The method of obtaining derivatives of 2-chloro-3-nitroquinoline, the method of obtaining 2-chloro-3,4-diaminopyridine, the method of obtaining derivatives of 4-chloro-1h-imidazo (4,5-c) quinoline, a method of deriving 1h-imidazo (4,5-c)quinoline, 2-chloro-3-nitroanisole, 2-chloro-3,4-diaminophenol

 

(57) Abstract:

Usage: in medicine. The inventive method of obtaining derivatives of 4-chloro-1H-imidazo (4,5-C) quinoline, intermediates for their production. Reagent 1: 2,4-chloro 3-nitroquinoline. The reagent 2 - amine RNH. Reaction conditions: an organic solvent, a base to obtain the corresponding chloro-nitro-diaminopyridine, which restores to the corresponding chlorine-diamino-chinoline, which interacts with trialkylphosphines. 6 S. p. f-crystals.

The invention relates to a method for producing derivatives of 1H-imidazo/4,5-c/quinoline, as well as new intermediate products obtained in the synthesis process.

The resulting synthesis of the compounds used as bronchodilators or antiviral drugs.

A method of obtaining 1H-imidazo/4,5-c/quinoline interaction derived nitroquinoline with aminoguanidinium R1NH2in the environment of an organic solvent that includes a base to obtain the corresponding aminoanthraquinone, the recovery of the past and receiving diaminopyridine, which is subjected to interaction with trialkylindium R2-C(O,5-c/ quinoline using processing chloronicotinamide aminoguanidinium in an inert organic solvent /1,2/.

An object of the invention is to simplify the method.

This object is achieved in a method of producing derivatives of 4-chloro-1H-imidazo/4,5-c/-quinoline General formula

< / BR>
where R1branched or non-branched C1-C8-alkyl, lower hydroxyalkyl;

R2branched or non-branched C1-C8-alkyl;

R is lower alkyl;

n=0, 1, 2,

interaction derived 2-chloro-3-nitroquinoline with aminoguanidinium formula

R1NH2,

where R1branched or unbranched alkyl, C1-C8in the environment of organic solvent in the presence of a base to obtain the corresponding aminoanthraquinone, the recovery of the past and receiving diaminopyridine, which is subjected to interaction with trialkylaluminium formula

R2-C(OAlK)3,

where AlK is lower alkyl;

R2branched or unbranched alkyl, C1-C8< / BR>
or with acid formula

R2CO2H,

where R2is above the value at which the derivative of nitroquinoline use 2, 4-dichloro-3-nitroquinoline General formula

< / BR>
where R, n have the noleen formula

< / BR>
where R1- a branched or non-branched C1-C8-alkyl;

R, n have the above values,

from which recovery receive the corresponding 2-chloro-3,4-diaminophenol formula

< / BR>
where R, R1n have the above values,

the last step of trialkylamine or acid formula

R2-C(OAlK)3or R2COOH,

where R2branched or non-branched C1-C8-alkyl;

AlK is a lower alkyl, translating into the target connection,

and in the method of deriving 1H-imidazo[4,5-c]quinoline General formula

< / BR>
where R1branched or unbranched alkyl, C1-C10; lower hydroxyalkyl,

R2alkyl branched or unbranched C1-C8;

R3lower alkyl/amino/-radical, di/lower/alkyl/amine, lower alkoxy, phenylthio, morpholinoethyl;

R is lower alkyl;

n 0, 1, 2,

interaction derived 2-chloro-3-nitroquinoline with aminoguanidinium formula:

R1NH2< / BR>
where R1branched or unbranched alkyl, C1-C8lowest hydroxyalkyl,

in the environment of organic solvent in the presence of a base to receive the of ohioline, which is subjected to interaction with trialkylindium formula

R2C(OAlK)3,

where AlK is a lower alkyl;

R2branched or unbranched alkyl, C1-C8,

or acid formula

R2CO2H,

where R2have the above values,

as derived nitroglicerina using 2,4-dichloro-3-nitroquinoline formula

< / BR>
where R, n have the above values,

which interaction with RNH2,

where R1have the above values,

transferred to 2-chloro-3-nitro-quinoline General formula

< / BR>
where R1, R, n have the above values,

from which recovery receive the corresponding 2-chloro-3,4-diaminophenol formula

< / BR>
where R1, R, n have the above values,

which action trialkylamine or acid formula

R2C(OAlK)3or R2COOH

where AlK is a lower alkyl;

R2branched or unbranched alkyl, C1-C8,

transferred in connection formulas

< / BR>
where R1, R2, R, n have the above values,

which the inert solvent is subjected to interaction with the compound of formulas is sabreena also relates to new compounds 2-chloro-3-nitroquinoline General formula

< / BR>
where R1branched or unbranched alkyl, C1-C8lowest hydroxyalkyl;

R is lower alkyl;

n= 0, 1, 2,

and 2-chloro-3,4-diaminophenol formula

< / BR>
where R1branched or unbranched alkyl, C1-C8lowest hydroxyalkyl;

R is lower alkyl;

n= 0, 1, 2.

The following examples illustrate the invention but do not restrict it.

Example 1. 4-hydroxy-3-nitro-2/H/-chinoline.

Fuming nitric acid /262 ml/ is added at a temperature of about 20oC to a suspension of 4-hydroxy-2/1H/-Hinayana /1.0 kg/ acetic acid /EUR 7.57 l/. The mixture is heated at 40oC for 2.5 hours the resulting solution was cooled to a temperature of about 20oC and poured into 8 l of water. The resulting mixture was stirred for 20 min, filtered, washed with water up until the filtrate becomes neutral, and dried. Allocate product 4-hydroxy-3-nitro-2/1H/-chinoline with the release of 98% when analyzed by thin layer chromatography gives only one spot /silica gel, chloroform in methanol 20:80 by volume/.

Example 2. 2,4-dichloro-3-nitroquinoline.

Oxychloride of phosphorus /50 ml/ added dropwise within 1 h to a mixture of 4-hydroxy-3-nitro-2/1H/the haunted refrigerator for 5 h, for which 40 ml of phosphorus oxychloride is distilled off by distillation. To the mixture slowly add cold water, keeping the temperature below 30oC. the resulting aqueous solution is extracted with chloroform. Products extraction, dried over sodium sulfate and concentrated. The solid product of 2,4-dichloro-3-nitroquinoline recrystallized from petroleum ether.

Example 3. 2-chloro-N-/2-methylpropyl/-3-nitro-4-chinoline.

2 methylpropylamine /0.5 ml/ add to suspension of 2,4-dichloro-3-nitroquinoline /1 g/ triethylamine /15 ml/ 40oC for 40 minutes and Then the solution is heated at 70oC for 1 hour Triethylamine and 2-methylpropylamine is removed by distillation and the residue is poured within 1 h in water 1 N. H. Solid product 2-chloro-N-/2-methylpropyl/-3-nitro-4-chinoline separated by filtration, washed with water and recrystallized from petroleum ether.

Analysis for C13H14ClN3O2< / BR>
Calculated: C 55,82% H 5,04% N 15,02%

Found: C 55,69% H 5.1% of N 14,9%

The temperature of the plasma 80-92oC.

Example 4.1 2-Chloro-N4-/3-methylpropyl/3,4-chinaindia.

A solution of 2-chloro-N-/2-methylpropyl/-3-nitro-4-Hinayana /120 g/, acetic acid /300 ml/, isopropyl alcohol /300 mg/. the received solution is filtered and the solvent removed from the filtrate under reduced pressure. The residue is dissolved in aqueous hydrochloric acid /1 l, 4 N./. The product is precipitated by adding the solution to the sodium hydroxide solution. The precipitate is filtered and washed with water to obtain a product of 2-chloro-N-/2-methyl-propyl/-3,4-chinaindia exit 73%

Example 5. 4-Chloro-1-/2-methylpropyl/-IH-imidazo 4,5-c quinoline.

A solution of 2-chloro-N4-/2-methylpropyl/-3,4-chinaindia /3 g/ triethylorthoformate /2.8 g/ heated at 80oC for 15 h the resulting solution was cooled to ambient temperature and add 20 ml of chloroform. The solution is washed with water. Get a concentrated solution of 4-chloro-1-/2-methyl-propyl/-1H-imidazo[4,5-c]-quinoline.

Example 6. 1-/2-Methylpropyl/-IH-imidazo[4,5-c] quinoline-4-amine.

A solution of 4-chloro-1-/2-methylpropyl/-IH-imidazo[4,5-c]quinoline /0,86 g/ 7 g of a methanol solution containing 20% by weight of ammonia is placed in a steel bomb for 20 hours at 150oC. After cooling to 20oC solid product is separated by filtration and washed with methanol. The crude product 1-/2-methylpropyl/-1H-imidazo[4,5-c] quinoline-4-amine recrystallized from N,N-dimethyl-formamide.

Example 7. 2,4-Dichloro-3-NITROPHENOL is alumina /152 g, 1.5 equiv./ and toluene /620 ml/ so that the temperature remained below the 50oC. thereafter, the suspension is heated at 110oC for 11 h, the resulting suspension is cooled to room temperature and poured into 1.7 l of water with such speed that the temperature remained below the 50oC. the Organic phase is separated and the aqueous phase is extracted with toluene /2x250 ml/. Organic products are collected and washed with water /3x250 ml/. The solvent is removed under reduced pressure with the release of the product of 2,4-dichloro-3-nitroquinoline, which when analyzed by thin layer chromatography gives a single spot /silica gel, methanol-chloroform, 1:1 by volume/ yield 70% according to the quantitative analysis.

Example 8. 2-Chloro-N-/2-methylpropyl/-3-nitro-4-chinoline.

A mixture of 2,4-dichloro-3-nitroquinoline /100 g/ and N,N-dimethylformamide /180 ml/ mix, and triethanolamine /42 g, 4 EQ/ added dropwise, and then added dropwise 2-methyl-Propylamine /a 21.5 g, 0.7 EQ/. The mixture is stirred at room temperature until the reaction is completed, what is judged by gas chromatography. With stirring, add water hydrochloric acid /250 ml, 4 N./. The resulting mixture is cooled under stirring to a temperature of about 0oArticle 2-chloro-N-/2-methylpropyl/-3-nitro-4-chinoline with a yield of about 90%

Example 9. 4-Chloro-1-/2-methylpropyl/-1H-imidazo[4,5-C]quinoline.

A suspension of 2-chloro-N4-/2-methylpropyl/-3,4 heelinenmek /35 g/ and triethylorthoformate /52,3 g, 2.5 equiv./ heated at 145oC for 10 h, and during this time the ethanol was removed by distillation. The resulting mixture was cooled to room temperature and the solid is separated by filtration. The solid is dissolved in hydrochloric acid /100 ml, 4 N./. The resulting solution was added to a solution of sodium hydroxide. The precipitate is filtered and washed with water to give the product 4-chloro-1-/2-methylpropyl/-1H-imidazo[4,5-C] quinoline with exit 92%

Example 10. 1-/2-Methylpropyl/-1H-imidazo[4,5-C]quinoline-4-amine.

A mixture of 4-chloro-1-/2-methylpropyl/-1H-imidazo[4,5-C] quinoline /66 g/, methanol /266 ml/ ammonia /46.2 g/ placed in a steel bomb and heated at 150oC for 8 hours the mixture is filtered, after which the solid residue washed with water and dried, obtaining the product 1-/2-methylpropyl/-1H[4,5-imidazo[4,5-C]-quinoline-4-amine to yield 70%

Example 11. Another way to obtain 2-chloro-N-/2-methylpropyl/-3-nitro-4-Hinayana.

Oxychloride of phosphorus /3,067 kg, 4.0 equiv./ add to a suspension of 4-hydroxy-3-nitro-2/1H/-Hinayana /1,031 kg/ triethylamine /1,045 l/ and Tolu who received the solution heated under reflux /95-100oC/ within 11 hours After which the mixture is cooled to 25oC and poured into water /6,5 l/ for 1.5 h, and the temperature remained below 35oC. the Organic phase is separated and the aqueous phase is extracted with toluene /2x1 l/. Mixed organic phase is washed with water /h l/ and filtered. To the filtrate add triethylamine /428 g/, after which the resulting solution was added 2-methylpropylamine /262,8 g/. A solution containing 2-methylpropylamine, heated at 50oC for 3 h, after which add another portion of 2-methylpropylamine /42 g/ and stirred the reaction mixture for 3 hours Add hydrochloric acid /37% aqueous solution of 1.41 l/. The suspension is cooled to room temperature, and precipitated precipitated product is separated by filtration, suspension in cold acetone /3l/ and neutralized with sodium hydroxide /4.5 l 20% by weight aqueous solution/. Precipitated precipitated product is filtered, washed with water and dried, obtaining a hard solid product 2-chloro-N-/2-methylpropyl/-3-nitro-4-chinoline /98% purity, determined by gas chromatography/ if 56%

Example 12. 1-[/2-Chloro-3-nitro-4-chinoline/amino]-2-methyl-2-propanol.

To a solution of 2,4-dichloro-3-nitroquinoline /11.5g/ from example 7, N,N-dimethylformamid the 2-propanol /3.6 g/, moreover, during the reaction temperature was increased to 35oC. After which the reaction mixture is heated at 55oC for 1 h, and then cooled to room temperature, then add water /50 ml and the resulting suspension filtered. The solid product is washed with water and dried, obtaining 12 g of 1-[/2-chloro-3-nitro-4-chinoline/amino]-2-methyl-2-propanol. The compound was analyzed in the form of a monohydrate.

Analysis for C13H16ClN3O4,

Calculated: C 49,77, H 5,14, N 13,39

Found: C 40,80, H 5,10, N 13,8

The temperature of the plasma 164-167oC.

Example 13. 1-[/3-Amino-2-chloro-4-chinoline/amino]-2-methyl-2-propanol.

A solution of 1-/2-chloro-3-nitro-4-chinoline amino-2-methyl-2-propanol /10 g of example 12/, isopropyl alcohol /100 ml) and 5% Pt/C /0.4 g/ placed in a steel bomb and leave for 8 h under hydrogen pressure /2 ATM/. The catalyst was filtered and washed with ethanol. Of the components of the filtrate to remove the solvent under reduced pressure, and the resulting material is dissolved in aqueous hydrochloric acid /4 ad 100 ml. The resulting solution is filtered, then the filtrate is added an aqueous solution of sodium hydroxide and extracted with chloroform /h ml/. From complex extract the solvent is evaporated when poigayil-1H-imidazo[4,5-C]quinoline-1-ethanol.

A suspension of 1-[/3-amino-2-chloro-4-chinoline/amino]-2-methyl-2-propanol /5 g of example 13/ acid /50 ml/ triethylorthoformate /5 ml/ heated at 80oC up until the starting material disappears, what is judged by the method of thin-layer chromatography. The resulting solution is cooled, and the precipitated precipitated product is separated by filtration and washed with xylene /h ml/.

Example 15. 1-Amino-2-methyl-2-propanol.

The methanol /32,5 l, 25.7 kg/ 10-gallon lined glass reactor, cooled to the 7oC add anhydrous liquid ammonia /60 kg 12,6 EQ./, while maintaining the temperature below 25oC. the Solution is cooled to 7oC, then one portion add /heat was not observed/. The solution is stirred during the 7oC for 4 h, and then for 64 hours at a temperature of about 20oC. Then the solution is slowly heated to 60oC for 2-3 h, letting out the ammonia through the exhaust fan. The excess methanol is distilled off at 65 to 70oC, and the product is distilled fractions at atmospheric pressure. The third faction /thermal head 118-160oC, the temperature of the tank 140-200oC/ contains 1,69 g /67,9%/ 1-amino-2-methyl-2-propanol of 98.3% purity by SS.

1. The method of obtaining the production 1 - C8-alkyl, lower hydroxyalkyl;

R is lower alkyl;

n 0,1,2,

wherein the 2,3-dichloronitrobenzene General formula

< / BR>
subjected to interaction with the compound of General formula

R1NH2,

where R1has the specified value,

in an organic solvent in the presence of a base.

2. The way to obtain 2-chloro-3,4-diaminopyridine General formula

< / BR>
where R1branched or unbranched1- C8-alkyl, lower hydroxyalkyl;

R is lower alkyl;

n 0,1,2,

wherein the 2,3-dichloronitrobenzene General formula

< / BR>
where R and n have the specified values,

subjected to interaction with the amine of General formula

R1NH2,

where R1has the specified value,

obtaining a derivative of 2-chloro-3-nitroquinoline General formula

< / BR>
where R1, R and n have the specified values,

which is subjected to recovery.

3. The method of obtaining derivatives of 4-chloro-1H-imidazo(4,5-C) quinoline of General formula

< / BR>
where R1branched or unbranched1- C8-alkyl, lower hydroxyalkyl;

R2branched or unbranched1
R1NH2,

where R1branched or unbranched alkyl WITH1- C8,

in the environment of organic solvent in the presence of a base to obtain the corresponding aminoanthraquinone, the recovery of the past and receiving diaminopyridine, which is subjected to interaction with trialkylaluminium General formula

R2C(OAlk)3,

where Alk is a lower alkyl;

R2branched or unbranched alkyl WITH1- C8,

or with an acid of General formula

R2CO2H,

where R2has the specified value,

characterized in that, to simplify the process, as derived nitroquinoline using 2,4-dichloro-3-nitroquinoline General formula

< / BR>
where R and n have the specified values,

which interaction with R1NH2transferred to 2-chloro-3-nitroanisole General formula

< / BR>
where R1branched or unbranched1- C8-alkyl, lower hydroxyalkyl;

R and n have the specified values,

from which recovery receive the corresponding 2-chloro-3,4-diaminophenol General formula

< / BR>
where R1, R1and n have the above Zn is R2COOH,

where R2branched or unbranched1WITH8- alkyl;

Alk is a lower alkyl;

transferred to the target connection.

4. The method of deriving 1H-imidazo(4,5-C) quinoline of General formula

< / BR>
where R1branched or unbranched alkyl WITH1- C8lowest hydroxyalkyl;

R2branched or unbranched alkyl WITH1- C8;

R3lower alkyl(amino)- radical, di(lower)alkylamino, lower alkoxy, phenylthio, morpholinoethyl;

R is lower alkyl;

n 0,1,2,

interaction derived 2-chloro-3-nitroquinoline with aminoguanidinium General formula

R1NH2,

where R1branched or unbranched alkyl WITH1- C8lowest hydroxyalkyl,

in the environment of organic solvent in the presence of a base to obtain the corresponding aminoanthraquinone, the recovery of the past and receiving diaminopyridine, which is subjected to interaction with trialkylindium General formula

R2C(OAlk)3,

where Alk is a lower alkyl;

R2branched or unbranched alkyl WITH1- C8,

or acid total f the d simplify the process, as derived nitroglicerina using 2,4-dichloro-3-nitroquinoline General formula

< / BR>
where R and n have the specified values,

which interaction with R1NH2where R1has these values translate to 2-chloro-3-nitro-chinoline General formula

< / BR>
where R, R1and n have the specified values,

from which recovery receive the corresponding 2-chloro-3,4-diaminophenol General formula

< / BR>
where R1, R and n have the specified values,

which action trialkylamine or acid of General formula

R2C(OAlk)3,

or

R2COOH,

where Alk is a lower alkyl;

R2branched or unbranched alkyl WITH1- C8,

transferred in connection with the General formula

< / BR>
where R1, R2and R have the above values,

which the inert solvent is subjected to interaction with the compound of General formula

R3H

or connection

R3M,

where R3has a specified value;

M is alkali metal.

5. 2-Chloro-3-nitroanisole General formula

< / BR>
where R1branched or unbranched alkyl WITH1- C8lowest R1branched or unbranched alkyl WITH1- C8lowest hydroxyalkyl;

R is lower alkyl;

n 0, 1, 2.

 

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< / BR>
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(I) where Z is oxygen or sulfur;

R is hydrogen or C1-3-alkyl; when Z stands for oxygen, R1is a halogen, amino group, acetylamino or-O-R2where R2is4-6-alkyl or C6-quinil; Z, meaning sulfur, R1is halogen, C1-8-alkyl, C6-alkenyl straight chain, cyclopropylmethyl, benzyloxypropionic, morpholino-, 4-methylpiperidino - or 4-hexylamino or a group-O-R2where R2linear or branched C3-6alkenyl,3-6-quinil, cyclopropylmethyl, -R3-O-R4or-R3-O-R4-O-R5where each of R3, R4and R5means1-4-alkyl, or R1represents a group S-R2where R2linear C2-8-alkyl, or their pharmaceutically acceptable salts

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< / BR>
where R1aryl with 6-10 carbon atoms, unsubstituted or once-three times substituted by identical or different substituents from the group comprising halogen atom, a nitro-group, cyano, trifluoromethyl, cryptometer and triptoreline,

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FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for preparing 3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-ene nitrile. Method involves interaction of 2-cyclopropyl-4-(4-fluorophenyl)quinoline-3-carbaldehyde with acetonitrile in the presence of a base to obtain mixture of 3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-ene nitrile and 3-[2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-yl]-3-hydroxypropionitrile and the following addition of a dehydrating agent to the reaction mixture for carrying out dehydration. Under usual conditions new 3-[2-cyclopropyl-4-(4-fluorophenyl)quinoline-3-yl]-3-hydroxyprionitrile is formed in the above said reaction as an intermediate compound. However, if the above said interaction reaction is carried out in organic solvent with dielectric permeability 10 or lower in the range of temperature from 20°C to 25°C then 3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-prop-2-ene nitrile is formed directly. 3-[2-Cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-prop-2-ene nitrile is used as the parent compound for synthesis of quinolyl propenal derivative that is used for synthesis of cholesterol-reducing agent. Invention provides simplifying method in preparing 3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-prop-2-ene nitrile.

EFFECT: improved preparing method.

18 cl, 7 ex

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

SUBSTANCE: invention relates to new biologically active heterocyclic retinoid compounds. Invention describes retinoid compounds corresponding to the formula (I): or their pharmaceutically acceptable salts, solvates or hydrates wherein n means a whole number from 0 to 2; A represents optionally substituted phenyl; B represents oxygen (O), sulfur (S) atom or -NR6 wherein R6 represents hydrogen atom or alkyl; Y represents -OR7 wherein R7 represents hydrogen atom, alkyl, optionally substituted phenyl, aralkyl wherein aryl fragment means optionally substituted phenyl, cycloalkyl or cycloalkylalkyl; Z represents -C(R101)2-, -R102C=CR102-, -C≡C-, -C(R103)2S-, -C(O)O- or -C(O)NR10- wherein each among R10, R101, R102 and R103 represents independently hydrogen atom or alkyl; R1 and R2 represent independently hydrogen atom or alkyl; R3 represents hydrogen atom or alkyl; R4 and R5 represent independently hydrogen atom, (C1-C8)-alkyl or arylalkyl wherein aryl fragment means optionally substituted phenyl. Also, invention describes methods for preparing retinoid compounds, a pharmaceutical composition based on thereof and a method for treatment and/or prophylaxis of respiratory ways obstructive disease, cancer or dermatological disturbance or disorder. Invention provides preparing new compounds possessing useful biological properties.

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

28 cl, 10 tbl, 16 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

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EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

17 cl, 2 tbl, 74 ex

Casr antagonist // 2315036

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SUBSTANCE: invention relates to a novel compound represented by the following formula (1) , its pharmaceutically acceptable salts or optically active isomers wherein each symbol is given in the invention description. Proposed compound possesses antagonistic effect with respect to calcium-sensitive receptor (CASR). Also, invention relates to a therapeutically medicinal agent used in treatment of osteoporosis based on this compound, to a method for treatment of osteoporosis, calcium receptor antagonist and to agent promoting secretion of parathyroid hormone (PTH).

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33 cl, 66 tbl, 5 ex

FIELD: organic chemistry, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel derivatives of aniline of the general formula (I): and their pharmaceutically acceptable salts and isomeric forms possessing properties of phosphodiesterase-4 inhibitors. Compounds can be used, fore example, for enhancing cognitive ability. In compounds of the general formula (I) R1 means linear or branched (C1-C4)-alkyl that can be unsubstituted or substituted with one or more halogen atoms; R2 means linear or branched (C1-C4)-alkyl that can be unsubstituted or substituted with one or more substitutes of the following order: halogen atom, (C1-C4)-alkoxy or their combinations, (C3-C10)-cycloalkyl, (C4-C16)-cycloalkylalkyl wherein alkyl fragment comprises from 1 to 4 carbon atoms, (C7-C11)-arylalkyl wherein aryl fragment comprises 6 carbon atoms, and alkyl fragment that can be linear or branched and comprises from 1 to 5 carbon atoms and wherein radical arylalkyl can be unsubstituted or substituted in aryl fragment with one or more substitutes of the following order: halogen atom, alkoxy group comprising from 1 to 4 carbon atoms or their combinations, and in alkyl fragment one group -CH2CH2- is optionally replaced for group -CH=CH-, and one group -CH2- is optionally replaced for -O- for -NH-, partially unsaturated carbocyclic group comprising from 5 to 9 carbon atoms that can comprise condensed benzene ring, heterocyclic group that can be saturated, partially saturated or unsaturated and comprises from 5 to 6 carbon atoms in cycle including one atom chosen from oxygen (O), or heterocyclylalkyl group wherein heterocyclic fragment can be saturated, partially saturated or unsaturated and comprises from 5 to 6 carbon atoms in cycle including 1-2 atoms chosen from nitrogen (N) or sulfur (S) atoms, and alkyl fragment that can be linear or branched comprises from 1 to 5 carbon atoms; R3 means partially unsaturated carbocyclylalkyl group wherein carbocyclic fragment comprises from 5 to 6 carbon atoms, and linear or branched alkyl fragment comprises from 1 to 5 carbon atoms, (C7-C11)-arylalkyl wherein aryl fragment comprises 6 carbon atoms, and linear or branched alkyl fragment comprises from 1 to 5 carbon atoms and wherein arylalkyl radical can be linear or substituted in aryl fragment with one or more substitutes of the following group: trifluoromethyl, (C1-C4)-alkyl, (C1-C4)-alkoxy or their combinations, heterocyclylalkyl group wherein heterocyclic fragment can be aromatic, partially or completely saturated and comprises from 5 to 10 atoms in cycle including 1-2 atoms chosen from N, O or S, and linear or branched alkyl fragment comprises from 1 to 5 carbon atoms and wherein heterocyclylalkyl group can be linear or substituted in heterocyclic fragment with one or more substitutes of the following order: halogen atom, (C1-C4)-alkyl, (C1-C4)-alkoxy or their combinations; R4 means (C6-C12)-aryl that can be linear or substituted with one or more substitutes of the following order: halogen atom, (C1-C4)-alkyl, (C2-C4)-alkenyl, hydroxy, (C1-C4)-alkoxy, (C2-C4)-alkoxyalkoxy, nitro, trifluoromethyl, -OCF3, amino group, aminoalkyl, aminoalkoxy, hydroxy-(C1-C4)-alkyl, hydroxamic acid, tetrazol-5-yl, 2-(heterocyclyl)-tetrazol-5-yl, carboxy, alkoxycarbonyl, cyano, acyl, alkylsulfonyl, phenoxy, trialkyloxy, R5-L or their combinations, or heteroaryl comprising from 5 to 10 atoms in cycle including 1-2 atoms chosen from N wherein heteroaryl can be linear or substituted with one or more substitutes of the following order: (C1-C4)-alkyl, (C1-C4)-alkoxy, carboxy, alkoxycarbonyl or their combinations; R5 means hydrogen atom, (C1-C8)-alkyl, (C3-C10)-cycloalkyl, C6-aryl, heterocyclic group that can be saturated, partially saturated or unsaturated and comprises from 5 to 10 atoms in cycle from which at least atom means N or O, and wherein heterocyclic group can be linear or substituted with one or more (C1-C4)-alkyls, or group heterocyclylalkyl, and others. Also, invention relates to intermediates compounds and to a method for enhancing the cognitive ability.

EFFECT: valuable biological and biochemical property of compounds.

49 cl, 8 sch, 26 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new substituted phenoxy-aceitic acids (I), in which: X is halogen, cyano, nitro or C1-4alkyl, which is substituted with one or more halogen atoms; Y is chosen from hydrogen, halogen or C1-C6alkyl, Z is phenyl, naphthyl or ring A, where A is a six-member heterocyclic aromatic ring containing one or two nitrogen atoms, or can be 6,6- or 6,5-condensed bicycle which contains one O, N or S atoms, or can be 6,5-condensed bicycle which contains two O atoms, where phenyl, naphthyl or ring A can all be substituted with one or more substitutes, independently chosen from halogen, CN, OH, nitro, COR9, CO2R6, SO2R9, OR9, SR9, SO2NR10R11, CONR10R11, NR10R11, NHSO2R9, NR9SO2R9, NR6CO2R6, NR9COR9, NR6CONR4R5, NR6SO2NR4R5, phenyl or C1-6alkyl, where the last group can possibly be substituted with one or more substitutes, independently chosen from halogen; R1 and R2 independently represent a hydrogen atom or C1-6alkyl group, R4 and R5 independently represent hydrogen, C3-C7cycloalkyl or C1-6alkyl, R6 is a hydrogen atom of C1-6alkyl; R8 is C1-4alkyl; R9 is C1-6alkyl, possibly substituted with one or more substitutes, independently chosen from halogen or phenyl; R10 and R11 independently represent phenyl, 5-member aromatic ring which contains two heteroatoms, chosen from N or S, hydrogen, C3-C7cycloalkyl or C1-6alkyl, where the last two groups are possibly substituted with one or more substitutes, independently chosen from halogen or phenyl; or R10 and R11 together with the nitrogen atom to which they are bonded, can form a 3- to 8-member saturated heterocyclic ring, which possibly contains one or more atoms chosen from O, S(O)n (where n= 0, 1 or 2), NR8.

EFFECT: invention relates to a method of modulating activity of CRTh2 receptors, involving administration of therapeutically effective amount of formula compound or its pharmaceutically acceptable salt to a patient.

9 cl, 170 ex

FIELD: medicine.

SUBSTANCE: invention is related to compound of formula (I), (values of radicals are described in formula of invention) or its pharmaceutically acceptable salts, to methods of its production, pharmaceutical composition, which contains it. Application of invention is described for manufacturing of medicinal agent intended for provision of inhibiting action in respect to HDAC in warm-blooded animal, in production of agent used for treatment of malignant tumor. Method is also described for provision of inhibiting action in warm-blooded animal.

EFFECT: compounds have inhibiting activity in respect to HDAC.

15 cl, 17 tbl, 24 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted quinoline derivatives of general formula (I) in which: m is an integer from 0 to 3; R1 is selected from a group comprising an acylamino group, ester carboxylic group and an alkyl with 1-5 carbon atoms, an optionally substituted hydroxy and a halogen; R2 denotes hydrogen or an alkyl with 1-5 carbon atoms; R3 denotes - C(=X)-A, where A is selected from a group comprising aryl, heteroaryl, heterocyclyl and cycloalkyl, each of which can optionally contain from 1 to 4 substitutes selected from a group comprising an alkyl with 1-4 carbon atoms, an alkoxy with 1-4 carbon atoms, a halogen, hydroxy or nitro, and X denotes oxygen or sulphur; R4 denotes alkylene-heterocyclyl or alkylene-NR7R8, where alkylene is a linear alkylene with 1-4 carbon atoms; R7 and R8 are independently selected from a group comprising hydrogen, an alkyl with 1-4 carbon atoms, arylalkyl, heteroarylalkyl, cycloalkyl or cyclo-alkylalkyl; R5 is selected from a group comprising L-A1, where A1 is selected from a group comprising aryl, heteroaryl, heterocyclyl and cycloalkyl, each of which can optionally contain from 1 to 4 substitutes selected from a group comprising an alkyl with 1-4 carbon atoms, an alkoxy with 1-4 carbon atoms, a halogen, hydroxy and nitro, and where L is selected from a group consisting of oxygen, -NR9, where R9 denotes hydrogen or alkyl; -S(O)q-, where q equals 0, 1 or 2, and an alkylene with 1-5 carbon atoms, optionally substituted with a hydroxy, halogen or acylamino; and R6 is selected from a group comprising an alkyl with 1-5 carbon atoms, an alkenyl with 2-5 carbon atoms, an alkynyl with 2-5 carbon atoms, -CF3, an alkoxy with 1-5 carbon atoms, a halogen and a hydroxy; or its pharmaceutically acceptable salts or esters, as well as to a pharmaceutical composition having anticancer activity or inhibitory effect on mitotic kinesin based on the said compounds, to a method of treating disorders and use of these compounds for making a medicinal agent.

EFFECT: novel compounds which can be useful in treating cancer are obtained and described.

40 cl, 3 ex, 1 tbl

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