Method of selective obtaining 3,3'-[methylenebis(1,4-phenylene)]-, 3,3'-[oxybis(1,4-phenylene)]- and 3,3'-(3,3'-dimethoxybiphenyl-4, 4'-diyl)-bis-1,5,3-dithiazepinanes

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry, namely to method of obtaining 3,3'-[methylenebis(1,4-phenylene)]-, 3,3'-[oxybis(1,4-phenylene)]- and 3,3'-(3,3'-dimethoxybiphenyl-4, 4'-diyl)-bis-1,5,3-dithiazepinanes of general formula (1): R=4-C6H4-CH2-C6H4-4/, 4-C6H4-O-C6H4-4/, 4-H3COC6H3-C6H3OCH3-4/ which consists in the following: arylamines [diaminodiphenylmethane, diaminodiphenyloxide, dimethoxybenzidine] undergo interaction with N-tert-butyl-1,5,3-dithiazepinane in presence of catalyst Sm(NO3)3·6H2O in argon atmosphere with molar ratio arylamine:N-tert-butyl-1,5,3-dithiazeoinane: Sm(NO3)3·6H2O = 10 : 20 : (0.3-0.7) at temperature ~20°C in system of solvents ethanol-chloroform for 2.5-3.5 h.

EFFECT: increased efficiency of applying compound as antibacterial, antifungal and antiviral agents, biologically active complexants, selective sorbents and extractants of precious metals, special reagents for suppressing bacterial vital activity in different technical media.

1 tbl, 1 ex

 

The present invention relates to organic chemistry, particularly to a method for selective receipt of 3,3'-[Methylenebis(1,4-phenylene)]-, 3,3'-[oxybis(1,4-phenylene)]and 3,3'-(3,3'-dimethoxybiphenyl-4,4'-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 Pharma, 1995, 45, 511; Tyukavkina N.A., Zurabyan SE, Beloborodov V.L. and other Organic chemicals. M: Bustard, 2008, 66). 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 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. atent of the Russian Federation No. 2206726, 2003).

The known method (Patent RF №2333910; B. I., 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'-[Methylenebis(1,4-phenylene)]-, 3,3'-[oxybis(1,4-phenylene)]and 3,3'-(3,3'-dimethoxybiphenyl-4,4'-diyl)-bis-1,5,3-diazepinone 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'-[Methylenebis(1,4-phenylene)]-, 3,3'-[oxybis(1,4-phenylene)]and 3,3'-(3,3'-dimethoxybiphenyl-4,4'-diyl)-bis-1,5,3-diazepinone General formula (1).

The known method (Seraphita, Vremeto, Lphraw, Tavakilov, Grenadilla, Rvenue, Aagrawal, Usmjerili. 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-dicease the Ana (3) three-component condensation of hydrogen sulfide with formaldehyde and Ethylenediamine, 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 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'-[Methylenebis(1,4-phenylene)]-, 3,3'-[oxybis(1,4-phenylene)]and 3,3'-(3,3'-dimethoxybiphenyl-4,4'-diyl)-bis-1,5,3-diazepinone General formula (1).

Thus, the literature contains no information about selective receipt of 3,3'-[Methylenebis(1,4-phenylene)]-, 3,3'-[oxybis(1,4-phenylene)]and 3,3'-(3,3'-dimethoxybiphenyl-4,4'-diyl)-bis-1,5,3-diazepinones General formula (1).

We propose a new method of obtaining 3,3'-[Methylenebis(1,4-phenylene)]-, 3,3'-[oxybis(1,4-phenylene)]and 3,3'-(3,3'-dimethoxybiphenyl-4,4'-diyl)-bis-1,5,3-diazepinones General formula (1).

The method consists in the interaction of arylamine General formula H2N-R-NH2where R=4-C6H4-CH2-C6H4-4', 4-C6H4-O-C6H4-4', 4-H3COC6H3-C6H3OCH3-4' (diaminodiphenylmethane, diaminodiphenylamine or dimethoxybenzidine) with N-tert-butyl-diazepinone in argon in the presence of catalyst S(NO 3)3·6H2O when the molar ratio arylamine:N-tert-butyl-1,5,3-diazepine:Sm(NO3)3·6H2O=10:20:(0.3-0.7), preferably 10:20:0.5, at room temperature (~20°C) and atmospheric pressure in the solvent system ethanol-chloroform for 2.5-3.5 hours the Yield of 3,3'-[Methylenebis(1,4-phenylene)]-, 3,3'-[oxybis(1,4-phenylene)]and 3,3'-(3,3'-dimethoxybiphenyl-4,4'-diyl)-bis-1,5,3-diazepine (1) is 52-65%. The reaction proceeds according to the scheme:

4-C6H4-CH2-C6H4-4', 4-C6H4-O-C6H4-4', 4-H3COC6H3-C6H3OCH3-4'

3,3'-[Methylenebis(1,4-phenylene)]-, 3,3'-[oxybis(1,4-phenylene)]and 3,3'-(3,3'-dimethoxybiphenyl-4,4'-diyl)-bis-1,5,3-diazepinone General formula (1) are formed only with the participation of diaminodiphenylmethane, diaminodiphenylamine or dimethoxybenzidine and N-tert-butyl-1,5,3-diazepinone under the action of catalyst Sm(NO3)3·6H2O. In the presence of other diamines (for example, alkeneamine) target products (1) are not formed.

Conducting the reaction in the presence of a catalyst Sm(NO3)3·6H2O more than 7 mol.% in relation to arylamino not lead to a significant increase of 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 decrease is the group of 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 the solvent system ethanol-chloroform, as they are highly soluble source reagents.

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 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'-[Methylenebis(1,4-phenylene)]-, 3,3'-[oxybis(1,4-phenylene)]and 3,3'-(3,3'-dimethoxybiphenyl-4,4'-diyl)-bis-1,5,3-diazepinone General formula (1).

In the proposed method, the reaction proceeds with the participation of as initial reagents N-tert-butyl-1,5,3-diazepinone and diaminodiphenylmethane, diaminodiphenylamine or dimethoxybenzidine 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'-[Methylenebis(1,4-phenylene)]-, 3,3'-[oxybis(1,4-phenylene)]and 3,3'-(3,3'-dimethoxybiphenyl-4,4'-diyl)-bis-1,5,3-diazepinone General formula (1), the synthesis of which in the literature is not OPI is an.

The method is illustrated by the following examples:

EXAMPLE 1. In the vessel Slanka mounted on a magnetic stirrer, an argon atmosphere was placed 198 mg (10 mmol) of diaminodiphenylmethane in 5 ml of ethanol, 22 mg (0.5 mmol) Sm(NO3)3·6H2O, and then added dropwise 382 mg (20 mmol) N-tert-butyl-1,5,3-diazepinone 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'-[methylene-bis-(1,4-phenylene)]bis-1,5,3-diazepine with the release of 60%.

Other examples of the method are given in table 1.

Table 1
№№ p/pSource α,ω-diamineThe ratio of α,ω-diamine, N-tert-butyl-1,5,3-diazepine: Sm(NO3)3-6H2O mmolReaction time, hoursOutput (1), %
1diaminodiphenylmethane10:20:0.5360
4-"-10:20:0.7 365
5-"-10:20:0.3355
6-"-10:20:0.53.564
7-"-10:20:0.52.552
8diaminodiphenylamine10:20:0.5355
9dimethoxybenzidine10:20:0.5353

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

The spectral characteristics of 3,3'-[methylene-bis-(1,4-phenylene)]bis-1,5,3-diazepinone1:

(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. The NMR spectra of 1D (1H13C) and 2D (COSY, HSQC, NMVS) removed the and spectrometer Broker Avance 400 (100.62 MHz for 13C and 400.13 MHz for1H) by standard methods (Bruker, internal standard Me4Si, solvent CDCl3. Mass spectra were obtained on the instrument MALDI TOF/TOF AUTOFLEX III (Bruker).

The white crystalline substance, TPL 145-147°C, Rf0.80 (Sorbfil, benzene-ethanol, 9:1). An NMR spectrum1H (400 MHz, CDCl3), δ, M. D. (J, Hz): 3.07 (8H, ush. C, H-6, H-6', H-7, H-7'); 3.87 (2H, ush. C, H-14); 4.77 (8H, ush. s, H-2, H-2', H-4, H-4'); 6.87 (4H, d, J=8.8 Hz, H-9, H-13, H-9', H-13'); 7.14 (4H, d, J=8.8 Hz, H-10, H-12, H-10', H-12'). An NMR spectrum13S, δ, M. D.: 35.8 (C-6, C-6', C-7, C-7'); 40.1 (C-14); 55.2 (C-2, C-2', C-4, C-4'); 116.1 (C-9, C-9', C-13, C-13'); 129.6 (C-10, C-10', C-12, C-12'); 133.1 (C-11, C-11'); 144.0 (C-8, C-8'). MALDI TOF, m/z 457.172 [M+Na]+(C21H26N2S4Na).

The spectral characteristics of 3,3'-[oxybis-1,4-phenylene)]bis-1,5,3-diazepinone2:

(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 NMR spectra of 1D (1H13C) and 2D (COSY, HSQC, NMVS) removed spectrometer Broker Avance 400 (100.62 MHz for13C and 400.13 MHz for1H) by standard methods (Bruker, internal standard Me4Si, solvent CDCl3. Mass spectra were obtained on the instrument MALDI TOF/TOF AUTOFLEX III (Bruker).

Light yellow oil, Rf0.85 (Sorbfil, benzene-ethanol, 9:1). An NMR spectrum1 H (400 MHz, CDC13), δ, M. D. (J, Hz): 3.06 (8H, ush. C, H-6, H-6', H-7, H-7'); 4.73 (8H, ush. s, H-2, H-2', H-4, H-4'); 6.89 (4H, d, J=9.2 Hz, H-9, H-13, H-9', H-13'); 6.96 (4H, d, J=8.8 Hz, H-10, H-12, H-10', H-12'). An NMR spectrum13C, δ, M. D.: 35.9 (C-6, C-6', C-7, C-7'); 55.7 (C-2, C-2', C-4, C-4'); 117.7 (C-9, C-9', C-13, C-13'); 119.5 (C-10, C-10', C-12, C-12'); 141.8 (C-8, C-8'); 151.3 (C-11, C-11'). MALDI TOF, m/z 436.228 [M] (C20H24N2OS4).

The spectral characteristics of 3.3'-(3.3'-dimethoxybiphenyl-4,4'-diyl)-bis-1,5,3-diazepinone3:

(3Control 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. The NMR spectra of 1D (1H13C) and 2D (COSY, HSQC, NMVS) removed spectrometer Broker Avance 400 (100.62 MHz for13C and 400.13 MHz for1H) by standard methods (Bruker, internal standard Me4Si, solvent CDCl3. Mass spectra were obtained on the instrument MALDI TOF/TOF AUTOFLEX III (Bruker).

The white crystalline substance, TPL 237-239°C, Rf0.95 (Sorbfil, benzene-ethanol, 9:1). An NMR spectrum1H (400 MHz, CDCl3), δ, M. D.: 3.12 (8H, ush. C, H-6, H-6', H-7, H-7'); 3.94 (6N, ush. C, H-14, H-14'); 4.80 (8H, ush. s, H-2, H-2', H-4, H-4'); 7.06 (4H, m, H-10, H-12, H-10', H-12'); 7.28 (2H, m, H-13, H-13'). An NMR spectrum13C, δ, ppm: 36.9 (C-6, C-6', C-7, C-7'); 55.6 (C-14, C-14'); 57.6 (C-2, C-2', C-4,C-4'); 110.4 (C-13, C-13'); 111.5 (C-10, C-10'); 119.3 (C-11, C-11'); 121.5 (C-12, C-12'); 147.4 (C-8, C-8'); 152.3 (C-9, C-9'). MALDI TOF, m/z 480.232 [M] (C22H28N2O2S4).

The way to obtain 3,3'-[Methylenebis(1,4-phenylene)]-, 3,3'-[oxybis(1,4-phenylene)]and 3,3'-(3,3'-dimethoxybiphenyl-4,4'-diyl)-bis-1,5,3-diazepinones General formula (1):

characterized in that arylamine [diaminodiphenylmethane, diaminodiphenylamine, dimethoxybenzidine] is subjected to interaction with N-tert-butyl-1,5,3-diazepinone in the presence of a catalyst Sm(NO3)3·6H2O in the atmosphere of argon at a molar ratio arylamine : N-tert-butyl-1,5,3-diazepine : Sm(NO3)3·6H2O = 10 : 20 : (0.3-0.7) at a temperature of ~20°C in the solvent system ethanol-chloroform for 2.5-3.5 hours



 

Same patents:

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

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: chemistry.

SUBSTANCE: invention relates to a compound of general formula I , where R1 is a hydrogen atom, a lower alkyl, CD3, -(CH2)n-CHO, -(CH2)n-O-lower alkyl, -(CH2)n-OH, -(CH2)n-cycloalkyl or is a heterocycloalkyl (where the heterocycloalkyl is a partially unsaturated ring containing up to 6 carbon atoms, at least one of which is substituted with O); R2 is a hydrogen atom, a halogen atom, hydroxy, lower alkyl, di-lower alkyl, -OCH2-O-lower alkyl or lower alkoxy; or the piperidine ring along with R2 forms a spiro-ring selected from 4-aza-spiro[2,5]oct-6-yl; Ar is an aryl or heteroaryl (where the heteroaryl is a cyclic aromatic hydrocarbon radical consisting of one ring and containing 6 ring atoms, and which contains at least one heteroatom selected from N), optionally having one, two or three substitutes selected from a halogen atom, lower alkyl, lower alkyl having as substitutes, a halogen atom, a lower alkoxy having as substitutes, a halogen atom, cycloalkyl, lower alkoxy, S-lower alkyl, heterocycloalkyl (where the heterocycloalkyl is a partially unsaturated ring containing up to 6 carbon atoms, at least one of which is substituted with N), or optionally having as substitutes, phenyl, optionally having R' as substitutes, and R' is a halogen atom, CF3, lower alkyl, lower alkoxy or a lower alkoxy having as substitutes, a halogen atom, or is a heteroaryl (where the heteroaryl is a cyclic aromatic hydrocarbon radical consisting of one ring and containing 6 ring atoms, and which contains at least one heteroatom selected from N and S); R is a lower alkyl, heterocycloalkyl (where the heterocycloalkyl is a partially unsaturated ring containing up to 6 carbon atoms, at least one of which is substituted with O), aryl or heteroaryl (where the heteroaryl is a cyclic aromatic hydrocarbon radical consisting of one ring and containing 6 ring atoms, and which contains at least one heteroatom selected from N), Where the aryl and heteroaryl optionally have as substitutes, one or two R'; n equals 0, 1, 2 or 3; or to a pharmaceutically acceptable acid addition salt, a racemic mixture or a corresponding enantiomer and/or optical isomer of said compound. The invention also relates to pharmaceutical compositions based on a glycine reuptake inhibitor of a compound of formula I.

EFFECT: obtaining novel compounds and a pharmaceutical composition based thereon, which can be used in medicine to treat neurological and psychoneurological disorders.

22 cl, 1 tbl, 128 ex

Cetp inhibitors // 2513107

FIELD: chemistry.

SUBSTANCE: invention relates to compound of formula I, or its pharmaceutically acceptable salt where: X stands for -O-; Z stands for -C(=O)-; Y stands for -(CRR1)-, where R1 is selected from -C1-C2alkyl; R stands for H or -C1-C5alkyl; R5 stands for H; R2 and B each is selected from A1 and A2, where one of R2 and B stands for A1, and the other from R2 and B stands for A2; where A1 has structure (a); A2 is selected from the group, which includes phenyl, pyridyl, pyrazolyl, thienyl, 1,2,4-triazolyl and imodazolyl; A3 is selected from the group including phenyl, thiazolyl and pyrazolyl; A4 is selected from the group, including phenyl, pyridyl, thiazolyl, pyrazolyl, 1,2,4-triazolyl, pyrimidinyl, piperidinyl, pyrrolidinyl and asetidinyl; A2 is optionally substituted with 1-3 substituents, independently selected from halogen atom, -OCH3 and -OCF3 and -C1-C3alkyl, optionally substituted with 1-3 halogen atoms; A3 is substituted with one A4 group and is optionally substituted with 1-2 substituents, independently selected from halogen atom, -OH, -OCH3, -OCF3 and -C1-C3alkyl, optionally substituted with 1-3 halogen atoms; A4 is optionally substituted with 1-3 substituents, independently selected from the group, which includes: (a) -C1-C5alkyl, optionally substituted with 1-3 halogen atoms and optionally substituted with group -OH, (b) -C2-C4alkenyl, optionally substituted with 1-3 halogen atoms, (c) -C(=O)C1-C2alkyl, optionally substituted with 1-3 halogen atoms and optionally substituted with one group selected from -OH, -CO2CH3, -C(=O)CH3, -NR3R4 and -OC1-C2alkyleneOC1-C2alkyl, (d) -C(=O)H, (e) -CO2H, (f) -CO2C1-C4alkyl, optionally substituted with one group, selected from -C(=O)C1-C2alkyl, -OH, -CO2CH3, -CO2H, -NR3R4 and -OC1-C2alkyleneOC1-C2alkyl, (g) -OH, (h) -S(O)xC1-C2alkyl, (i) halogen atom, (j) -CN, (k) -NO2, (l) -C(=O)NR3R4, (m) -OC1-C2alkyleneOC1-C2alkyl, (n) -OC1-C3alkyl, optionally substituted with 1-3 halogen atoms, (o) -C(=O)OC1-C2alkyl, optionally substituted with 1-3 halogen atoms and optionally substituted with one group, selected from -OH, -CO2CH3, -NR3R4 and -OC1-C2alkyleneOC1-C2alkyl, (q) -NR3R4 and (r) -S(O)xNR3R4, on condition that A4 stands for heterocyclic group, attached to A3 by means of ring carbon atom in A4, at least, one substituent in A4 must be selected from Re, where Re is selected from the group including: (a) -C1-C5alkyl, substituted with -OH group and optionally substituted with 1-3 halogen atoms, (b) -C2-C4alkenyl, optionally substituted with 1-3 halogen atoms, (c) -C(=O)C1-C2alkyl, optionally substituted with 1-3 halogen atoms and optionally substituted with one group selected from -OH, -CO2CH3, -C(=O)CH3, -NR3R4 and -OC1-C2alkyleneOC1-C2alkyl, (d) -C(=O)H, (e) -CO2H, (f) -CO2C1-C4alkyl, optionally substituted with one group, selected from -C(=O)C1-C2alkyl, -OH, -CO2CH3, -CO2H, -NR3R4 and -OC1-C2alkyleneOC1-C2alkyl, (g) -OH, (h) -S(O)xC1-C2alkyl, (i) -CN, (j) -NO2, (k) -C(=O)NR3R4, (l) -OC1-C2alkyleneOC1-C2alkyl, (m) -C(=O)C1-C2alkyl, optionally substituted with 1-3 halogen atoms and optionally substituted with one group, selected from -OH, -CO2CH3, -NR3R4 and -OC1-C2alkyleneOC1-C2alkyl, (n) -NR3R4(=O)OC1-C2alkyl, (o) -NR3R4 and (p) -S(O)xNR3R4; p equals 0, 1 or 2; and Ra is selected from halogen atom, -CH3, -CF3, -OCH3 and -OCF3; R3 and R4 each is independently selected from H and CH3; and x equals 0, 1 or 2.

EFFECT: formula (I) compound is applied for medication, which possesses properties of CETP inhibitor, for increase of HDL-C and for reduction of LDL-C Technical result is compounds, inhibiting cholesterol ether transferring protein (CETP).

10 cl, 140 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: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds being aspartyl protease inhibitors applicable for treating cardiovascular, neurodegenerative disorders and fungal infection of formula , wherein W represents -C(=O)-; X represents -NH-; U represents -C(R6)(R7)-; R1 represents methyl, R2, R3 and R6 represent H, R4 and R7 represent optionally substituted phenyl, as well as tautomers and pharmaceutically acceptable salts thereof.

EFFECT: there are presented new effective aspartyl protease inhibitors specified in rennin, cathepsin D, BACE-1, for treating cardiovascular diseases, cognitive and neurodegenerative diseases, as well as fungal infections.

67 cl, 1 tbl, 4393 ex

FIELD: chemistry.

SUBSTANCE: invention describes compounds of formula I , where R1 and R2 independently denote hydrogen, C3-C7cycloalkyl, C1-C6alkyl, C2-C6alkynyl, hydrogen or pyridine; or R1 and R2 together with a nitrogen atom which binds them form a pyrroline group; R3 denotes hydrogen, C1-C6halogenalkyl, C1-C6alkyl, halogen, cyano group, nitro group, C1-C4alkoxy group, phenyl, halogen-substituted phenyl, (R51)(R52)(R53)Si-(C2-C6alkynyl)-, where R51, R52, R53 independently denote halogen, cyano group, C1-C6alkyl, C2-C6alkenyl, C3-C8cycloalkyl, C5-C8cycloalkenyl, C2-C6alkynyl, C1-C6alkoxy group, benzyl or phenyl; R4 denotes hydrogen, halogen, phenyl, imidazolyl, amino group, C1-C6alkoxy group or C1-C6alkyl; R5 denotes C1-C12alkyl or a group A, where A denotes a 3-10-member monocyclic or condensed bicyclic ring system which can be aromatic, partially unsaturated or completely saturated, where said 3-10-member ring system can be mono- or polysubstituted with substitutes independently selected from a group comprising halogen, C1-C6alkyl, C1-C6halogenalkyl, C1-C6alkoxy group and C1-C6alkylthio group; R6 denotes hydrogen; and R7 denotes hydrogen or C1-C6alkyl and agronomically acceptable salts/metal complexes/metalloid complexes/isomers/structural isomers/stereoisomers. The invention also relates to methods of controlling infection of useful plants by phytopathogenic microorganisms by applying a compound of formula I onto the plants, a part thereof or place where said plants grow, as well as a composition for controlling infection by phytopathogenic microorganisms.

EFFECT: novel compounds which are suitable for use as microbiocides are obtained and described.

7 cl, 48 ex, 151 tbl

Amide compound // 2479576

FIELD: chemistry.

SUBSTANCE: compounds exhibit antagonistic activity towards the EP4 receptor, which enables use thereof as an active ingredient in a pharmaceutical composition for treating chronic kidney disease or diabetic nephropathy.

EFFECT: high efficiency of the compounds.

27 cl, 228 tbl, 86 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of general formula:

or its pharmaceutically acceptable salt wherein the ring A represents a phenyl group which can contain 1-3 substitutes specified in a group of substitutes, or a thienyl group which can contain 1-3 substitutes specified in a group of substitutes α; L represents a single bond or a group of formula -NRC CO- (wherein Re represents a hydrogen atom), the ring B represents C6-14 aryl group which can contain 1-3 substitutes specified in a group of substitutes α, or a 5-10-member heterocyclic group which can contain 1-3 substitutes specified in a group of substitutes α; the X, Y, Z , R1 and R2 , R3, R4, R5 and R6 radical values are presented in cl.1 of the patent claim which possess an effect of Aβ protein production inhibition or an effect of BACE1 inhibition.

EFFECT: preparing the compound which is applicable as a preventive or therapeutic agent for neurodegenerative disease caused by Aβ.

13 cl, 35 tbl, 285 ex

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

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new cyclopropylamine derivatives of formula: or its pharmaceutically acceptable salt, wherein: one of R1 and R2 means a group of formula -L2-R6a-L3-R6b; the other of R1 and R2 means H, C1-10alkyl, C1-10alkoxy, halogen, CN; each R3, R3a R3b independently means H, C1-6alkyl, trifluoromethyl, C1-10alkoxy, CN; R4 and R5 taken together with a nitrogen atom whereto each attached form a non-aromatic cycle of formula: R7, R8, R9 and R10 each H, C1-10alkyl; R6a means cyanophenyl, phenyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, [1,2,3]triazolyl, [1,2,4]triazolyl, azepanyl, azetidinyl, azetidin-2-onyl, pyridazin-3(2H)-onyl, pyridin-2(1H)-onyl, pyrimidin-2(1H)-onyl, pyrrolidin-2-onyl, benzothiazolyl wherein the pyridinyl and pyrimidinyl groups optionally contain 1-3 substitutes specified in a group consisting of C1-10alkyl and C1-10alkoxy; R6b means H; L means - [C(R16)(R17)]k; L2 means a bond, C2-10alkylene, -O-, -C(=O)-, -NH-, -N(R16)C(=O), -C(=O)N(R16) and -N(C1-6alkyl)-;L3 means a bond; R15 means H, C1-6alkyl, C1-6alkoxycarbonyl, amido and formyl R16 , R17 in each specific case means H, C1-6alkyl; Rx and Ry in each specific case independently mean H, C1-6alkyl, C1-6alkoxy, C1-6alkylamino, fluorine, diC1-6alkylamino; k is equal to 1, 2 or 3; m is equal to 2.

EFFECT: compounds show H3 receptor inhibitory activity that makes them applicable in a pharmaceutical composition.

10 cl, 7 dwg, 44 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

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