyl]-4-nitrobenzamide, corresponding to structural formula (I) or its pharmaceutically acceptable salts. Method mainly relates to hydrochloride of formula (I) compound (niferidil hydrochloride). Niferidil hydrochloride is used as medication for treatment of atrial fibrillation in people. In accordance with claimed method formula (I) compound is obtained by interaction of ethyl ether of 4-fluorobenzoic acid with 4-picoline in tetrahydrofurane in presence of catalyst or condensing means with obtaining 1-(4-fluorophenyl)-2-(4-pyridyl)ethanol. It is preferable to use sodium bis(trimethylsilyl)amide as condensing agent in amount 1-2 moles per a mole of 4-fluorobenzoate. Obtained compound is alkylated with ethylhalogenide with obtaining respective pyridinium salt. The latter is subjected to catalytic reduction with hydrogen in presence of palladium or platinum catalyst with addition of concentrated hydrochloric acid for obtaining 2-(1-ethylpiperidin-4-yl)-1-(4-fluorophenyl)ethanol of formula (II) which is subjected to reductive amination with obtaining [2-(1-ethylpiperidin-4-yl)-1-(4-fluorophenyl)-ethyl]amine, with further interaction of the latter with acid chloride of 4-nitrobenzoic acid with obtaining ()N-[1-(4-fluorophenyl)-2-(1-ethylpiperidin-4-yl)ethyl]-4-nitrobenzamide of formula (I) in free form or in form of its pharmaceutically acceptable salt. Formula (II) compound is a novel intermediate compound.

EFFECT: method makes it possible to simplify and cheapen the process due to reduction of number of stages, as well as to improve quantity of obtained target product to 99,6% by HPLC data.

5 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a novel trans-2-decenoic acid derivative of formula (I') or a pharmaceutically acceptable salt thereof , possessing preventive or therapeutic effect for peripheral nervous system disorders, caused by anti-cancer agents, and/or neurotrophic factor-like activity and/or analgesic action, as well as to a pharmaceutical agent based thereon.

EFFECT: prevention and treatment of nervous system disorders.

14 cl, 11 tbl, 56 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel hexafluoroisopropanol-substituted ether derivatives of formula (I) to their pharmaceutically acceptable salts and to esters which are capable of bonding with LXR-alpha and/or LXR-beta, as well as to pharmaceutical compositions based on said compounds. In formula (I) R1 is hydrogen, lower alkyl or halogen, one of groups R2 and R3 is hydrogen, lower alkyl or halogen, and the second of groups R2 and R3 is -O-CHR4-(CH2)m-(CHR5)n-R6. Values of R4, R5, R6 m and n are given in the formula of invention.

EFFECT: novel compounds have useful biological properties.

22 cl, 4 dwg, 102 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula

, where R1 is a

or or or group, R2 is morpholine or OR' or N(R")2; R' is a lower alkyl, a lower alkyl substituted with a halogen, or -(CH2)n-cycloalkyl; R" is a lower alkyl; R is NO2 or SO2R'; R4 is hydrogen, hydroxy, halogen, NO2, lower alkoxy, SO2R' or C(O)OR"; R5/R6/R7 denote hydrogen, halogen, lower alkyl; X'/X1 denote CH or N, provided that X1 /X1' are not CH at the same time; X2 is O or S; n equals 0 or 1, and to their pharmaceutically active acid-addition salts. The invention also relates to a drug.

EFFECT: obtaining novel biologically active compounds which are active as glycine transporter 1 inhibitors.

11 cl, 24 ex, 1 tbl

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