Method of producing bis-2,4-dialkyl-1,5,3-dithiazepan-3-yls

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and a method of producing bis-2,4-dialkyl-1,5,3-dithiazepan-3-yls of general formula (1): R=Me, Et, nPr, nBu, which involves reaction of a prepared mixture of ethane dithiol and aldehyde at 0°C (acetic or propionic or butyric or valeric) with hydrazine hydrate (60%) with molar ratio aldehyde: ethane dithiol: hydrazine=40:20:10 at temperature 0°C and atmospheric pressure for 2-4 hours.

EFFECT: method of producing novel compounds which can be used as antibacterial, antifungal and antiviral agents.

1 cl, 1 tbl, 1 ex

 

The present invention relates to the field of organic chemistry, specifically, a method for producing bis-2,4-dialkyl-1,5,3-diazepan-3-silts General formula (I):

R=Me, Et,nPrnBu.

Connection diazepamdosage series known as antibacterial, antifungal, and antiviral agents (M.R. Stillings, Welbourn A.P., D.J. Walter Substituted 1,3,4-thiadiazoles with anticonvulsant activity // Med. Chem. 1986. 29. P.2280-2284. Kidwai M, N. Negi, Director S.R. Cyclothiomethylation of arge hydrazines with formaldehyde // Acta Pharma. 1995. 45. P.511. Tyukavkina N.A., Zurabyan SE, Beloborodov V.L. and other Organic chemicals. M.: bustard, 2008. 66-67).

The known method ([1]. Vremeto, Grenadilla, Seraphita, Hren, Iaarabene; RV Kunakova, Usmjerili. Cyclocondensation hydrazine, formaldehyde and hydrogen sulfide in the presence of acids and bases. Zhur.org.chem., 2006, 1, S-153) obtain the N, S-containing bicyclic compounds (2) cyclocondensation of hydrazine with H2S and CH2In the presence of a promoter BuONa at a temperature of 0-5°C according to the scheme:

The known method cannot be carried out the synthesis of bis-2,4-dialkyl-1,5,3-diazepan-3-silts General formula (1).

The known method ([2]. Vremeto, Grenadilla, NAV, Sashanikova, Mountain, Rvenue. Features of the heterocyclization of hydrazine with acetic aldehyde and H2S // Izv. An., Ser. chem., 2009, 5, S-1065) is received from the art N - and S-containing heterocyclic compounds with ties N-N [(2,4,6,8-tetramethyl-3,7-dithia-1,5-diazabicyclo[3.3.0]octane (3), 2,4,6-trimethyl-(1,3,5-diazinon-5-yl)amine (4), bis-diazinon (5)] the interaction of hydrazine with a mixture of acetaldehyde and H2S in the ratio 1:6:4 at 0°C according to the scheme:

The known method cannot be obtained bis,4-dialkyl-1,5,3-diazepan-3-Elah General formula (1).

Thus, the literature contains no information on obtaining bis-2,4-dialkyl-1,5,3-diazepan-3-silts General formula (1).

We propose a new method of obtaining bis-2,4-dialkyl-1,5,3-diazepan-3-silts General formula (1).

The method consists in the preliminary mixing of the aldehyde (acetic or propionic, or butyric, or valeric) atadditional at 0°C for 30 min followed by the addition of hydrazine hydrate is added (60%), taken in a molar ratio of aldehyde:acondition:hydrazine=40:20:10. The mixture is stirred for 2-4 h at 0°C and atmospheric pressure, produce bis-2,4-dialkyl-1,5,3-diazepan-3-silts of formula (1) with output 64-86%. The reaction proceeds according to the scheme:

Bis-2,4-dialkyl-1,5,3-diazepan-3-silts of formula (1) are formed only with the participation of alkyl substituted aldehydes, ethicial and hydrazine taken in a molar ratio of 40:20:10. When a different ratio of initial reagents decreases the selectivity of the reaction. In the presence of other aldehydes (for example, aryl-substituted ALD the guides), other serosoderjaschei compounds (for example, carbon disulfide, hydrogen sulfide) or other substituted hydrazines (e.g., diacylhydrazine, diarylpyrazole, alkylhalides) target products (1) are not formed.

The reaction was carried out at a temperature of 0°C. At temperatures above 0°C (e.g., 40°C) decreases the selectivity of the reaction and increase energy costs, and at temperatures below 0°C (for example, -10°C) decreases the reaction rate.

Significant differences of the proposed method:

In the proposed method, as the initial reagents are applied alkyl substituted aldehydes, acondition and hydrazinehydrate (60%), taken in a molar ratio of 40:20:10 (in terms of hydrazine), the reaction proceeds at a temperature of ~0°C. In contrast to the known methods, the proposed method allows to synthesize individual bis-2,4-dialkyl-1,5,3-diazepan-3-Elah General formula (1).

The method is illustrated by the following examples:

EXAMPLE 1. In a glass reactor fitted with mechanical stirrer, addition funnel at a temperature of 0°C is placed 40 mmol aldehyde mixed with acondition (20 mmol) for 30 min, add 10 mmol of hydrazine (hydrazinehydrate 60%). The reaction mixture is stirred at a temperature of ~0°C for 3 h, extracted with chloroform bis-2,4-dimethyl-1,5,3-diazepan-3-yl exit 72%.

Other examples of ways is, shown in table 1.

Table 1
№ p/pThe original aldehydeReaction time, hoursOutput (1), %
1acetaldehyde372
2-"-477
3-"-264
4propionic371
5oil375
6Valerian386

All experiments were performed at a temperature of about 0°C. Source alkyl substituted aldehydes, acondition and hydrazine taken in a molar ratio of 40:20:10.

The spectral characteristics of bis-2,4-dialkyl-1,5,3-diazepan-3-silts General formula (1).

Bis-2,4-dimethyl-1,5,3-diazepan-3-yl.
The oil is light yellow in color. Found (percent): C, 44.32; H, 7.09; N, 8.24; S, 39.39. C12H24N2S4. Calculated (%): C, 44.40; H, 7.45; N, 8.63; S, 39.52. An NMR spectrum1H (δ, ppm, J, Hz, 20°C): 1.2 (s, N, CH3(8, 16, 17, 18)); 2.9 (s, 8H, CH2(6, 7, 12, 13)); 3.1 (s, 4H, CH (2,4,10,15)). An NMR spectrum13With (δ, ppm): 24.0 (,(8, 16, 17, 18)); 37.7 (t, (6, 7, 12, 14)); 42.3 (d, (2, 4, 10, 15)).
Bis-2,4-diethyl-1,5,3-diazepan-3-yl.
The oil is light yellow in color. Found (percent): C, at 50.08; H, 8.29; N, 7.15; S, 33.32. C16H32N2S4. Calculated (%): C, 50.48; H, 8.47; N, 7.36; S, 33.69. An NMR spectrum1H (δ, ppm, J, Hz, 20°C): 0.77 (t, N, CH3(9, 18, 20, 21)); 1.61 (K, 8H, CH2(8, 17, 19, 20)); 2.73 (d, 4H, CH(7, 6, 13, 14), J=4.3); 4.59 (t, 4H, CH(2, 4, 11, 16)). An NMR spectrum13With (δ, ppm): 10.9 (,(9, 18, 20, 21)); 28 ( t, With(8, 17, 19, 20)); 34.2 (t, (7, 6, 13, 14); 67.6 (d, (2, 4, 11, 16)).
Bis-2,4-dipropyl-1,5,3-diazepan-3-yl.
The oil is light yellow in color. Found (percent): C, 54.58; H, 9.19; N, 6.00; S, 29.32. C20H40N2S4. Calculated (%): C, 54.99; H,

<>
9.24; N, 6.41; S, 29.36. An NMR spectrum1H (δ, ppm, J, Hz, 20°C): 0.84-0.91 (USS, N, CH3(10, 20, 26, 34)); 1.1-1.7 (USS, N, CH2(8, 9, 18, 19, 21-25)); 2.85 (d, 8H, CH2(6, 7, 14, 15), J.=6.8); 4.83 (t, 4H, CH(2, 4, 12, 17), J1=6.8, J2=7.6). An NMR spectrum13With (δ, ppm): 11.8 (,(10, 20, 26, 34)); 17.34 (t, (9, 19, 22, 25)); 20.47 (t, (8, 18, 21, 24)); 37.53 (t, (7, 6, 15, 14)); 66.2 (d, (2, 4, 12, 17)).
Bis-2,4-dibutil-1,5,3-diazepan-3-yl.
The oil is light yellow in color. Found (percent): C, 58.38; H, 9.19; N, 5.50; S, 25.92. C24H48N2S4. Calculated (%): C, 58,48; H, 9.82; N, 5.68; S, 26.02. An NMR spectrum1H (δ, ppm, J, Hz, 20°C): 0.74 (USS, N, CH3(11, 22, 26, 30)); 0.9-1.4 (USS, N, CH2(9, 10, 20, 21, 24, 25, 28, 29)); 1.56 (s, 8H, CH2(8, 19, 23, 27)); 2.59 (t, 4H, CH2(7, 6, 15, 16), J1=3.54, J2=5.46); 4.74 (t, 4H, CH (2, 4, 13, 18) J1=6.8, J2=7.3). An NMR spectrum13With (δ, ppm): 13.5 (With(11, 22, 26, 30)); 21.7 (t, (10, 21, 25, 29)); 28.2 (t, (9, 20, 24, 28)); 29.0 (t, (8, 19, 23, 27)); 34.7 (t, (7, 6, 15, 16)); 66.12 (d, (2, 4, 13, 18)).

The way to obtain bis-2,4-dialkyl-1,5,3-diazepan-3-silts General formula (1):

R is Me, Et,nPrnBu, wherein the pre-prepared mixture at 0°C ethicial and al is Devida (acetic, or propionic, or butyric, or valeric) is subjected to interaction with hydrazinehydrate (60%) at a molar ratio of aldehyde:acondition:hydrazine = 40:20:10 at a temperature of 0°C and atmospheric pressure for 2-4 hours



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pyridine-3-yl derivatives of formula (I)

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18 cl, 92 ex, 2 tbl

FIELD: chemistry.

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FIELD: medicine, pharmaceutics.

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15 cl, 1 tbl, 15 dwg, 82 ex

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2 cl, 2 dwg, 6 tbl, 21 ex

FIELD: chemistry.

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20 cl, 10 tbl, 8 ex

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13 cl, 14 dwg, 8 ex

FIELD: chemistry.

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40 cl, 162 ex, 2 tbl

FIELD: chemistry.

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15 cl, 17 dwg, 13 tbl, 16 ex

FIELD: organic chemistry, medicine, pharmacy.

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EFFECT: improved method for prophylaxis and treatment, valuable medicinal properties of compound.

26 cl, 2 tbl, 253 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of benzodiazepine of the general formula (I)

and their pharmaceutically acceptable acid-additive salts wherein X means a ordinary bond or ethynediyl group; when X means ordinary bond then R1 means halogen atom, (lower)-alkyl, (lower)-alkylcarbonyl, (lower)-cycloalkyl, benzoyl, phenyl substituted optionally with halogen atom, hydroxyl, (lower)-alkyl, (lower)-alkoxy-group, halogen-(lower)-alkoxy-group or cyano-group; styryl, phenylethyl, naphthyl, diphenyl, benzofuranyl, or 5- or 6-membered heterocyclic ring representing thiophenyl, furanyl, pyridinyl, dihydropyridinyl, tetrahydropyridinyl which are optionally substituted; when X means ethynediyl group then R1 means hydrogen atom, (lower)-alkyl substituted optionally with oxo-group; (lower)-cycloalkyl substituted with hydroxyl; (lower)-cycloalkenyl substituted optionally with oxo-group; (lower)-alkenyl, optionally substituted phenyl; 5- or 6-membered heterocyclic ring representing thiophenyl, thiazolyl, pyridinyl, dihydropyridinyl, tetrahydropyridinyl or dihydropyranyl and substituted optionally; R3 means phenyl, pyridyl, thiophenyl or thiazolyl which are substituted optionally. These compounds can be used for treatment or prophylaxis of acute and/or chronic neurological diseases, such as psychosis, schizophrenia, Alzheimer's disease, disorder of cognitive ability and memory disorder. Also, invention describes a medicinal agent based on these compounds and a method for preparing compounds of the formula (I).

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

10 cl, 1 tbl, 173 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of benzodiazepines of the general formula (I):

wherein X means ordinary bond or ethynediyl group wherein if X mean ordinary bond then R1 means halogen atom or phenyl substituted with halogen atom optionally or (C1-C7)-alkyl group; in case when X means ethynediyl group then R1 mean phenyl substituted with halogen atom optionally; R2 means halogen atom, hydroxy-group, lower alkyl, lower alkoxy-group, hydroxymethyl, hydroxyethyl, lower alkoxy-(ethoxy)n wherein n = 1-4, cyanomethoxy-group, morpholine-4-yl, thiomorpholine-4-yl, 1-oxothiomorpholine-4-yl, 1,1-dioxothiomorpholine-4-yl, 4-oxopiperidine-1-yl, 4-(lower)-alkoxypiperidine-1-yl, 4-hydroxypiperidine-1-yl, 4-hydroxyethoxypiperidine-1-yl, 4-(lower)-alkylpiperazine-1-yl, lower alkoxycarbonyl, 2-di-(lower)-alkylaminoethylsulfanyl, N,N-bis-(lower)-alkylamino-(lower)-alkyl, (lower)-alkoxycarbonyl-(lower)-alkyl, (lower)-alkylcarboxy-(lower)-alkyl, lower alkoxycarbonylmethylsulfanyl, carboxymethylsulfanyl, 1,4-dioxa-8-azaspiro[4,5]dec-8-yl, carboxy-(lower)-alkoxy-group, cyano-(lower)-alkyl, 2-oxo[1,3]dioxolane-4-yl-(lower)-alkoxy-group, 2,2-dimethyltetrahydro[1,3]dioxolo[4,5-c]pyrrole-5-yl, (3R)-hydroxypyrrolidine-1-yl, 3,4-dihydroxypyrrolidine-1-yl, 2-oxooxazolidine-3-yl, carbamoylmethyl, carboxy-(lower)-alkyl, carbamoylmethoxy-, hydroxycarbamoyl-(lower)-alkoxy-, lower alkoxycarbamoyl-(lower)-alkoxy-, (lower)-alkylcarbamoylmethoxy-group; R3 means phenyl, thiophenyl, pyridinyl that are substituted with halogen atom, cyano-group, carbamoyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl or isoxazolyl wherein groups of 1,2,3-triazolyl, 1,2,4-triazolyl or isoxazolyl are substituted optionally with (C1-C7)-alkyl or (C1-C7)-alkylsulfanyl, and to their pharmaceutically acceptable salts. Also, invention describes a medicinal agent that is antagonist of mGlu receptors of the group II based on compound of the formula (I). The medicinal agent can be used in treatment and prophylaxis of acute and/or chronic neurological disturbances including psychosis, schizophrenia, Alzheimer's disease, disturbances in cognitive ability and memory damage.

EFFECT: valuable medicinal properties of compounds.

7 cl, 1 tbl, 98 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to biologically active compounds, in particular, to substituted 5R1,6R2-thiadiazine-2-amines and pharmaceutical compositions comprising thereof that can be used in medicine as potential pharmacologically active substances eliciting the unique combination of properties: expressed anticoagulant activity in combination with capacity to inhibit aggregation of platelets. Effect of these substances differ from preparations used in medicinal practice and they can be used therefore in treatment of such diseases as myocardium infarction, disturbance in cerebral circulation, rejection of transplanted organs and tissues and so on. Indicated compounds correspond to the formula (I):

wherein values of radicals R1, R2 and R3 are given in the invention claim.

EFFECT: valuable medicinal properties of compounds.

4 cl, 2 tbl, 7 dwg, 33 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to applying compounds of the general formula (1):

as inhibitors of caspase-3 that allows their applying as "molecular tools" and as active medicinal substances inhibiting selectively the scheduling cellular death (apoptosis). Also, invention relates to pharmaceutical compositions based on compounds of the formula (1), to a method for their preparing and a method for treatment or prophylaxis of diseases associated with enhanced activation of apoptosis. Also, invention relates to new groups of compounds of the formula 91), in particular, to compounds of the formulae (1.1):

and (1.2):

. In indicated structural formulae R1 represents inert substitute; R2, R3 and R4 represent independently of one another hydrogen atom, fluorine atom (F), chlorine atom (Cl), bromine atom (Br), iodine atom (J). CF3, inert substitute, nitro-group (NO2), CN, COOH, optionally substituted sulfamoyl group, optionally substituted carbamide group, optionally substituted carboxy-(C1-C6)-alkyl group; R5 represents oxygen atom or carbon atom included in optionally condensed, optionally substituted and optionally comprising one or some heteroatoms; R6 represents hydrogen atom or inert substitute; X represents sulfur atom or oxygen atom.

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

3 cl, 1 dwg, 2 tbl, 1 sch, 8 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of 4-phenylpyridine N-oxides of the general formula (I) and their pharmaceutically acceptable acid-additive salts wherein R means hydrogen atom, lower alkyl or halogen atom; R1 means hydrogen atom; R2 and R2' mean independently of one another hydrogen, halogen atom, trifluoromethyl group, (lower)-alkoxy-group; or R2 and R2' can mean in common the group -CH=CH-CH=CH- optionally substituted with one or two substitutes taken among lower alkyl or (lower)-alkoxy-group; R3 and R3' mean independently of one another hydrogen atom, lower alkyl; R4 and R4' mean independently of one another -(CH2)mOR6 or lower alkyl; or R4 and R4' form in common with N-atom to which they are bound substituted R5-cyclic tertiary amine representing pyrrolidine-1-yl, piperidine-1-yl, piperazine-1-yl, morpholine-4-yl or 1,1-dioxomorpholine-4-yl; R5 means hydrogen atom, hydroxyl, -COOR3, -N(R3)CO-lower alkyl or -C(O)R3; R6 means hydrogen atom, lower alkyl; X means -C(O)N(R6)-, -N(R6)C(O)-; n = 0, 1, 2, 3 or 4; m = 1, 2 or 3. Also, invention describes a medicinal agent comprising these compounds. Compounds can be used as drugs in treatment or prophylaxis of diseases associated with antagonists of NK-1 receptor.

EFFECT: valuable medicinal properties of agent.

6 cl, 32 ex

FIELD: organic chemistry, medicine, oncology.

SUBSTANCE: invention relates to new derivatives of 2-arylimino-2,3-dihydrothiazoles of the general formula (I): wherein radical values R1, R2, R3 and R4 are given in the claim invention. New compounds are useful in treatment of pathological states or diseases wherein one or some somatostatin receptors are implicated, for example, acromegaly, hypophysis adenomas or gastroenteropancreatic endocrine tumors with carcinoid syndrome and gastroenteric bleedings.

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

14 cl, 2825 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to derivatives of dihydronaphthalene represented by the formula (I):

wherein radical values are determined in the description and to its nontoxic salts. The proposed compound is a regulator of receptors activated by a peroxisome proliferator (PPAR) of α- and γ-type. The agent can be useful as a hypoglycemic agent, hypolipidemic agent, agent for prophylaxis and/or treatment of diseases associated with metabolic disturbances, agent increasing the content of HDL-cholesterol and reducing the content of LDL-cholesterol and/or VLDL-cholesterol and agent for weakening diabetes mellitus factor risk, and/or X-syndrome. Also, invention claims derivative of dihydronaphthalene representing 3-{5-{2-[2-(4-methylphenyl)-5-methyloxazol-4-yl]ethoxy}-3,4-dihydronaphthalen-1-yl}propanoic acid.

EFFECT: valuable medicinal properties of compounds and agent.

21 cl, 15 tbl, 14 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula: or wherein x means 1, 2, 3 or 4; m means 1 or 2; n means 1 or 2; Q represents carbon atom (C) or nitrogen atom (N); A represents oxygen atom (O) or sulfur atom (S); R1 represents lower alkyl; X represents -CH; R2 represents hydrogen (H) or halogen atom; R2a, R2b and R2c can be similar or different and they are chosen from hydrogen atom (H), alkyl, alkoxy-group or halogen atom; R3 represents aryloxycarbonyl or alkoxyaryloxycarbonyl; Y represents -CO2R4 wherein R4 represents hydrogen atom (H) or alkyl, and including all their stereoisomers, their prodrugs as esters and their pharmaceutically acceptable salts. These compounds are useful antidiabetic and hypolipidemic agents and agents used against obesity also.

EFFECT: valuable medicinal properties of compounds.

29 cl, 12 tbl, 587 ex

FIELD: organic chemistry, medicine, neurology, pharmacy.

SUBSTANCE: invention relates to derivatives of pyridazinone or triazinone represented by the following formula, their salts or their hydrates: wherein each among A1, A2 and A3 represents independently of one another phenyl group that can be optionally substituted with one or some groups chosen from the group including (1) hydroxy-group, (2) halogen atom, (3) nitrile group, (4) nitro-group, (5) (C1-C6)-alkyl group that can be substituted with at least one hydroxy-group, (6) (C1-C6)-alkoxy-group that can be substituted with at least one group chosen from the group including di-(C1-C6-alkyl)-alkylamino-group, hydroxy-group and pyridyl group, (7) (C1-C6)-alkylthio-group, (8) amino-group, (9) (C1-C6)-alkylsulfonyl group, (10) formyl group, (11) phenyl group, (12) trifluoromethylsulfonyloxy-group; pyridyl group that can be substituted with nitrile group or halogen atom or it can be N-oxidized; pyrimidyl group; pyrazinyl group; thienyl group; thiazolyl group; naphthyl group; benzodioxolyl group; Q represents oxygen atom (O); Z represents carbon atom (C) or nitrogen atom (N); each among X1, X2 and X3 represents independently of one another a simple bond or (C1-C6)-alkylene group optionally substituted with hydroxyl group; R1 represents hydrogen atom or (C1-C6)-alkyl group; R2 represents hydrogen atom; or R1 and R2 can be bound so that the group CR2-ZR1 forms a double carbon-carbon bond represented as C=C (under condition that when Z represents nitrogen atom (N) then R1 represents the unshared electron pair); R3 represents hydrogen atom or can be bound with any atom in A1 or A3 to form 5-6-membered heterocyclic ring comprising oxygen atom that is optionally substituted with hydroxyl group (under condition that (1) when Z represents nitrogen atom (N) then each among X1, X2 and X3 represents a simple bond; and each among A1, A2 and A3 represents phenyl group, (2) when Z represents nitrogen atom (N) then each among X1, X2 and X3 represents a simple bond; A1 represents o,p-dimethylphenyl group; A2 represents o-methylphenyl group, and A3 represents phenyl group, or (3) when Z represents nitrogen atom (N) then each among X1, X2 and X3 represents a simple bond; A1 represents o-methylphenyl group; A2 represents p-methoxyphenyl group, and A3 represents phenyl group, and at least one among R2 and R means the group distinct from hydrogen atom) with exception of some compounds determined in definite cases (1), (3)-(8), (10)-(16) and (19) given in claim 1 of the invention. Compounds of the formula (I) elicit inhibitory activity with respect to AMPA receptors and/or kainate receptors. Also, invention relates to a pharmaceutical composition used in treatment or prophylaxis of disease, such as epilepsy or demyelinization disease, such as cerebrospinal sclerosis wherein AMPA receptors take part, a method for treatment or prophylaxis of abovementioned diseases and using compound of the formula (I) for preparing a medicinal agent used in treatment or prophylaxis of abovementioned diseases.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

32 cl, 10 tbl, 129 ex

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