Derivatives thienylallylamine or their pharmaceutically compatible acid additive salt

 

(57) Abstract:

Usage: in medicine, in particular in antiarrhythmic tools. The inventive product is a 5 - derivatives thienylallylamine f-crystals (see Fig. ), where r is different is hydrogen or a group-O-CH2-CH2-NR1R2when R1, R2- alkyl or together with the nitrogen form pyrrolidinyl, n =1-5. Reagent 1: the corresponding derived Occitania. Reagent 2: the corresponding amine. Reaction conditions: in the presence of a strong base in an inert organic solvent.

The invention relates to new therapeutically valuable derivative thienylallylamine General formula

(I) and-O-CH2-CH2-N (R1,R2) can stand in position 4 or 5 of the thiophene ring and

R1and R2- same or different and represent respectively an alkyl containing 1-8 carbon atoms, or R1and R2together with the nitrogen atom form pyrrolidinyl;

n denotes an integer from 1 to 5, and their pharmaceutically compatible acid additive salts.

New derivatives of thienylallylamine are beneficial antiarrhythmic action and find particular application in Zabol the her is the compound of General formula

(II) with the OH group can be in position 4 or 5 of the thiophene ring, make connection with the General formula

X-CH2-CH2-N (III) in which R1and R2have the above meaning and X denotes a chlorine, bromine or iodine, in the presence of at least the equivalent of a strong base in an inert organic solvent, and the obtained base of the formula I, if necessary, transferred to the acid additive salt.

The method of obtaining it is best carried out in such a way that the compound of formula II is dissolved in an inert organic solvent, such as dimethylformamide, dimethyl sulfoxide or diethylmalonate, and mix of at least one equivalent of a strong base, preferably an alkali alcoholate or alkali hydride and, in the case of alkaline alcoholate, distilled forming or serving as a solvent, the alcoholate of the alcohol. The temperature of transformation lies between 60 and 120aboutC. Then there is a transformation with a compound of General formula III at 50-100aboutC. the reaction Time is from 30 minutes to 2 hours

Because the free base of General formula I is present in most SL is: clean through the well-crystallising acidic additive compounds as, for example, hydrochloride that can well precrystallization.

To do this, dissolve the crude base in a suitable solvent, for example in a lower alcohol or ether, add at least an equivalent amount of a proton acid, the solvent is evaporated in vacuum and the residue is recrystallized from methanol, ethanol or preferably acetone, if necessary, with the addition of simple ether.

These acid salt additive can be translated then in a known manner, for example by means of alkalis or ion exchangers, loose connections, of which the transformation from inorganic or organic acids, especially those which are suitable for the formation used in the treatment of salts, you can get other salts.

The compounds of formula III, if they are not known in the literature and is not available commercially, you can get well-known specialist way.

Acid additive salts of the final compounds can be obtained in a known manner, for example by addition of alkali or ion exchanger to transfer to a free base. Other salts can be formed from them by transformation with inorganic or organic acids, especially with the cat the examples for this is acceptable pharmaceutical salts along with a salt of hydrochloric acid are salts of Hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, sulphonic acids, acetic acid, benzoic acid, maleic acid, tartaric acid, citric acid, etc., But you can also use other acids.

The new compounds of formula I and their pharmaceuticals salts are extremely antiarrhythmic properties.

Based on these pharmacological properties the new compounds can be used as a drug, alone or in mixtures with other active substances in the form of an ordinary herbal medicines for diseases that are caused by cardiac arrhythmias, such as tachycardia.

The new compounds may be contained in the pharmaceutical compositions according to the invention in an amount of about 20-200 mg/tablet, and the remainder represents a pharmaceutically acceptable filler.

A suitable dose for the appointment of the new compounds is about 2-20 mg/kg / day, however, depending on the patient's condition, use, and other doses. The new compounds may be administered in larger doses and oral routes apply.

In contrast to existing antiarrhythmic means class 1, such as Amiodarone or is Sugimoto and refractory periods of the heart, therefore there is also no arrhythmogenic ability. The model re-perfusion arrhythmias in the dog connection is effective at the dosage of 2 mg per 1 kg of body weight with ventricular arrhythmias and translate the latest in sinus rhythm. In contrast to conventional antiarrhythmic means class 1 has no effect on hemodynamics.

The following examples explain the invention in more detail without limiting it last.

P R I m e R 1. [3-(2-Butyl-benzo[b]furanyl]-[5-(2-diethylamino-ethoxy-2-thienyl]- methanon, hydrochloride

To a solution of 7.1 g (23,7 mmol) (2-butyl-3-benzo) (b) furanyl-(5-hydroxy-2-thienyl)-methanone in 140 ml of diethylmalonate add 29.5 ml of 1 M methanol solution of sodium methylate and then immersed in a hot oil bath with a temperature of 132aboutC. Distilled MeO until then, until the reaction mixture reaches a temperature 110-112aboutC. then cooled and 35-40aboutTo add a solution of 4.1 g (30.2 mmol) of 2-diethylaminoethylamine (distribution obtained 5.8 g of 2-diethylaminoethylamine, hydrochloride between 100 ml of saturated sodium bicarbonate solution and 40 ml of a simple ester, a three-time extraction of the aqueous phase each time with 30 ml of a simple ether, drying and viparitakarani falls fine yellow precipitate. After 50 min, evaporated, distribute oily crystalline residue between 350 ml of saturated sodium bicarbonate solution and 200 ml of simple ether, stirred and separated phases, the combined organic phases are dried over sodium sulfate/activated carbon and evaporated. Obtain 9.0 g of orange oil (95% of theory).

The crude product is dissolved in 120 ml of absolute simple ether and injected under cooling with dry gaseous HCl. The resulting first slightly oily hydrochloride crystallized and sucked off light yellow crystals. Thus obtained about 10 g of the crude product is dissolved in 180 ml of absolute acetone, filtered, and concentrate the solution to 100 ml. His cool and complement the crystallization during the night in the low-temperature refrigerating Cabinet.

The precipitated crystals are sucked off and washed with cold acetone.

Yield 7.5 g of colorless crystals (73% of theory); so pl. 130-132aboutC.

C23H29NO3S (436,02).

Calculated,%: C 63,36; H 6,94; N Is 3.21.

Found,%: C 63,22; H 6,93; N 3,15.

1H NMR (CDCl3):

(ppm): 13-11 (very broad, 1H,HCl), to 7.61-7,19 (m,5H), 4 B2-H and Th-H3); 6,37 (d; 1H; Th-H4), 4,79 (t, 2H,-OCH2), 3,52 (t, 2H,-NCH2), or 3.28 (q, 4H, N(CH2).

The original product can be obtained in the following way:

The acid chloride of 5-methoxy-2-thiophencarboxylic acid

15.0 g (94,8 mmol) 5-methoxy-2-thiophencarboxylic acid is heated for 30 min when the phlegm in 100 ml chloride tiomila and 1 ml of absolute dimethylformamide. Then distilled off excess chloride thionyl in vacuum. The crude product (about 18 g of brownish oil) is subjected to molecular distillation.

Yield 14.6 g of a yellowish oil (87% of theory); so bales. 70-75aboutWith/0,04 mbar.

(2-Butyl-3-benzo[b]furanyl)-(5-marks-the-sea-2-thienyl)-methanon

3.0 g (17,2 mmol) of 2-butyl-benzo[b]furan was dissolved in 30 ml of absolute chloroform, cooled the solution to 0aboutWith and mixed with 3.6 g (to 20.4 mmol) of acid chloride of 5-methoxy-2-thiophencarboxylic acid, dissolved in 5 ml of absolute chloroform, and then buried with 0-3aboutWith 2.8 ml of SnCl4. Stirred for further 2 h at 0aboutC. the Reaction mixture under ice cooling empty 50 ml of 2n.HCl, split phase and the aqueous phase is exhaustively extracted with simple ether. The chloroform phase and the phase of simple ether washed with respectively 50 ml of 2n. NaOH, combined, dried over sodium sulfate and evaporated. The crude product was subjected to molecular distillation.


A solution of 10.0 g (of 31.8 mmol) (2-butyl-3-benzo[b]furanyl)-(5-methoxy-2-thienyl)-IU-Tanana in 100 ml of absolute chloroform is cooled to 15aboutAnd 15-20aboutWith mixed with 10 ml (106 mmol) trichromate boron. Then the reaction mixture is heated when the phlegm.

After 1.5 h void in 300 ml of 2n.HCl, intensively stirred for 10 min, split phase and the aqueous phase is extracted with a further 2 times with methylene chloride. The combined organic phases are extracted by shaking 5 times with 120 ml of saturated sodium bicarbonate solution. The combined aqueous phases are oxidized with concentrated HCl and extracted with methylene chloride. The combined organic phases are dried over sodium sulfate/activated carbon, filtered and evaporated. The crude product is sent directly to the next stage.

Yield 7.6 g of a viscous oil (80% of theory).

Elemental microanalysis: C17H16O3S (300,21).

Calculated,%: C 67,98; H Lower Than The 5.37.

Found,%: C 68,04; H 5,42.

1N-range nuclear magnetic resonance:

(In CDCl3the connection exists in three tautomeric forms a,b and C).

< / BR>
a) (ppm): 7,60-to 7.15 (m, 4H, BZ-H), 7,42 (d, 1H, Th-H3), 6,18 (d, 1H, Th-H4), 2,85 (t, 2H, AZ CH2), 1,98-1,10 (m, 4H,-CH2), 1,98-1,10 (m, 4H,-CH2-CH2), of 0.90 (t, 3H,-CH3).

c) (ppm): of 7.70 (dd, 1H, Th-H4), 7,60-to 7.15 (m, 4H, BZ-H), of 6.45 (dd, 1H, Th-H3), 5,88 (dd, 1H, Th-H2), 2,85 (t, 2H, A-CH2), 1,98-1,10 (m, 4H, -CH2-CH2), of 0.90 (t, 3H,-CH3).

P R I m m e R 2. [3-(2-Butyl-benzo[b]furanyl)]-[5-(2-(1-pyrrolidinyl)-ethoxy)-2 - thienyl]-methanon, hydrochloride

6,00 g (20.0 mmol) [3-(2-butyl-benzo[b]furanyl)]-(5-hydroxy-2-thienyl)-meta - Nona dissolved in 120 ml of diethylmalonate and mixed with 4,60 ml of 5.6 M solution of sodium methylate. Then immersed in a hot oil bath with a temperature of 135aboutAnd distilled methanol in the stream of nitrogen, until the boiling point of the reaction mixture reaches 115aboutC. then cooled and when the temperature of 35-40aboutWith buried a solution of 3.50 g (to 26.3 mmol) of 1-(2-chloroethyl)-pyrrolidine (highlighted 4,50 g of the hydrochloride in 60 ml of diethylmalonate. At the end of additives is heated to 90-95aboutC. After one hour, evaporated, the oily crystalline residue is partitioned between 300 ml of saturated sodium bicarbonate solution and 200 ml of simple ether, stirred and separated phases. The aqueous phase is shaken out three times with only 300 ml simple ether, and the combined organic phases are dried over sodium sulfate and evaporated. Get of 6.73 g is E. Then neutralized with 4n. sodium lye and extracted 5 times with only 500 ml of a simple ester. The combined organic phases are dried over sodium sulfate, filtered and evaporated.

The crude product is absorbed in 100 ml of absolute simple ether and miss when cooled hydrogen chloride. Precipitated crystalline product is sucked off and recrystallized from ethyl acetate.

The output of 7.00 g of colorless crystals (80.7% of theory); so pl. 137-139aboutWith (ethyl acetate).

Elemental microanalysis: C23H28NClO3S (434,00).

Calculated,%: C 63,65; H 6,50; N 3,23.

Found,%: C 63,42; H Is 6.54; N 3,17.

1H-NMR (CDCl3):

(ppm): 7,56-7,19 (m, 5H, BZ-HTh-H3), 6,37 (d, 1H, Th-H4), and 4.75 (t, 2H, -O-CH2-), 3,80-to 3.50 (m, 6H,-CH2N(-CH)2): 2,96 (t, 2H, Ar-CH2), 2,10 (m, 4H, PYr: -CH2-CH2), 1,90-of 1.30 (m, 4H,-CH2-CH2-CH3); of 0.91 (t, 3H,-CH3).

P R I m e R 3. [3-(2-Butyl-benzo[b]furanyl]-[4-(2-diethylaminoethoxy)-2 - thienyl]-methanon, hydrochloride

3.50 g (11.7 mmol) [3-(2-butyl-benzo[b]furanyl)]-(4-hydroxy-2-thienyl)-meta - Nona dissolved in 70 ml of diethylmalonate and mixed with 2,70 ml of 30% aqueous solution of sodium methylate. Then immersed in a hot oil bath with temperatureaboutC. then cooled and at a temperature of from 35 to 40aboutWith buried a solution of 1.74 (12.6 mmol) of 2-diethylaminoethylamine (isolated from 2.20 g of the hydrochloride) in 20 ml of diethylmalonate. At the end of additives is heated to 90-95aboutC and stirred overnight. The solvent is distilled off, the residue is partitioned between 100 ml of saturated sodium bicarbonate solution and 100 ml of simple ether, stirred and separated phases. The aqueous phase is extracted with 3 times 200 ml of simple ether and the combined organic phases are dried over sodium sulfate and evaporated.

The residue (3,20 g brown oil purified by chromatography on a column (100 g silica gel, solvent: ethyl acetate). Get 1,95 g yellow oil.

Last absorbed in 50 ml of absolute simple ether and injected to the saturation of hydrogen chloride. The resulting first fatty hydrochloride bring friction to crystallization and sucked off light yellow crystals. Thus obtained crude product is recrystallized from 20 ml of ethyl acetate.

Yield 1.52 g of light-yellow, hygroscopic crystals (29.9% of theory); so pl. 70-71aboutWith (ethyl acetate),

Elemental microanalysis: C23H30NClOS.1,1 H2O (455,83).

Vic (m, 5H, BZ-H and Th-H3), of 6.96 (d, 1H, ThH5), of 4.95 (t, 2H, -O-CH2-); 3,52-3,00 (m, 6H,-CH2-N (-CH2)2, 3,00-2,52 (m, 5H, Ar-CH2- +HCl+H2O), 1,94-of 1.42 (m, 4H,-CH2-CH2), to 1.42 (t, 6H,-N-CH2-CH3), of 0.91 (t, 3H,-CH3).

The original product can be obtained in the following way:

The acid chloride of 4-methoxy-2-thiophencarboxylic acid

24,0 g (152 mmol) of 4-methoxy-2-thiophenecarboxylic acid are suspended in 250 ml of chloride tiomila and heated 2 h at the phlegm. Then distilled off excess chloride thionyl in vacuum. The crude product was subjected to molecular distillation and vykristallizovyvalas in the collection.

The output of 20.0 g of light yellow crystals (74.6% of theory), so pl. 40aboutC.

So Kip. 122-124aboutWith/15 mbar.

[3-(2-butyl-benzo[b]furanyl)]-(4-labels-si-2-thienyl)-methanon

15.0 g (87,1 mmol) of 2-butyl-benzo[b]furan was dissolved in 75 ml of absolute chloroform and mixed at room temperature with 18.6 g (0.11 mol) of acid chloride of 4-methoxy-2-thiophencarboxylic acid in 20 ml of absolute chloroform. At room temperature, buried within 10 min of 31.8 g (0.12 mol) chloride tin (IV). After 2 h stirring at 25aboutTo pour the reaction mixture into a mixture of 150 ml of ice, 15.0 ml of concentrated hydrochloric acid is ski phases are washed with 100 ml saturated sodium bicarbonate solution, dried and evaporated. Get to 29.4 g of brown oil, which was purified by chromatography on a column (400 g of silica gel, solvent: petroleum ether:benzene = =3:1). Collected pure fractions are subjected to molecular distillation.

Output 9,12 g Golden-yellow, viscous oil 33.3% of theory); so bales. 140-150aboutWith/0.007 mbar.

Elementary molecular analysis: C18H18O3S (314,41).

Calculated,%: C 68,76; H 5,77.

Found,%: C 68,81; H 5,74.

1H-NMR (CDCl3):

(ppm): 7,53-to 7.18 (m, 5H, BZ-H and Th-H3), 6,77 (d, 1H, Th-H), of 3.80 (S, 3H-OCH3), and 2.79 (t, 2H, Ar-CH2-), 1,97-of 1.15 (m, 4H, -CH2-CH2-), of 0.90 (t, 3H, -CH3).

[3-(2-Butyl-benzo[b]furanyl)]-(4-hydro-XI-2-thienyl) methanon

8,54 g (of 27.0 mmol) [3-(2-butyl-benzo[b]furanyl)]-(4-methoxy-2-thienylmethyl - dissolved in 100 ml of absolute chloroform and cooled to - 10aboutC. At a temperature between - 10 and - 5aboutWith buried 22,5 g trichromate boron for 10 min, and then stirred the reaction mixture at 0aboutWith 30 minutes

Then poured into a mixture of 100 ml of methylene chloride, 50 g of ice and 25 ml of concentrated hydrochloric acid, mix, split phase and the aqueous phase is extracted with 3 times 200 ml of methylene chloride. 're asked with activated carbon, filtered and evaporated.

Output 6,32 g black, viscous oil (77,9% of theory).

Elemental microanalysis: C17H16O3S (300,38).

Calculated,%: C 67,98; H Lower Than The 5.37.

Found,%: C 67,73; H 5,41.

1NAMR: CDCl3: (ppm): to 7.61-to 7.15 (m, 5H, BZ-H and Th-H3), 7,50-7,30) (S, width, 1H, -OH), 6,77 (d, 1H, Th-H), with 2.93 (t, 2H, Ar-CH2-), 1,95-1,11 (m, 4H,-CH2-CH2), to 0.88 (t, 3H,-CH3).

DERIVATIVES THIENYLALLYLAMINE OR THEIR PHARMACEUTICALLY COMPATIBLE ACID ADDITIVE SALT.

Derivatives thienylallylamine General formula

< / BR>
where the group - O - CH2- CH2- N(R1R2can be placed in 4 - or 5-position;

R1and R2- C1- C8-alkyl, or R1and R2together with the nitrogen atom form pyrrolidinyl;

n = 1 to 5

or their pharmaceutically compatible acid additive salt.

 

Same patents:

The invention relates to new chemical compound, specifically to 5H-3,4,6,7-tetrahydro-10-methoxy-5-methyl-6-(1', 1'-dioxide)-3'- metalorigin-4'-methoxy-benzo[B] thiophene-7 yl)-furo-[4.3.2

The invention relates to new chemical compound, particularly to a 10-methoxy-5-methyl-6-(1', 1'-dioxido-2' -meta-chlorvinyls-3'-hydroxy-4' -methoxy-benzo[b] thiophene-7-yl)-5H-3,4,6,7-tetrahydro[4,3,2-Q]-[3]benzazocine formula

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The invention relates to pharmaceutical industry and relates to a method of obtaining a crystalline sodium salt of 5-chloro-3-(2-thenoyl)-2-oxindole-1-carboxamide

FIELD: organic synthesis.

SUBSTANCE: invention provides compounds of general formula I:

, where R1 represents -CO-Ra, -SO2-Rb, or aryl optionally substituted by lower alkoxy, wherein Ra represents cycloalkyl, cycloalkyl(lower)alkyl, cycloalkyloxy, aryl, aryloxy, aryl(lower)alkyl, aryl(lower)alkoxy, aryloxy(lower)alkyl, aryl-S-(lower)alkyl, aryl(lower)alkenyl, provided that aryl group can be optionally substituted by halogen, lower alkyl, hydroxy, nitro, cyano, lower alkoxy, phenyl, CF3, cyano(lower)alkyl, lower alkyl-C(O)NH, lower alkyl-CO, and lower alkyl-S; heteroaryl, heteroaryl(lower)alkyl, or heteroaryl(lower)alkoxy, provided that heteroaryl group is 5- or 6-membered ring or bicyclic aromatic group constituted by two 5- or 6-membered rings including 1-3 heteroatoms selected from oxygen, nitrogen, and sulfur and that heteroaryl group can be optionally substituted by lower alkoxy; Rb represents aryl, aryl(lower)alkyl, or heteroaryl, aryl group optionally substituted by halogen, cyano, or lower alkyl-C(O)NH; R2 and R3 represent hydrogen atoms; R4 representshydrogen or lower alkyl; R5 represents hydrogen, lower alkyl, cycloalkyl, benzodioxyl, or aryl optionally substituted by lower alkyl, halogen, lower alkoxy, hydroxy, or (lower)alkyl-C(O)O; n is 1 or 2; and pharmaceutically acceptable salts thereof and/or pharmaceutically acceptable esters thereof. Invention also provides a pharmaceutical composition exhibiting inhibitory activity with regard to cysteine proteases of the cathepsin family, which composition comprises compound of formula I, pharmaceutically acceptable recipient, and/or adjuvant.

EFFECT: increased choice of cysteine protease inhibitors.

34 cl, 1 tbl, 13 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a new compound of the general formula (2) and a method for its preparing wherein R1 represents hydrogen atom or salt-forming metal; R2 represent a direct or branched (C1-C7)-halogenalkyl group; m represents a whole number from 2 to 14; n represents a whole number from 2 to 7; A represents a group taken among the following formulae: (3) , (4) ,

(5) ,

(6) ,

(17) , (18) , (19) , (20) , (23) , (25) and (26) wherein R3 in formula (6) represents a direct or branched group (C1-C5)-alkyl group; R8 in formulae (18) and (20) represents a direct or branched (C1-C5)-alkyl group, a direct or branched (C2-C5)-alkenyl group or a direct or branched (C2-C5)-alkynyl group; in formula (23) each R21, R22, R23 and R24 represents independently hydrogen atom, a direct or branched (C1-C5)-alkyl group, a direct or branched (C1-C7)-halogenalkyl group, halogen atom or acyl group; in formulae (25) and (26) X represents halogen atom; or enantiomers of compound, or hydrates, or pharmaceutically acceptable salts of compound, or its enantiomers. Also, invention relates to a pharmaceutical composition containing indicated compound as an active component and to a therapeutic agent used against breast cancer based on thereof.

EFFECT: valuable medicinal properties of compounds.

10 cl, 2 tbl, 39 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to new biphenylsulfonylcyanamides of the formula (I): wherein R1 means: 1. (C1-C8)-alkyl; 4. -CnH2n-nn-Y wherein nn = 0 or 2 and n = 0-4, and n is not 0 or 1 if nn = 2; 5. CnH2n-nn-Y wherein nn = 0 or 2 and n = 1-4, and n is not 1 if nn = 2, and 1 hydrogen atom in bivalent residue CnH2n-nn is substituted with amino-group or NR(22)R(23); R2 means: 2. (C1-C)-alkyl; 4. (C2-C12)-alkenyl; 5. (C2-C8)-alkynyl; 6. -CnH2n-nn-Z wherein nn = 0 or 2; n = 0-4, and n is not or 1 if nn = 2; 7. -CnH2n-nn-Z wherein nn = 0 or 2; n = 1-4, and n is not 1 if nn = 2, and 1 hydrogen atom in bivalent residue CnH2n-nn is substituted with a residue taken among a series: 1. phenyl; 3. NR(22)R(23); 5. COOR(16); R3 and R4 mean hydrogen atom; R5, R6 and R7 mean independently of one another hydrogen atom (H), (C1-C8)-alkyl; SO2-(C1-C4)-alkyl, F, Cl, Br, J, OR(10) wherein R(10) means hydrogen atom, (C1-C4)-alkyl that is substituted if necessary with methoxy- or ethoxy-group; R(9) means OR(13) wherein R(13) means hydrogen atom, H,(C1-C8)-alkyl;X means carbonyl group, -CO-CO- or sulfonyl group; Y and Z mean independently of one another: 1. phenyl, 1-naphthyl, 2-naphthyl; 2. one of residues determined in cl. 1 substituted with 1-5 similar or different residues taken among a series: phenyl, F, Cl, Br, J, CF3, SOqR(18), OR(16), NR(19)R(20), -CN, NO2, COR(9), or two residues form methylenedioxy-group; 3. furyl, thienyl, pyridyl, benzimidazolyl, indolyl, benzothiophenyl, dihydroquinazolinyl; 5. (C3-C10)-cycloalkyl wherein cyclopropyl, cyclopentyl, cyclohexyl and indalyl are preferable; 6. one of residues determined in cl. 5 substituted with phenyl; R(16) means: 1. hydrogen atom; 2. (C1-C4)-alkyl; 3. (C1-C4)-alkyl substituted with (C1-C4)-alkoxy-group; R(19) and R(20) mean independently: hydrogen atom (H), (C1-C4)-alkyl; R(22) and R(23) mean independently of one another hydrogen atom (H) or CO-OR(24) wherein R924) means -CnH2n-phenyl wherein n = 1-4; q = 2; and their physiologically acceptable salts. Compound of the formula (I) inhibit sodium-dependent chloride-bicarbonate exchange "NCBE".

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

4 cl, 2 tbl, 568 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compositions eliciting an antilipidemic effect and comprising inhibitor of bile acid transport in jejunum of the general formula (I): and inhibitor of HMG-CoA-reductase. Also, invention relates to a method for carrying out the combined therapy.

EFFECT: improved treatment method, valuable medicinal properties of compositions.

15 cl, 9 tbl, 1401 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, 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 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.

SUBSTANCE: invention relates to new lipoic acid derivatives of general formula Ia

1, wherein n = 0-4, integer; -X-Y represents -O(CH2)r-, -CO-N(R3)-(CH2)r-, -N(R4)-CO-(CH2)r; -X'-Y' represents -(CH2)r-, -(CH2)r-N(R3)-(CH2)r-, -(CH2)r-CO-N(R3)-(CH2)2-; R3 and R4 are the same or different and represent hydrogen or alkoxycarbonyl; r = 0-4, integer; Ω represents piperazinyl, piperidyl or phenyl. Also disclosed are method for production the claimed derivatives and pharmaceutical composition, containing the same. Compounds are useful as NO-syntase inhibitors and/or reagents mediating redox state of thiol groups.

EFFECT: new lipoic acid derivatives.

7 cl, 17 ex

FIELD: medicine, pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical composition used in stomatology in the topical anesthesia. The pharmaceutical composition comprising articaine hydrochloride and epinephrine hydrochloride and accessory substances, such as sodium metabisulfite, sodium chloride and water for injection involves additionally glycine and pH-regulating substance taken in the definite ratio of components. Invention provides preparing the preparation that is stable, non-toxic and doesn't cause allergic response reactions and elicits highly expressed infiltration and conducting anesthetic activity, good tissue tolerance and activity promoting to accelerated wound-healing in the post-operative period.

EFFECT: improved and valuable medicinal properties of composition.

3 cl, 3 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of carboxylic acids of the formula: wherein Y is taken independently in each case among the group comprising C(O), N, CR1, C(R2)(R3), NR5, CH; q means a whole number from 3 to 10; A is taken among the group comprising NR6; E is taken among the group comprising NR7; J is taken among the group comprising O; T is taken among the group comprising (CH2)b wherein b = 0; M is taken among the group comprising C(R9)(R10), (CH2)u wherein u means a whole number from 0 to 3; L is taken among the group comprising NR11 and (CH2)n wherein n means 0; X is taken among the group comprising CO2H, tetrazolyl; W is taken among the group comprising C, CR15 and N; R1, R2, R3 and R15 are taken independently among th group comprising hydrogen atom, halogen atom, hydroxyl, alkyl, alkoxy-group, -CF3, amino-group, -NHC(O)N(C1-C3-alkyl)-C(O)NH-(C1-C3-alkyl), -NHC(O)NH-(C1-C6-alkyl), alkylamino-, alkoxyalkoxy-group, aryl, aryloxy-, arylamino-group, heterocyclyl, heterocyclylalkyl, heterocyclylamino-group wherein heteroatom is taken among N atom or O atom, -NHSO2-(C1-C3-alkyl), aryloxyalkyl; R4 is taken among the group comprising hydrogen atom, aryl, aralkyl, benzofuranyl, dihydrobenzofuranyl, dihydroindenyl, alkyl, benzodioxolyl, dihydrobenzodioxynyl, furyl, naphthyl, quinolinyl, isoquinolinyl, pyridinyl, indolyl, thienyl, biphenyl, 2-oxo-2,3-dihydro-1H-benzimidazolyl, pyrimidinyl and carbazolyl. Other values of radicals are given in the claimed invention. Also, invention relates to pharmaceutical composition used for inhibition binding α4β1-integrin in mammal based on these compounds. Invention provides preparing new compounds and pharmaceutical composition based on thereof in aims for treatment or prophylaxis of diseases associated with α4β1-integrin.

EFFECT: improved method for inhibition, valuable medicinal properties of compounds.

33 cl, 7 tbl, 42 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to new 5-aryl-1-phenyl-4-heteroyl-3-hydroxy-3-pyrroline-2-ones of the formula:

wherein (1) X means sulfur atom (S); R means (CH3)2CH; (2) X means sulfur atom (S); R means (CH3)3C; (3) X means oxygen atom (O); R means (CH3)3C. Compounds of the formula (I) are prepared by interaction of the corresponding heteroylpyruvic acid methyl ester with mixture of aniline and aromatic aldehyde in acetic acid medium at short-time heating. Compounds elicit an anti-bacterial activity with value MIC = 3.9-7.8 mcg/ml as compared with 62-1000 mcg/ml for analogue.

EFFECT: valuable properties of compounds.

1 tbl, 3 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to benzimidazole derivatives or their salts useful in medicine of the general formula (1): wherein R1 and R2 can comprise similar or different values and represent independently of one another hydrogen atom, halogen atom, cyano-group, hydroxyl group, alkyl group comprising 1-4 carbon atoms, alkoxy-group comprising 1-4 carbon atoms, trifluoromethyl group; A represents unsubstituted, linear alkylene group comprising 1-7 carbon atoms; E represents group -COOR3 comprising 1-6 carbon atoms; G represents unsubstituted, linear alkylene group comprising 1-6 carbon atoms; M represents a simple bond or -S(O)m- wherein m represents a whole number in the range 0, 1 or 2; J represents substituted or unsubstituted heterocyclic group comprising 4-10 carbon atoms and one heteroatom in ring taken among the group consisting of nitrogen atom or sulfur atom excluding unsubstituted pyridine ring; a substitute in indicated aromatic heterocyclic group is taken among halogen atom, cyano-group, linear alkyl group comprising 1-6 carbon atoms, linear alkoxy-group comprising 1-6 carbon atoms, trifluoromethyl group and trifluoromethoxy-group wherein one or more indicated substituted can be replaced by random positions in ring; X represents methane group (-CH=). Also, invention relates to a pharmaceutical composition used in inhibition of human chymase activity based on these compounds. Invention provides preparing new compounds and pharmaceutical composition based on thereof in aims for prophylaxis and/or treatment of inflammatory disease, cardiovascular disease, allergic disease, respiratory disease or osseous either cartilaginous metabolic disease.

EFFECT: valuable medicinal properties of compounds and composition.

14 cl, 3 tbl, 20 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of imidazole of the formula (I):

or its pharmaceutically acceptable salts wherein X represents -CH2-(CH2)p-, -O-; R1 represents phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, (C3-C7)-cycloalkyl wherein indicated phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, (C3-C7)-cycloalkyl are substituted optionally with 1-3 substitutes taken independently among halogen atom, -OH, halogen-(C1-C6)-alkyl, (C1-C6)-alkyl, (C1-C6)-alkoxy group and OH-(C1-C6)-alkyl; R2 represents hydrogen atom (H) or (C1-C6)-alkyl; R3 represents H or (C1-C6)-alkyl; R4 represents H or (C1-C6)-alkyl; R5 represents H, or R5 and R7 form in common a bond; each R6 represents independently halogen atom, -OH, halogen-(C1-C6)-alkyl, (C1-C6)-alkyl, (C1-C6)-alkoxy group or OH-(C1-C6)-alkyl; R7 represents H, or R7 and R5 form in common a bond; each R8 represents independently -OH, (C1-C6)-alkyl, halogen-(C1-C6)-alkyl or (C1-C6)-alkoxy group; m = 0, 1, 2 or 3; n = 0 or 1; p = 0 or 1; r = 0 or 1; t = 0. Also, invention relates to a method for preparing compounds of the formula (I) and to a pharmaceutical composition showing affinity to alpha-2-adrenoceptors based on these compounds. Invention provides preparing new compounds and pharmaceutical composition based on thereof used in aims for treatment of neurological disturbances, psychiatric disorders or disturbances in cognitive ability, diabetes mellitus, lipolytic diseases, orthostatic hypotension or sexual dysfunction.

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

25 cl, 1 tbl, 14 ex

Chalcone coumarins // 2266291

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): or their pharmaceutically acceptable salts or solvates wherein Ar represents a substituted or unsubstituted (preferably aromatic one) carbocyclic or heterocyclic group wherein abovementioned carbocyclic or heterocyclic group comprises 5 or 6 atoms in cyclic structure wherein a heteroatom is taken among the group consisting of nitrogen (N) and sulfur (S) atom and any substitutes at Ar group are taken independently of one another of the group consisting of Cl, Br, F atoms and OR10 wherein R10 represents saturated or unsaturated lower hydrocarbon (C1-C6)-radical of normal or branched structure; R represents OR10 wherein R10 corresponds to above given value; R1 represents lower hydrocarbon (C1-C6)-radical of normal or branched structure under condition that if R1 represents -CH3 and R means -OCH3 or -OH then Ar group can't represent 4-methoxyphenyl or 3,4-dimethoxyphenyl. Also, invention proposes a component of medicinal agent used in treatment or prophylaxis of neoplasms. Also, invention proposes a pharmaceutical composition possessing with an anti-proliferative activity and comprising the effective amount of one or some compounds of the formula (I) in combination with one or some pharmaceutically acceptable additives. Invention provides the development of chalcone coumarins possessing with the enhanced anti-proliferative effect with respect to sensitive tumor cells, cells with resistance to conventional chemotherapeutic agents, among them, to anti-tumor medicinal agents of the last generation represented by paclitaxel and docetaxel.

EFFECT: valuable medicinal properties of compounds and compositions.

1 tbl, 21 ex

FIELD: organic chemistry, chemical technology, herbicides, agriculture.

SUBSTANCE: invention relates to new sulfonamides of the formula (I):

and their salt wherein A represents substituted or unsubstituted benzene ring or 5-membered, or 6-membered substituted or unsubstituted heteroaromatic ring taken among the group comprising thienyl, pyrazolyl, imidazolyl, pyridyl wherein optional substitutes are taken among the group consisting of halogen atom, substituted or unsubstituted (C1-C4)-alkyl, unsubstituted or substituted (C1-C4)-alkoxy-group, nitro-group, phenyl, phenoxy-group, benzoyl and (C1-C4)-alkylcarboxylate when any alkyl fragment in the latter indicated substituted is substituted with one or some halogen atoms, (C1-C4)-alkoxy-groups, cyano-group and phenyl; Q represents -O-, -S- or group of the formula: -CXX' wherein X and X' can be similar or different and each represents hydrogen atom, halogen atom, cyano-group, alkyl comprising 1-8 carbon atoms, or the group -ORa, -SRa; or one of X and X' represents hydroxy-group and another has values determine above; Ra means (C1-C8)-alkyl, phenyl; Rb means (C1-C8)-alkyl, phenyl; Y means nitrogen atom or the group CR9; R1 means unsubstituted (C1-C8)-alkyl or that substituted with halogen atom, cyano-group, phenyl or (C1-C4)-alkoxycarbonylamino-group, or it represents phenyl; R2 means hydrogen atom (H), (C1-C4)-alkyl; R3 and R4 can be similar or different and each represents (C1-C4)-alkyl, (C1-C4)-alkoxy-group, halogen atom; R9 means hydrogen atom (H) under condition that when Q represents oxygen atom (O) or -S- then ring A represents 5-membered substituted or unsubstituted heteroaromatic ring and determined above. Compounds of the formula (I) possess the herbicide activity that allows their using for eradication of weeds. Also, invention describes a method for preparing compounds of the formula (I).

EFFECT: improved preparing method, valuable properties of compounds.

9 cl, 5 tbl, 18 ex

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