Method of obtaining 3,3'-(1,2-phenylene)-bis-1,5,3-dithiazepinane and 3,3,-[methylene-bis-(1,4-phenylene)]-bis-1,5,3- dithiazepinane

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry, namely to method of obtaining 3,3'-(1,2-phenylene)-bis-1,5,3-dithiazepinane and 3,3'-[methylene-bis-(1,4-phenylene)]-bis-1,5,3-dithiazepinane of general formula (1):

, R=1,2-C6H4; 4-C6H4-CH2C6H4-4, which lies in the following: α,ω-diamines (1,2-phenylenediamine or 4,4'-diaminodiphenylmethane) is subjected to interaction with 1,3,6-oxadithiapinane in presence of catalyst Sm(NO3)3·6H2O in mole ratio α,ω-diamine : 1,3,6-oxadithiapinane : Sm(NO3)3·6H2O = 10 : 20 : (0.3-0.7) in chlorophorm and argon atmosphere for 2.5-3.5 h.

EFFECT: elaborated is method of obtaining novel compounds, which cam be applied as antibacterial, antifungal and antiviral agents, as biologically active complexing agents, selective sorbents and extractants of precious metals, special reagents for suppression of vital activity of bacteria in various technical media.

1 cl, 1 tbl, 1 ex

 

The present invention relates to organic chemistry, specifically to a method for producing 3,3'-(1,2-phenylene)bis-1,5,3-diazepinone and 3,3'-[methylene-bis-(1,4-phenylene)]bis-1,5,3-diazepinone General formula (1)

Nitrogen and sulfur-containing heterocycles are known as antibacterial, antifungal, and antiviral agents (M.R. Stillings, Welbourn, A.R., 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 H.A., Zurabyan SE, Beloborodov V.L. and other Organic chemicals. M: bustard, 2008. p.66-67). They are promising as catalysts, biologically active agents, selective sorbents and extractants precious metals [Deutsche Gold - und Silber-Scheideanstalt vormals Roessler. F.P. 1,341,792/1963 (Chem. Abs., 1964, 60, 5528d)], special reagents to inhibit bacterial activity in different technical environments (from light industry to oil) (Dzhemilev sea level, Aleev R.S., galinova US, Kunakova W., Khafizova S.R., Kovtunenko S. C., Kalimullin A.A. Andrianov V.M., Ismagilov FR, Gafiatullin P.P. Tool to inhibit the growth of sulfate reducing bacteria. Pat. Of the Russian Federation No. 2160233, 2000; Dzhemilev sea level, Aleev R.S., galinova US, Kunakova W., Khafizova S.R. Means to inhibit the growth of sulfate reducing bacteria. Pat. Of the Russian Federation No. 2206726, 2003).

Known methods for the (Patent RF №2333910; B, 2008, No. 26) to obtain 5-{2-[5-{2-[1,3,5-diazinon-5-yl]ethyl}-4-methyl-1,3,5-thiadiazine-3-yl]-ethyl}1,3,5-diazinane (2) interaction methyldiethylamine saturated with hydrogen sulfide in an aqueous solution of formaldehyde, taken in a molar ratio methyldiethylamine: formaldehyde: hydrogen of 1:6:4 at a temperature of 20°C with a yield of 63.5%.

The known method cannot be obtained 3,3'-(1,2-phenylene)bis-1,5,3-diazepine and 3,3'-[methylene-bis-(1,4-phenylene)]bis-1,5,3-diazepine General formula (1).

The known method [Fr. Pat. 1,341, 792/1963 (Chem. Abs., 1964, 60, 5528d)] obtain derivatives of bis-1,3,5-diazinane, in particular 5-[2-[1,3,5-diazinon-5-yl]ethyl]1,3,5-diazinane (3), the interaction of sodium hydrosulfide (NaHS) with Ethylenediamine and formaldehyde according to the scheme

The known method does not allow to obtain 3,3'-(1,2-phenylene)bis-1,5,3-diazepine and 3,3'-[methylene-bis-(1,4-phenylene)]bis-1,5,3-diazepine General formula (1).

The known method (Seraphita, Vremeto, Lphraw, Tavakilov, Grenadilla, Rvenue, Aagrawal, Usmjerili. Multicomponent condensation of aliphatic amines with formaldehyde and hydrogen sulfide. WPI. An. Ser. chem., 2005, 2, 423) obtain 5-[2-[1,3,5-diazinon-5-yl]ethyl]1,3,5-diazinane (3) three-component condensation of hydrogen sulfide with formaldehyde and Ethylenediamine, taken in the Aulnay ratio of 1:6:4, respectively, at a temperature of 80°C with a yield of 44%.

The known method does not technological, as it implies the use of gaseous and highly toxic hydrogen sulfide, which at high concentrations, has no smell, but even once its inhalation may cause instant death. In addition, the known method cannot be obtained 3,3'-(1,2-phenylene)bis-1,5,3-diazepine and 3,3'-[methylene-bis-(1,4-phenylene)]bis-1,5,3-diazepine General formula (1).

Thus, the literature contains no information about selective receipt of 3,3'-(1,2-phenylene)bis-1,5,3-diazepinone and 3,3'-[methylene-bis-(1,4-phenylene)]bis-1,5,3-diazepinone General formula (1).

We propose a new method of obtaining 3,3'-(1,2-phenylene)bis-1,5,3-diazepinone and 3,3'-[methylene-bis-(1,4-phenylene)]bis-1,5,3-diazepinone General formula (1).

The method consists in the interaction of α,ω-diamine of the General formula H2N-R-NH2where R=1,2-C6H4, 4-C6H4-CH2-C6H4-4' (1,2-phenylenediamine or 4,4'-diaminodiphenylmethane) with 1,3,6-oxidationand in the presence of a catalyst Sm(NO3)3·6H2O, taken in a molar ratio of α,ω-diamine:1,3,6-oxidational:Sm(NO3)3·6H2O=10:20:(0.3-0.7), preferably 10:20:0.5, at room temperature (~20°C) and atmospheric pressure in chloroform as solvent in those is giving 2.5-3.5 hours The output of 3,3'-(1,2-phenylene)bis-1,5,3-diazepinone and 3,3'-[methylene-bis-(1,4-phenylene)]bis-1,5,3-diazepinone (1) is 54-72%. The reaction proceeds according to the scheme

3,3'-(1,2-Phenylene)bis-1,5,3-diazepine and 3,3'-[methylene-bis-(1,4-phenylene)]bis-1,5,3-diazepine General formula (1) are formed only with the participation of 1,2-phenylenediamine or 4,4'-diaminodiphenylmethane and 1,3,6-oxidationin under the action of catalyst Sm(NO3)3·6H2O. In the presence of other α,ω-diamines (for example, α,ω-alkadiene) or without catalyst target products (1) are not formed.

Conducting the reaction in the presence of a catalyst Sm(NO3)3·6H2O more than 7 mol.% with respect to α,ω-diamine does not lead to a significant increase in the yield of the target product (1). Use in the reaction of the catalyst Sm(NO3)3·6H2O less than 3 mol. % reduces output (1), which is associated with reduced catalytically active sites in the reaction mass. The reaction was carried out at room temperature ~20°C. At a higher temperature (e.g. 60°C) decreases the selectivity of the reaction and increase the energy consumption, at a lower temperature (for example, 0°C) decreases the reaction rate. The experiments were carried out in chloroform, as well dissolve both the source and target products.

Significant differences of the proposed method

In the known with the special reaction takes place with the participation as a source of reactant gaseous hydrogen sulfide at a temperature of 80°C with the formation of six-membered N,S-containing heterocycles, namely 5-[2-[1,3,5-diazinon-5-yl]ethyl]1,3,5-diazinane (3). The known method does not allow you to obtain an individual 3,3'-(1,2-phenylene)bis-1,5,3-diazepine and 3,3'-[methylene-bis-(1,4-phenylene)]bis-1,5,3-diazepine General formula (1).

In the proposed method, the reaction proceeds with the participation of as initial reagents 1,3,6-oxidationin and 1,2-phenylenediamine or 4,4'-diaminodiphenylmethane under the action of catalyst Sm(NO3)3·6H2O at a temperature of 20°C. In contrast to the known proposed method allows you to obtain an individual 3,3'-(1,2-phenylene)bis-1,5,3-diazepine and 3,3'-[methylene-bis-(1,4-phenylene)]bis-1,5,3-diazepine General formula (1), the synthesis of which are not described in literature.

The method is illustrated by the following examples.

EXAMPLE 1. In the vessel Slanka mounted on a magnetic stirrer, an argon atmosphere was placed 10 mmol of 1,2-phenylenediamine in 5 ml of chloroform, 0.5 mmol Sm(NO3)3·6H2O, and then added dropwise 20 mmol 1,3,6-oxidationin in 5 ml of chloroform. The reaction mixture was stirred at room temperature (~20°C) for 3 hours, add 2 ml of distilled water and extracted with chloroform. Chloroform fraction chromatographic on a column with SiO2and produce 3,3'-(1,2-phenylene)bis-1,5,3-diazepine with the release of 65%.

Other examples of the method are given in table 1.

Table 1
№ p/pSource α,ω-diamineThe ratio of α,ω-diamine:1,3,6-oxidational:Sm(NO3)3·6H2O mmolReaction time, hoursOutput (1), %
11,2-phenylenediamine10:20:0.5365
4-"-10:20:0.7372
5-"-10:20:0.3354
6-"-10:20:0.53.569
7-"-10:20:0.52.557
84,4'-diaminodiphenylmethane10:20:0.5359

All experiments were performed in polypropylene cotton the dress is forme at room temperature (~20°C).

The spectral characteristics of 3,3'-(1,2-phenylene)bis-1,5,3-diazepinone (Control reaction was carried out by TLC on Silufol plates W-254, showed pairs I2. For column chromatography was used silica gel KSK (100-200 μm). The melting point is defined on the device OOC 80/2617. The NMR spectra of 1D (1H,13C) and 2D (COSY, NOESY, HSQC, NMVS) removed spectrometer Broker Avance 400 (100.62 MHz for13And 400.13 MHz for1N) by standard methods (Bruker, internal standard Me4Si, solvent CDCl3. Mass high resolution spectra obtained on the instrument MALDI TOF/TOF AUTOFLEX III (Bruker).)

TPL 210-212°C. Eluent benzene:ethanol (9:1), Rf0.9. An NMR spectrum1N, δ, ppm: 3.08 (USS, 8H, CH2(6, 6', 7, 7')); 4.77 (USS, 8H, CH2(2, 2', 4, 4')); 7.06 (K, J=3.2 Hz, 2H, CH (10, 13)); 7.21 (K, J=3 Hz, 2H, CH (11, 12)). An NMR spectrum13S, δ, ppm: 37.31 (t, C-6, C-6', C-7, C-7'), 56.67 (t, C-2, C-2', C-4, C-4'), 122.14 (d, C-11, C-12), 124.09 (d, C-10, C-13), 142.11 (s, C-8, C-9). MALDI TOF, m/z: 345.227 [M+H]+, 367.184 [M+Na]+, 383.132 [M+K]+. C14H20N2S4. M.

The spectral characteristics of 3,3'-[methylene-bis-(1,4-phenylene)]bis-1,5,3-diazepinone (Control reaction was carried out by TLC on Silufol plates W-254, showed pairs I2. For column chromatography was used silica gel KSK (100-200 μm). The melting point is defined on the device is OOC 80/2617. The NMR spectra of 1D (1H,13C) and 2D (COSY, NOESY, HSQC, NMVS) removed spectrometer Bruker Avance 400 (100.62 MHz for13And 400.13 MHz for1N) by standard methods (Bruker, internal standard Me4Si, solvent CDCl3. Mass high resolution spectra obtained on the instrument MALDI TOF/TOF AUTOFLEX III (Bruker).)

TPL 145-147°C. Eluent benzene:ethanol (9:1), Rf0.80. An NMR spectrum1N, δ, ppm: 3.07 (USS, 8H, CH2(6, 6', 7, 7')); 3.87 (USS, 2H, CH2(14)); 4.77 (USS, 8H, CH2(2, 2', 4, 4')); 6.87 (d, J=8.8 Hz, 4H, CH(9, 13, 17, 19)); 7.14 (d, J=8.8 Hz, 4H, CH(10, 12, 16, 20)). An NMR spectrum13S, δ, ppm: 35.83 (t, C-6, C-6', C-7, C-7'), 40.11 (t, C-14), at 55.20 (t, C-2, C-2', C-4, C-4'), 116.18 (d, C-9, C-13, C-17, C-19), 129.68 (d, C-10, C-12, C-16, C-20), 133.10 (s, C-11, C-15), 144.09 (s, C-8, C-18). MALDI TOF, m/z: 433.205 [M-N]+, 457.172 [M+Na]+, 473.124 [M+K]+. C21H26N2S4. M.

The way to obtain 3,3'-(1,2-phenylene)bis-1,5,3-diazepinone and 3,3'-[methylene-bis-(1,4-phenylene)]bis-1,5,3-diazepinone General formula (1):

characterized in that the α,ω-diamines (1,2-phenylenediamine or 4,4'-diaminodiphenylmethane) is subjected to interaction with 1,3,6-oxidationand in the presence of a catalyst Sm(NO3)3·6N2O in a molar ratio of α,ω-diamine:1,3,6-oxidational:Sm(NO3)3·6N2O=10:20:(0,3-0,7) in chloroform and argon atmosphere for 2.5 to 3.5 hours



 

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8 cl, 24 tbl, 262 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new biologically active derivatives of dihydrobenzo[b][1,4]diazepine-2-one. Invention describes derivatives of dihydrobenzo[b][1,4]diazepine-2-one of the general formula (I): wherein X means a simple bond or ethynediyl group wherein if X means a simple bond then R1 means cyano-group, halogen atom, lower alkyl, (C1-C3)-cycloalkyl, (lower)-alkoxyl, fluoro-(lower)-alkyl or it means pyrrole-1-yl that may be free or substituted with 1-3 substitutes taken among the group consisting of fluorine, chlorine atom, cyano-group, -(CH2)1-4-hydroxyl group, fluoro-(lower)-alkyl, lower alkyl, -(CH2)n-(lower)-alkoxyl, -(CH2)n-C(O)OR'', -(CH2)1-4-NR'R'', hydroxy-(lower)-alkoxyl and -(CH2)n-COR'R'', or it means free phenyl or phenyl substituted with one or two substitutes taken among the group consisting of halogen atom, lower alkyl, fluoro-(lower)-alkyl, (lower)-alkoxyl, fluoro-(lower)-alkoxyl and cyano-group; if X means ethynediyl group then R1 means free phenyl or phenyl substituted with 1-3 substituted taken among the group consisting of halogen atom, lower alkyl, fluoro-(lower)-alkyl, (C3-C6)-cycloalkyl, (lower)-alkoxyl and fluoro-(lower)-alkoxyl; R2 means -NR'R'', fluoro-(lower)-alkoxyl or 3-oxopiperazin-1-yl, pyrrolidin-1-yl, or piperidin-1-yl wherein their rings are substituted optionally with R''; R' means hydrogen atom, lower alkyl, (C3-C6)-cycloalkyl, fluoro-(lower)-alkyl or 2-(lower)-alkoxy-(lower)-alkyl; R'' means hydrogen atom, lower alkyl, (C3-C6)-cycloalkyl, fluoro-(lower)-alkyl, 2-(lower)-alkoxy-(lower)-alkyl, -(CH2)2-4-di-(lower)-alkylamino-group, -(CH2)2-4-morpholinyl, -(CH2)2-4-pyrrolidinyl, -(CH2)2-4-piperidinyl or 3-hydroxy-(lower)-alkyl; Y means -CH= or =N-; R3 means halogen atom, lower alkyl, fluoro-(lower)-alkyl, (lower)-alkoxyl, cyano-group, -(CH2)n-C(O)OR'', -(CH2)1-4-NR'R'' or it means optionally substituted 5-membered aromatic heterocycle that can be substituted with halogen atom, fluoro-(lower)-alkyl, fluoro-(lower)-alkoxyl, cyano-group, -(CH2)n-NR'R'', -(CH2)n-C(O)OR'', -(CH2)n-C(O)NR'R'', -(CH2)n-SO2NR'R'', -(CH2)n-C(NH2)=NR'', hydroxyl, (lower)-alkoxyl, (lower)-alkylthio-group or lower alkyl that is optionally substituted with fluorine atom, hydroxyl, (lower)-alkoxyl, cyano-group or carbamoyloxy-group; n means 0, 1, 2, 3 or 4, and their pharmaceutically acceptable additive salts. Also, invention describes a medicinal agent as antagonist of mGlu receptors of group II based on compounds of the formula (I). Invention provides preparing new compounds eliciting valuable biological properties.

EFFECT: valuable medicinal properties of compounds.

17 cl, 496 ex

FIELD: organic chemistry, technology of organic compounds.

SUBSTANCE: invention relates to heterocyclic o-dicarbonitriles. Invention describes heterocyclic o-dicarbonitriles of the general formula: wherein R means the following compounds: . Heterocyclic o-dicarbonitriles can be used for preparing hexazocyclanes-fluorophores as a donor-fragment used for preparing hexazocyclanes-bifluorophores and hexazocyclanes-trifluorophores. Invention provides preparing new compounds possessing valuable properties.

EFFECT: valuable properties of compounds.

2 tbl, 10 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of compound of the formula (1): wherein Y means -O-, -S- or -N(R2)- wherein R2 means hydrogen atom, (C1-C10)-alkyl or aralkyl; Z means 2,5-furanyl, 2,5-thiophenyl, 4,4'-stilbenyl or 1,2-ethyleneyl residue; R1 means hydrogen or halogen atom, (C1-C10)-alkyl, (C1-C10)-alkoxy-group, cyano-group, -COOM or -SO3M wherein M means hydrogen atom or alkaline or alkaline-earth metal atom. Method for synthesis involves carrying out the reaction of compound of the formula (2): with dicarboxylic acid of the formula: HOOC-Z-COOH (3) or with it ester wherein Y, Z and R1 have values given above in N-methylpyrrolidone or N,N-dimethylacetamide medium in the presence of an acid catalyst and optionally in the presence of an accessory solvent able to remove water from the reaction mixture.

EFFECT: improved method of synthesis.

11 cl, 7 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivative compound of carboxylic acid represented by the formula (I): , wherein each X and Y represents independently (C1-C4)-alkylene; Z means -O-; each R1, R2, R3 and R4 means independently hydrogen atom or (C1-C8)-alkyl; R5 means (C2-C8)-alkenyl; A means -O- or -S-; D means D1, D2, D3, D4 or D5 wherein D1 means (C1-C8)-alkyl; D2 means compound of the formula: wherein ring 1 represents saturated 6-membered monoheteroaryl comprising one nitrogen atom and, optionally, another one heteroatom chosen from oxygen, sulfur and nitrogen atoms; D3 means compound of the formula: wherein ring 2 represents (1) completely saturated (C3-C10)-monocarboxylic aryl, or (2) optionally saturated 5-membered monoheteroaryl comprising 3 atoms chosen from nitrogen and sulfur atoms, or completely saturated 6-membered monoheteroaryl comprising 1 heteroatom representing oxygen atom; D4 means compound of the formula: ; D5 means compound of the formula: ; R6 represents (1) hydrogen atom, (2) (C1-C8)-alkyl, (3) -NR7R8 wherein R7 or R8 represent hydrogen atom or (C1-C8)-alkyl, or R7 and R8 taken in common with nitrogen atom to which they are added form saturated 5-6-membered monoheteroaryl comprising one nitrogen atom and, optionally, another one heteroatom representing oxygen atom; E means -CH or nitrogen atom; m means a whole number 1-3, or its nontoxic salt. Invention relates to a regulator activated by peroxisome proliferator receptor, agent used in prophylaxis and/or treatment of diseases associated with metabolism disorders, such as diabetes mellitus, obesity, syndrome X, hypercholesterolemia or hyperlipoproteinemia, hyperlipidemia, atherosclerosis, hypertension, diseases coursing with circulation disorder, overeating or heart ischemic disease, and to an agent that increases cholesterol level associated with HDL, reduces cholesterol level associated with LDL and/or VLDL, eliminates risk factor in development of diabetes mellitus and/or syndrome X and comprising a compound represented by the formula (I) or its nontoxic salt as an active component and a carrier, excipient or solvent optionally. Invention proposes derivative compounds of carboxylic acid possessing the modulating activity with respect to peroxisome proliferator receptor (PPAR).

EFFECT: valuable medicinal properties of compounds.

15 cl, 5 tbl, 48 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel substituted derivatives of 4-phenyltetrahydroisoquinoline of the general formula (I): wherein R1, R2, R3 and R4 mean independently of one another hydrogen (H), fluorine (F), chloride (Cl), bromine (Br) atoms, CaH2a+1 wherein one or more atoms H are substituted with F, -NR11R12 or -SOj-R15 wherein a = 1-8; R11 and R12 mean independently of one another H, CeH2e+1 or CrrH2rr-1 wherein e = 1-4; rr = 3, 4, or in common with nitrogen atom to which they are bound form a cycle chosen from group consisting of pyrrolidinyl, piperidinyl, N-methylpiperazinyl, piperazinyl or morpholine; j = 1 or 2; R15 means CkH2k+1 wherein k = 1-8; R5 means CpH2p+1 or CssH2ss-1; p = 1-8; ss = 3-8; R6 means H; R7, R8 and R9 mean independently of one another mean -SOwR23, -NR32COR30, NR32CSR30, -NR32SObbR30, H, F, Cl, Br, -OH, -NH2, CeeH2ee+1, -NR40R41, -CONR40R41 or -COOR42 wherein w = 0, 1 or 2; bb = 2 or 3; R23 means NR25R26 wherein R25 and R26 mean independently of one another H or CzH2z+1, CzzH2zz-1 wherein z = 1-8; zz = 3-8 wherein in CzH2z+1 and CzzH2zz-1 one or more H atoms are substituted with fluorine atom and one or more CH2-groups are substituted with -C(=O) or NR27 wherein R27 means H or CaaH2aa+1 wherein aa = 1-4; or R25 and R26 in common with nitrogen atom to which they are bound form 5-, 6- or 7-membered cycle; R30 means H, CccH2cc+1, CyyH2yy-1, pyrrolydinyl, piperidinyl wherein in their cycles CH2-group can be substituted with oxygen atom (O) or -NR33; R32 and R33 mean independently of one another H or ChH2h+1 wherein cc = 1-8; yy = 3-8; h = 1-8 wherein in the group ChH2h+1 one or more hydrogen atoms are substituted with fluorine atom, and in the groups CccH2cc+1 and CyyH2yy-1 one or more hydrogen atoms can be substituted with fluorine atom, and CH2-group can be substituted with O or -NR31 wherein NR31 means H, methyl, ethyl, acetyl or -SO2CH3; or R30 means 6-membered heteroaryl with 1-4 nitrogen atoms, 0 or 1, S-atoms or 0, or 1 O-atom that represents unsubstituted or substituted with up to three substitutes chosen from group consisting of F, Cl, Br, J, CooH2oo+1 wherein one or more hydrogen atoms can be substituted with fluorine atom, -NO2 or -NR70R71 wherein oo = 1-8; R70 and R71 mean independently of one another H, CuuH2uu+1 or -COR72 wherein uu = 1-8; R72 means H, CvvH2vv+1 wherein vv = 1-8; ee = 1-8; R40 and R41 mean independently of one another H, CttH2tt+1 or -C(NH)NH2 wherein tt = 1-8 and wherein in the group CttH2tt+1 one or more CH2-groups can be substituted with NR44 wherein R44 means CggH2gg+1 wherein gg = 1-8; R42 means H or ChhH2hh+1 wherein hh = 1-8 being, however, two substitutes from group R7, R8 and R9 can't mean -OH simultaneously, and at least one residue from R7, R8 and R9 must be chosen from group consisting of -CONR40R41, -OvSOwR23, -NR32COR30, -NR32CSR30 and -NR32SObbR30. Also, invention relates to using above given compounds for preparing a medicinal agent. Also, invention considers a medicinal agent representing inhibitor of sodium-proton exchange of subtype III (NHE3) based on proposed compounds. Invention provides synthesis of novel compounds, a medicinal agent based on thereof for aims of treatment of such diseases as nervous system ischemia, insult and brain edema, in treatment of snore, shock, impaired respiratory impulse, as purgative agents, as agents against extoparasites, for prophylaxis of gall stones formation, as anti-atherosclerotic agents, agents against diabetes mellitus later complications, cancer diseases, fibrous diseases, endothelial dysfunction, hypertrophies and hyperplasia of organs and others.

EFFECT: valuable medicinal properties of compounds and medicinal agents.

21 cl, 15 tbl, 221 ex

FIELD: organic chemistry, medicine, endocrinology.

SUBSTANCE: invention relates to novel compounds representing C-glycoside derivatives and their salts of the formula: wherein ring A represents (1) benzene ring; (2) five- or six-membered monocyclic heteroaryl ring comprising 1, 2 or 4 heteroatoms chosen from nitrogen (N) and sulfur (S) atoms but with exception of tetrazoles, or (3) unsaturated nine-membered bicyclic heterocycle comprising 1 heteroatom representing oxygen atom (O); ring B represents (1) unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (2) saturated or unsaturated five- or six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (3) unsaturated nine-membered bicyclic carbocycle, or (4) benzene ring; X represents a bond or lower alkylene wherein values for ring A, ring B and X correlate so manner that (1) when ring A represents benzene ring then ring B is not benzene ring, or (2) when ring A represents benzene ring and ring B represents unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O and comprising benzene ring or unsaturated nine-membered bicyclic carbocycle comprising benzene ring then X is bound to ring B in moiety distinct from benzene ring comprised in ring B; each among R1-R4 represents separately hydrogen atom, -C(=O)-lower alkyl or lower alkylene-aryl; each R5-R11 represents separately hydrogen atom, lower alkyl, halogen atom, -OH, =O, -NH2, halogen-substituted lower alkyl-sulfonyl, phenyl, saturated six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N and O, lower alkylene-OH, lower alkyl, -COOH, -CN, -C(=O)-O-lower alkyl, -O-lower alkyl, -O-cycloalkyl, -O-lower alkylene-OH, -O-lower alkylene-O-lower alkyl, -O-lower alkylene-COOH, -O-lower alkylene-C(=O)-O-lower alkyl, -O-lower alkylene-C(=O)-NH2, -O-lower alkylene-C(=O)-N-(lower alkyl)2, -O-lower alkylene-CH(OH)-CH2(OH), -O-lower alkylene-NH, -O-lower alkylene-NH-lower alkyl, -O-lower alkylene-N-(lower alkyl)2, -O-lower alkylene-NH-C(=O)-lower alkyl, -NH-lower alkyl, -N-(lower alkyl)2, -NH-lower alkylene-OH or NH-C(=O)-lower alkyl. Indicated derivatives can be used as inhibitor of co-transporter of Na+-glucose and especially as a therapeutic and/or prophylactic agent in diabetes mellitus, such as insulin-dependent diabetes mellitus (diabetes mellitus 1 type) and non-insulin-dependent diabetes mellitus (diabetes mellitus 2 type), and in diseases associated with diabetes mellitus, such as insulin-resistant diseases and obesity.

EFFECT: valuable medicinal properties of compounds.

11 cl, 41 tbl, 243 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compound of the formula (I): wherein R1 represents azido, -OR4, -NHR4 wherein R4 represents hydrogen atom or unsubstituted groups chosen from acyl, thioacyl, (C1-C6)-alkoxycarbonyl, (C3-C6)-cycloalkoxythiocarbonyl, (C2-C6)-alkenyloxycarbonyl, (C2-C6)-alkenylcarbonyl, (C1-C6)-alkoxythiocarbonyl, (C2-C6)-alkenyloxythiocarbonyl, -C(=O)-C(=O)-(C1-C6)-alkoxy, -C(C=S)-S-(C1-C6)-alkyl, -(C=S)-NH2, -(C=S)-NH-(C1-C6)-alkyl, -C(=S)-N-((C1-C6)-alkyl)2, -C(=S)-NH-(C2-C6)-alkenyl, -C(C=S)-(C=O)-(C1-C6)-alkoxy, thiomorpholinylthiocarbonyl; R2 and R3 can be similar or different and represent independently hydrogen atom, halogen atom, (C1-C6)-alkyl group, halogen-(C1-C6)-alkyl; heterocyclic moiety represents 5-membered heterocycle wherein Z represents sulfur (S), oxygen (O) atom or -NRb wherein Rb represents hydrogen atom or unsubstituted (C1-C6)-alkyl, (C3-C6)-cycloalkyl, aryl or aryl-(C1-C6)-alkyl; Y1 represents group =O or =S ; Y2 and Y3 represent independently hydrogen atom, and if Y2 and Y3 present in common on adjacent carbon atoms then they form 6-membered aromatic cyclic structure substituted if necessary with (C1-C6)-alkyl, or to its pharmaceutically acceptable salt. Also invention relates to a pharmaceutical composition possessing antibacterial activity and containing as an active compound the compound of the formula (I) taken in the effective dose and a pharmaceutically acceptable carrier, diluting agent, excipient. Also, invention relates to method for synthesis of compound of the formula (I). Method for synthesis of compound of the formula (I) wherein R1 represents group -NHR4 wherein R4 means acyl, (C1-C6)-alkoxycarbonyl, (C2-C6)-alkenyloxycarbonyl, (C2-C6)-alkenylcarbonyl, -C(=O)-C(=O)-(C1-C6)-alkoxy and -(C=S)-S-(C1-C6)-alkyl involves acetylation of compound of the formula (I) wherein R1 represents -NHR4 group wherein R4 represents hydrogen atom and all symbols are given above and using halide. Method for synthesis of compound of the formula (I) wherein R1 represents -NHR4 group wherein R4 means thioacyl, (C3-C6)-cycloalkoxythiocarbonyl, (C1-C6)-alkoxythiocarbonyl, (C2-C6)-alkenyloxythiocarbonyl involves the following steps: (i) conversion of compound of the formula (I) wherein R1 represents -NHR4 wherein R4 represents hydrogen atom, and all symbols are given above to compound of the formula (I) wherein R1 represents isothiocyanate group by reaction with thiophosgene, and (ii) conversion of compound of the formula (I) wherein R1 represents isothiocyanate group to compound of the formula (I) wherein R1 represents -NHR4 wherein R4 represents -C(=S)-OR4d wherein R4d represents (C1-C6)-alkyl, (C3-C6)-cycloalkyl, (C2-C6)-alkenyl, and all symbols are given above, in reaction with alcohol. Compounds of the formula (I) are used in treatment of bacterial infection that involves administration of compound of the formula (I) in a patient needing in this treatment. Invention provides synthesis of oxazolidinone compounds possessing antibacterial activity.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved method of synthesis.

7 cl, 1 tbl, 144 ex

FIELD: chemistry.

SUBSTANCE: there are disclosed 1-(2-aminobenzol)piperazine derivatives of formula (I) and pharmaceutically acceptable acid-additive salts with radical values specified in patent claim. The compounds are characterised with inhibiting effect on glycine I carrier. There is also disclosed medical product based on the compounds of formula (I).

EFFECT: compound can be used for treatment of the diseases associated with glycine uptake inhibition.

12 cl, 5 tbl, 396 ex

FIELD: chemistry.

SUBSTANCE: invention claims compounds of the formula (I) with radicals as described in the claim, and medicine with inhibition effect on glycine absorption, based on compound of the formula (I) .

EFFECT: medicine for diseases treatment where glycine absorption inhibition can be effective.

21 cl, 1 tbl, 173 ex

Cynnamide compound // 2361872

FIELD: chemistry.

SUBSTANCE: invention relates to a compound with formula (I) , where Ar1 is an imidazolyl group, which can be substituted with 1-3 substitutes; Ar2 is a pyridinyl group, pyrimidinyl group or phenyl group, which can be substituted with 1-2 substitutes; X1 is (1) -C≡C- or (2) double bond etc., which can be substituted, R1 and R2 are, for example, C1-6-alkyl group or C3-8-cycloalkyl group, which can be substituted; or to a pharmacologically acceptable salt of the said compound and pharmaceutical drugs for lowering production of Aβ42, containing formula (I) compound as an active ingredient.

EFFECT: wider field of use of the compounds.

26 cl, 1119 ex, 31 tbl

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