Annelated azaheterocyclic amides, which include pyrimidine fragment, method of obtaining and their application

FIELD: chemistry.

SUBSTANCE: present invention relates to new annelated azaheterocyclic amides, including a pyrimidine fragment, with the general formula 1, method of obtaining them and their application in the form of free bases or their pharmaceutically accepted salts as inhibitors of P13K kinase, in compounds with the general formula 1: , where: X represents an oxygen atom, sulphur atom or not necessarily substituted at the nitrogen NH group, where the substitute is selected from lower alkyls and possibly a substituted aryl; Y represents an atom of nitrogen or substituted at the carbon atom CH group, where the substitute is selected from lower alkyls; Z represents an oxygen atom; R1 represents a hydrogen atom or not necessarily substituted C1-C6alkyl, or Z represents a nitrogen atom, which is together with a carbon atom, with which it is joined, form through Z and R1 annelated imidazole cycle; R2 and R3 independently from each other represent hydrogen, not necessarily substituted with C1-C6alkyl, C3-C6cycloalkyl, not necessarily substituted with phenyl, not necessarily substituted with 6-member aza-heteroaryl, under the condition, when Y represents a nitrogen atom, or R2 and R3 independently from each other represent not necessarily substituted C1-C6alkyl, not necessarily substituted with phenyl, not necessarily substituted with 5-7-member heterocycle with 1-2 heteroatoms, selected from nitrogen and oxygen, and possibly annelated with a phenyl ring, under the condition, when Y does not necessarily represent a substituted carbon atom at the CH group, and X represents an oxygen atom, sulphur atom, or R2 represents hydrogen, and R3 represents a substituted aminoC1-C6alkyl and not necessarily substituted 5-6-member aza-heterocycloalkyl, under the condition, when Y represents a group which is substituted at the CH atom, and X represents an oxygen atom, sulphur atom, or R2 represents hydrogen, and R3 represents phenyl which is not necessarily substituted, pyridyl which is not necessarily substituted, pyrimidinyl which is not necessarily substituted, under the conditions, when R1 represents a substituted aminoC1-C6alkyl, substituted C2-C3hydroxyalkyl and aza-heterocycloalkyl not necessarily substituted, Y represents a group with CH substituted, and X represents an oxygen atom, sulphur, and the substitute of the above indicated substituted alkyl, phenyl, heterocycle, pyridyl, pyrimidyl are selected from groups of hydroxyl-, cyano-groups, hydrogen, lower alkyls, possibly mono- or di-substituted lower alkyl sulfamoyl, carbamoyl, C1-C6alkoxycarbonyl, amino, mono- or di-lower alkyl-amine, N-(lower alkyl), N-(phenylC1-C6alkyl)amine, phenyl, possibly substituted with a halogen atom, C1-C6alkyl, haloid-C1-C6alkyl; phenylC1-C6alkyl, saturated or non-saturated 5-6-member heterocycle containing 1-2-heteroatoms, selected from nitrogen, oxygen and sulphur, and possible condensation with a benzene ring R4 represents hydrogen or a lower alkyl.

EFFECT: obtaining new annelated aza-heterocyclic amides, including a pyrimidine fragment, with the general formula with the possibility of their application in the form of free bases or their pharmaceutically accepted salts as inhibitors of PI3K kinase.

16 cl, 5 tbl, 5 ex

 

The text descriptions are given in facsimile form.

1. Kannelirovannye azaheterocycle, including pyrimidine fragment of General formula 1 in the form of free bases or pharmaceutically acceptable salts

where X represents an oxygen atom, a sulfur atom or optionally substituted nitrogen NH group, where the Deputy is selected from lower alkyl or possibly substituted aryl;

Y represents a nitrogen atom or substituted by an atom in which laroda CH group, where the Deputy is selected from lower alkyl;

Z represents an oxygen atom;

R1 represents a hydrogen atom or optionally substituted C1-C6alkyl, or

Z represents a nitrogen atom, which, together with the carbon atom to which it is linked, form a through Z and R1 annelirovannymi imidazolinones cycle;

R2 and R3 independently of one another represent hydrogen, optionally substituted C1-C6alkyl, C3-C6Alcaucin, optionally substituted phenyl, optionally substituted 6-membered usageerror, provided that when Y represents a nitrogen atom, or

R2 and R3 independently of one another represent an optionally substituted C1-C6alkyl, optionally substituted phenyl, optionally substituted 5-7-membered heterocyclyl with 1-2 heteroatoms, selected from nitrogen and oxygen, and possibly annelirovannymi with the phenyl ring, or R2 and R3 together with the nitrogen atom to which they are bound, form an optionally substituted 5-7-membered azaheterocyclic possibly condensed with benzene ring or pyrocondensation with dioxalane, provided that when Y represents an optionally substituted on the carbon atom of CH group, and X represents an oxygen atom, a sulfur atom, or

R2 represents the FDS is th hydrogen, a R3 represents a substituted amino1-C6alkyl or optionally substituted 5-6-membered azaheterocyclic, provided that when Y represents an optionally substituted on the carbon atom of CH group, and X represents an oxygen atom, a sulfur atom, or

R2 represents hydrogen and R3 represents optionally substituted phenyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, provided that, when R1 represents a substituted amino1-C6alkyl, substituted C2-C3hydroxyalkyl or optionally substituted azaheterocyclic, Y represents optionally substituted on the carbon atom of CH group, and X represents an oxygen atom, a sulfur atom;

when the substituents in the aforementioned substituted alkyl, phenyl, heterocyclyl, pyridine, pyrimidine selected from the group hydroxy, ceanography, halogen, lower alkyl, possibly mono - or disubstituted by lower alkyl sulfamoyl, carbamoyl,1-C6alkoxycarbonyl, amino, mono - or di-lower alkylamine, N-(lower alkyl), N-(panels1-C6alkyl)amine, phenyl possibly substituted by a halogen atom, a C1-C6by alkyl, halogen-C1-C6by alkyl; phenyls1-C6of alkyl, saturated or unsaturated 5-6-membered, heterocycle is a, containing 1 to 2 heteroatoms selected from nitrogen, oxygen and sulfur, and possibly condensed with a benzene ring,

R4 represents hydrogen or lower alkyl;

excluding 4,5-dihydro-6-methyl-4-oxo-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide; 4,5-dihydro-4-oxo-1-diphenyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide; 4,5-dihydro-4-oxo-1β-D-ribofuranosyl-1H-pyrazole,4-pyrimidine-3-carboxamide.

2. Compounds according to claim 1, which represents a substituted amides of 4-oxo-3,4-dihydrofuro(or thieno)[2,3-b]pyrimidine-5-carboxylic acids of General formula 1.1 or their pharmaceutically acceptable salts

where R1 and Z have the above meanings; X1represents an oxygen atom, a sulfur atom; R2 and R3 independently of one another represent optionally substituted alkyl, optionally substituted phenyl, optionally substituted heterocyclyl, or R2 and R3 together with the nitrogen atom to which they are bound, form an optionally substituted 5-7-membered azaheterocyclic possibly condensed with benzene ring, or

R2 represents hydrogen and R3 represents a substituted amino C1-C6alkyl or optionally substituted azaheterocyclic, or

R2 represents hydrogen and R3 represents an optional samewe the hydrated phenyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, provided that, when R1 represents a substituted aminoalkyl or optionally substituted azaheterocyclic;

R5 represents hydrogen or lower alkyl.

3. Compounds according to claim 2, represents a substituted amides of 4-oxo-3,4-dihydrofuro[2,3-b]pyrimidine-5-carboxylic acids of General formula 1.1.1, substituted amides of 4-oxo-3,4-dihydrothieno[2,3-b]pyrimidine-5-carboxylic acids of General formula 1.1.2, substituted amides of 2,3-dihydrofuro[3,2-e]imidazo[1,2-C]pyrimidine-9-carboxylic acid 1.1.3 and substituted amides of 2,3-dihydrothieno[3,2-e]imidazo[1,2-C]pyrimidine-9-carboxylic acid 1.1.4 or their pharmaceutically acceptable salts

where R1 and R5 have the above meanings;

R2 and R3 independently of one another represent an optionally substituted C1-C6alkyl, optionally substituted phenyl, optionally substituted heterocyclyl, or R2 and R3 together with the nitrogen atom to which they are bound, form an optionally substituted 5-7-membered azaheterocyclic possibly condensed with benzene ring, or

R2 represents hydrogen and R3 represents a substituted amino C1-C6Ala is l or optionally substituted azaheterocyclic, or

R2 represents hydrogen and R3 represents optionally substituted phenyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, provided that, when R1 represents a substituted amino1-C6alkyl or optionally substituted azaheterocyclic;

R6 and R7 independently of one another represent hydrogen.

4. Compounds according to claim 3, represents a substituted amides of 3-aminoalkyl-6-methyl-4-oxo-3,4-dihydrofuro[2,3-b]pyrimidine-5-carboxylic acids of General formula 1.1.1.1, 1.1.1.2, and 1.1.1.3, substituted amides of 3-aminoalkyl-6-methyl-4-oxo-3,4-dihydrothieno[2,3-b]pyrimidine-5-carboxylic acids of General formula 1.1.1.4, 1.1.1.5 and 1.1.1.6, substituted amides of 3-hydroxyalkyl-6-methyl-4-oxo-3,4-dihydro-furo[2,3-b]pyrimidine-5-carboxylic acids of General formula 1.1.1.7 and 1.1.1.8 and substituted amides of 3-hydroxyalkyl-6-methyl-4-oxo-3,4-dihydrothieno[2,3-b]pyrimidine-5-carboxylic acids of General formula 1.1.1.9 and 1.1.1.10 or their pharmaceutically acceptable salts

where R3 represents with the battle optionally substituted phenyl, optionally substituted pyridyl, optionally substituted pyrimidinyl;

R1a and R1b independently from each other represent a hydrogen atom, optionally substituted lower alkyl or together with the carbon atom to which they are bound, form a 5-7 membered azaheterocyclic;

R1c, R1d and R1e represents a hydrogen atom or optionally substituted lower alkyl, or one of R1c, R1d and R1e together with the carbon atom to which it is linked, and R1a together with the nitrogen atom to which it is linked, form a 5-6-membered saturated heterocyclyl with 1-2 heteroatoms, selected from nitrogen and oxygen, when the other two of R1c, R1b and R1e and R1d are hydrogen.

5. Compounds according to claim 1, which represents a substituted amides of 4-oxo-4,5-dihydro-azolopyrimidine-3-carboxylic acids of General formula 1.2 or their pharmaceutically acceptable salts:

where R1, R4, X and Z have the above meanings; R2 and R3 independently of one another represent hydrogen, optionally substituted C1-C6alkyl, optionally substituted phenyl, optionally substituted 6-membered nitrogen-containing heterocyclyl or R2 and R3 together with the nitrogen atom to which they are bound, form an optionally substituted 5-7-membered AZ is heterocyclyl.

6. The method of obtaining compounds of General formula 1 according to any one of claims 1 to 5 by the interaction of the corresponding acids of General formula F1 with amines of General formula F2 in the presence of condensing reagents

where X, Y, Z, R1, R2, R3 and R4 have the above for compounds of General formula 1 values.

7. Inhibitors of PI3 kinases, which are compounds of General formula 1 according to claim 1.

8. Selective inhibitors of the isoform R-alpha PI3 kinase according to claim 7, representing compounds of General formula 1 according to claim 1.

9. Selective inhibitors of the isoform R-beta PI3 kinase according to claim 7, representing compounds of General formula 1 according to claim 1.

10. Selective inhibitors of the isoform R-gamma PI3 kinase according to claim 7, representing compounds of General formula 1 according to claim 1.

11. Selective inhibitors of the isoform R-Delta PI3 kinase according to claim 7, representing compounds of General formula 1 according to claim 1.

12. Selective inhibitors of the isoform R-alpha PI3 kinase with a mutation in exon 20(H1047R) according to claim 7, representing compounds of General formula 1 according to claim 1.

13. Compounds of General formula 1 according to claim 1, as a biologically active ingredients to obtain drugs for the treatment of cancer.

14. Pharmaceutical composition having the properties of an inhibitor of PI3 kinase, containing as the active ingredient, at least one compound of General formula 1 according to claim 1 or a compound according to any one of claim 2 to 5, or its pharmaceutically acceptable salt in an effective amount.

15. A method of obtaining a pharmaceutical composition according to 14 the mixture of the biologically active ingredient indicated in paragraph 13 with an inert filler and/or diluent.

16. The drug is in the form of tablets, capsules, or injections, placed in pharmaceutically acceptable packing, including the inhibitor of P13 kinase according to any one of claims 7 to 12, or a pharmaceutical composition according to 14 in an effective amount.



 

Same patents:

FIELD: chemistry; pharmacology.

SUBSTANCE: present invention relates to mono-sodium salt 5-[[(2,3-difluorophenyl)methyl]thio]-7-[[2-hydroxy-1-(hydroxymethyl)-1-methylethyl]amino]thiazole[4,5-d]pyrimidine-2(3H)-on as a modulator of the activeness of chemokine receptors, method of obtaining it and pharmaceutical composition on its basis, and also its application in production of medicinal agents.

EFFECT: obtaining compounds, which can find application in treatment of diseases mediated by chemokine receptors, such as asthma, allergic rhinitis, COPD (chronic obstructive pulmonary disease), inflammatory bowel disease, osteoarthritis, and rheumatoid arthritis.

10 cl, 2 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: present invention relates to new condensed dicyclic nitrogen-containing heterocycles with the general formula (I), their pharmaceutically accepted salts and stereoisomers, possessing DGAT inhibiting action. In the compound of formula (I): , X is selected from a group, which consists of C(R1) and N; Y is selected from a group, which consists of C(R1), C(R2)(R2), N and N(R2); Z is selected from a group, which consists of O; W1 is selected from cyclo(C3-C6)alkyl, aryl and 5- or 6-member heteroaryl, containing 1-2 heteroatoms, selected from a group, which comprises of nitrogen and sulphur, W2 selected from cyclo(C3-C8)alkyl, (C5-C6)heterocycloalkyl, containing 1 or 2 heteroatoms, selected from groups, consisting of nitrogen or oxygen, benzol and 5-or 6-member heteroaryl, containing 1-2 nitrogen atoms as heteroatoms, L1 is the link; L2 is selected from a group consisting of links, 0, (C1-C4)alkylene and (C1-C4)oxyalkylene; m denotes 0 or 1; its not a must that when m denotes 1 and L2 denotes a link, the substitute for W2 can be integrated with the substitute for W1 forming a 5-or 6-member ring, condensed with c W1 forming a spiro-system or condensed with W2, where specified ring could be saturated or unsaturated and has 0 or 1 atom O, as a member of the ring R1 is H; R2 is H; R3 and R4 are independently selected from groups consisting of H and (C1-C8) alkyl; optionally, R3 and R4 can together form 3-, 4-, 5- or 6-member spirorings, R5 and R6 are independently H; optionally, when Y includes the group R1 or R2, R5 or R6 can be joined with R1 and R2 forming a 5- or 6-member condensate ring, containing a nitrogen atom, to which R5 or R6 are joined, and optionally containing an oxo-group; R7 is selected from a group, composed of H, (C1-C8) alkyl, halogen(C1-C4)alkyl, 0Ra and NRaRb ; Ra selected from groups composed of H and (C1-C8)alkyl; and Rb selected from groups consisting of H and (C1-C8)alkyl; a dotted line indicates a possible bond. The invention also relates to pharmaceutical compositions and applications of the compounds.

EFFECT: obtaining compounds which can be used for getting medicinal agents to treat or prevent diseases or a mediated action state of DGAT, such as obesity, diabetes, syndrome X, resistance of insulin, hyperglycemia, hyperinsulinemia, hypercholesterolemia, hyperlipidemia, hypertriglyceridemia, disease of non-alcoholic fatty infiltration of the liver, atherosclerosis, arteriosclerosis, coronary artery disease and myocardial infarction.

33 cl, 17 dwg, 11 tbl, 391 ex

FIELD: chemistry.

SUBSTANCE: in general formula (I) , R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and R12 can be similar or different and represent, each independently, hydrogen, halogen, hydroxyl, unsubstituted (C1-C6)alkyl, (C1-C6)alkoxy, or neighbouring groups R2 and R3 together with carbon atoms to which they are bound, can form benzol ring; R13 and R14 can be similar or different and represent each independently, hydrogen, unsubstituted (C1-C6)alkyl, optionally, R13 and R14 together with nitrogen atom can form 5-, 6-member heterocyclic ring, where heterocycle also can be substituted (C1-C6)alkyl, and it can have "additional heteroatoms", selected from O, N; "n" is an integer in interval from 1 to 4, and carbon chain, to which it relates is linear.

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15 cl, 67 ex

FIELD: chemistry.

SUBSTANCE: claimed are novel pyrazole derivatives of formula II or its pharmaceutically acceptable salts, where C ring is selected from phenyl or pyridinyl ring and R2, R2', Rx and Ry are such as said in given description. C ring has ortho-substituent and is optionally substituted in non-ortho positions. R2 and R2' , optionally taken with their intermediate atoms, form condensed ring system, such s indazole ring, and Rx and Ry, optionally taken together with their intermediate atoms, form condensed ring system, such a quinazoline ring.

EFFECT: possibility to use compositions as inhibitors of protein kinases as inhibitors GSK-3 and other kinases and apply them for protein kinase-mediated diseases.

41 cl, 8 tbl, 423 ex

FIELD: chemistry.

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19 cl, 5 tbl, 165 ex

FIELD: chemistry.

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EFFECT: obtaining solutions, which ca be used for treatment and prevention of diseases, mediated by activity of neuropeptide FF receptor.

6 cl, 4 tbl, 106 ex

FIELD: chemistry.

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6 cl, 4 dwg, 4 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention refers to cyclic sulphonamide derivatives of general formula I where bonds indicated with wavy lines represent mutually cis- in relation to cyclohexane ring; R3 represents H or hydrocarbon group having up to 10 carbon atoms; Ar1 and Ar2 independently represent phenyl which carries 0-3 substitutes independently selected from halogen, CF3, CHF2; or its pharmaceutically acceptable salt. Besides, invention refers to technology of compounds of general formula I and to pharmaceutical composition based on compounds of general formula I and applied as gamma-secretase inhibitor.

EFFECT: new derivatives of cyclic sulphonamide, activating gamma-secretase inhibition and suitable for treatment and prevention of Alzheimer's disease.

9 cl, 7 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to the obtaining of the new derivatives of benzamide of the formulas (I), which possess the activating influence on glucokinase, which can be used for treating of diabetes and obesity: where X1 and X2 represent oxygen, R1 represents alkylsufonyl, alkaneyl, halogen or hydroxyl; R2 represents alkyl or alkenyl, R3 represents alkyl or hydroxyalkyl, ring A represents phenyl or pyridyl, the ring B represents thiazolyl, thiadiazolil, isoxazoleyl, pyridothiazolyl or pyrazolyl, in which the atom of carbon of ring B, which is connected with the atom of nitrogen of the amide group of the formula(I), forms C=N bond with ring B.

EFFECT: obtaining new bioactive benzamides.

12 cl, 166 ex, 4 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the general formula (I): wherein R1 is chosen from group consisting of hydrogen atom (H), -(CH2)3-, -(CH2)4-, -CH2-S-CH2-, -S-CH2-CH2-; R2 is chosen from group consisting of nitrogen (N), sulfur (S) atom; n = 0 or 1; Z is chosen from group consisting of (C2-C10)-alkyl; R3 is chosen from group consisting of H; m = 0-2; R4 is chosen from group consisting of oxygen atom (O), -CH2-; R5 is chosen from group consisting of the following groups:

wherein R6 is chosen from group consisting of H, alkyl-(C1-C5)-alkoxyl; W is chosen from group consisting of -NH wherein each "alkyl" can be linear or branched and can be also cyclic or linear, or branched and comprises such cyclic residues, and each "aryl" comprises monocyclic aromatic group comprising 5-12 carbon atoms bound with one or some heteroatoms chosen from N, O or S atoms, and to their salts and solvates. Also, invention relates to a pharmaceutical composition, to a method for their synthesis and using compounds by claims 1-6. Invention provides synthesis of novel active compounds and pharmaceutical compositions based on thereof that possess affinity to serotonin receptors of subtype 5-HT1A.

EFFECT: valuable medicinal properties of compounds, improved method of synthesis.

10 cl, 4 tbl, 26 ex

FIELD: chemistry.

SUBSTANCE: novel chemical compounds of formula (I) or their pharmaceutically acceptable salts possess inhibiting activity with respect to kinase p-38 MAP and kinase FGFR, and can be used in treatment of such diseases as arthritis, obstructive lung disease, Alzheimer's disease or oncological and other diseases. In general formula (I) , R1 is hydrogen, R2 is 6-member oxygen-containing heterocyclyl, aryl, selected from unsubstituted phenyl or phenyl substituted with aliphatic acyl group which contains 1-6 carbon atoms, halogen cyano, hydroxyl, C1-6alkylsulfinyl, C1-6alkylsulfonyloxy, C1-6alkylsulfonyl, C1-6alkylsulfanyl, tret-butydimethylsilanyloxy, 6-member heterocyclyl, containing 1-2-heteroatoms, selected from nitrogen and oxygen, R3 is C1-6alkyl, Ar1 is phenyl, substituted with 1-2 substituents, selected from atoms of halogen, C1-6alkyl, C1-6alkoxy, C1-6alkylamino, di(C1-6alkyl)amino, X1 is oxygen and X2 is chemical bond.

EFFECT: efficient application of invention compounds in pharmaceutical composition.

13 cl, 1 tbl, 64 ex

FIELD: chemistry.

SUBSTANCE: claimed are novel pyrazole derivatives of formula II or its pharmaceutically acceptable salts, where C ring is selected from phenyl or pyridinyl ring and R2, R2', Rx and Ry are such as said in given description. C ring has ortho-substituent and is optionally substituted in non-ortho positions. R2 and R2' , optionally taken with their intermediate atoms, form condensed ring system, such s indazole ring, and Rx and Ry, optionally taken together with their intermediate atoms, form condensed ring system, such a quinazoline ring.

EFFECT: possibility to use compositions as inhibitors of protein kinases as inhibitors GSK-3 and other kinases and apply them for protein kinase-mediated diseases.

41 cl, 8 tbl, 423 ex

FIELD: chemistry.

SUBSTANCE: invention relates to application of the substituted esters of 1,2,3,7-tetrahydro-pyrrolo [3,2-f][1,3]benzoxazine-5-carboxylic acid of general formula 1 or their racemoids, or their pharmaceutically acceptable and/or hydrates as substances of pharmaceutical compositions having anti-influenza virus activity: , where: R1 and R4 independently represent amines substitute selected from hydrogen, optionally substituted by liner or branched alkyl, containing 3-12 carbon atoms, optionally substituted cycloalkyl containing 3-10 carbon atoms, optionally substituted aryl, and probably, annelated heterocyclyl, which can be aromatic or non-aromatic and contains from 3 to 10 atoms in the ring, with one or several heteroatoms selected from nitrogen, oxygen or sulphur or their oxides; R2 represents alkyl substitute selected from hydrogen, optionally substituted mercapto group, optionally substituted amino group, optionally substituted hydroxyl; R3 represents lower alkyl; R5 represents substitute of the cyclic system selected from hydrogen, optionally substituted linear or branched alkyl, containing 3-12 carbon atoms, optionally substituted cycloalkyl containing 3-10 carbon atoms optionally substituted aryl or optionally substituted and optionally substituted annelated heterocyclyl, which can be aromatic or non-aromatic and contains from 3 to 10 atoms in the ring with one or several heteroatoms selected from nitrogen, hydrogen or sulphur or their oxides; R6 represents substitute of cyclic system selected from hydrogen, halogen atom, cyano group, optionally substituted aryl or optionally substituted annelated heterocycle, which can be aromatic or non-aromatic and contains from 3 to 10 atoms in the ring with one or several heteroatoms selected from nitrogen, hydrogen or sulphur or their oxides.

EFFECT: production of the pharmaceutical compositions having anti-influenza virus activity.

12 cl, 2 dwg, 2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to non-peptide antagonists GnRH, with general formula 1 , where each of A1, A2 and A3 are independently chosen from A5 and A6; and A4 represents either a covalent bond, or A5; under the condition that, if A4 is a covalent bond, then one of A1-A3 represent A6, and the other two represent A5, and that, if A4 represents A5, then all of A1-A3 represent A5; A5 is chosen from C-R13 and N; A6 is chosen from N-R14, S and O; R1 is chosen from H, NHY1 and COY2, and R2 represents H; or and R1, and R2 represents methyl or together represent =O; each of R3, R4 and R5 independently represents H or low alkyl; each of R6, R7, R8, R9, R10, R11 and R12 are independently chosen from H, NH2, F, CI, Br, O-alkyl and CH2NMe2; R13 is chosen from H, F, CI, Br, NO2, NH2, OH, Me, Et, OMe and NMe2; R14 is chosen from H, methyl and ethyl; W is chosen from CH and N; X is chosen from CH2, O and NH; Y1 is chosen from CO-low alkyl, CO(CH2)bY3, CO(CH2)bCOY3 and CO(CH2)bNHCOY3; Y2 is chosen from OR15, NRI6R17 and NH(CH2)cCOY3; Y3 is chosen from alkyl, OR15 and NR16R17; R15 represents H; each of R16 and R17 is independently chosen from H, low alkyl and (CH2)aR18, or together represent -(CH2)2-Z-(CH2)2-; R18 is chosen from OH, pyridyl, pyrizinyl and oxadiazolyl; Z represents NH; a represents 0-4; and b and c represent 1-3. The invention also relates to use of formula 1 a compound as a therapeutic agent and pharmaceutical composition, with antagonistic effect to GnRH receptor. Description is also given of the method of obtaining compounds with the given formula.

EFFECT: obtaining new compounds, with useful biological properties.

27 cl, 70 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds of the formula (1a) or its pharmaceutically acceptable salt, esters or imides where A is a thiophenyl group containing, probably, substitution, the thiophenyl group A containing, probably, substitution with one or several groups as follows: alkyl, halo or arylalkyl, Y is O, S or NR2 where R2 is hydrogen or alkyl group containing 1 to 6 carbon atoms, and R1 is an non-ramified alkyl group containing 6 to 25 carbon atoms, ramified alkyl group containing 6 to 25 carbon atoms, aryl alkyl group where the alkyl group contains 2 to 25 carbon atoms or phenyl group containing substitution with one or several groups as follows: phenyloxy, phenylthio, SO2-phenyl, alkylphenyl, CO-phenyl, CONR16- phenyl, NR16CO-phenyl or NR16 -phenyl containing, probably, substitution where R16 is hydrogen or alkyl group containing 1 to 4 carbon atoms, the groups phenyloxy, phenylthio, SO2-phenyl, alkylphenyl, CO-phenyl, CONR-phenyl or NR-phenyl containing, probably, substitution with one or several groups as follows: halo, alkyl, alkylhalo or phenyl group containing substitution with one or several groups or alkyl groups provided the above compound is not 5-methyl-2-(4-metoxyphenyl)amino-4H-thieno[2,3-d][1,3]oxazine-4-on, 6-amyl-2-(4-chlorophenyl)amino-4H-thieno[2,3-d][1,3]oxazine-4-on or 6-amyl-2-(4-metoxyphenyl)amino-4H-thieno[2,3-d][1,3]oxazine-4-on Invention also relates to method of obtaining compounds of the formula (Ia) or (IIa), to pharmaceutical compound and application, as well as cosmetic technique.

EFFECT: obtaining of new biologically active compounds and pharmaceutical compounds based on them.

27 cl, 4 ex, 1 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): , wherein X represents heteroatom, such as oxygen (O) or sulfur (S) atoms; X and Z mean independently of one another one or some identical or different substitutes bound any available carbon atom and they can represent hydrogen atom or halogen atom; R1 represents a substitute of the formula (II): , wherein R2 and R3 can represent simultaneously or independently of one another hydrogen atom or (C1-C4)-alkyl, or R1 can represent hydrogen, halogen atom, (C1-C7)-alkyl, -CHO, -(CH2)2COOH, -(CH2)2CO2Et, (CH2)mL wherein L means -OH or bromine atom (Br); m represents a whole number from 1 to 3; n represents a whole number from 0 to 3; Q1 and Q2 represent independently of one another oxygen atom or group of the formula: wherein substitutes y1 and y2 represent hydrogen atom, and to their pharmacologically acceptable salts. Also, invention relates to use of these compounds as intermediate substances used in synthesis of novel compounds of dibenzoazulene class, and to their using for preparing drugs.

EFFECT: valuable medicinal properties of compounds.

9 cl, 4 tbl, 13 ex

FIELD: organic chemistry, medicine, pharmacy, chemical technology.

SUBSTANCE: invention relates to novel substituted esters of 1,2,3,7-tetrahydropyrrolo[3,2-f][1,3]benzoxazin-5-carboxylic acids of the general formula (1): or their racemates, or their optical isomers, or their pharmaceutically acceptable salts and/or hydrates possessing the antiviral effect. In compounds of the general formula (1) each R1 and R4 represents independently of one another a substitutes of amino group chosen from hydrogen atom, optionally substituted linear or branched alkyl comprising 3-12 carbon atoms, optionally substituted cycloalkyl comprising 3-10 carbon atoms, optionally substituted aryl or optionally substituted and possibly an annelated heterocyclyl that can be aromatic or nonaromatic and comprising from 3 to 10 atoms in ring with one or some heteroatoms chosen from nitrogen, oxygen or sulfur atoms or their oxides; R2 represents alkyl substitute chosen from hydrogen atom, optionally substituted mercapto group, optionally substituted amino group, optionally substituted hydroxyl; R3 represents lower alkyl or cycloalkyl; R5 represents a substitute of cyclic system chosen from hydrogen atom, optionally substituted linear or branched alkyl comprising 3-12 carbon atoms, optionally substituted cycloalkyl comprising 3-10 carbon atoms, optionally substituted aryl or optionally substituted and optionally an annelated heterocyclyl that can be aromatic or nonaromatic and comprising from 3 to 10 atoms in ring with one or some heteroatoms chosen from nitrogen, oxygen or sulfur atoms or their oxides; R6 represents a substitute of cyclic system chosen from hydrogen atom, halogen atom, cyano group, optionally substituted aryl or optionally substituted and optionally annelated heterocyclyl that can be aromatic or nonaromatic and comprising from 3 to 10 atoms in ring with one or some heteroatoms chosen from nitrogen, oxygen or sulfur atoms or their oxides. Also, invention relates to methods for treatment, drugs and pharmaceutical compositions using compounds of this invention. Proposed compounds can be used as active components of drugs used in treatment of such diseases as infectious hepatitis, human immunodeficiency, atypical pneumonia and avian influenza.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved methods of synthesis.

22 cl, 3 tbl, 6 dwg, 7 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel azaheterocycles of the general formula (I): possessing inhibitory effect on activity of tyrosine kinase and can be used in treatment of different diseases mediated by these receptors. In compound of the general formula (1) W represents azaheterocycle comprising 6-13 atoms that can be optionally annelated with at least one (C5-C7)-carbocycle and/or possibly annelated with heterocycle comprising 4-10 atoms in ring and comprising at least one heteroatom chosen from oxygen (O), sulfur (S) or nitrogen (N) atom; Ra1 represents a substitute of amino group but not hydrogen atom, such as substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-10-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; Rb represents carbamoyl group -C(O)NHRa wherein Ra represents a substitute of amino group but not hydrogen atom, such as possibly substituted alkyl, possibly substituted aryl, possibly substituted 5-10-membered heterocyclyc comprising at least one heteroatom chosen from O, S or N; Rc represents a substitute of cyclic system, such as possibly substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-6-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; or Rb and Rc form in common aminocyanomethylene group [(=C(NH2)CN], or their pharmaceutically acceptable salts. Also, invention relates to methods for synthesis of these compounds (variants), a pharmaceutical composition, combinatory and focused libraries.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved methods for synthesis and preparing.

35 cl, 16 sch, 13 tbl, 43 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to compounds of general formula 1 (G1 is group of general formulae 2 G1 is group of general formulae ; meanings of the rest substituents are as described in specification) or pharmaceutically acceptable salts thereof and use thereof in srug production. Said compounds are useful in treatment of male and female sexual disorders.

EFFECT: new oxytocin antagonists.

30 cl, 177 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to compounds of general formula I and pharmaceutically acceptable salt thereof, wherein R1, R3, R4, R5, and R10 are independently H, halogen, C1-C4-alkyl, etc.; R2 is H, halogen, NO2, etc.; R6 is H, C1-C6-alkyl, C1-C6-alkoxy-substituted C1-C4-alkyl, etc.; R7 is H, C1-C4-alkyl or C2-C4-alkenyl, optionally substituted with halogen; R8 and R9 are H, R11 and R12; meanings of the rest substituents are as define in specification.

EFFECT: new compounds with value biological properties and useful as drug having activity in relates to progesterone receptor.

15 cl, 3 tbl, 80 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to method of obtaining derivatives of 8-thieno[2,3-b]indole of general formula I and can be used for obtaining biologically active substances. Method is characterised by the fact that derivatives of 2-alkyl-5-(2-isothiocyanoaryl)furanes are mixed in 1,2-dichloroethane in presence of aluminium chloride with molar ratio of initial substance and aluminium chloride 1:1÷1:2 at temperature from room temperature to temperature of 1,2-dichloroethane boiling for from 30 min to 48 hours. I a-e, Ia R1 = H, R2 = CH3, b R1 = H, R2 = CH2CH3, c R1 = CI, R2 = CH3, d R1 = CH3, R2 = CH3, e R1 = OCH3, R2 = CH3.

EFFECT: extension of series of potentially biologically active derivatives of the said agent.

1 cl, 6 ex, 3 tbl

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