Method of producing 3-(2-substituted-1,3-oxazol-4-yl)pyridin-2(1h)-ones

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 3-(1,3-oxazol-4-yl)pyridin-2(1H)-one derivatives of general formula 1, , where 1a R=Br, R'=CH2OCH3, R"=CH3; 1b R=H, R'=CH2, R"=CH3; 1c R=H, R1=CH2OCH3, R"=Ph; 1d R=H, R'=CH3, R"=Ph; 1e R=Br, R=CH3, R" - fur-2-yl, which can be used as potential biologically active substances and intermediate products for synthesis of novel heterocyclic systems. The method of producing 3 -(2-substituted-1,3 -oxazol-4-yl)pyridin-2( 1 H)-ones of general formula I involves formation of a heterocyclic system of 3-(1,3-oxazol-4-yl)pyridin-2(1H)-one as a result of base-catalysed regrouping of 3-acylamino-2-furfurylfuro[2,3-b]pyridines while boiling said compounds in ethanol for 4-20 hours with addition of 6-7 mmol of potassium hydroxide per 1 mol of the initial 3-acylamino-2-furfurylfuro[2,3-b]pyridine.

EFFECT: high yield.

1 cl, 2 tbl, 5 ex

 

The invention relates to the field of organic chemistry - synthesis of heterocyclic compounds - 3-(2-substituted-1,3-oxazol-4-yl)pyridine-2(1H)-ones containing in position 2 oxazoline aliphatic ring, an aromatic or heteroaromatic Deputy.

The invention relates to a developing method of obtaining derivatives of 3-(1,3-oxazol-4-yl)pyridine-2(1H)-it General formula 1,

where 1a R=Br, R'=CH2Och3, R"=CH3;

1B R=H, R'=CH3, R"=CH3;

1B R=H, R'=CH2Och3, R"=Ph;

1G R=H, R'=CH3, R"=Ph;

1D R=Br, R'=CH3, R"=FSD-2-yl,

which can find application as potential biologically active substances and intermediates for the synthesis of new heterocyclic systems.

Such structures are not described in the scientific literature, so the proposed method of producing unparalleled.

The technical result is the formation of a new, not previously described heterocyclic system - 3-(1,3-oxazol-4-yl)pyridine-2(1H)-it contains in position 2 oxazoline aliphatic ring, an aromatic or heteroaromatic Deputy, the base catalyzed rearrangement of the corresponding 3-acylamino-2-furfurylthio[2,3-b]pyridines.

The technical result is achieved in that in the method of obtaining 3-(2-substituted-1,3-oxazol-4-espiridion-2(1H)-ones of General formula I,

where 1a R=Br, R'=CH2Och3, R"=CH3;

1B R=H, R'=CH3, R"=CH3;

1B R=H, R'=CH2Och3, R"=Ph;

1G R=H, R'=CH3, R"=Ph;

1D R=Br, R'=CH3, R"=FSD-2-yl,

including the formation of heterocyclic systems 3-(1,3-oxazol-4-yl)pyridine-2(1H)-it is in the base catalyzed rearrangement of 3-acylamino-2-furfurylthio[2,3-b]pyridines; the reaction is carried out at the boiling these compounds in ethanol for about 4-20 hours adding 6-7 mmol of potassium hydroxide per 1 mmol of the original 3-acylamino-2-furfurylthio[2,3-b]pyridine 2A-D.

In the proposed method of obtaining derivatives of 3-(2-substituted-1,3-oxazol-4-yl)pyridine-2(1H)-she I as starting compounds used synthetically easily accessible 3-N-acylamino-2-furfurylthio[2,3-b]pyridine 2A-d, which are obtained by alkylation of 2-alkylborane alcohols series 3-minotoro[2,3-b]pyridine by the method similar to that shown in [Butin A.V.; Smirnov S.K., Stroganova T.A.; Bender W.; Krapivin G.D. Simple route to 3-(2-indolyl)-1-propanones via a furan recyclization reaction // Tetrahedron, 2007, 63, 474-491].

The choice of solvent of ethanol allows to achieve good dissolution as starting compounds and reaction products. The use of hydroxide Kali is due to its good solubility in ethanol, that allows the reaction in a homogeneous system.

All of the above contributes to the reaction and allows you to achieve complete conversion of the starting materials in derivatives of 3-(1,3-oxazol-4-yl)pyridine-2(1H)-it is for 4-20 hours without pitch starting compounds and reaction products during the process, which in turn reduces loss when cleaning and contributes to obtaining high yields of the target products.

On the basis of the obtained experimental data it was established that the optimum is to conduct the reaction by boiling in ethanol with the addition of 6-7 mmol of potassium hydroxide per 1 mmol of the original 3-acylamino-2-furfurylthio[2,3-b]pyridine 2A-d, since in this case the outputs of 3-(2-substituted-1,3-oxazol-4-yl)pyridine-2(1H)-ones 1A-d reach 65-73%, and the process duration is from 4 to 20 hours.

Thus, the set of essential features set forth in the claims, allows to achieve the desired technical result.

The identity and structure of the synthesized compounds I confirmed1H NMR spectroscopy and elemental analysis.

The original 3-acylamino-2-furfurylthio[2,3-b]pyridine 2 a-d are obtained by alkylation of 2-methylfuran alcohols series 3-alluminio[2,3-b]pyridine with outputs from 74 to 83%. Physico-chemical characteristics of the compounds 2A-d are shown in table 1.

The lower the presents examples of the implementation of the proposed method of obtaining derivatives of 3-(2-substituted-1,3-oxazol-4-yl)pyridine-2(1H)-one.

Example 1.

To a solution of furo[2,3-b]pyridine 2A (0,483 g, 1 mmol) in 20 ml of ethanol is added 0.4 g (7 mmol) of potassium hydroxide, and the resulting mixture is refluxed for 4 hours. Upon termination of the reaction mixture is diluted with 100 ml of ice water and acidified with diluted hydrochloric acid to pH~7. Dropped the precipitate was separated by filtration, washed with water and dried in air. After recrystallization from a mixture of ethyl acetate - petroleum ether to obtain 3-oxazolopyridine 1A in the form of a white powder with a yield of 67%. The melting point and spectral characteristics of the product are shown in table 2.

Example 2.

The reaction is carried out in similar conditions, using 0.34 g (6 mmol) of potassium hydroxide. The duration of reaction for 7 hours, the yield of the target product is 65%.

Example 3.

The reaction is carried out under similar conditions using 0.56 g (0.01 mol) of potassium hydroxide. The duration of reaction for 4 hours, the yield of 66%.

Example 4.

To a solution of furo[2,3-b]pyridine 2A (0,483 g, 1 mmol) in 20 ml of ethanol is added 0.4 g (7 mmol) of potassium hydroxide, and the mixture was incubated at 50°C for 30 hours. Upon termination of the reaction mixture is diluted with 100 ml of ice water and acidified with diluted hydrochloric acid to pH~7. Dropped the precipitate was separated by filtration, washed with water and dried in air. After recrystallization from a mixture of utilized the t - petroleum ether get 3-oxazolopyridine 1A in the form of a white powder with a yield of 60%.

Example 5.

To a solution of furo[2,3-b]pyridine 2A (0,483 g, 1 mmol) in 20 ml of butanol is added 0.4 g (7 mmol) of potassium hydroxide, and the resulting mixture was kept at boiling for 3 hours. After the reaction mixture was poured into 150 ml of water, acidified with diluted hydrochloric acid to pH~7 and leave at night. The product stands out as the evaporation of the butanol. The resulting substance was separated by filtration, washed with water and recrystallized from a mixture of ethyl acetate - petroleum ether, passing the hot solution through a layer of silica gel. Output 3-oxazolopyridine 1A in the form of a white powder is 47%.

As follows from the above examples, the product yield is greatly influenced by the temperature of the process and the amount of potassium hydroxide. At low temperatures the conversion of properidine → oxazolopyridine proceeds slowly, while the temperature increase due to the use of more high-boiling solvent (butanol) leads to leakage of unwanted side reactions that, because of the large losses when cleaning, lowers the yield of the target product.

At the same time, the use in the reaction of smaller quantities of potassium hydroxide increases the length of the process, which also causes a reduction in the yield of the target product is and because of proceeding in the reaction side processes.

Thus, the best option is to conduct the reaction by boiling 3-alluminio[2,3-b]pyridine 2A in ethanol in the presence of 7 mmol of potassium hydroxide per 1 mmol of compound 2A, as in this case, the output of 5-bromo-4-(methoxymethyl)-6-methyl-3-{2-methyl-5-[(5-methyl-2-furyl)(phenyl)methyl]-1,3-oxazol-4-yl}pyridine-2(1H)-she (1A) reaches 67%, and the process duration is 4 hours.

The claimed method obtained a number of 3-oxazolopyridine 1B-d, for which table 2 shows the duration of the reaction, the yields, melting points and spectral characteristics.

The method of obtaining 3-(2-substituted-1,3-oxazol-4-yl)pyridine-2(1H)-ones of General formula I

where 1a R=Br, R'=CH2OCH3, R"=CH3;
1B R=H, R'=CR3, R"=CH3;
1B R=H, R'=CH2OCH3, R"=Ph;
1G R=H, R'=CH3, R"=Ph;
1D R=Br, R'=CH3, R"=FSD-2-Il,
including the formation of heterocyclic systems 3-(1,3-oxazol-4-yl)pyridine-2(1H)-it is in the base catalyzed rearrangement of 3-acylamino-2-furfurylthio[2,3-b]pyridines and the reaction is carried out at the boiling these compounds in ethanol for 4-20 h with the addition of 6-7 mmol of potassium hydroxide per 1 mmol of the original 3-acylamino-2-furfurylthio[2,3-b]pyridine.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 2-quinolyloxazoles of formula (I) or pharmaceutically acceptable salts thereof, having PDE4 inhibiting properties, a pharmaceutical composition based on said compounds and use thereof to prepare a medicinal agent which inhibits inflammatory cell recruitment in respiratory tracts. , where is , X is O, R1 is alkyl, R3 and R4 are independently selected from H, R5 and R6 are independently selected from a group comprising H, alkyl, hydroxyalkyl, t equals 1 or 2. Values of substitutes R7-R11, R13 are given in the formula of invention.

EFFECT: high efficiency of using the composition.

24 cl, 1 dwg, 64 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to oxazolidinone derivatives covered by general graphic formula (I) and to their pharmaceutically acceptable salts. In formula (I) R1, R2, R3 and R4 are independently chosen from a group including -H and halogen; A is chosen from a group including R5 and R6 are independently chosen from a group including -H, -F, -CI, -Br, -OH, alkyl(C1-C6), haloalkyl(C1-C6), alkoxygroup(C1-C6); R7 is chosen from a group including -H, alkyl(C1-C6); either R7 and R5 or R6 taken together form a cycle of 2 carbon atoms and include 1 group chosen from O which in turn can be substituted by one substitute chosen from alkyl(C1-C6); R12 is chosen from a group including -H, -COR14, -CSR14, -COOR14; R14 is chosen from a group including alkyl (C1-C6), cycloalkyl(C3-C6), alkenyl(C2-C6), R16, R17 and R18 represent -H; R21 is chosen from a group including -H, alkyl(C1-C6); X is chosen from a group including O, S, and Y is chosen from a group including O, S, SO, SO2, and NR12; and optional substitutes of alkyl(C1-C6) groups can represent one or two groups chosen from the following: -OR21, -CN.

EFFECT: invention refers to methods for preparing the compounds of the invention, to application of oxazolidinone derivatives for preparing a drug for treating bacterial infections and to a pharmaceutical composition for treating bacterial infections, including a therapeutically effective amount of the compound of the invention.

36 cl, 10 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates or tautomers thereof, where substitute M is selected from groups D1 and D2, having structural formulae given below, and R1, E, A and X are as described in the formula of invention. Disclosed also are pharmaceutical compositions which contain these compounds, methods for synthesis of these compounds, intermediate compounds and synthesis methods thereof, as well as use of compounds of formula (I) in preventing or treating diseases mediated by CDK kinases, GSK-3 kinases or Aurora kinases.

EFFECT: high effectiveness of the compounds.

40 cl, 8 dwg, 18 tbl, 84 ex

Aromatic compound // 2416608

FIELD: chemistry.

SUBSTANCE: invention describes a novel compound of general formula (1), where radicals R1, R2, X1, Y and A are as described in claim 1 of the invention. The invention also describes a method of obtaining compounds of formula (1), as well as a pharmaceutical composition based on said compounds, for treating fibrosis.

EFFECT: novel compounds with excellent collagen formation suppression, cause fewer side-effects and which are safer are obtained.

62 cl, 2717 ex, 432 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula 1, compounds of formula 5 and pharmaceutically acceptable salts thereof. In formulae 1 5 Y denotes -C(O)-, X denotes -N(R11)-, R1 denotes a residue of formula 1a or 1b - for formula 1 or residue of formulae 5a or 5b - for formula 5 1a 1b 5a 5b, R2 and R7 independently denote H, hydroxyl or (C1-C6)alkyl; R3 and R6 each independently denotes H, hydroxyl or (C1-C6)alkyl; R4 and R5 each independently denotes H or (C1-C6)alkyl; the rest of the radicals are described in the formula of invention. The invention also relates to separate compounds given in the formula of invention, a pharmaceutical composition having Bcl bound protein inhibiting properties, which contains a therapeutically effective amount of the disclosed compound, a method of treating a bc1 mediated disorder, involving introduction of a therapeutically effective amount of the disclosed compound and a method of treating a bc1 mediated disorder involving administration to a patient in need of treatment of an effective amount of camptothecin and therapeutically effective amount of the disclosed compound.

EFFECT: high efficiency of the composition.

84 cl, 12 tbl, 1 dwg, 217 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds described by formula in which radical and symbol values are specified in the patent claim, and their pharmaceutically acceptable salts. These compounds inhibit tompomyosine-related kinases (Trk), and can find application in treating a malignant growth, such as breast cancer, rectal cancer and prostate cancer. Also, the invention relates to a method for producing these compounds, a based pharmaceutical composition and to methods of application thereof.

EFFECT: preparation of the pharmaceutical composition which can find application in treating a malignant growth.

18 cl, 134 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: compound of formula pharmaceutically acceptable salt or solvate of a compound or salt (I), ring Q represents optionally substituted monocyclic or condensed (C6-C12)aryl or optionally substituted monocyclic or condensed heteroaryl where said substitutes are chosen from: halogen; (C1-C6)alkyl optionally substituted by 1-3 halogen atoms; (C1-C6)alkylsulphonyl; phenyl optionally substituted by 1 or 2 substitutes chosen from halogen, (C1-C6)alkyl which can be substituted by 1-3 halogen atoms, groups (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and (C1-C6)alkylthio; monocyclic or condensed heteroaryl optionally substituted by halogen; or oxo; Y1 represents a bond or -NR6-CO-, where R6 represents hydrogen, ring A represents optionally substituted a nonaromatic heterocyclyldiyl where said substitutes are chosen from (C1-C6)alkyl optionally substituted by groups hydroxy, (C1-C6)alkylamino, di(C1-C6)alkylamino, morpholino, (C1-C6)alkylaminocarbonyl, di(C1-C6)alkylaminocarbonyl; cyano; (C3-C6)cycloalkyl; (C1-C6)alkoxy; (C1-C6)alkoxy(C1-C6)alkyl; phenyl; benzyl; benzyloxymethyl; thienyl; 4-8-members monocyclic nonaromatic heterocycle having 1 or 2 heteroatoms chosen from N or O, and optionally substituted by 1 or 2 substitutes chosen from (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and oxo; (C1-C6)alkylamino; di(C1-C6)alkylamino; a group of formula: -Y2Z'- represents a group of formula: [Formula 2] each R7 independently represents hydrogen, (C1-C6)alkyl or (C3-C6)cycloalkyl, each of R8 and R9 independently represents hydrogen or (C1-C6)alkyl, n is equal to an integer 0 to 3, Z1 represents a bond, -O-, -S- or-NR9 - where R9 represents hydrogen, (C1-C6)alkyl, acyl or (C1-C6)alkylsulphonyl, ring B represents optionally substituted aromatic carbocyclediyl or optionally substituted aromatic heterocyclediyl where said substitutes are chosen from (C1-C6)alkyl, halogen, (C1-C6)alkoxy and oxo; Y3 represents a bond optionally substituted (C1-C6)alkylene or (C3-C6)cycloalylene, optionally interrupted -O- or optionally substituted (C2-C6)alkenylene where said substitutes are chosen from (C1-C6)alkyl, (C3-C6)cycloalkyl, halogen and (C1-C6)alkoxycarbonyl; Z2 represents COOR3; R3 represents hydrogen or (C1-C6)alkyl.

EFFECT: preparation of new compounds.

30 cl, 9 tbl, 944 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described 3,4-substituted piperidines applicable in diagnostics and drug therapy of a warm-blooded animal, preferentially for therapy of a disease which depends on renin activity; application of a compound of such kind for preparing a pharmaceutical composition for therapy of the disease which depends on renin activity; application of the compound of such kind for therapy of the disease which depends on renin activity; the pharmaceutical compositions containing 3,4-substituted piperidine, and/or a therapeutic mode involving administration of 3,4-substituted piperidine, a method for producing 3,4-substituted piperidine. The preferential compound (which also can be presented in the form of salts) are described by formula I' wherein R1, R2, T, R3 and R4 are such as described by the patent claim.

EFFECT: production of the compounds for therapy of the disease which depends on renin activity.

28 cl, 1 tbl, 375 ex

FIELD: medicine.

SUBSTANCE: invention refers to the compound 3-{[5-(azetidine-1-ylcarbonyl)pyrazine-2-yl] oxy}-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazine-5-yl)benzamide or to its pharmaceutically acceptable salt. Also, it refers to a pharmaceutical composition for treating insulin-independent diabetes or obesity containing said compound.

EFFECT: there is produced and described a new compound which can be effective in treating insulin-independent diabetes and obesity.

5 cl, 64 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I) , where the dotted line is either absent or denotes a double bond; R1 denotes H or C1-6-alkyl, possibly substituted with a CN group, or denotes a phenyl or sulphonyl phenyl, substituted with one or more B groups, or denotes -(CH2)m-Ra, where Ra denotes: NRiRii, C3-6-cycloalkyl, 6-member heterocycloalkyl, which denotes a univalent saturated group which contains one nitrogen heteroatom, the rest are carbon atoms, aryl, which can be substituted with one or more B groups, or denotes -(CH2)n-(CO)-Rb or -(CH2)n-(SO2)-Rb, where Rb denotes: NRiRii, 5-6-member heterocycloalkyl, which denotes a univalent saturated group containing one or more heteroatoms selected from nitrogen, oxygen, the rest are carbon atoms, aryl or 5- or 6-member heteroaryl, which denotes an aromatic ring containing two heteroatoms as ring members, the said heteroatoms selected from N or O, the rest are carbon atoms; which can possibly be substituted with one or more B groups, R2 denotes one or more H, halo, C1-6-alkyl, C1-6-alkoxy, R3 denotes H or-(CO)-Rc, where Rc denotes: C1-6-alkyl, 5-member heterocycloalkyl, which denotes a univalent saturated group containing one nitrogen heteroatom, the rest are carbon atoms possibly substituted with C1-6-alkyl, or denotes C1-6-alkyl; R4 denotes H; R5 denotes H, C1-6-alkyl, -(CH2)m-NRiRii, -(CH2)n-(CO)-Rb, where Rb denotes NRiRii or a 6-member heterocycloalkyl which denotes a univalent saturated group which contains one nitrogen heteroatom, the rest are carbon atoms, when the dotted line is absent or is absent when the dotted line denotes a double bond; R6 is absent, when the dotted line denotes a double bond; R7 denotes Cl or NReRf, where Re and Rf denotes H or C1-6-alkyl, or Re and Rf together with the nitrogen atom to which they are bonded form a 6-member heterocycloalkyl which denotes a univalent saturated group containing one or two heteroatoms selected from nitrogen, oxygen, the rest are carbon atoms; which can be substituted with C1-6-alkyl, or R6 and R7 together form a C=O group, when the dotted line is absent; B denotes halogen, C1-6-alkoxy, (CRiiiRiv)n-phenyl; Ri and Rii denote H, C1-6-alkyl -C(O)-C1-6-alkyl; Riii and Riv denote C1-6-alkyl; m equals to 1 or 2, n equals 0 or 1; as well as to pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition, as well as to use of compounds of formula (I), (I-a) or (1-b).

EFFECT: obtaining novel biologically active compounds having activity on V1a receptor.

12 cl, 48 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I): where: A is a monocyclic or polycyclic aryl or heteroaryl group, where the heteroaryl radical denotes a 5-10-member cyclic system containing at least one heteroaromatic ring and containing at least one heteroatom selected from O, S and N; optionally substituted with one or more substitutes independently selected from a group comprising halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, C1-4alkoxy and a hydroxyl group; B is a monocyclic nitrogen-containing heteroaryl group, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from S and N; optionally substituted with one or more substitutes selected from a group consisting of halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, aryl and C1-8alkylthio; either a) R1 is a group of formula: -L-(CR'R")n-G, where L is a binding group selected from a group consisting of a direct bond, -(CO)-, -(CO)NR'- and -SO2-; R' and R" is independently selected from hydrogen atoms; n assumes values from 0 to 1; and G is selected from a group consisting of a hydrogen atom and C1-4alkyl, aryl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O, S and N; C3-8cycloalkyl and saturated heterocyclic groups, where heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one or two carbon atoms are substituted with a N heteroatom; where alkyl, C3-8cycloalkyl, aryl or heteroaryl groups are unsubstituted or substituted with one or more substitutes selected from halogen atoms; and R2 is a group selected from hydrogen atoms, halogen atoms and C1-4alkyl, C2-5alkynyl, C1-4alkoxy, -NH2 and cyano groups, where alkyl and alkynyl groups may be unsubstituted or substituted with one aryl group; or b) R2, R1 and -NH- group to which R1 is bonded form a group selected from groups of formulae and , where: Ra is selected from a hydrogen atom or groups selected from C1-4alkyl, C3-8cycloalkyl, aryl, aryl-C1-4alkyl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O and N; saturated heterocyclic rings, where the heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one carbon atom is substituted with a heteroatom selected from O and N; and C1-4alkylthio; where the aryl or heteroaryl groups are unsubstituted or substituted with one or more groups selected from halogen atoms, cyano group, trifluoromethoxy and carbamoyl; Rb denotes hydrogen; and pharmaceutically acceptable salts thereof and N-oxides; provided that the compound is not selected from N-[6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, and N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]formamide. The invention also relates to a pharmaceutical composition, use of compounds in any of claims 1-20, a method of treating a subject, as well as a composite product.

EFFECT: obtaining novel biologically active compounds having adenosine A2B receptor antagonist activity.

27 cl, 160 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 2-quinolyloxazoles of formula (I) or pharmaceutically acceptable salts thereof, having PDE4 inhibiting properties, a pharmaceutical composition based on said compounds and use thereof to prepare a medicinal agent which inhibits inflammatory cell recruitment in respiratory tracts. , where is , X is O, R1 is alkyl, R3 and R4 are independently selected from H, R5 and R6 are independently selected from a group comprising H, alkyl, hydroxyalkyl, t equals 1 or 2. Values of substitutes R7-R11, R13 are given in the formula of invention.

EFFECT: high efficiency of using the composition.

24 cl, 1 dwg, 64 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates or tautomers thereof, where substitute M is selected from groups D1 and D2, having structural formulae given below, and R1, E, A and X are as described in the formula of invention. Disclosed also are pharmaceutical compositions which contain these compounds, methods for synthesis of these compounds, intermediate compounds and synthesis methods thereof, as well as use of compounds of formula (I) in preventing or treating diseases mediated by CDK kinases, GSK-3 kinases or Aurora kinases.

EFFECT: high effectiveness of the compounds.

40 cl, 8 dwg, 18 tbl, 84 ex

Aromatic compound // 2416608

FIELD: chemistry.

SUBSTANCE: invention describes a novel compound of general formula (1), where radicals R1, R2, X1, Y and A are as described in claim 1 of the invention. The invention also describes a method of obtaining compounds of formula (1), as well as a pharmaceutical composition based on said compounds, for treating fibrosis.

EFFECT: novel compounds with excellent collagen formation suppression, cause fewer side-effects and which are safer are obtained.

62 cl, 2717 ex, 432 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds described by formula in which radical and symbol values are specified in the patent claim, and their pharmaceutically acceptable salts. These compounds inhibit tompomyosine-related kinases (Trk), and can find application in treating a malignant growth, such as breast cancer, rectal cancer and prostate cancer. Also, the invention relates to a method for producing these compounds, a based pharmaceutical composition and to methods of application thereof.

EFFECT: preparation of the pharmaceutical composition which can find application in treating a malignant growth.

18 cl, 134 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described 3,4-substituted piperidines applicable in diagnostics and drug therapy of a warm-blooded animal, preferentially for therapy of a disease which depends on renin activity; application of a compound of such kind for preparing a pharmaceutical composition for therapy of the disease which depends on renin activity; application of the compound of such kind for therapy of the disease which depends on renin activity; the pharmaceutical compositions containing 3,4-substituted piperidine, and/or a therapeutic mode involving administration of 3,4-substituted piperidine, a method for producing 3,4-substituted piperidine. The preferential compound (which also can be presented in the form of salts) are described by formula I' wherein R1, R2, T, R3 and R4 are such as described by the patent claim.

EFFECT: production of the compounds for therapy of the disease which depends on renin activity.

28 cl, 1 tbl, 375 ex

FIELD: medicine.

SUBSTANCE: invention refers to the compound 3-{[5-(azetidine-1-ylcarbonyl)pyrazine-2-yl] oxy}-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazine-5-yl)benzamide or to its pharmaceutically acceptable salt. Also, it refers to a pharmaceutical composition for treating insulin-independent diabetes or obesity containing said compound.

EFFECT: there is produced and described a new compound which can be effective in treating insulin-independent diabetes and obesity.

5 cl, 64 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to administration of formula (I) described new triazole derivatives as greline-like ligands of growth hormone secretion stimulating receptors (GHSS receptors) that can be effective in treatment or prevention of GHSS receptors mediated physiological and/or pathophysiological conditions in mammals, preferentially in humans. Formula (I): where R1 is chosen from a group including hydrogen atom, (C1-C12)alkyl phenyl, naphthyl, (C5-C14)phenyl(C1-C12)alkyl, indolylalkyl which can contain up to 3 substitutes independently chosen from a group including halogen, -F, -CI, -Br, -I, -NO2, (C1-C12)alkyl, phenyl, naphthyl, -O-(C1-C12)alkyl; R2 is chosen from a group including (C1-C12)alkyl, phenyl, naphthyl, (C5-C14)phenyl (C1-C12)alkyl, indolylalkyl which can contain up to 3 substitutes independently chosen from a group including halogen, -F, -Cl, -Br, -I, -NO2, (C1-C12)alkyl, phenyl, naphthyl, -O-(C1-C12)alkyl; one of radicals R3 and R4 represents hydrogen atom, and other radical are chosen from a group including hydrogen atom, phenyl, naphthyl, indolylalkyl; R5 is chosen from a group including hydrogen atom, phenyl, naphthyl, -CO-(C3-C8)cycloalkyl, -CO-phenyl, -CO-(C5-C7)heteroaryl containing 1, 2 nitrogen atoms, -CO-(C3-C7)heteroaryl(C1-C4)alkyl containing 1, 2 nitrogen atoms, -CO-(C5-C6)heterocyclyl containing 1, 2 nitrogen or oxygen atoms, -CO-C*(R9R10)-NH2, -CO-CH2-C*(R9R10)-NH2, -CO-C*(R9R10)-CH2-NH2, phenylsulfonyl which can contain up to 3 substitutes independently chosen from a group including halogen, -F, -CI, -Br, -I, -N3, -CN, -NR7R8, -OH, -NO2, (C1-C4)alkyl; R6 represents hydrogen atom; R7 and R8 represent hydrogen atom; R9 and R10 are independently chosen from a group including hydrogen atom and (C1-C4)alkyl; m relates to 0, 1 or 2, and preferentially 0; and * means carbon atom in a R or S configurations, if it is chiralene.

EFFECT: invention refers to GHSS receptors antagonists and agonists which can be used for modulation of these receptors and are effective in treatment of said conditions, particularly growth impairment, cachexia, short-term, intermediate and/or long-term energy balance control; short-term, intermediate and/or long-term food intake control (stimulation and/or suppression); adipogenesis, adiposity and/or obesity; body weight growth and/or reduction in mammals.

22 cl, 6 tbl, 15 ex, 46 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I), where R2 denotes H, [(C1-C6) alkylene]0-1-R'; R3 denotes H; R4 denotes H, halogen or (C1-C6) alkyl; R5 denotes H or halogen; R6 denotes H, (C1-C8) alkyl, R', (C1-C6) alkylene-R'; R7 and R8 independently denote H, halogen, (C1-C6) alkyl, O-(C1-C6) alkyl, R'; R9 denotes (C1-C6)alkyl; n equals 0 or 1; L denotes O or O-(C1-C6)alkylene; where R' denotes (C3-C8) cycloalkyl; (C5-C10)heterocyclyl, which denotes an aromatic or saturated mono- or bicyclic ring system which, besides a carbon atom, includes one or more heteroatoms such as nitrogen, oxygen and sulphur atoms; or (C6-C10) aryl; where in the heterocyclyl is unsubstituted or substituted with (C1-C6)alkyl, and the aryl is unsubstituted or substituted with a halogen, (C1-C4)alkyl, -O-(C1-C4)alkyl, SO2- (C1-C4) alkyl or N[(C1-C4) alkyl]2; and where in groups R4, R6 and R7 the alkyl can be halogenised in one or more positions; or pharmaceutically acceptable salts and/or stereo isomer forms thereof. The invention also relates to use of formula (I) compounds, as well as a medicinal agent.

EFFECT: obtaining novel biologically active compounds having Rho-kinase inhibiting activity.

21 cl, 320 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compounds of general formula in which R1 stands for C1-C4-alkyl; R2 stands for C1-C4-alkyl; R3 stands for phenyl, which optionally contains 1-3 any substituents, selected from the group, including halogen, C1-C6-alkyl and C1-C4-alkoxygroup; R4 stands for hydrogen; C1-C6-alkyl or C3-C7-cycloalkyl -C1-C4-alkyl, R5 stands for hydrogen; and R6stands for hydrogen; and R7 stands for hydrogen; and R9 stands for C1-C4-alkyl; and R10 stands for C1-C6-alkyl, phenyl-C0-C4-alkyl or pyridinyl-C0-C4-alkyl; on condition that R10 does not stand for phenyl, if R5 and R9 together form C2-alkylene; or R5 R9 together form C1-C3-alkylene; or R6 and R9 together form C1-C3-alkylene; or R7 and R9 together form C2-C4-alkylene or C1-C3-alkyleneoxygroup; or R8 and R9 together form C3-C5-alkylene; or R9 and R10 together form C4-C6-alkylene; and n equals 0 or 1, or its any physiologically compatible salts. In addition, the invention relates to pharmaceutical composition, containing formula I compounds and intended for treatment of cardio-vascular diseases, to application of said compounds for preparation of medication, as well as to method of obtaining formula I compounds.

EFFECT: obtained and described are novel compounds, possessing cardio-vascular activity.

16 cl, 8 ex, 5 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of indolylpiperidine of the formula (I): wherein A1 means (C1-C7)-alkylene, (C1-C7)-alkyleneoxy-, (C1-C7)-alkylenethio-, (C1-C7)-alkanoyl, hydroxy-(C1-C7)-alkylene; A2 means a single bond, (C1-C7)-alkylene, (C2-C5)-alkenylene; W means a single bond, phenylene, furanylene that is unsubstituted or substituted with one or more halogen atoms, (C1-C7)-alkoxy- and/or alkyl groups; R1 means hydrogen atom (H), (C1-C7)-alkyl, (C2-C7)-alkenyl, (C2-C7)-alkynyl, (C2-C5)-alkoxyalkyl, (C3-C7)-alkenyloxyalkyl, (C3-C7)-alkynyloxyalkyl, (C3-C7)-alkoxyalkoxyalkyl, phenyl-(C1-C7)-alkyl wherein phenyl is unsubstituted or substituted with one or more halogen atoms, (C1-C7)-alkyl, (C1-C7)-alkoxy- or arylalkoxy- (preferably with phenylalkoxy-) groups, or means (C3-C10)-cycloalkyl-(C1-C7)-alkyl wherein cycloalkyl is unsubstituted or substituted with one or more halogen atoms, (C1-C7)-alkyl, (C1-C7)-alkoxy-groups; R2 means hydrogen atom (H), halogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-; R3 means carboxyl, tetrazolyl, and to their pharmaceutically acceptable salts. Compounds of the formula (I) elicit antihistaminic and anti-allergic activity that allows their using in composition used for treatment of allergic diseases including bronchial asthma, rhinitis, conjunctivitis, dermatitis and nettle rash. Also, invention describes methods for preparing compounds of the formula (I).

EFFECT: valuable medicinal properties of compounds.

15 cl, 2 sch, 3 tbl, 162 ex

Up!