The method of obtaining derivatives of quinoline-carboxylic acids or their pharmaceutically acceptable salts

 

(57) Abstract:

Usage: as preparations possessing antibacterial activity. The inventive method of obtaining derivatives of quinoline-carboxylic acid f-ly I the interaction of compound II with compound III and the resulting compound IV hydrolyzing, with the release of compound I in free form or in salt form. The structure of the compounds I, II, III, IV with the corresponding values of the radicals given in the text description. 8 C. p. F.-ly.

The invention relates to a new method of obtaining derivatives of 1-substituted-7-(unsubstituted or substituted, piperazine derivatives)-6-fluoro-8-(unsubstituted or fluoro-substituted)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid of General formula I

and their pharmaceutically acceptable salts, where R1means unsubstituted or substituted by 1 or 2 halogen atom phenyl or a group of General formula-CH2CR6R7R8in which R6, R7and R8means a hydrogen atom or halogen;

R2piperazinil or 4-methylpiperazine;

R3a hydrogen atom or fluorine.

It is known that the group of derivatives of 7-substituted carboxylic acids of General formula I, in which R2means piperazinil, 4-P> and R8means a hydrogen atom or halogen, and R3the fluorine atom has a high antibacterial activity (J. Med. Chem. 1986, , 445; of Drugs Fut 1984, 23-I Intersci. Conf. Antimicrob. Agents Chemother. 1983, Abst, 658, 7th Int. Symp. Fut. Trends Chemother 1986, ). These compounds can be obtained by reacting 6,7,8-Cryptor-4-oxo-1,4-dihydroquinoline-3-carboxylic acid and cyclic amines (Belgian application 887874, the United Kingdom patent 2057444, patent Austria 537813 and European patent 1064489).

Another group of 7-substituted-quinoline-3-carboxylic acids of General formula I, in which R1means unsubstituted or substituted by 1 or 2 atoms of halogen phenyl, R2-piperazinil or 4-methylpiperazine, and R3a hydrogen atom, also has high antibacterial activity (24 Intersci Conf. Antimicrob Agents Chemother. 1984, Abst. 72-79, Antimicrob Agents Chemother. 1987, 619, Antimicrob Agents Chemother. 1986, 192-208). These compounds can be obtained by reacting a 1-substituted phenyl-6-fluoro-7-chloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid and cyclic amines in the presence of a solvent at 100aboutC for 20 h (European patent 131839 J. Med. Chem. 1558, J. Med. Chem. 1987, 504).

The aim of the invention is a new method of obtaining derivatives of quinoline-3-carboxylic acid of General formula I, SPE2CR6R7R8in which R6, R7and R8means a hydrogen atom or halogen; R2piperazinil or 4-methylpiperazine, and R3a hydrogen atom or fluorine, and their pharmaceutically acceptable salts, including the interaction of the compounds of General formula II

where R is halogen atom, aliphatic, acyloxy group with 2-6 carbon atoms or aromatic acyloxy group with 7 to 11 carbon atoms, R4the fluorine atom or chlorine, and R1and R2have the above definition, with an amine of General formula III

R5NNH where R5means a hydrogen atom or methyl, or salts thereof; hydrolysis, the resulting compounds of General formula IV

where R, R1, R2and R3have the above definition, after or without isolating it from the reaction mixture and, if desired, transfer the obtained compounds of General formula I in its salt or its transformation into a free form of its salts.

The advantage of the method in accordance with the present invention is that it can be used to obtain compounds of General formula I in a simple way with very high yield and short duration of the reaction.

Macrozone General formula IV are n the water with the General formula IV is transferred to the target quinoline-3-carboxylic acid of General formula I without selecting it from the reaction mixture.

The reaction besprozvannyh General formula II with the amine of General formula III optionally performed in the presence of an inert organic solvent and kislorodsvyazyvayushchei agent.

As the inert organic solvent is preferable to use acid amides, such as dimethylformamide, dimethylacetamide, ketones, such as acetone, methyl ethyl ketone, ethers such as dioxane, tetrahydrofuran, diethyl ether, esters such as ethyl acetate, methylacetate, ethylpropane, sulfoxidov, for example dimethyl sulfoxide, alcohols, such as methanol, ethanol, 1-decanol, butanol.

As kislorodsvyazyvayushchei agent can be used organic or inorganic bases. As examples of organic bases can be called trialkylamine, in particular pyridine, 1,5-diazabicyclo(5,4,0)undec-5-ene, 1,5-diazabicyclo(4,3,0)non-ene, 1,4-diazabicyclo(2,2,2)octane, and the preferred inorganic bases are the hydroxides or carbonates of alkaline or alkaline-earth metals. Thus, as kislorodsvyazyvayushchei agent, it is preferable to use potassium carbonate, potassium bicarbonate, sodium hydroxide, calcium hydroxide, etc., or an excess of amine of the General from the used solvent can be conducted at temperatures from 0 to 200aboutC. the Duration of the reaction may vary between half an hour and 10 o'clock It depends also on temperature. If the reaction is carried out at a higher temperature, the duration may be reduced. The conditions of the reaction are preferred. Its however possible under other conditions.

Compounds of General formula IV can be subjected to hydrolysis with the formation of the corresponding quinoline-3-carboxylic acid of General formula I after or without isolating them from the reaction mixture. The hydrolysis can be carried out in an acidic or alkaline environment. Compounds of General formula IV are precipitated from the reaction mixture, for example by cooling, and if desired can be selected, for example, by filtration or centrifugation.

Alkaline hydrolysis is preferably carried out with heating, using a hydroxide or carbonate of alkali metal or alkali earth metal hydroxide used in the form of aqueous solutions. It is preferable to use for this purpose an aqueous solution of sodium hydroxide or potassium hydroxide, sodium carbonate or potassium or calcium hydroxide. On stage hydrolysis to use organic amines, for example trannoy acid. In a preferred variant of the hydrolysis of compounds of General formula IV is carried out by heating it with an aqueous solution of hydrochloric acid, hydrogen bromide, sulfuric or phosphoric acids. It is possible to carry out the hydrolysis and with organic acids, for example acetic, propionic, etc.

The hydrolysis of compounds of General formula IV can be carried out in aqueous medium in the presence miscible with water and organic solvent. For this purpose it is possible to use, for example alcohols, such as methanol, ethanol, ketones, such as acetone, ethers such as dioxane, acid amides, such as dimethylformamide, sulfoxidov, such as dimethylsulfoxide or pyridine.

The resulting hydrolysis of the quinoline-3-carboxylic acid of General formula I may be isolated from the reaction mixture, for example by establishing the desired pH of the aqueous solution and separating the drop-down crystals, for example by filtration or centrifugation, or freeze-drying the aqueous reaction mixture.

Compounds of General formula I can be converted in a known manner in pharmaceutically acceptable salts. Thus, preferably, can be obtained acid additive salts, such as colotomy, sulfuric acid or organic acids. The preferred salts are the chlorides, bromides, arylsulfonate, methansulfonate, maleate, fumarate, benzoate, etc. of Compounds of General formula I form salts of alkali and alkaline earth metals, and other metal ions. Thus, it is possible to obtain sodium, potassium, magnesium, silver, copper and other salts.

Compounds of General formula I and their pharmaceutically acceptable salts can be converted into hydrates (e.g palpitate, trihydrate and so on). This translation is carried out in the usual way.

The object of the present invention are also new compounds of General formula IV in which R, R1, R2and R3have the above definition.

Starting materials of General formula II can be obtained by reacting 1-phenyl-6-fluoro-7-chloro-4-oxo-1,4-dihydro - quinoline-3-carboxylic acid (European patent 131839) or 1-ethyl-6,7,8-Cryptor-4-oxo-1,4-dihydroquinoline-3-carbon - howl acid (patent UK 2057440) macrozones, for example a compound of General formula V

BR where R denotes a halogen atom or an aliphatic, acyloxy group with 7 to 11 carbon atoms, or perborate in water or organic is limited to these examples.

P R I m e R 1. 1,59 g (1-ethyl-6,7,8-Cryptor-1,4-dihydro-4-oxoindole-3-carboxylate-(-deferror subjected to interaction with the 100aboutfor 3 h with 1.29 g of piperazine in 8 ml of dimethylsulfoxide. Then to the reaction mixture of 12.6 ml of 6 wt./about. an aqueous solution of sodium hydroxide and carry out the hydrolysis by heating the mixture for 2 hours then the reaction mixture was filtered, added to 96 wt./about. acetic acid establish its pH is equal to 7 and diluted with 15 ml of water. The reaction mixture was cooled for crystallization during the night falling, the crystals are filtered, washed with water and dried. The result of 1.61 g of 1-ethyl-6,8-debtor-1,4-dihydro-4-oxo-7-piperazine derivatives-quinoline-3-carboxylic acid. So pl. 234-236aboutC.

Calculated C 56,90; H 5,07; N 12,45.

C16H17F2N3O3.

Found, C 56,75; H 5,02; N 12,48.

P R I m m e R 2. 1,99 g (1-ethyl-6,7,8-Cryptor-1,4-dihydro-4-oxoindole-3-carboxy - lat-, )-bis (diacetate-)-Bora is subjected to interaction with 1.29 g of piperazine in 8 ml of dimethylsulfoxide at 110aboutC for 2 hours thereafter, to the reaction mixture are added 20 ml of 3 wt./about. aqueous sodium hydroxide solution, boil it for one hour under reflux, filtered and Stanly filtered off and dried. The result of 1.59 g of 1-ethyl-6,8-debtor-1,4-dihydro-4-oxo-7-piperazinyl - Lin-3-carboxylic acid Golden brown. So pl. 234aboutC.

Calculated C 56,90; H 5,07; N 12,45.

C16H17F2N3O3.

Found, C 57,03; H 5,11; N 12,51.

P R I m e R 3. As in the case of example 2, are subjected to interaction 1.06 g (1-ethyl-6,7,8-Cryptor-1,4-dihydro-4-oxo-quinoline-3-carboxylate-)-bis(ol opional-- boron with 0.64 g of piperazine in 4 ml of dimethylsulfoxide, and then to the reaction mixture add 6.3 ml 6 wt./about. an aqueous solution of sodium hydroxide and boil it for one hour under reflux. After filtration the pH of the mixture is set to 7 by adding 96 wt./about. acetic acid, then add to it 10 ml of water and cooled during the night. Drop down the crystals are filtered, washed with water and dried. The result is 0.74 g of 1-ethyl-6,8-debtor-1,4-dihydro-4-oxo-7-piperazinyl-3-carboxylic acid. So pl. 232-236aboutC.

Calculated C 56,90; H 5,07; N 12,45.

C16H17F2N3O3.

Found, C 56,85; H 5,00; N KZT 12.39.

P R I m e R 4. In the same way as in the case of example 1, 1,59 g (1-ethyl-6,7,8-Cryptor-1,4-dihydro-4-oxoindole-3 - carboxyl is to obtain 1.54 g of 1-ethyl-6,8-debtor-1,4-dihydro-4-oxo-7-(1 - methylpiperazine)-quinoline-3-carboxylic acid. So pl. 237-240aboutC.

Calculated C 58,10; H The 5.45; N 11,91.

C17H19F2N3O3< / BR>
Found, C 58,00; H 5,46; N 11,95.

P R I m e R 5. In the same way as in the case of example 2, a, 1,99 g (1-ethyl-6,7,8-Cryptor-1,4-dihydro-4-oxoindole-3-carboxy - lat-, )-bis(acetate)-boron is subjected to interaction with 1.5 g of 1-methylpiperazine. The result of 1.5 g of 1-ethyl-6,8-debtor-1,4-dihydro-4-oxo-7-(1-methylpiperid - Zino)-quinoline-3-carboxylic acid. So pl. 238-240aboutC.

Calculated C 58,10; H The 5.45; N 11,91.

C17H19F2N3O3.

Found, C 58,19; H Of 5.53; N, 11.87 Per.

P R I m e R 6. In the same way as in the case of example 3, 1.06 g (1-ethyl-6-7,8-Cryptor-1,4-dihydro-4-oxoindole-3-carboxy - lat-, )- bis-(propionate-)-Bora is subjected to interaction with 0.75 g of 1-methylpiperazine. The result of 0.79 g of 1-ethyl-6,8-debtor-1,4-dihydro-4-oxo-7-(1-methylpiperazine)-quinoline-3-carbon howl acid. So pl. 239-240aboutC.

Calculated C 58,10; H The 5.45; N 11,91.

C17H19F2N3O3.

Found, C 57,95; H Lower Than The 5.37; N 11,90.

P R I m e R 7. and 0.46 g of 1-(4'-forfinal)-6-fluoro-7-chloro-1,4-dihydro-4-oxoindole-3-carboxylate- )- bis(acetate)-boron is subjected to interaction with 0.6 g of N-metile is authorized mixture is added 10 ml of 5 wt./about. aqueous sodium hydroxide solution, boil it for 2 hours under reflux, set with 96 wt./about. acetic acid, pH 7, cool, drop-down, the crystals are filtered and washed with cold water. The result of 3.54 g of 1-(4'-forfinal)-6-fluoro-7-(N-methylpiperazine)-1,4-dihydro-4-oxo - quinoline-3-carboxylic acid. So pl. 282-284aboutC. the Obtained carboxylic acid is dissolved by heating in dilute hydrochloric acid, the solution evaporated in vacuum and the result is the monohydrochloride salt of 1-(4'-forfinal)-6-fluoro-7-(N-methylpiperazin - nil)-1,4-dihydro-4-oxoindole-3-carboxylic acid. The product decomposes at temperatures above 270aboutC.

Calculated C 63,15; H 4,79; N 10,52.

C21H19F2N3O3.

Found, C 63,27; H 4,89; N 10,35.

1. The method of obtaining derivatives of quinoline-carboxylic acids of General formula I

< / BR>
where R1unsubstituted or substituted by 1 or 2 halogen atoms of the phenyl or the group of General formula CH2CR6R7R8where R6, R7and R8hydrogen or halogen;

R2piperazinil or 4-methylpiperazine;

R3hydrogen or fluorine,

th formula II

< / BR>
where R is an aliphatic alloctype with 2 to 6 carbon atoms or aromatic alloctype from 7 to 11 carbon atoms;

R4chlorine or fluorine,

with piperazine derivatives of General formula III

< / BR>
where R5hydrogen or methyl, or salts thereof,

hydrolysis of the resulting compounds of General formula IV

< / BR>
where R R3have the specified values,

after or without isolating it from the reaction mixture with the translation of the obtained compounds of General formula I in its free form of its salts.

2. The method according to p. 1, characterized in that the compound of General formula II is subjected to interaction with the amine of General formula III in the presence of an organic solvent, preferably acid amide, sulfoxide, ketone, alcohol, simple or complex ester.

3. The method according to p. 2, characterized in that the organic solvent used sulfoxide.

4. The method according to p. 1, characterized in that the reaction of compounds of General formula II with a compound of General formula III is carried out in the presence of kislorodsvyazyvayushchei agent.

5. The method according to p. 4, characterized in that as kislorodsvyazyvayushchei agent using amine or an excess of compounds of General the persons under item 6, wherein the reaction is carried out using organic or inorganic acids, mainly of hydrochloric, sulfuric or acetic acid.

8. The method according to p. 1, characterized in that the hydrolysis is carried out in an alkaline medium.

9. The method according to p. 8, characterized in that the use of hydroxide of alkali or alkaline earth metal or organic base, preferably an aqueous solution of triethylamine.

 

Same patents:

The invention relates to new indole derivative of General formula

I where R1hydrogen or C1-4-alkyl;

R2hydrogen or C1-4-alkyl;

R3hydrogen or C1-3-alkyl,

or their pharmaceutically acceptable salt, or solvate having NC1-like receptor antagonistic activity

The invention relates to new derivatives of azetidine General formula:

O-R7 (I) where a nitrogen atom or the group-CH-, or C-HaI, where HaI, a chlorine atom or fluorine;

R1lower alkyl or cycloalkyl, lower halogenated or phenyl substituted mono - or Diptera;

R2, R3and R5the same or different and signify hydrogen or lower alkyl;

R4hydroxyl, amino, aminoalkyl, alkylamino, dialkylamino, pyrrolyl-1 or pyrrolidinyl-1, acylaminoalkyl, trifurcated;

R6hydrogen or amino group,

or

A and R1together form a group-O-CH2-and in this case have a chiral center configuration R or S,

R7hydrogen or lower alkyl,

or their pharmaceutically acceptable salts

The invention relates to new derivatives of intellipedia General formula

where R1phenyl substituted by substituents selected from the group consisting of lower alkyl, hydroxyl, protected hydroxyl, halogen or lower alkoxy,

And lower alkylen,

In the lower albaniles, or their pharmaceutically acceptable salts which exhibit anti-allergic effect

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FIELD: chemistry.

SUBSTANCE: invention relates to derivatives with anticancer activity of formulae:

, , , , ,

R2', R3', R4', R5' and R6' are selected from H, Y(CH2)nCH3, X and (CH2)nNR8R9; Y is selected from O and S; X is selected from F, Cl and Br; R8 and R9 are selected from (CH2)nCH3; R2, R3, R4 and R5 are selected from H, Y(CH2)nCH3, X and (CH2)nNR8R9, or R3 and R4 together form -Y(CH2)nY-; R1 and R1' are selected from H, Li+, Na+, K+, N+R8R9R10R11 or benzyl, where R10 and R11 are selected from H, (CH2)nYH, (CH2)nN(CnH2n+1)(CmH2m+1) or (CH2)nCH3, where n and m are integers from 0 to 4, q is an integer from 1 to 4.

EFFECT: obtaining novel compounds with anticancer activity.

37 cl, 3 dwg, 10 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new quinolone derivatives of general formula (1) or a pharmaceutically acceptable salts thereof, wherein R1 represents a hydrogen atom, a lower alkyl group, cyclo C3-8 alkyl, a lower alkyl group or a lower alkoxy, a lower alkyl group; R2 represents a hydrogen, a lower alkyl group or a halogen-substituted lower alkyl group; R3 represents a phenyl group, a difurylglyoxal group, a thienyl group or pyridyl group with each group of the above is optionally substituted by one or two groups specified in a group consisting of the following (1) to (16) in an aromatic or heterocyclic ring, presented by the above R3: (1) lower alkyl groups, (2) lower alkoxy groups, (3) halogen-substituted lower alkoxy groups; (4) a phenoxy group, (5) lower alkylthio groups, (6) a hydroxy group, (7) hydroxy lower alkyl groups, (8) halogen atoms, (9) lower alkanoyl groups, (10) lower alkoxycarbonyl groups, (11) amino groups optionally substituted by one or two lower alkyl groups, (12) carbamoyl groups optionally substituted by one or two lower alkyl groups, (13) cyclo C3-8 alkyl lower alkoxy groups, (14) pyrrolidinyl carbonyl groups, (15) morpholinyl carbonyl groups and (16) a carboxyl group; R1 represents a halogen atom; R5 represents a hydrogen atom or a halogen atom; R6 represents a hydrogen atom; and R7 represents any of the above groups (1) to (15): (1) a hydroxyl group, (2) a halogen atom, (3) a lower alkoxy group, (4) a halogen-substituted lower alkoxy group, (5) a hydroxy lower alkoxy group, (6) a lower alkoxy lower alkoxy group, (7) an amino group optionally substituted by one or two members specified in a group consisting of lower alkyl groups, lower alkoxy lower alkyl groups and cyclo C3-8 alkyl groups, (8) an amino lower alkoxy group optionally substituted in an amino group by one or two members specified in a group consisting of lower alkyl groups, lower alkanoyl group, lower alkyl sulphonyl groups and carbamoyl groups optionally substituted by one or two lower alkyl groups, (9) a cyclo C3-8 alkoxy group, (10) a cyclo C3-8 alkyl lower alkoxy group, (11) a tetrahydrofuryl lower alkoxy group, (12) a lower alkylthio group, (13) a heterocyclic group specified in a group consisting of morpholinyl groups, pyrrolidinyl groups, difurylglyoxal groups, thienyl groups and benzothienyl groups, (14) a phenyl lower alkoxy lower alkoxy group and (15) a pyrrolidinyl carbonyl group. Also, the invention refers to a pharmaceutical composition, and a preventive and/or therapeutic agent based on the compound of formula (1), using the compound of formula (1), a method of treating or preventing the above diseases, to a method of preparing the compound of formula (1).

EFFECT: there are prepared new quinolone derivatives effective for treating and/or preventing the neurodegenerative diseases, diseases caused by neurological dysfunction, or diseases induced by deterioration of mitochondrial function.

11 cl, 1 tbl, 104 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to naphthalene carboxamide derivatives of general formula I which possess the properties of protein kinase or histone deacetylase inhibitors. The compounds can find application for preparing a drug for treating inflammatory diseases, autoimmune diseases, oncological disease, diseases of the nervous system and neurodegenerative diseases, allergies, asthma, cardiovascular diseases and metabolic diseases or disease related to hormonal diseases. In general formula I: , Z represents CH or N; each of the groups R1, R2 and R3 represents hydrogen, halogen, alkyl, alkoxy or trifluoromethyl; R4 represents or X represents a benzene ring or a pyridine ring; R5 represents one or more substitutes specified in a group consisting of hydrogen, halogen, alkyl, alkoxy or trifluoromethyl. The invention also refers to a method for preparing the above compounds, a pharmaceutical preparation and using them.

EFFECT: preparing the compounds which possess the properties of protein kinase or histone deacetylase inhibitors.

13 cl, 10 tbl, 6 dwg

FIELD: chemistry.

SUBSTANCE: claimed invention relates to field of organic chemistry, namely to novel compound of formula (I), where Y and Z, each independently, are selected from group, consisting of: a) phenyl, if necessary substituted with 1 or 2 R6; b) pyridine, imidazole, thiazole, furan, triazole, quinoline or imidazopyridine, if necessary substituted with 1 R6; and c) substituent, independently selected from group, consisting of hydrogen, C1-C6alkyl or pyperidine; R1, R2 and R3, each independently selected from group, consisting of hydrogen and halogen; A and B is each independently selected from hydrogen, OH and C1-C6alkyl; RA and RB are independently selected from group, consisting of hydrogen, C1-C6alkyl and C3-C8cycloalkyl; or RA and RB together with atom, to which they are attached, form 4-6-membered heterocycle, if necessary having additionally one heteroatom or functional heterogrpoup, selected from group, consisting of -O-, -NH, -N(C1-C6-alkyl)- and -NCO(C1-C6-alkyl)-, and 6-membered heterocycle can be additionally substituted with one or two C1-C6-alkyl groups; R4 and R5, each stands for hydrogen; and each R6 is selected from Br, Cl, F, I, C1-C6-alkyl, pyrrolidine, if necessary substituted with one C1-C6-alkyl, C1-C6alkoxy, halogen-C1-C6alkyl, hydroxyl-C1-C6alkylene, -(NRARB)C1-C6alkylene and (NRARB)carbonyl; or to its individual isomer, stereoisomer or enantiomer, or their mixture, if necessary pharmaceutically acceptable salt. Invention also relates to compound of formula (II), particular compounds of formula (I) and (II), pharmaceutical composition and industrial product based on compound of formula (I) and (II), method of treating said pathological conditions, method of obtaining formula (I) compound and to intermediate compound of formula 3.

EFFECT: novel compounds, useful as inhibitors of poly(ADP-ribose)polymerase, are obtained.

50 cl, 1 tbl, 159 ex

FIELD: chemistry.

SUBSTANCE: invention relates to formula compound or to its pharmaceutically acceptable salt, where R represents COOH or CH2OH. Invention also relates to pharmaceutical composition based on formula I, method of modulating CFTR activity in biological sample, based on application of formula I compound, method of treatment, based on application of formula I compound, set based on formula I compound.

EFFECT: obtained are novel derivatives of quinolin-4-one, useful as CFTR modulators.

18 cl, 1 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to field of organic chemistry, namely to method of obtaining compound of formula

1,

including condensation of carboxylic acid of formula

2

with aniline of formula

3 in presence of TZR®, where each R2 and R4 independently represents C1-6 alkyl with linear or branched chain, and each C1-6 alkyl with linear or branched chain is independently and optionally substituted with -OR'; each R5 represents OC(O)OR' or R4 and R5, taken together, form group , y represents 0, each R' represents C1-4 alkyl group, optionally substituted with one or more groups, selected from oxo and -O-C1-4-alkyl group. Invention also relates to intermediate compounds and methods of their obtaining.

EFFECT: elaborated is novel method of obtaining formula 1 compound, which can be useful as modulator of cystic fibrosis transmembrane conductance regulator (CFTR).

52 cl, 10 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to field of organic chemistry, namely to novel quinolyl-containing compounds of hydroxamic acid of general formula (I), wherein each of V1 and V2 independently represents halogen; one of R and R' represents group Q, containing hydroxamic acid, and the other represents methoxy, wherein group Q, containing hydroxamic acid, is represented by formula ; A represents O; L represents C1-6alkyl; J represents NH, piperidinyl, or J is absent; X is absent; Y represents C1-6alkyl, or Y is absent. The invention also relates to method for obtaining formula (I) compound, pharmaceutical composition, based on formula (I) compound and its application for treatment of diseases, caused by proteinkinase and/or histone deacetylase activity.

EFFECT: novel compounds, which can be applied in cancer treatment, have been obtained.

25 cl, 7 dwg, 7 tbl, 45 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I and pharmaceutically acceptable salts thereof , where R is hydrogen, RO(OH)2, P(=O)(O-(C1-C6)alcylenphenyl)2 or P(=O)(OM)2; W represents 2-halogenphenyl, 3-halogenphenyl or 4-halogenphenyl; R5 is (C1-C6)alkoxy, hydroxyl or OR8; R6 is hydroxyl or (C1-C6)alkoxy; R7 represents hydrogen, hydroxyl or O-(C1-C6)alcylenphenyl; R8 represents a RO(OH)2, P(=O)(O-(C1-C6)alcylenphenyl)2 or P(=O)(OM)2, and m is monovalent metal ion; or where R is hydrogen, RO(OH)2, P(=O)(O-(C1-C6)alcylenphenyl)2 or P(=O)(OM)2; W represents 2-halogenphenyl, 3-halogenphenyl or 4-halogenphenyl; R5 represents hydrogen, (C1-C6)alkoxy, hydroxyl or OR8; R6 is (C1-C6)alkoxy; R7 is hydroxyl or O-(C1-C6)alcylenphenyl; R8 represents PO(OH)2, P(=O)(O-(C1-C6)alcylenphenyl)2 or P(=O)(OM)2, and m is monovalent metal ion. Disclosed compounds have anti-cancer activity. Invention also relates to compounds of formula I, radicals of which are presented in patent claim and to using pharmaceutical composition containing effective amount of compound of invention for treating cancer.

EFFECT: technical outcome is new compounds possessing anticancer activity.

17 cl, 23 dwg, 7 tbl, 4 ex

FIELD: pharmaceutics.

SUBSTANCE: in formula I R1 and R3 independently represent hydrogen, and R2 represents , , , , or R1 independently represents hydrogen, R3 is methyl, and R2 represents or or R2 and R3 independently represent hydrogen, and R1 is . Invention also refers to pharmaceutical compositions containing said compound, a method for increasing Src homology-2 containing proteintyrosinephosphatase-1 (SHP-1) expression in a cell, method of treating diseases or pathological condition characterised by low expression SHP-1, and to use of said compounds for preparing a drug for treating diseases or pathological condition characterised by low expression of SHP-1.

EFFECT: disclosed are novel compounds of formula I, having Src homology-2 containing protein tyrosine phosphatase-1 (SHP-1) agonist activity.

11 cl, 6 tbl, 23 dwg, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new aminomethyl quinolone derivative of formula (I) or its pharmaceutically acceptable salt, where R is -C(=O)A, -C(=O)OA, -C(=O)NHA, -C(=N-C≡N)A, -C(=N-C≡N)NHA or A; A is C1-6-alkyl, phenyl, lower cycloalkyl, adamantyl, heterocycloalkyl selected from benzodioxin, pyrrolidine, piperidine, morpholine or piperazine, heteroaryl selected from pyridine, pyrazole, thiazole, triazole or pyrimidine or bicyclic heteroaryl selected from quinoline, quinazoline, indole, benzothiazole, benzoimidazole or imidazopyridine optionally substituted with one or two A1; each A1 independently represents A2 or A3; each A2 is independently halo or oxo; each A3 is independently C1-6-alkyl, C1-6-alkoxy, phenyl, benzyl, heterocycloalkyl selected from morpholine, piperidine, diazepane, pyrrolidine, azepane or piperazine, bicyclic heterocycloalkyl selected from benzodioxole or diazobicycloheptane, heteroaryl selected from oxazole, triazole, pyrazole, imidazole, thiadiazole, oxadiazole, thiazole or tetrazole, amino, C1-6-alkylamino, C1-6-dialkylamino, amido, C1-6-alkyl ester group, sulfonyl, sulfonamido, -C(=O) or -C(═O)O, optionally substituted by one, two or three groups, selected from halo, hydroxy, C1-6-alkylamino, C1-6-alkyloxy, C1-6-alkyl, C1-6-alkoxy, phenyl, hydroxycycloalkyl wherein cycloalkyl is adamantyl, amino, C1-6-alkylamino, C1-6-dialkylamino, t-butyl complex of carbamic acid ester, (C1-6-alkyl) sulfonyl-piperidinyl or hydroxy- (C1-6-alkyl); R' is H or methyl; X is CX'; X' is H or halo; X1 is H, 2-oxazolyl, dimethylamido or C1-6-alkyl ester group; Y is CH or N; and Y1 is H, halo, C1-6- alkoxy or halo (C1-6alkyl). The invention also relates to particular aminomethyl quinolone derivatives and to the use of said aminomethyl quinolone derivatives.

EFFECT: obtained new aminomethyl quinolone derivatives, useful in the treatment of JNK-mediated disorder.

15 cl, 2 tbl, 211 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention relates to the benzo-iso-selenium zolonyl derivatives with the general formula (I) or (II) , where R - C1-C6-alkylen, phenyliden, biphenyliden, R' - polysaccharide residue or residue , where M - Pt or Pd.

EFFECT: compounds possess anti-inflammatory, antiviral and antithrombotic activities.

12 cl, 7 ex, 8 tbl

FIELD: chemistry.

SUBSTANCE: compound has formula I: |Chemical formula 1| where A is O, NR, S, S(=O), S(=O)2 or Sc; B is hydrogen or ; R1 is hydrogen, C1-C8 alkyl or halogen; R2 is hydrogen, C1-C8 alkyl, or ; Xa and Xb is independently CR or N; R is hydrogen or C1-C8 alkyl; R3 is hydrogen, C1-C8 alkyl; R4 and R5 are independently hydrogen, halogen or C1-C8 alkyl; R6, is hydrogen. C1-C8 alkyl, or a pharmaceutically acceptable organic salt; R21, R22 and R23 are independently hydrogen, halogen, NO2, C1-C7 alkyl, unsubstituted or substituted with halogen, C3-C12 heteroaryl, containing one or more heteroatoms selected from N, O and S; m equals an integer from 1 to 4; p equals an integer from 1 to 5; s equals an integer from 1 to 5; u equals an integer from 1 to 3; w equals an integer from 1 to 4; and alkyl in R1, R3, R4, R5 and R6 can further be substituted with one or more halogens, C3-C7 cycloalkyl or C1-C5 alkylamine. Also disclosed are methods of producing selenazole derivatives, a pharmaceutical composition, a functional feed additive composition, a functional beverage, a food additive, animal feed, a functional cosmetic composition, a peroxisome proliferator-activated receptor (PPAR) activator composition.

EFFECT: invention enables to obtain a selenazole derivative which activates a peroxisome proliferator-activated receptor.

15 cl, 1 dwg, 6 tbl, 298 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 2,3-dihydro[1,3]tellurazolo[3,2-α]pyrimidinium chlorides of general formula , where R1 is an alkyl or phenyl, R2 is an alkyl, phenyl or hydrogen, R1+R2 is cycloalkyl. The method includes reacting the corresponding olefin with 4,6-dimethyl-2-pyrimidine tellurenylchloride hydrochloride in equimolar ratio in an acetonitrile medium.

EFFECT: invention enables to obtain novel compounds which can be used in fine organic synthesis, in production of medicinal drugs and biologically active substances.

4 ex

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