Method of obtaining 3, 3'-[oxa(thia)alkane-alpha, omega-diyl]-bis-1,5,3-dithiazepinanes

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining 3,3'-[oxa(thia)alkane-α,ω-diyl]-bis-1,5,3-dithiazepinanes of general formula (1) R=CH2CH2OCH2CH2, (CH2CH2O)2CH2CH2, (CH2CH2S)2 , which consists in the following: oxa(thia)alkane-α,ω-diamine (3-oxapentane-1,5-diamine, 3,6-dioxaoctane-1,8-diamine, 3,4-dithiahexane-1,6-diamine) undergoes interaction with 1-oxa-3,6-dithiacycloheptane in ethanol-chloroform system of solvents in argon medium in presence of catalyst SmCl3·6H2O with molar ratio oxa(thia)alkane-α,ω-diamine: 1-oxa-3,6-dithiacycloheptane: SmCl3·6H2O = 10 : 20 : (0.3-0.7) at room (~20°C) temperature for 2.5-3.5 h.

EFFECT: elaborated is method of obtaining novel compounds which can be applied as selective sorbents and extractants of precious metals, preparations for protection of leather, fur, fabrics against biodamage, biologically active substances with respect to various microorganisms and sulfate-reducing bacteria.

1 tbl, 1 ex

 

The present invention relates to organic chemistry, particularly to a method for selective receipt of 3,3'-[oxa(thia)alkane-α,ω-diyl]-bis-1,5,3-diazepinones General formula (1):

Nitrogen and sulfur-containing heterocycles are known as antibacterial, antifungal, and antiviral agents (Stillings .R., Welbourn, A.R., D.J. Walter Substituted 1,3,4-thiadiazoles with anticonvulsant activity // Med. Chem., 1986, 29, 2280; Kidwai, M., N. Negi, Director S.R. Cyclothiomethylation of arge hydrazines with formaldehyde // Acta Pharm., 1995, 45, 511; Tyukavkina N.A., Zurabyan SE, Beloborodov V.L. and other Organic chemicals. M: bustard, 2008, 66), 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, Kulakova W., Khafizova S.R., Kovtunenko SV, Kalimullin A.A. Andrianov V.M., Ismagilov FR, Gafiatullin RR Means to inhibit the growth of sulfate reducing bacteria. RF patent №2160233, 2000; Dzhemilev sea level, Aleev R.S., galinova US, Kunakova W., Khafizova S.R. Means to inhibit the growth of sulfate reducing bacteria. RF patent №2206726, 2003).

The known method (S.R. Khafizova, V.R. Akhmetov is, L. F. Korzhova, T.V. Khakimov, BORN in Nadyrgulova; RV Kunakova, E.A. Kruglov, sea level Dzhemilev. Multicomponent condensation of aliphatic amines with formaldehyde and hydrogen sulfide, " Izv. An. Ser. chem., 2005, 2, 423) obtain 5-[2-[1,3,5-diazinon-5-yl]ethyl]1,3,5-diazinane (2) three-component condensation of Ethylenediamine with formaldehyde and hydrogen sulfide, taken in a molar ratio of 1:6:4, respectively, at a temperature of 80°C with a yield of 44%.

The known method does not allow to obtain 3,3'-[oxa(thia)alkane-α,ω-diyl]-bis-1,5,3-diazepinone General formula (1).

The known method (Vremeto, Ebergenova, Abinee, Rvenue, Nugglemama. Cyclotrimethylene hetero-chain α,ω-diamines formaldehyde and H2S // Zhur.org.chem., 2012, 2) obtain 5,5'-[oxa(thia)alkane-α,ω-diyl]bis-1,3,5-diazinane (3) three-component condensation oxa(thia)alkane-α,ω-diamines (3-oxapentane-1,5-diamine, 3,6-dioxaoctyl-1,8-diamine, 3,4-ditegakkan-1,6-diamine) with formaldehyde and hydrogen sulfide, taken in a molar ratio of 1:6:4, respectively, at 60°C outputs 62-68%.

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 swelling l is gcih. In addition, the known method cannot be obtained 3,3'-[oxa(thia)alkane-α,ω-diyl]-bis-1,5,3-diazepinone General formula (1).

Thus, the literature contains no information about how to obtain 3,3'-[oxa(thia)alkane-α,ω-diyl]-bis-1,5,3-diazepinones General formula (1).

We propose a new method of obtaining 3,3'-[oxa(thia)alkane-α,ω-diyl]-bis-1,5,3-diazepinones General formula (1).

The method consists in the interaction of oxa(thia)alkane-α,ω-diamine (3-oxapentane-1,5-diamine, 3,6-dioxaoctyl-1,8-diamine, 3,4-ditegakkan-1,6-diamine) with 1-oxa-3,6-ditzikloverina in argon in the presence of a catalyst SmCl3·6H2O, taken in a molar ratio of oxa(thia)alkane-α,ω-diamine:1-oxa-3,6-directloan:SmCl3·6H2O=10:20:(0.3-0.7), preferably 10:20:0.5. The mixture is stirred for 2.5-3.5 hours at a temperature of 20°C and atmospheric pressure in the solvent system ethanol-chloroform (1:1, volume ratio). The output of 3,3'-[oxa(thia)alkane-α,ω-diyl]-bis-1,5,3-diazepine (1) is 67-85%. The reaction proceeds according to the scheme:

3,3'-[oxa(thia)alkane-α,ω-diyl]-bis-1,5,3-diazepinone (1) are formed only with the participation of 1-oxa-3,6-ditzikloverina and oxa(thia)alkane-α,ω-diamine (3-oxapentane-1,5-diamine, 3,6-dioxaoctyl-1,8-diamine, 3,4-ditegakkan-1,6-diamine), taken in a molar ratio of 20:10 (stoichiometric amount). With each other with the respect to the initial reagents reduces the yield of the target product (1). Without catalyst, the reaction proceeds with output not exceeding 40%. The conduct of a specified reaction in the presence of a catalyst SmCl3·6H2O more than 7 mol.% does not lead to a significant increase in the yield of the target product (1). The use of catalyst SmCl3·6H2O less than 3 mol.% reduces output (1), which is connected, possibly, with a reduction of catalytically active sites in the reaction mass. The reaction was carried out at a temperature of 20°C. At temperatures above 20°C (e.g., 60°C) increase energy costs, and at temperatures below 20°C (for example, 0°C) decreases the reaction rate.

Significant differences of the proposed method:

In the known method the reaction proceeds with participation as a source of reactant gaseous hydrogen sulfide at a temperature of 60°C with the formation of six-membered N,S-containing heterocycles, namely, 5,5'-[oxa(thia)alkane-α,ω-diyl]bis-1,3,5-diazinane (3). The known method does not allow you to obtain an individual 3,3'-[oxa(thia)alkane-α,ω-diyl]-bis-1,5,3-diazepinone (1).

In the proposed method, the reaction proceeds with participation as a source of reagent 1-oxa-3,6-ditzikloverina at 20°C under the action of catalyst SmCl3·6H2O. In contrast to the known proposed method allows you to obtain an individual 3,3'-[oxa(thia)alkane-α,ω-diyl]-bis-1,5,3-diazepinone (1), the synthesis of which in the literature does not describe what.

The method is illustrated by examples.

Example 1. In the vessel Slanka mounted on a magnetic stirrer, an argon atmosphere at a temperature of ~20°C is placed 104 mg (10 mmol) 3-oxapentane-1,5-diamine in 5 ml of ethanol and 22 mg (0.5 mmol) SmCl3·6H2O, then add 272 mg (20 mmol) of 1-oxa-3,6-ditzikloverina in 5 ml of chloroform. The reaction mixture is stirred at a temperature of ~20°C for 3 hours, add 5 ml of H2O and extracted with chloroform (15 ml). Chloroform fraction purified column chromatography on SiO2allocate 3,3'-(3-oxapentane-1,5-diyl)-bis-1,5,3-diazepine with yield 74%.

Other examples of the method are given in table 1.

Table 1

№№ p/pSource oxa(thia)alkane-α,ω-diamineThe ratio of oxa(thia)alkane-α,ω-diamine:1-oxa-3,6-directloan:SmCl3·6H2O mmolReaction time, hoursOutput (1), %
13-oxapentane-1,5-diamine10:20:0.5374
2- "-10:20:0.3367/td>
3- "-10:20:0.7385
4- "-10:20:0.53.579
5- "-10:20:0.52.568
63,6-dioxaoctyl-1,8-diamine10:20:0.5382
73,4-ditegakkan-1,6-diamine10:20:0.5377

All experiments were performed at room temperature (~20°C) in the solvent system ethanol-chloroform (1:1, volume ratio).

The spectral characteristics of the1(1Control reactions were 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. NMR spectra (1H,13C) removed spectrometer Bruker Avance 400 (100.62 MHz for13And 400.13 MHz for1H by standard methods (Bruker, internal standard Me4Si, solvent CDCl3. Mass high resolution spectra obtained on the instrument MALDI TOF/TOF AUTOFLEX III (Bruker).) 3,3'-(3-oxapentane-1,5-diyl)bis-1,5,3-diazepinone:

The white crystalline substance. TPL 53-55°C. an NMR Spectrum1H (δ, ppm, J, CDCl3): 2.94 m (4H, H-8, H-8/; 3.06 USS (8H, H-6, H-6/, H-7, H-7/); 3.59 t (4H, J=5.4 Hz, H-9, H-9/); 4.22 USS (8H, H-2, H-2/N-4, N-4/). An NMR spectrum13With (δ, ppm): 35.89 (C-6, C-6/C-7, C-7/); 50.38 (C-8, C-8/); 60.01 (C-2, C-2/C-4, C-4/); 68.62 (C-9, C-9). MALDI TOF, m/z: 341.216 [M+H]+. C12H25N2OS4.

The spectral characteristics of the2(2Control reactions were 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. NMR spectra (1H,13C) removed spectrometer Bruker Avance 400 (100.62 MHz for13And 400.13 MHz for1H) by standard methods (Bruker, internal standard Me4Si, solvent CDCl3. Mass high resolution spectra obtained on the instrument MALDI TOF/TOF AUTOFLEX III (Bruker).) 3,3'-(3,6-dioxaoctyl-1,8-diyl)bis-1,5,3-diazepinone:

The white crystalline substance. TPL 74-75°C. an NMR Spectrum1H (δ, ppm, J, CDCl3): 2.93 t (4H, J=5.4 Hz, H-8, is -8 /); 3.06 USS (8H, H-6, H-6/, H-7, H-7/); 3.62 m (8H, H-9, H-9/, H-10, H-10/); 4.23 USS (8H, H-2, H-2/N-4, N-4/). An NMR spectrum13C (δ, ppm): 35.87 (C-6, C-6/C-7, C-7/); 50.40 (C-8, C-8/); 59.97 (C-2, C-2/C-4, C-4/); 68.83 (C-9, C-9/), 70.41 (C-10, C-10/). MALDI TOF, m/z: 385.321 [M+H]+. C14H29N2O2S4.

The spectral characteristics of the3(2Control reactions were 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. NMR spectra (1H,13C) removed spectrometer Bruker Avance 400 (100.62 MHz for13And 400.13 MHz for1H) by standard methods (Bruker, internal standard Me4Si, solvent CDCl3. Mass high resolution spectra obtained on the instrument MALDI TOF/TOF AUTOFLEX III (Bruker).) 3,3'-(3,4-ditegakkan-1,6-diyl)bis-1,5,3-diazepinone:

An NMR spectrum1H (δ, ppm, CDCl3): 2.84 m (4H, H-9, H-9/); 2.90 t (4H, J=5.2 Hz, H-8, H-8/); 3.06 USS (8H, H-6, H-6/, H-7, H-7/); 4.18 USS (8H, H-2, H-2/N-4, N-4/). An NMR spectrum13C (δ, ppm): 35.85 (C-6, C-6/C-7, C-7/); 36.71 (C-9, C-9/); At 50.06 (C-8, C-8/); 59.40 (C-2, C-2/C-4, C-4/). MALDI TOF, m/z: 387.173 [M-H]+. C12H23N2S 6.

The way to obtain 3,3'-[oxa(thia)alkane-α,ω-diyl]-bis-1,5,3-diazepinones General formula (1):

wherein oxa(thia)alkane-α,ω-diamine (3-oxapentane-1,5-diamine, 3,6-dioxaoctyl-1,8-diamine, 3,4-ditegakkan-1,6-diamine) is subjected to interaction with 1-oxa-3,6-ditzikloverina in the solvent system ethanol-chloroform in the environment of argon in the presence of a catalyst SmCl3·6H2O when the molar ratio oxa(thia)alkane-α,ω-diamine : 1-oxa-3,6-directloan : SmCl3·6H2O = 10 : 20 : (0.3-0.7) under room temperature (~20°C) temperature for 2.5-3.5 hours



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to field of organic chemistry, namely, to method of obtaining N-(1,5,3-dithiazonan-3-yl)amides of general formula (1) where R=p-C5H4N (a), (CH3)3CO (b), m-C5H4N (c), which consists in the fact, that N1,N1,N8,N8-tetramethyl-2.7-dithiaoctane-1.8-diamine is subjected to interaction with hydrazide of general formula RC(O)NHNH2 [R=upper said] in presence of catalyst samarium nitrate crystalhydrate Sm(NO3)3·6H2O, at molar ratio N1,N1,N8,N8-tetramethyl-2.7-dithiaoctane-1.8-diamine: RC(O)NHNH2 : Sm(NO3)3·6H2O = 10 : 10 : (0.3-0.7) at temperature 75-85°C and atmospheric pressure in mixture of solvents ethyl alcohol-chloroform for 20-28 h.

EFFECT: method of obtaining novel compounds, which can be applied as biologically active compounds, selective sorbents and extractants of noble and precious metals, is developed.

1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula or , where Ar1 represents phenyl group, optionally substituted with one or several identical or non-identical halogen atoms; R1 represents hydrogen atom; R4, R5, R6a, R6b represent hydrogen atoms; Y, Z independently represent linear C1-4 alkylene group, optionally substituted with one linear C1-4 alkyl group; Ar2 stands for condensed with benzene 5-membered heterocyclic ring, containing one nitrogen atom and one sulphur atom, substituted with one linear C1-4 alkyl group, or derivative of 5- or 6-membered heterocyclic ring, containing one nitrogen atom and one sulphur atom, condensed with heteroaromatic 6-memebered ring, containing one or two nitrogen atoms, substituted with one linear C1-4 alkyl group, linear C1-4 alkoxygroup or group -NR7R8, where R7 and R8 independently stand for hydrogen atom, linear or branched C1-4 alkyl group, or R7 and R8 together with nitrogen atom form group of general formula , where R2, R3 represent linear C1-4 alkyl groups, A stands for group -CHR12, oxygen atom or group -NR9, where R12 and R9 stand for hydrogen atom or linear C1-4 alkyl group, m has value 1 or 2, n has value 1 or 2, o has value 0 or 1, p has value 0 or 1, Q stands for group -O-, group -N--H or group -N--CO-R10, where R10 stands for linear C1-4 alkyl group or -NH-R11 group, where R11 represents linear C1-4 alkyl group; and to their salts. Invention also relates to methods of obtaining therein and to based on them pharmaceutical composition, possessing antagonistic activity with respect to receptor CCR3.

EFFECT: obtained are novel compounds and based on them pharmaceutical compositions, which can be applied in medicine for obtaining medication, intended for treating asthma, allergic rhinitis, atopic dermatitis, eczema, inflammatory intestinal diseases, ulcerous colitis, Crohn's disease, allergic conjunctivitis, multiple sclerosis or HIV-infection and AIDS-associated diseases.

14 cl, 3 tbl, 26 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a method of producing a salt of tetrazole methanesulphonic acid of formula (I) , which involves acylating a compound (II) with a compound (III) and then adding methanesulphonic acid. The invention also relates to an intermediate compound of formula (II) and a method for production thereof.

EFFECT: method according to the present invention can cut reaction time, improve safety and enables to obtain salts of tetrazole methanesulphonic acid of high purity with high output without using a column chromatography technique.

22 cl, 2 tbl, 3 ex

FIELD: biotechnologies.

SUBSTANCE: invention refers to a compound of formula (I):

,

where R1 represents NR7C(O)R8 or NR9R10; R2 represents hydrogen; R3 represents halogen; R4 represents hydrogen, halogen, cyano, hydroxy, C1-4alkyl, C1-4alkoxy, CF3, OCF3, C1-4alkylthio, S(O)(C1-4alkyl), S(O)2(C1-4alkyl), CO2H or CO2(C1-4alkyl); R5 represents C1-6alkyl (replaced with NR11R12 or heterocyclyl that represents nonaromatic 5-7-membered ring containing 1 or 2 heteroatoms independently chosen from a group containing nitrogen, oxygen or sulphur); R6 represents hydrogen, halogen, hydroxy, C1-4alkoxy, CO2H or C1-6alkyl (possibly replaced with NR15R16 group, morpholinyl or thiomorpholinyl); R7 represents hydrogen; R8 represents C3-6cycloalkyl (possibly replaced with NR24R25 group), phenyl or heteroaryl, which represents aromatic 5- or 6-membered ring containing 1 to 3 heteroatoms independently chosen from the group containing nitrogen, oxygen and sulphur, and which is probably condensed with one 6-membered aromatic or nonaromatic carbocyclic ring or with one 6-membered aromatic heterocyclic ring, where the above 6-membered aromatic heterocyclic ring includes 1 to 3 heteroatoms independently chosen from a group containing nitrogen, oxygen and sulphur; R9 represents hydrogen or C1-6alkyl (possibly replaced with pyrazolyl); R10 represents C1-6alkyl (possibly replaced with phenyl or heteroaryl group, which represents aromatic 5- or 6-membered ring containing 1 or 2 heteroatoms independently chosen from the group containing nitrogen, oxygen or sulphur, and which is possibly condensed with one 6-membered heterocyclic ring, where the above 6-membered aromatic heterocyclic ring contains 1 or 2 heteroatoms independently chosen from the group containing nitrogen, oxygen or sulphur; where the above phenyl and heteroaryl groups in R8, R9 and R10 are possibly independently replaced with the following group: halogen, hydroxy, C(O)R42, C1-6alkyl, C1-6hydroxyalkyl, C1-6halogenoalkyl, C1-6alkoxy(C1-6)alkyl or C3-10cycloalkyl; unless otherwise stated, heterocyclyl is possibly replaced with group of C1-6alkyl, (C1-6alkyl)OH, (C1-6alkyl)C(O)NR51R52 or pyrrolidinyl; R42 represents C1-6alkyl; R12, R15 and R25 independently represent C1-6alkyl (possibly replaced with hydroxy or NR55R56 group); R11, R16, R24, R51, R52, R55 and R56 independently represent hydrogen or C1-6alkyl; or to its pharmaceutically acceptable salts.

EFFECT: new compounds are obtained, which can be used in medicine for treatment of PDE4-mediated disease state.

10 cl, 2 tbl, 202 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to compounds of formula or a pharmaceutically acceptable salt of such a compound, where - X is a carbon atom and R1a and R2a together form a bond; or - X is a carbon atom, R1a and R2a together form a bond, and R1 and R2 together form a moiety , where the asterisk shows the bonding site of R2; or - X is a carbon atom, R1a is hydrogen or (C1-4)alkoxy, and R2a is hydrogen; and R1 and R2, unless indicated otherwise, independently denote hydrogen; (C1-5)alkyl; aryl, where aryl denotes naphthyl or phenyl, where said aryl is unsubstituted or independently mono- or disubstituted, where the substitutes are independently selected from a group consisting of (C1-4)alkyl, (C1-4) alkoxy and halogen; or heteroaryl, selected from pyridyl, thienyl, oxazolyl or thiazolyl, where said heteroaryl is unsubstituted; under the condition that if R2 is aryl or heteroaryl, R1 cannot be aryl or heteroaryl, where the aryl and heteroaryl are independently unsubstituted or substituted as defined above; R3 is hydrogen or -CO-R31; R31 is (C1-5)alkyl, (C1-3)fluoroalkyl or (C3-6)cycloalkyl; n equals 1, 2, 3 or 4; B is a -(CH2)m- group, where m equals an integer from 1 to 3; A is-(CH2)P-, where p equals 2 or 3; R4 is (C1-5)alkyl; W is , where R5 is hydrogen or (C1-5)alkyl; R8, R9 and R10 is independently hydrogen, halogen, (C1-5)alkyl, hydroxy, -(C1-5)alkoxy, -O-CO-(C1-5)alkyl, (C1-3)fluoroalkyl, (C1-3)fluoroalkoxy, -CO-(C1-5)alkoxy, (C1-2)alkoxy-(C1-4)alkoxy or -NH-CO-(C1-5)alkyl. The invention also relates to a pharmaceutical composition based on a compound of formula (I).

EFFECT: novel compounds which are useful as calcium channel blockers are obtained.

11 cl, 2 tbl, 166 ex

FIELD: chemistry.

SUBSTANCE: invention relates to triazole compounds which are represented by specific chemical formulae and which can be used for preventing or treating diseases in which 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) participates, particularly dementia. It was found that the triazole derivative, in which one of 3rd and 5th positions of the triazole ring accommodates a (di)alkyl methyl or cycloalkyl, each substituted, -O-aryl or heterocyclic group, each of which can be substituted, or (lower alkylene)cycloalkyl, and the other position accommodates an aryl, heterocyclic or cycloalkyl group, each of which can be substituted, or a pharmaceutically acceptable salt thereof, has powerful inhibiting action on 11β-HSD1.

EFFECT: improved properties of the derivatives.

8 cl, 141 tbl, 89 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) , where is a substituted 5-member heteroaryl ring selected from thienyl, thiazolyl, oxazolyl, pyrrolyl, imidazolyl or pyrazolyl, W is selected from a group comprising N and -C=; M is selected from a group comprising -C(O)N(R1)OR2, -CXCONR1R2 and -C(O)OR1, or M is -C1-C2alkyl-C(O)N(R1)OR2, wherein is , R1 and R2 are independently selected from a group comprising -H, C1-C3-alkyl, C6-aryl, and C1-C3-alkyl-C6-aryl; R is selected from a group comprising H, C1-C3alkyl, halogen, NR1R2, -OR1 and C6aryl; n is an integer from 0 to 1; L and Y are as indicated in the claim; and to compounds of formula (II) , where L2 is selected from a group comprising H, - C0-C3alkyl- C6aryl, -C0-C3alkyl-heteroaryl, where the heteroaryl is pyridyl; -C1-C6alkyl, Y and M are the same as for compounds of formula (I). The invention also relates to a pharmaceutical composition based on compounds (I) and (II), having inhibiting action on histone deacetylase (HDAC), a method of inhibiting and a method of treating a disease which is sensitive to the HDAC inhibitor.

EFFECT: compounds of formula I and II as histone deacetylase inhibitors.

18 cl, 18 dwg, 10 tbl, 19 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel phenylaminopyrimidine compounds of formula I, which are JAK kinase inhibitors. In particular, these compounds selectively act on JAK2 kinase. The compounds can be used to treat diseases such as immunological and inflammatory diseases; hyperproliferative diseases, myeloproliferative diseases; viral diseases; metabolic diseases; and vascular diseases. In the compound of formula I , Q and Z are independently selected from N and CR1; R1 is independently selected from hydrogen, halogen, R2, OR2, OH, R4, OR4, CN, CF3, (CH2)nN(R2)2, where n equals 1,2 or 3, NO2, R2R4, NR2SO2R3, COR4, NR2COR3, CO2H, CO2R2, NR2COR4, R2CN, R2OH, R2OR3 and OR5R4; or two substitutes R1 together with carbon atoms with which they are bonded form an unsaturated 5- or 6-member heterocyclic ring containing 1-4 N atoms; R2 is C1-4alkyl; R4 is R2, C2-4alkenyl or phenyl; R4 is NH2, NHR2, N(R1)2, substituted or unsubstituted morpholine, CH2morpholine, substituted or unsubstituted thiomorpholine, substituted or unsubstituted thiomorpholino-1-oxide, substituted or unsubstituted thiomorpholino-1,1-dioxide, substituted or unsubstituted piperazinyl, substituted or unsubstituted piperidinyl, substituted or unsubstituted pyridinyl, substituted or unsubstituted pyrrolidinyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted imidazolyl, substituted or tetrahydrofuranyl unsubstituted and substituted or unsubstituted tetrahydropyranyl; R5 is C2-4alkylene; R6-R9 are independently selected from H, RXCN, halogen, substituted or unsubstituted C1-4alkyl, OR1, CO2R1, N(R1)2, NO2 and CON(R1)2, wherein at least one of R6-R9 is RXCN; the rest of the values of the radicals are given in the claim.

EFFECT: high efficiency of treatment.

29 cl, 7 dwg, 2 tbl, 93 ex

FIELD: chemistry.

SUBSTANCE: invention relates organic chemistry and specifically to novel pyridine amide derivatives of general formula I where n equals 1; R1 and R2 together denote a residue selected from a group consisting of -CH=N-NH- and -CH=CH-N=CH-, which is bonded in any desirable direction to the parent structure or R2 and R3 together denote a residue selected from a group consisting of -CH=N-NH-; -CR28=N-NH-; -S-C(=S)-NH-; -S-CR29=N-; -N=CR30-O-; -N=CH-NH-; -N=N-NH-; -O-CH2-O-; -CH2-CH2-CH2-NH, -O-CH2-CH2-O-; -N=CH-CH=N-; -CH=CH-CH=N-, which is bonded in any desirable direction to the parent structure, or R3 and R4 together denote a -CH=N-NH- residue, which is bonded in any desirable direction to the parent structure, or R4 and R5 together denote a -CH=N-NH- residue, which is bonded in any desirable direction to the parent structure, and the rest of the residues R1, R2, R3, R4 and R5, mutually independently, in each case denote H; where R28 denotes F; Cl; Br or I; R29 and R30, mutually independently, in each case denote -NH-C(=O)-R31; -NH2; -NH-S(=O)2-R32; -NH-C(=O)-O-R33; -S-R34; where R31, R32, R33 and R34, mutually independently, in each case denote a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; R6 denotes H or denotes a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; R7 denotes hydrogen or -OH; R denotes -CF3; or denotes an unsubstituted tert-butyl residue; T denotes C-R35 and U denotes C-R36, V denotes N and W denotes C-R38; where R35 and R36 denote H; where R38 denotes -NR40R41; -OR42 or -SR43; where R40, R41, R42 and R43, mutually independently, in each case denote a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; or denote a saturated, unsubstituted 3-, 4-, 5-, 6-, 7-, 8- or 9-member cycloaliphatic residue, or where R40 and R41 in each case together with a nitrogen atom as a ring member which binds them together, form a saturated 6-member heterocycloaliphatic residue, optionally substituted with one R57 residue, where R57 denotes a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; in each case in form of corresponding physiologically acceptable salts. The invention also relates to a method of producing a compound of formula I, a medicinal agent based on the compound of formula I and use of the compound of formula I.

EFFECT: obtaining novel amide derivatives of pyridine, useful in treating vanilloid receptor 1 mediated diseases.

25 cl, 1 tbl, 18 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula or a pharmaceutically acceptable salt thereof, wherein G1 is phenyl or pyridyl, each of which is optionally additionally substituted by one substitute presented by T; G2 is phenyl, 1,3-thiazolyl or 1,3-oxazolyl, wherein G2 is bound to G1 in the para position in relation to a place of attachment of G1 to group NH in formula (I), wherein G2 means phenyl, G3 is bound to G2 in the para position of G2 in relation to G1, and wherein provided G2 represents 1,3-thiazolyl or 1,3-oxazolyl, G2 is bound to G1 in the position of 5 G2 and G3 is bound to G2 in the position of 2 G2; T in each case is independently specified in a group containing C1-6alkyl and halogen; G3 is presented by formula or by formula ; W1 is -C(R3)(R4)-C(R3)(R4)-, and W2 represents N; or W3 represents O; W4 is -C(R3)(R4) -; each R3 and R4 is hydrogen; each R5 and R6 kis hydrogen; Rc and Rd together with a carbon atom whereto attached, are a 4-5-member cycloalkyl or monocyclic heterocycle of formula ; wherein one hydrogen atoms attached to the carbon atom of the cycloalkyl ring and monocyclic heterocycle is optionally substituted by a radical specified in a group -C(O)O(R8); W5 is -CH2- or -CH2-CH2-; W6 is O or N(RX), wherein Rx is hydrogen, C1-6alkyl or -C(O)O(Rz); RZ in each case is independently C1-6alkyl; R8 is hydrogen; L1 is O; and X is hydrogen, C1-6alkyl, or - (CRgRh)u-C(O)O(R10); or L1 is -CH2- and X is -C(O)OH; R10 is hydrogen; or Q is G4 or Y1-Y3; or Q is described for formula wherein Z is phenyl; G4 is benzothiazole or benzoxazole optionally additionally substituted by 1 or 2 substitutes specified in a group consisting of C1-6alkyl, halogen and -OR1; Y1 in each case is independently -C(O)-, -C(O)O- or -C(O)N(Rw)-, wherein the right side -C(O)O- and -C(O)N(Rw)- of the groups is attached to Y3 or (CRJRk)v, Y3 in each case is independently phenyl, benzyl, piperidinyl or bicyclo[4.2.0]octa-1,3,5-triene, wherein the phenyl and benzyl residues are optionally additionally substituted by 1 or 2 substitutes specified in a group consisting of halogen and haloC1-6alkyl; Rg and Rh in each case is independently hydrogen, or C1-6alkyl; R1 in each case is independently halogenC1-6alkyl; Rw is hydrogen; and u means 1.

EFFECT: compounds being the type 1 diacylglycerol O-acyltransferase (DGAT-1) enzyme inhibitors.

7 cl, 1 tbl, 61 ex

FIELD: organic chemistry, heterocyclic compounds, medicine, pharmacy.

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

wherein m = 1, 2 or 3; q means NH or oxygen atom (O); R1, R2, R3, R4 and R5 are taken independently among the group including hydrogen atom, (C1-C15)-alkyl, OR20 wherein R20 represents hydrogen atom; R6, R7 and R8 represent hydrogen atom; R9, R10, R11, R12, R13, R14, R15 and R16 are taken independently among the group including hydrogen atom, (C1-C4)-alkyl; or R9 and R10 in common with carbon atom to which they are joined form carbonyl group; R17 means heteroaryl that is taken among the group including indolyl, benzoxazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, pyridyl, benzopyrazinyl substituted optionally with 1-2 substitutes taken among the group including hydrogen atom, CF3 group, (C1-C8)-alkyl, phenyl, CON(R20)2. Compounds elicit property as a partial inhibitor of oxidation of fatty acids and can be used in therapy for protection of skeletal muscles against results of muscular or systemic diseases. Also, invention describes a pharmaceutical composition based on the claimed compounds.

EFFECT: valuable medicinal properties of compounds.

39 cl, 3 tbl, 25 ex

FIELD: organic chemistry, pharmaceutical composition.

SUBSTANCE: new isoindoline-1-on-glucokinase activators of general formula I , as well as pharmaceutically acceptable salts or N-oxide thereof are disclosed. In formula A is phenyl optionally substituted with one or two halogen or one (law alkyl)sulfonyl group, or nitro group; R1 is C3-C9cycloalkyl; R2 is optionally monosubstituted five- or six-membered heterocyclic ring bonded via carbon atom in cycle to amino group, wherein five- or six-membered heteroaromatic ring contains one or two heteroatoms selected form sulfur, oxygen or nitrogen, one of which is nitrogen atom adjacent to carbon atom bonded to said amino group; said cycle is monocyclic or condensed with phenyl via two carbon atoms in cycle; said monosubstituted with halogen or law alkyl heteroaromatic ring has monosubstituted carbon atom in cycle which in not adjacent to carbon atom bonded to amino group; * is asymmetric carbon atom. Claimed compounds have glucokinase inhibitor activity and useful in pharmaceutical composition for treatment of type II diabetes.

EFFECT: new isoindoline-1-on-glucokinase activators useful in treatment of type II diabetes.

23 cl, 3 dwg, 43 ex

FIELD: pharmaceutical industry, medicine.

SUBSTANCE: invention relates to 5-membered N-heterocyclic compounds and salts thereof having hypoglycemic and hypolipidemic activity of general formula I , wherein R1 is optionally substituted C1-C8-alkyl, optionally substituted C6-C14-aryl or optionally substituted 5-7-membered heterocyclic group, containing in ring 1-4 heteroatoms selected from oxygen, sulfur and nitrogen; or condensed heterocyclic group obtained by condensation of 5-7-membered monoheterocyclic group with 6-membered ring containing 1-2 nitrogen atoms, benzene ring, or 5-membered ring containing one sulfur atom; { is direct bond or -NR6-, wherein R6 is hydrogen atom or C1-C6-alkyl; m = 0-3, integer; Y is oxygen, -SO-, -SO2- or -NHCO-; A ring is benzene ring, condensed C9-C14-aromatic hydrocarbon ring or 5-6-membered aromatic heterocyclic ring containing 1-3 heteroatoms selected from oxygen and nitrogen, each is optionally substituted with 1-3 substituents selected from C7-C10-aralkyloxy; hydroxyl and C1-C4-alkoxy; n = 1-8, integer; B ring is nitrogen-containing 5-membered heterocycle optionally substituted with C1-C4-alkyl; X1 is bond, oxygen or -O-SO2-; R2 is hydrogen atom, C1-C8-alkyl, C7-C13-aralkyl or C6-C14-aryl or 5-6-membered heterocyclic group containing in ring 1-3 heteroatoms selected from oxygen, sulfur and nitrogen, optionally substituted with 1-3 substituents; W is bond, C1-C20-alkylene or C1-C20-alkenylene; R3 is -OR8 (R8 is hydrogen or C1-C4-alkyl) or -NR9R10 (R9 and R10 are independently hydrogen or C1-C4-alkyl). Compounds of present invention are useful in treatment of diabetes mellitus, hyperlipidemia, reduced glucose tolerance, and controlling of retinoid-associated receptor.

EFFECT: new medicines for treatment of diabetes mellitus, hyperlipidemia, etc.

26 cl, 518 ex, 3 tbl

FIELD: organic chemistry.

SUBSTANCE: method relates to new method for production of 5-chloro-4-[(2-imidazoline-2-yl)amino]-2,1,3-benzothiadiazole hydrochloride of formula I . Claimed compound is high effective drug and is used in medicine as myorelaxant of central action. Claimed method includes condensation of N,N-dimethyldichloromethyleneammonium chloride with 5-chloro-4-amino-1,1,3-benzothiadiazole in organic solvent followed by treatment of formed alpha-chloroformamidine of formula R-N=C(Cl)N(CH3)2, wherein R is 5-chloro-2,1,3-benzothiazol-4-yl, with ethylenediamine. Formed intermediate of formula R-N=C(NH-CH2-CH2-NH2)N(CH3)2 is treated with hydrochloric acid, heated in organic solvent and 5-chloro-4-[(2-imidazoline-2-yl)amino]-2,1,3-benzothiadiazole hydrochloride of formula I is isolated.

EFFECT: simplified method for preparation of target compound directly in hydrochloride form.

FIELD: organic chemistry, chemical technology, agriculture.

SUBSTANCE: invention describes substituted azadioxocycloalkenes of the general formula (I): wherein A means unsubstituted or methyl-substituted dimethylene; Ar means unsubstituted or fluorine-substituted ortho-phenylene, thiophendiyl or pyridindiyl; E means group of the formula: wherein G means oxygen atom, groups -O-CH2-, -CH2-O- or -C(CH3)=N-O-CH2-; Z means unsubstituted or substituted phenyl, pyrimidinyl or thiadiazolyl, or naphthyl. Invention describes 4 methods for preparing compounds of the formula (I), 5 species of intermediate compounds used for preparing compounds of the formula (I), fungicide agents comprising compound of the formula (I) as an active substance, a method for preparing fungicide agents, method for control of harmful fungi using compound of the formula (I). Compounds of the formula (I) show fungicide properties and therefore they can be used in agriculture.

EFFECT: improved preparing methods, valuable properties of compounds.

13 cl, 5 tbl, 18 ex

FIELD: organic chemistry, pesticides, agriculture.

SUBSTANCE: invention relates to compounds that elicit high pesticide activity and can be used in control of pests of domestic and agricultural animals. Indicated compounds show the formula (I):

wherein R1 means halogen atom, (C1-C6)-halogenalkyl; R2 means hydrogen atom (H), (C1-C6)-alkyl, (C1-C6)-alkylene-phenyl; X1 means nitrogen atom (N); X2 means group C(CN); X3 means oxygen atom (O); Q means CH; R3 and R4 mean independently of one another hydrogen atom (H) or in common with carbon atom with which they are bound form (C3-C7)-cycloalkyl ring; R5 means a substitute taken among group including (C1-C6)-halogenalkyl, halogen atom being if m above 1 then substitutes R5 can be similar or different; m = 1, 2 or 3; n = 0 or 1. Also, invention describes a method for their preparing and method for control of pests.

EFFECT: valuable pesticide properties of compounds.

7 cl, 3 tbl, 14 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, chemical technology, medicine.

SUBSTANCE: invention relates to a method for preparing derivatives of indole of the general formula (I):

wherein R1 represents hydroxy-group; R2 represents hydrogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, (C2-C6)-alkoxyalkyl or 4-methoxybenzyl; R3 represents hydrogen atom or (C1-C6)-alkyl; each among R4 and R represents independently hydrogen atom, (C1-C6)-alkyl or (C1-C6)-alkoxy-group; D represents an ordinary bond, (C1-C6)-alkylene, (C2-C6)-alkenylene or (C1-C6)-oxyalkylene; in the group-G-R6 wherein G represents an ordinary bond, (C1-C6)-alkylene; R represents saturated or unsaturated carbocyclic ring (C3-C15) or 4-15-membered heterocyclic ring comprising 1-5 atoms of nitrogen, sulfur and/or oxygen wherein this ring can be substituted. Also, invention describes a method for preparing derivatives of indole and DP-receptor antagonist comprising derivative of the formula (I) as an active component. As far as compounds of the formula (I) bind with DP-receptors and they are antagonists of DP-receptors then they can be useful for prophylaxis and/or treatment of diseases, for example, allergic diseases.

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

11 cl, 7 tbl, 353 ex

FIELD: pharmaceutical chemistry, medicine.

SUBSTANCE: invention relates to substituted pyridines and pyridazines with angiogenesis inhibition activity of general formula I

(I)1, wherein ring containing A, B, D, E, and L represents phenyl or nitrogen-containing heterocycle; X and Y are various linkage groups; R1 and R2 are identical or different and represent specific substituents or together form linkage ring; ring J represents aryl, pyridyl or cycloalkyl; and G's represent various specific substituents. Also disclosed are pharmaceutical composition containing claimed compounds, as well as method for treating of mammalian with abnormal angiogenesis or treating of increased penetrability using the same.

EFFECT: new pyridine and pyridazine derivatives with angiogenesis inhibition activity.

26 cl, 6 tbl, 114 ex

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention elates to novel derivatives of uracil of the formula [I] possessing herbicide activity, a herbicide composition based on thereof and to a method for control of weeds. In derivatives of uracil of the formula [I] the group Q-R3 represents a substituted group taken among:

wherein a heterocyclic ring can be substituted with at least a substitute of a single species taken among the group involving halogen atom, (C1-C6)-alkyl-(C1-C6)-alkoxy; Y represents oxygen, sulfur atom, imino-group or (C1-C3)-alkylimino-group; R1 represents (C1-C3)-halogenalkyl; R2 represents (C1-C3)-alkyl; R3 represents OR7, SR8 or N(R9)R10; X1 represents halogen atom, cyano-group, thiocarbamoyl or nitro-group; X2 represents hydrogen or halogen atom wherein each among R7, R8 and R10 represents independently carboxy-(C1-C6)-alkyl and other substitutes given in the invention claim; R9 represents hydrogen atom or (C1-C6)-alkyl. Also, invention relates to intermediate compounds used in preparing uracil derivatives.

EFFECT: improved preparing method, valuable properties of compounds.

40 cl, 16 sch, 12 tbl, 65 ex

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