Derivatives of 2-r1-4-r2-6-polynitromethyl-1,3,5-triazines, possessing antibacterial activity

FIELD: chemistry.

SUBSTANCE: invention relates to application of 2-R1-4-R2-6-polynitromethyl-1,3,5-triazines of general formula: , where n=0, X=NO2, Cl, Br, R1=R2=OR3, OAr (R3=CH3, C2H5, CH2(CH2)6CH3, CH2CH2Cl, Ar=metha-C6H4CH3), R1=OR3, OAr, R2=N(C2H5)2; n=1, X=Cl, R1=OR3, R2=NH(CH2)2NH2, N(CH2CH2)2NCH3 as compounds, which possess antibacterial activity.

EFFECT: identification of compounds based on 1,3,5-triazine derivatives, which possess high antibacterial activity.

3 tbl, 7 ex

 

The invention relates to biologically active compounds, namely polyaromatic-1,3,5-triazines and their derivatives which possess antibacterial activity, and can be used in medicine, veterinary science and Microbiology.

The problem of development of antibacterial drugs topical throughout the history of Microbiology. Among bacterial infections are the causative agents of especially dangerous infections such as Yersinia pestis and Vibrio cholerae belonging to I and group II pathogenicity and cause severe disease in humans with mortality (80-90% in the absence of timely treatment. There is also the range is not so dangerous pathogens related to III and group IV pathogenicity, however, sometimes leading to severe forms of disease, such as pneumonia, typhoid fever, meningitis, otitis media, salmonellosis, etc. Due to the ongoing adaptation of pathogens to common medicinal substances, a well-known antibiotics has lost much of its antibacterial activity, and cannot cope with the assigned role. Thus, the need for new effective antibacterial agents that possessed high activity, low toxicity and prolonged activity against prokaryotic pathogenic for humans.

Bacter the social DNA methyltransferase modifies cytosine residues at positions C 5or N4or residue of the adenine at position N6. In the systems of restriction-modification in bacteria and phages Mtase play a major role in the protection of bacterial DNA from cleavage of the corresponding specificity of restriction endonucleases. However, many bacteria and their phages) code and a "single" Mtisi, among which the most numerous family of enzymes Dam catalyzing methylation ekzoticheskoy N6-amino group of adenine in palindromic the sequence GATC. This family includes more than a hundred GATC-specific MTAs (http://rebase.neb.com), all enzymes are characterized by a high level of homology of the primary structures (PL.1).

It is known that Dam methylation affects bacterial phenotype, gene expression, replication initiation and postreplicative reparation unpaired DNA bases. In recent years also shows that the Dam Mtase often responsible for regulation of genes involved in various processes of bacterial pathogenesis, and affect the pathogenicity and/or viability of strains of Yersinia spp., Salmonella spp., V. cholerae, H. influenzae, E. coli, P. gingivalis, P. multocida, etc. as an example of the control of education pyelonephritis-associated pilej (cilia) and functioning of the PAP operon in uropathogenic strains of E. coli [Hemday A., Krabbe, M., Braaten C., Low, D. Self-perpetuating pili epigenetic switches in bacteria // Proc. Nat. Acad. Sci U. S. A. 2002. V. 99 Suppi 4. P. 16470-16476].

Dam mutant strain of S. enterica was avirulence when oral or intraperitoneal introduction mice 10000-fold lethal dose [D. M. Heithoff, Smsheimer R. L., Low, D. A., Mahan, M. J. An essential role for DNA adenine methylation m bacterial virulence // Science. 1999. V. 284. No.5416. P. 967-970]. Dam-minus mutants of Vibrio cholerae and Yersinia pseudotuberculosis was not viable [Julio S. M., D. M. Heithoff, D. Provenzano, Klose K. E., Sinsheimer, R. L., Low, D. A., M. J. Mahan DNA adenine methylase is essential for viability and plays a role in the pathogenesis of Yersinia pseudotuberculosis and Vibrio cholerae II Infect. Immun. 2001. V. 69. No.12. P. 7610-7615].

Known data on the biological activity of derivatives of 1,3,5-triazines. A known number of derivatives of 1,3,5-triazine, having antiviral activity: derivatives of 1,3,5-triazine, having activity against viral hepatitis And [the international application (WO) No. 96/04914, publ. 22.02.1996]; derivatives of 1,3,5-triazine, having activity against retroviruses [Japan's Bid No. 6016561, publ. 25.01.1994]; derivatives of 1,3,5-triazine, with activity against hepatitis b [U.S. Patent No. 6335339, publ. 01.01.2002].

It is known that the number of derivatives of 1,3,5-triazine has the property to inhibit the activity of malaria and coccidioses Plasmodium, 2,6-diamino-1,2-dihydro-animetake-1,3,5-triazine possess antimalarial activity [U.S. Patent No. 3876785, publ. 08.04.1975]; 1-phenyl-substituted 1,3,5-triazines are effective against coccidiosis in humans and the animal [U.S. Patent No. 3948893, publ. 06.04.1976].

It is known that derivatives of 2-R1-4-R2-6-polyaromatic-1,3,5-triazines (where R1, R2- the same or different CNS (substituted CNS), azlocillin (substituted alloxanthine), amine substituents (including cyclic amines and diamines); polymicrogyria group: C(NO2)2CH2OH, C(NO2)2CH3C(NO2)2CH2CH2CN, C(NO2)2CH2CH2COOR, C(NO2)2Cl, C(NO2)2Br, C(NO2)3) have cytotoxic and antitumor activity [Bakharev centuries, gidaspow A. A., Bulychev Y. N. Synthesis and cytotoxic activity of 2,4-disubstituted 1,3,5-treatyeliminates and dinitroethane // Chem.-Pharm. log: 2000, T. 34 No. 7, S. 6-12; gidaspow A. A., Bakharev centuries, the Kachanivska E. C., N. Yakunin.G., Bulychev Y. N. Synthesis and cytotoxic activity of esters and NITRILES 1,3,5-triethynylbenzene acids // Chem. Pharm. journal, 2002, T. 36, No. 7, S. 26-32; gidaspow A. A., Bakharev centuries, Galkin, M. C., E. Ekimov Century, Bulychev Y. N., Kachanivska E. C., Kosareva E. A., Yakunin, N. G. Synthesis and cytotoxic activity of halogencontaining derivatives of 1,3,5-triazine // Chem.-Pharm. journal, 2004, T. 38, S. 9-15; gidaspow A. A., Bakharev centuries, Bulychev Y. N. Synthesis and cytotoxic activity of trinitromethyl derivatives of 1,3,5-triazine // Chem.-Pharm. journal, 2008, T. 42, No. 5, S. 11-13], and is also antimetastatic (inhibition of metastasis) activity [gidaspow A. A., Bakharev Centuries, Fedorov, B. S. Fadeev, M. A., N. Konovalov.P. New antimetastatic drugs on the basis of chloronitromethane-1,3,5-triazines // Journal of applied chemistry, 2009, T. 82, vol.10, S. 1664-1668]. A number of polyaromatic-1,3,5-triazines has the ability to generate nitric oxide NO [gidaspow A. A., Bakharev centuries, the Kachanivska E. C., Bulychev Y. N., Levin, C. I., Azizov O. C., A. Arzamastsev P., Grigoriev N. B. Granin Century, Synthesis and electrochemical investigation of NO-generating ability printsomething derivatives of 1,3,5-triazine // Chem. Pharm. journal, 2003, No. 9, S. 12-16].

Known data on antitumor and anticancer activity of derivatives as other triazines - effective antitumor drug "Tirapazamine" (Tirazone®, tirapazamine) - 1,2,4-benzotriazin-3-Amin-1,4-dioxide, [the international application (WO) No. 97/11699, publ. 03.04.1997] and 1,3,5-triazines in particular [Application U.S. No. 10/673521, publ. 10.06.2004; Application U.S. No. 10/594994, publ. 20.11.2008; U.S. Patent No. 7750001, publ. 06.07.2010].

However, these compounds have no information that they possess antibacterial activity.

The first works in the field of medical use of derivatives of 1,3,5-triazines were made in 1956, when as possible antibiotics minimal toxicity were presented 2-arylsulfonate-1,3,5-triazine [U.S. Patent No. 2774756, publ. 18.12.1956]. Later in 1964, it was shown that when used and small amounts of 2,6-diamino-1,3,5-triazines in conjunction with sulfonamidnuyu the generic antibacterial activity of this mixture may be increased to 20% [U.S. Patent No. 3123527, publ. 03.03.1964]. After further work in this direction for a long time stopped.

It is known that derivatives of benzo-1,2,4-triazines have the ability to suppress the activity of pathogenic bacteria [U.S. Patent No. 4027022, publ. 31.05.1977]. One can see a significant difference in the structure of the presented compounds provided in this application for the invention. The minimum inhibiting concentration (MIC) obtained in preparations of various cell lines, almost 2-6 times higher than the effective inhibitory concentrations (IC50) compounds presented in this invention application.

The closest analogue (prototype) are 2,4-diamino-1,3,5-triazine which possess antibacterial activity [U.S. Patent No. 7622469, IPC A61K 31/53, publ. 24.11.2009].

However, provided in this application for the invention compounds differ from the prototype structural, because they are not 2,4-diamino-derivative, and 2-amino-4-alkoxy (aryloxy)- or 2,4-alkoxy(aryloxy)-derivatives of 1,3,5-triazine, which contain polymicrogyria group. The minimum inhibiting concentration (MIC) obtained on drugs prototype different cell lines, almost 10-12 times higher than the effective inhibitory concentrations (IC50) compounds presented in this application for the invention is E.

Disclosure of inventions

The technical result of the claimed invention is the creation of new compounds based on derivatives of 1,3,5-triazine with a higher antibacterial activity, including against a human pathogenic strains.

This technical result is achieved by using derivatives of 2-R1-4-R2-6-polyaromatic-1,3,5-triazines having the General formula:

where

n=0, X=NO2, Cl, Br, R1=R2=OR3, OAr (R3-CH3With2H5CH2(CH2)6CH3CH2CH2Cl, Ar=meta-C6H4CH3). R1=OR3, OAr, R2=N(C2H5)2.

n=1, X Is Cl, R1=OR3, R2-NH(CH2)2NH2N(CH2CH2)2NCH3,

as compounds with antibacterial activity.

Provided in this application connection derivatives of 1,3,5-triazine-oriented suppression process, Dam DNA-methylation is essential for life and pathogenesis of bacteria, but absent in the host cell. As shown above, for a number of pathogens Dam-minus mutants of avirulent or unviable, thus, it is believed that inhibitors Dam MTAs can have a wide spectrum of antibacterial action [Casadesus ., Low D. Epigenetic gene regulation in the bacterial world // Environ. Mol. Biol. Rev. 2006. V. 70, No. 3, P. 830-856; Wion D., J. Casadesus N6-methyl-adenine: an epigenetic signal for DNA-protein interactions // Nat. Rev. Environ. 2006. V. 4. No. 3. P. 183-192]. In this regard such work, the search for selective inhibitors of bacterial Dam MTAs, conducted recently in the US "EpiGenX Pharmaceuticals" [Mashhoon, N., C. Pruss, Carroll M., Johnson, P. H., Reich, N. O. Selective inhibitors of bac terial DNA adenine methyltransferases // Journal of Biomolecular Screening. 2006. V. 11. No. 5. P. 497-510].

In the prior art to the claimed compounds with antibacterial action is not known, so this solution has the novelty and meets the criterion of "inventive step".

Below are given as examples of the information about the synthesis of the claimed compounds.

Example 1. Hydrochloric acid salt of 2-methoxy-4-(4'-methylpiperazin-1'-yl)-6-chloro-dinitromethyl-1,3,5-triazine (sat-12179). The synthesis described in [gidaspow A. A., Bakharev centuries, Fedorov, B. S. Fadeev, M. A., N. Konovalov.P. New antimetastatic drugs on the basis of chloronitromethane-1,3,5-triazines // Journal of applied chemistry, 2009, T. 82, vol.10, S. 1664-1668].

Example 2. Hydrochloric acid salt of 2-methoxy-4-(ethyl-1',2'-diamine)-6-jardiniere-methyl-1,3,5-triazine (sat-12180). The synthesis described in [gidaspow A. A., Bakharev centuries, Fedorov, B. C., M. Fadeev A., Konovalov, N. P. New antimetastatic drugs on the basis of chloronitromethane-1,3,5-triazines // Journal of applied chemistry, 2009 T. 82, vol.10, S. 1664-1668].

Example 3. 2,4-octyloxy-6-bromonitromethane-1,3,5-triazine (cam-12183). The synthesis described in [gidaspow A. A., Bakharev centuries, Galkin, M. C., E. Ekimov Century, Bulychev Y. N., Kachanivska E. C., Kosareva E. A., Yakunin, N. G. Synthesis and cytotoxic activity of halogencontaining derivatives of 1,3,5-triazine // Chem. Pharm. log. in 2004, T. 38, S. 9-15].

Example 4. 2,4-bis-(m-tolyloxy)-6-trinitromethyl-1,3,5-triazine (cam-12380). The synthesis described in [Century. Century. Bakharev, A. A. Gidaspov, E. C. Kachanivska. Synthesis of 2,4-diarylike-6-trinitromethyl-1,3,5-triazines // the Journal of organic chemistry. 2007, T. 43, No. 3, S. 455-458].

Example 5. 2 ethoxy-4-diethylamino-6-chloronitromethane-1,3,5-triazine (cam-12446). The synthesis described in [gidaspow A. A., Bakharev centuries, Galkin, M. C., E. Ekimov Century, Bulychev Y. N., Kachanivska E. C., Kosareva E. A., Yakunin, N. G. Synthesis and cytotoxic activity of halogencontaining derivatives of 1,3,5-triazine // Chem.-Pharm. log. in 2004, T. 38, S. 9-15].

Example 6. 2-('2-chloroethoxy)-diethylamino-6-chloronitromethane-1,3,5-triazine (cam-12448). In the suspension of 0.003 mole of the potassium salt of 2-(2'-chloroethoxy)-4-diethylamino-6-dinitromethyl-1,3,5-triazine in 15 ml of carbon tetrachloride at 20-25°C and stirring was barbotirovany gaseous chlorine before moving yellow potassium salt in white (formed KCl). The reaction mass was stirred 0.5 hours the Precipitate was filtered, carbon tetrachloride was removed with a rotary will evaporate the La. The residue was evacuated for 1 h at room temperature and a residual pressure of 1 mm RT.article The target of the sat-12448 obtained in the form of a viscous yellowish oil with a yield of 90%. Found, %: C 32.49, H 3.88, N 22.73, Cl 19.22. C10H14N6O5Cl2. Calculated, %: C 32.54, H 3.82, N 22.76, Cl 19,21. IR spectrum, ν, cm-1: 2979,6; 2937,2; 2877,4; 1589,1; 1510,1; 1465,7; 1427,1; 1321,1; 1299,9; 1243,9; 1191,9; 1095,4; 1020,2; 977,8; 908,4; 835,1; 815,8; 788,8. Range1H-NMR (CDCl3internal standard - TMC), δ, M. D.: 1.15,1.22 two t (6H, CH3, J=8 Hz), 3.54, 3.66 two q (4H, NCH2I , J1=8 Hz, J=7.8 Hz), 3,80 t (2H, OCH2, J=8 Hz), It 4,7 (2H, CH2Cl, J=8 Hz). 1,3,5-Triazine General formula 1 to chemical structure different from previously reported as antibacterial drugs 1,3,5-triazines [Application U.S. No. 10/539234, publ. 13.07.2006; U.S. Patent No. 7622469, publ. 24.11.2009] by the presence of combined cycle polynitromethanes functional groups, namely C(NO2)2Cl or C(NO2)2Br, or C(NO2)3.

Example 7. Study of antibacterial activity of the claimed compounds

Main objects of study in vitro served as homogeneous preparations Dam DNA methyltransferase bacteriophage T2 (T2Dam), structural and functional properties similar to Dam Mtase Escherichia coli [Hattman, S., E. G. Malygin Bacteriophage T2Dam and T4Dam DNA-[N6-adenine]-methyltransferases // Prog. Nucleic Acid Res. Mol. Biol. 2004. V. 77. P. 67-126; J. R. Horton, K. Liebert, Hattman, S., Jeltsch, A., Cheng X. Transition from nonspecifi to specific DNA interactions along the substrate-recognition pathway of dam methyltransferase // Cell. 2005. V. 121. No.3. P. 349-361] and Yersinia pseudotuberculosis (YpsDam).

Evaluation of the potential of low molecular weight chemical compounds in relation to the inhibition reactions Dam-methylation was performed on preparations T2Dam and YpsDam standard method of enzymatic transfer of [3H]-radioactive label from [3H-CH3]-AdoMet on the DNA substrate [Marzabal S., Dubois, S., Thielking V., Cano, A., Eritja, R., W. Guschlbauer Dam methylase from Escherichia coli: kinetic studies using modified excl. reaction: hemimethylated substrates // Nucleic Acids Res. 1995. V. 23. No.18. P. 3648-3655]. For each connection was found the dependence of enzyme activity on the concentration of inhibitors (C-ing). After analyzing the data dependencies, according to the standard expression: A=Amax/(1+([C ing] / IC50)n), where n is the hill coefficient were computed 50% inhibiting concentration - IC50listed in the table.2.

Table 2
Inhibiting activity IC50in vitro reactions Dam-methylation on the DNA preparations-methyltransferase T2Dam and YpsDam:
Cipher Conn.Molar massIC50T2Dam (µm)IC50YpsDam (µm)
cam-12179420,64>27,40 8,2
cam-12180380,58of 5.46,2
cam-12183520,432,33,5
cam-12380442,350,54,8
cam-12446334,72>309,6
cam-12448369,17>307,9

To assess the cytotoxic activity of the claimed compounds obtained in accordance with examples 1-6, used the following method. The culture of Vero cells were grown in the wells of flat-bottomed 96-well plates. In culture medium were added in serial dilution of the compounds under study. After incubation for 3-5 days monolayer cells were progressively the vital dye neutral red, after removal of the dye and wash excess dye was made lyse solution and the amount of dye included in the monolayer of cells was taken into account on the spectrophotometer at a wavelength of 490 nm. As a control cell culture used the hole Board is a, which didn't make any connections. This methodology is based on the ability of test compounds to penetrate into the eukaryotic cell and affect vital cellular processes, and therefore the cells die and do not retain the ability to phagocytose neutral red.

To determine the antibacterial activity of the above compounds used cell culture of E. coli(BL). Culture of E. coli cells(BL) were grown in 25 ml test tubes of 10 ml culture medium was added serial dilution of the compounds under study. Samples were incubated and produced sampling every 30 min, the amount of biomass of the cell culture was measured on a spectrophotometer at a wavelength of 550 nm. Antibacterial activity was determined by comparing the reduction kinetics of growth in samples of cell culture of E. coli(BL) in the presence of compounds derivatives of 1,3,5-triazine and a control sample. As a control cell culture used samples that did not make any connections. This methodology is based on the ability of test compounds to penetrate into prokaryotic cells and inhibit the activity of bacterial Dam DNA methyltransferase, in connection with which cells die or partially lose their activity, and the rate of growth of cell cultures decreases. The results of determination of cytotoxic and antibacter the social activity are given in table.3.

Table 3
Cytotoxic activity of 50% (TC50on the culture of eukaryotic cells Vero and antibacterial activity of the culture prokaryotes E. coli(BL) (IC50). Index selectivity as the ratio of cytotoxic and antibacterial activity
Cipher Conn.TC50(μm)) on cultured VeroIC50(μm) in the culture of E. coli(BL)Index selectivity (TC50/IC50)
cam-1217987,60,23380,9
cam-1218028,30,04707,5
cam-12183to 25.30,03843,4
cam-1238010,80,1668,8
cam-1244616,00,11152,7
cam-1244814,5 1,410,2

Analysis of the data presented in table.3 shows that polyaromatic-1,3,5-triazine General formula 1 have high antibacterial activity. A high index of selectivity indicates that these chemical compounds are quite suitable for use as drugs aimed at suppressing bacterial infections.

Application 2-R1-4-R2-6-polyaromatic-1,3,5-triazines of the General formula:

where:
n=0, X=NO2, Cl, Br, R1=R2=OR3, OAr (R3=CH3With2H5CH2(CH2)6CH3CH2CH2Cl, Ar=meta-C6H4CH3), R1=OR3, OAr, R2=N(C2H5)2,
n=1, X=Cl, R1=OR3, R2=NH(CH2)2NH2N(CH2CH2)2NCH3,
as compounds with antibacterial activity.



 

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22 cl, 2 tbl, 211 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new dihydroindenamide specified in compounds described by general formula II, or their pharmaceutically acceptable salts. In general formula II, R1 represents piperazinyl which can be optionally substituted by one R1a; R1a represents H, CH3, C(O)Rd or C(O)ORa; Y represents pyrimidyl; Z represents pyridyl or pyrimidyl; Ra represents tert-butyl and Rd represents CH3. The above compounds represent tert-butyl-4-{5-[({(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl}amino)carbonyl)-2,3-dihydro-1H-inden-1-yl}piperazine-1-carboxylate; N-(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl)-1-piperazin-1-yl-2,3-dihydro-1H-indene-5-carboxamide; 1-[4-acetylpiperazin-1-yl)-N-(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl)-2,3-dihydro-1H-inden-5-carboxamide; (1R)-1-(4-methylpiperazin-1-yl)-N-(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl)-2,3-dihydro-1H-inden-5-carboxamide; (1S)-N-[3-(4,5′-bipyrimidin-2-ylamino)-4-methylphenyl]-1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-inden-5-carboxamide; (1R)-N-[3-(4,5′-bipyrimidin-2-ylamino)-4-methylphenyl]-1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-inden-5-carboxamide; (1S)-1-(4-methylpiperazin-1-yl)-N-(4-methyl-3-[(4-pyridin-4-ylpyrimidin-2-yl)amino]phenyl)-2,3-dihydro-1H-inden-5-carboxamide and (1S)-1-(4-methylpiperazin-1-yl)-N-(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl)-2,3-dihydro-1H-inden-5-carboxamide sulphate.

EFFECT: compounds inhibit activity of protein kinases specified in Abl, c-Kit and PDGFR, and can find application for treating diseases related to disturbed activity of the above protein kinases, eg leukaemia and other cancers.

4 cl, 4 tbl, 16 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I), wherein A means morpholinyl, 1,4-oxazepamyl, piperidinyl, pyrrolidinyl or azetidinyl which is bound to N; R1 means C1-C6-alkyl group; R2 means bicyclic aryl group specified in 1H-indolyl, 1H-pyrrolo[3,2-b]pyridyl, quinolyl, naphthyl, 1H-pyrrolo[2,3-b]pyridyl, 5H-pyrrolo[3,2-d]pyrimidinyl, 7H-pyrrolo[2,3-d]pyrimidinyl, benzo[b]thiophenyl, imidazo[1,2-a]pyridyl, benzo[b]thiazolyl, 5H-pyrrolol[2,3-b]pyrazinyl and quinoxalinyl which can be substituted by R4; R3 means hydrogen or halogen atom; R4 means C1-C6-alkyl group, C1-C6-halogenalkyl group, OR1A, halogen, -(CH2)aOH, CN, NHCOR1A, SO2R1A or NHSO2R1A; R5 means C1-C6-alkyl group, -(CH2)aOH, -(CH2)aOR1B, halogen or CONH2; provided p is a plural number, R5 can be identical or different, or R5 can be combined with another R5; each of R1A and R1B independently means C1-C6-alkyl group; a is equal to 0, 1 or 2; n is equal to 1 or 2; p is equal to 0, 1, 2, 3, 4 or 5. Besides, the invention refers to intermediate compounds of formulas (IA) and (IB) for preparing the compounds of formula (I), to a preventive or therapeutic agent containing the compounds of formula (I), pharmaceutical compositions, using the compounds of formula (I) and to a method for preventing or treating diseases.

EFFECT: compounds of formula (I) as selective 5-HT2B receptor antagonists.

11 cl, 1 dwg, 18 tbl, 88 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to imidazole derivatives of general formula or its pharmaceutically acceptable salt, wherein R1 means halogen, C1-6-alkyl or C1-6-alkoxy; R2 means C1-6-alkyl; R3 means hydrogen, C1-6-alkyl; Q means -N= or -CH=; R4 represents a group of formula or , wherein X, Y and Z independently represent -CH= or -N=, and only one of X or Y can be a nitrogen atom; R5 and R6 independently represent a hydrogen atom, C1-6-alkyl, C1-6-hydroxyalkyl, C1-6-alkoxyalkyl, -(CH2)m-(CO)O-C1-6-alkyl, -(CH2)m-S(O)2-C1-6-alkyl, -(CH2)m-C(O)-NR'R" and wherein m=1 and R' and R" independently represent hydrogen or C1-6-alkyl. Also, the invention refers to a therapeutic agent based on the compound of formula (I) and using the compound of formula (I).

EFFECT: there are prepared new imidazole derivatives effective for treating and preventing mGluR5 receptor mediated disorders.

26 cl, 60 ex

FIELD: chemistry.

SUBSTANCE: description is given of a method of producing 2,4-diaryloxy-6-trinitromethyl-1,3,5-triazines with general formula , where R1-R5=H; C1-6 alkyl, F; Cl; Br, I, NO2; COOAIk. Cyanuric chloride, trinitromethane salt Kt+C(NO2)3-, where Kt+ - cation, and R1, R2, R3, R4, R5 - substituted phenol, where R1-R5 assume values given above, are reacted in a medium of inert organic solvent such as acetone or acetonitrile. The method is realised in a single stage with 20-65% output of desired product.

EFFECT: said compounds can be used as biologically active substances and intermediate products in synthesis of the latter.

1 cl, 1 tbl, 1 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to the improved method for preparing compounds of the formula (I) or their salts. Compounds of the formula (I) can be synthesized by the chlorination reaction of compounds of the formula (II) wherein X means hydrogen atom (H), (C1-C6)-alkyl; R1 means (C1-C6)-alkyl substituted with halogen atom(s); R2 and R3 mean hydrogen atom (H) in the presence of a water-free protonic organic solvent. Proposed compounds are useful for preparing active substances among class of aminotriazines, for example, herbicide active substances.

EFFECT: improved preparing method.

7 cl, 1 tbl, 1 ex

The invention relates to new derivatives of phenylsulfonylacetate General formula (I), which are herbicide and regulating plant growth properties and can find application in agriculture

The invention relates to new substituted aminomethanesulfonic General formula (I) possessing a highly effective herbicide action, as well as the way they are received, herbicide tool based on these intermediate compounds of General formula (II)

The invention relates to a new method of production (its variants) aminophenylalanine formula I, having the properties of plant growth regulators or herbicides, as well as intermediate products for their production

The invention relates to novel acylated to aminophenylacetylene General formula I which possess herbicide action and selectivity of action in comparison with the previously known compounds of this series

The invention relates to the technical field of herbicides and plant growth regulators, in particular of herbicides for selective control of weeds in cultivated plants

The invention relates to chemical means of weed control in crops based on derivatives sulfonilmocevina, in particular salts of 2-chloro-N-/(4-methoxy-6-methyl-1,3,5-triazine-2-yl) aminocarbonyl/benzosulfimide(chlorsulfuron) and specifically to its potassium salt of formula I:

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The invention relates also to a method of controlling undesirable vegetation in crops of flax by processing plants weed-killing drug on the basis of salts of formula I, as well as its mixture with other herbicide-active compounds, for example with dimethylamine salt of 2-methyl-4-chlorophenoxyacetic acid

FIELD: chemistry.

SUBSTANCE: method of producing a carbon sorbent with antibacterial and antimycotic properties includes impregnating granules of a carbon hemosorbent with 10-50% aqueous solution of glycolic acid for 7-9 hours at room temperature. The ratio of the hemosorbent to the modifier solution of glycolic acid is 1:1. Further, drying is carried out for an hour at 100-110°C. Polycondensation of glycolic acid on the carbon hemosorbent is carried out in two steps: at 185-205°C for 1 hour, at 215-235°C for not less than 5 hours, on a sand bath. The disclosed modified carbon sorbent with antibacterial and antimycotic properties is granules with a round shape, contains not less than 5% polyglycolide, characterised by a specific adsorption surface area of less than 250 m2/g and total pore volume of less than 0.50 cm3/g.

EFFECT: improved properties of the sorbent.

2 cl, 2 tbl, 2 dwg

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