Heteroaromatic derivatives of urea and use thereof as glucokinase activators

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) and to their pharmaceutically acceptable salts, optical isomers or their mixture as glucokinase activators. In general formula (I) where R1 is C3-8-cycloalkyl, C3-8-cycloalkenyl, a 6-member heterocyclyl with 1 nitrogen atom, condensed phenyl-C3-8-cycloalkyl, each of which is possibly substituted with one or two substitutes R3, R4, R5 and R6; R2 is C3-8-cycloalkyl, a 5-6-member heterocyclyl with 1-2 heteroatoms selected from N, O, or S, each of which can be substituted with one or two substitutes R30, R31, R32 and R33, and R3, R4, R5, R6, R30, R31, R32 and R33 are independently selected from a group consisting of halogen, hydroxy, oxo, -CF3; or -NR10R12; or C1-6-alkyl, phenyl, C1-6-alkoxy, C1-6-alkyl-C(O)-O-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; or -C(O)-R27, -S(O)2-R27; or two substitutes selected from R3, R4, R5 and R6 or R30, R31, R32 and R33, bonded to the same atom or to neighbouring atoms, together form a -O-(CH2)2-O- radical; R10 and R11 independently represent hydrogen, C1-6-alkyl, -C(O)-C1-6-alkyl, -C(O)-O- C1-6-alkyl, -S(O)2- C1-6-alkyl; R27 is C1-6-alkyl, C1-6-alkoxy, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, phenyl, phenyl-C1-6-alkyl, a 5-6-member heteroaryl with 1-2 heteroatoms selected from N or S, a 6-member heteroaryl-C1-6-alkyl with 1 nitrogen atom, a 6-member heterocyclyl-C1-6-alkyl with 1-2 heteroatoms selected from N or O, R10R11-N- C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; R12 is a halogen, CF3, C1-6-alkoxy, -NR10R11; A is a 5-9-member heteroaryl with 1-3 heteroatoms selected from N, O or S, which is possibly substituted with one or two substitutes independently selected from R7, R8 and R9; R7, R8 and R9 are independently selected from halogen, cyano, -CF3; or C1-6-alkyl, C2-6-alkenyl, C1-6-alkoxy, C1-6-alkylthio, -C(O)-O-C1-6-alkyl, formyl, - C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-O-C(O)-C1-6-alkyl or hydroxy-C1-6-alkyl, each of which is possibly substituted with a substitute independently selected from R16; or phenyl, 5-member heteroaryl-C1-6-alkylthio with 2-4 nitrogen atoms, phenylthio, 5-6-member heteroarylthio with 1-2 nitrogen atoms, each of which is possibly substituted on the aryl or heteroaryl part with one or two substitutes independently selected from R17; or C3-8-cycloalkyl; or a 6-member heterocyclyl with 2 nitrogen atoms, 5-7-member heterocyclyl-C1-6-alkylthio with 1-2 heteroatoms selected from N or O, each of which is possibly substituted with one substitute independently selected from R16; or C1-6-alkyl-NR19R20, -S(O)2-R21 or -S(O)2-NR19R20; or -C(O)NR22R23; R16, R17 and R18 independently represent C1-6-alkyl, carboxy, -C(O)-O-C1-6-alkyl, -NR19R20, -C(O)NR19R20; R19 and R20 independently represent hydrogen, C1-6-alkyl, phenyl, 5-member heteroaryl with 2 heteroatoms selected from N or S, 6-member heterocyclyl with 1 nitrogen atom, -C(O)-O-C1-6-alkyl or -S(O)2-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R24; or R19 and R20 together with a nitrogen atom to which they are bonded form a 5-7-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring possibly contains one additional heteroatom selected from nitrogen, oxygen and sulphur, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R21 is selected from C2-6-alkenyl; or R22 and R23 are independently selected from hydrogen, -C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-S(O)2-C1-6-alkyl, C3-8-cycloalkyl; or R22 and R23 together with a nitrogen atom to which they are bonded form a 6-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R24 is oxo, C1-6-alkyl, carboxy- C1-6-alkyl, a 6-member heterocyclyl with 1 nitrogen atom, -NH-S(O)2R28 or -S(O)2R28, where each cyclic group is possibly substituted with one substitute independently selected from R29; R28 is C1-6-alkyl, -C1-6-alkyl-C(O)-O- C1-6-alkyl or -N(CH3)2; R29 is C1-6-alkyl.

EFFECT: obtaining compounds which can be used for treating and preventing diseases mediated by low glucokinase activity.

21 cl, 1 dwg, 608 ex, 1 tbl

 

The text descriptions are given in facsimile form.

1. The compound of General formula (I)

where R1represents a C3-8-cycloalkyl,3-8-cycloalkenyl, 6-membered heterocyclyl with 1 nitrogen atom, condensed phenyl-C3-8-cycloalkyl, each of which may substituted by one or two substituents R3, R4, R5and R6;
R2represents a C3-8-cycloalkyl, 5-6-membered heterocyclyl with 1-2 heteroatoms, selected from N, O or S, each of which may substituted by one or two to cover the firs R 30, R31, R32and R33and
R3, R4, R5, R6, R30, R31, R32and R33independently selected from the group consisting of
of halogen, hydroxy, oxo, -CF3; or
- NR10R11; or-C1-6-alkyl, phenyl, C1-6-alkoxy, C1-6-alkyl-C(O)-O-C1-6-alkyl, each of which may substituted by one Deputy, is independently selected from R12; or-C(O)-R27, -S(O)2-R27; or two substituent selected from R3, R4, R5and R6or R30, R31, R32and R33attached to the same atom or to adjacent atoms together form a radical-O-(CH2)2-O-;
R10and R11independently represent hydrogen, C1-6-alkyl, -C(O)-C1-6-alkyl, -C(O)-O-C1-6-alkyl, -S(O)2-C1-6-alkyl;
R27represents a C1-6-alkyl, C1-6-alkoxy, C3-8-cycloalkyl,3-8-cycloalkyl-C1-6-alkyl, phenyl, phenyl-C1-6-alkyl, 5-6-membered heteroaryl with 1-2 heteroatoms, selected from N or S, a 6 membered heteroaryl-C1-6is alkyl with 1 nitrogen atom, a 6-membered heterocyclyl-C1-6-alkyl with 1-2 heteroatoms, selected from N or O, R10R11-N-C1-6-alkyl, each of which may substituted by one Deputy, is independently selected from R12;
R12predstavljaet a halogen, -CF3C1-6-alkoxy, -NR10R11;
But a 5-9-membered heteroaryl with 1-3 heteroatoms selected from N, O or S, which may substituted by one or two substituents, independently selected from R7, R8and R9;
R7, R8and R9independently selected from halogen, cyano, -CF3; or-C1-6-alkyl, C2-6-alkenyl, C1-6-alkoxy, C1-6-alkylthio, -C(O)-O-C1-6-alkyl, formyl, -C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-O-C(O)-C1-6-alkyl or hydroxy-C1-6-alkyl, each of which may substituted by one Deputy, is independently selected from R16; or phenyl, 5-membered heteroaryl-C1-6-alkylthio with 2 to 4 nitrogen atoms, phenylthio, 5-6-membered, heteroaromatic with 1-2 nitrogen atoms, each of which may substituted on the aryl or heteroaryl part with one or two substituents, independently selected from R17; or - C3-8-cycloalkyl; or - 6-membered heterocyclyl with 2 nitrogen atoms, 5-7 membered heterocyclyl-C1-6-alkylthio with 1-2 heteroatoms, selected from N or O, each of which may substituted by one Deputy, is independently selected from R16; or
- C1-6-alkyl-NR19R20, -S(O)2-R21or-S(O)2-NR19R20; or-C(O)NR22R23;
R16, R17and R1 independently represents a C1-6-alkyl, carboxy, -C(O)-O-C1-6-alkyl, -NR19R20, -C(O)NR19R20;
R19and R20independently represent hydrogen, C1-6-alkyl, phenyl, 5-membered heteroaryl 2 heteroatoms selected from N or S, a 6 membered heterocyclyl with 1 nitrogen atom, -C(O)-O-C1-6-alkyl or-S(O)2-C1-6-alkyl, each of which may substituted by one Deputy, is independently selected from R24; or R19and R20together with the nitrogen atom to which they are attached, form a 5-7-membered heterocyclic ring with the indicated nitrogen atom, where the heterocyclic ring may contain one additional heteroatom selected from nitrogen, oxygen and sulfur, where the heterocyclic ring may substituted by one Deputy, is independently selected from R24;
R21selected from
-C2-6-alkenyl; or
R22and R23independently selected from hydrogen, -C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-S(O)2-C1-6-alkyl, C3-8-cycloalkyl; or R22and R23together with the nitrogen atom to which they are attached, form a 6-membered heterocyclic ring with the indicated nitrogen atom, where the heterocyclic ring may substituted by one Deputy, is independently selected from R24;
R24depict is to place an oxo, C1-6-alkyl, carboxy-C1-6-alkyl, 6-membered heterocyclyl with 1 nitrogen atom, -NH-S(O)2R28or-S(O)2R28where each cyclic group possibly substituted by one Deputy, is independently selected from R29;
R28represents a C1-6-alkyl, -C1-6-alkyl-C(O)-O-C1-6-alkyl or-N(CH3)2;
R29represents a C1-6-alkyl;
or any of its salts with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture.

2. The compound according to claim 1, where R1selected from
,,,
,,,or

3. The compound according to claim 2, where R1selected from
,,,,
,,,or

4. The compound according to claim 1, where R2selected from
,,, ,
,,,or

5. The compound according to claim 4, where R2selected from
,,,,,
,,,,or

6. The compound according to claim 1, where R1and R2both represent cyclohexyl.

7. The compound according to claim 1, where R1represents a

and R2represents cyclohexyl.

8. The compound according to claim 1, where R3, R4, R5, R6, R30, R31, R32and R33independently selected from the group consisting of
halogen, -CF3; or methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, phenyl, methoxy, ethoxy, propoxy, each of which may substituted by one Deputy, is independently selected from R12; or-C(O)-R27or-S(O)2-R27.

9. The connection of claim 8, where R3, R4, R5, R6, R30, R31, R32and R33independently selected from the group, with the standing of F, Cl-CF3, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, methoxy, ethoxy, propoxy, -C(O)-R27or-S(O)2-R27.

10. The compound according to claim 1, where R10and R11independently represent hydrogen, methyl, ethyl, propyl, -C(O)-CH3-C(O)-CH2CH3, -S(O)2CH3.

11. The connection of claim 10, where R10and R11independently represent hydrogen, methyl, ethyl, -C(O)-CH3, -S(O)2CH3.

12. The connection of claim 10, where R27represents methyl, ethyl, propyl, n-butyl, isobutyl, cyclopropyl, cyclopentyl, cyclopropylmethyl, phenyl or pyridyl, thiophene, imidazole, or thiazole.

13. The compound according to claim 1, where R12represents a halogen, -CF3.

14. The compound according to claim 1, where a is a
,,,,or

15. The compound according to claim 1, where R7, R8and R9independently selected from Cl, F, Br, -CF3, -S-CH3, -S-CH2CH3, -S-CH2CH2CH3, methyl, ethyl, methoxy, ethoxy, -CH2-C(O)-O-CH2CH3-C(O)-O-CH3or-C(O)-O-CH2CH3, each of which may substituted by one Deputy, is independently selected from R16; or heteroaromatic, where GE is Eroare represents a pyridyl or imidazolyl, every possibly substituted on the heteroaryl part with one or two substituents, independently selected from R17or heterocyclyl-C1-6-alkylthio where heterocyclyl is pyrrolidinyl, piperidyl, piperazinil or morpholinyl, each of which may substituted by one Deputy, is independently selected from R16.

16. The compound according to claim 1, where R16, R17and R18independently represent methyl, ethyl, propyl, carboxy, -C(O)-O-CH3-C(O)-O-CH2CH3, -C(O)-O-CH2CH2CH3.

17. The compound according to claim 1, where R16, R17and R18independently represents a C1-6-alkyl, -NR19R20-C(O)-O-C1-6-alkyl or-C(O)NR19R20.

18. The compound according to claim 1, where R19and R20independently represent hydrogen, methyl, ethyl or propyl, or R19and R20together with the nitrogen atom to which they are attached, form a 5-7-membered heterocyclic ring with the indicated nitrogen atom, where the heterocyclic ring is pyrrolidyl, piperidyl; where the heterocyclic ring may substituted by one Deputy, is independently selected from R24.

19. The compound according to claim 1, where R22and R23together with the nitrogen atom to which they are attached, form a 6-membered heterocyclic ring with the indicated nitrogen atom is, where the heterocyclic ring is piperidyl; and this heterocyclic ring may substituted by one Deputy, is independently selected from R24.

20. The compound according to claim 1, where R24represents oxo, C1-6-alkyl, carboxy-C1-6-alkyl, 6-membered heterocyclyl with 1 nitrogen atom or-S(O)2R28and where each of the cyclic group possibly substituted by one Deputy, is independently selected from R29.

21. The compound according to claim 1, where R28represents a C1-6-alkyl, -C1-6-alkyl-C(O)-O-C1-6-alkyl or-N(CH3)2.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (XXI) where values of R1, Y, Ra and Rb are given in subparagraphs 1 and 2 of the formula of invention, as phosphatidylinositol-3-kinase inhibitors, a pharmaceutical composition based on said compounds and their use.

EFFECT: compounds can be used for treating and preventing diseases mediated by phosphatidylinositol-3-kinase.

5 cl, 5 tbl, 146 ex

FIELD: chemistry.

SUBSTANCE: described are compounds of formula (I)

Values of radicals R1-R6 are given in the formula of invention. The compounds inhibit protein kinase MEK1/2. Also described is a pharmaceutical composition for administration in diseases mediated by MEK1/2.

EFFECT: compounds are highly efficient.

16 cl, 27 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula

or

or to their pharmaceutically acceptable salts, where ring A, R2, R3, R4 and X are as defined in the description. The disclosed compounds are useful as 11βHSD1 inhibitor. The invention also relates to a pharmaceutical composition, an agent for treating or preventing pathology related to glucocorticoids, a 11βHSD1 inhibitor containing the disclosed compound or its pharmaceutically acceptable salt, and use of the disclosed compounds.

EFFECT: compounds are highly effective.

40 cl, 48 tbl, 191 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula and their pharmaceutically acceptable salts and esters. The disclosed compounds have cdk4 inhibition properties. In formula (I) n equals 0 or 1; R1 and R2 are each independently selected from a group consisting of H, lower alkyl, CO2R5, SO2R6 and COR6; or alternatively, R1 and R2 can form a ring containing 5-6 atoms in the ring, where the said ring contains carbon atoms, where the said carbon atoms are optionally substituted with oxygen, and the said atoms in the ring are optionally substituted with OR6; R3 is selected from a group consisting of H, lower alkyl, O-lower alkyl, halogen, OH, CN, NO2 and COOH; R4 is selected from a group consisting of H, lower alkyl, C3-C6-cycloalkyl, O-lower alkyl, halogen, NO2, S-lower alkyl, NR5R6, CONR7R8, OH and CN; or alternatively R3 and R4, together with two carbon atoms and the bond between them from the benzene ring, to which R3 and R4 are bonded, can form a ring containing 5-7 atoms, where the said 5-7-member ring contains carbon atoms, where the said carbon atoms are optionally substituted with one or two heteroatoms selected from O and N, and the said atoms in the ring are optionally substituted with CO2R6; R4 represents H or halogen; R5 and R6 are each independently selected from a group consisting of H and lower alkyl; R7 and R8 each represents H. The invention also relates to a pharmaceutical composition for treating or controlling diseases progression of which can be enhanced by inhibiting cdk4, containing an effective amount of the disclosed compound as an active ingredient, to use of disclosed compounds for preparing medicinal agents and method of producing said compounds.

EFFECT: more effective treatment.

30 cl, 1 tbl, 142 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I: where A,Y,R and R2 assume values given in the description. The invention also relates to methods of producing compounds of formula I and their intermediate compounds, pharmaceutical compositions and methods of using the compounds and their pharmaceutical compositions for inhibiting caspase.

EFFECT: novel compounds have useful biological properties.

44 cl, 5 tbl, 66 ex

FIELD: chemistry.

SUBSTANCE: crystalline monohydrate has X-ray powder pattern which includes four or more values 2θ, selected from a group consisting of: 18.0 ± 0.2, 18.4 ± 0.2, 19.2 ± 0.2, 19.6 ± 0.2, 21.2 ± 0.2, 24.5 ± 0.2, 25.9 ± 0.2 and 28.0 ± 0.2. The invention also relates to a method of producing crystalline monohydrate, to a pharmaceutical composition for treating disorders caused by protein tyrosine kinase containing crystalline monohydrate, to a crystalline butanol solvate of formula and to a crystalline ethanol solvate compound of formula (IV).

EFFECT: increased effectiveness of using said compounds.

8 cl, 1 tbl, 6 dwg, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (1) and their pharmaceutically acceptable salts as chemokine receptor CCR3 activity modulators, a pharmaceutical composition based on the said compounds, to synthesis method and use thereof. Said compounds can be used for treating and preventing diseases mediated by chemokine receptor CCR3 activity, such as inflammatory and allergic diseases etc. In general formula , R1 represents phenyl, [1,2,4]triazolo[4,3-a]pyridinyl, thiazolo [5,4-b]pyridinyl, benzothiazolyl, benzoxazolyl, pyridinyl, where each of the said phenyl or heterocycles can be substituted with one, two or three radicals R2; R2 each independently represents (C1-C6)halogenalkyl, halogen, COOR3; CONR3R4; R3 represents H or (C1-C6)alkyl; R4 represents H or (C1-C6)alkyl, R5 represents (C1-C6)alkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyl; R6 each independently represents (C1-C6)alkoxy, (C1-C6)halogenalkyl, halogen, OR3, CN, CONR3R4; A represents C(CH3)2-CH2-CH2-, CH2-CH2-CH2- or B represents phenyl; D-E represents CH-CH2- or C=CH-, X-W-V represents N-C=CR7 or C=C-NR7; R7 represents H or (C1-C6)alkyl; Y represents NR4, O, S(O)n; i, j, m each equals 1, n equals 0 or 2.

EFFECT: increased effectiveness of using said compounds.

13 cl, 37 ex

FIELD: chemistry.

SUBSTANCE: invention relates to benzothiazole derivatives with general formula (I) and their pharmaceutically acceptable acid addition salts, optically pure enantiomers, racemates and diastereomer mixtures as adenosine receptor ligands and to a pharmaceutical preparation based on said compounds. In general formula (I), R1 represents C3-7cycloalkyl substituted with a OR group, or 2-(7-oxa-bicyclo[2.2.1]hept-1-yl)-ethyl; R represents hydrogen or C(O)-lower alkyl; X represents -CHR'-; and R' represents hydrogen or lower alkyl.

EFFECT: compounds can be used for treating or preventing diseases mediated by adenosine A2A receptors, for example Alzheimer's disease, certain depressive conditions, toxicomania and Parkinson's disease.

8 cl, 8 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to piperidine-amino-benzidazoles having formula (I) and to addition salts or stereochemically isomeric forms, where Q is C1-6alkyl optionally substituted with one or two substitutes, each independently selected from a group consisting of trifluoromethyl, C3-7cycloalkyl, Ar2, hydroxyl, Ar2 - oxy-, hydroxycarbonyl, aminocarbonyl, C1-4alkylcarbonyl, aminocarbonyloxy, C1-4alkoxycarbonyl, Ar2(CH2)ncarbonyloxy, C1-4alkoxycarbonyl-(CH2)noxy, mono- or di(C1-4alkyl)aminocarbonyl, aminosulfonyl, mono(C1-4alkyl)aminosulfonyl, or heterocycle selected from a group consisting of pyrrolidinyl, dihydropyrrolyl, imidazolyl, triazolyl, homopiperidinyl, pyridyl and tetrahydropyridyl; or where Q is C1-6alkyl substituted with two substitutes, where substitute is an amino group and the other is C1-6alkyloxycarbonyl; G is -CH2-; R1 is pyridyl optionally substituted with two substitutes selected from a group consisting of hydroxyl, C1-6alkyl; each n equals 1; one of R2a and R3a is C1-6alkyl and the other is hydrogen; when R2a is not hydrogen, R2b is C1-6alkyl and R3b is alkyl; and R3a, R2a, R2b all represent hydrogen; or R5 is hydrogen; t equals 2; Ar2 is phenyl or phenyl substituted with one or more, for example 2 substitutes selected from halogen, C1-6alkyloxy, aminosulfonyl and C1-4alkoxycarbonyl. The invention also relates to a pharmaceutical composition based on compound of formula I and use of the said compounds in making medicinal agents.

EFFECT: novel piperadine-amino-benzimidazoles are obtained, having inhibitory effect on respiratory syncytial virus replication.

10 cl, 3 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to 2-cycloalkylamino-5-thienyl-1,2,3-thiadiazines hydrobromides with antiaggregant activity , where R=H; CH3; Br, = morpholino-; thiomorpholino-; pyrrolidino-; 2,6-dimethylmorpholino-; hexamethylenimino-.

EFFECT: obtaining novel compounds which can be used in medicine for treating and preventing such diseases as myocardial infarcation, stroke, rejection of transplanted organs and tissue, and can also prevent embolism and thrombosis formation.

1 cl, 5 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: described are compounds of formula (I)

Values of radicals R1-R6 are given in the formula of invention. The compounds inhibit protein kinase MEK1/2. Also described is a pharmaceutical composition for administration in diseases mediated by MEK1/2.

EFFECT: compounds are highly efficient.

16 cl, 27 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula and their pharmaceutically acceptable salts and esters. The disclosed compounds have cdk4 inhibition properties. In formula (I) n equals 0 or 1; R1 and R2 are each independently selected from a group consisting of H, lower alkyl, CO2R5, SO2R6 and COR6; or alternatively, R1 and R2 can form a ring containing 5-6 atoms in the ring, where the said ring contains carbon atoms, where the said carbon atoms are optionally substituted with oxygen, and the said atoms in the ring are optionally substituted with OR6; R3 is selected from a group consisting of H, lower alkyl, O-lower alkyl, halogen, OH, CN, NO2 and COOH; R4 is selected from a group consisting of H, lower alkyl, C3-C6-cycloalkyl, O-lower alkyl, halogen, NO2, S-lower alkyl, NR5R6, CONR7R8, OH and CN; or alternatively R3 and R4, together with two carbon atoms and the bond between them from the benzene ring, to which R3 and R4 are bonded, can form a ring containing 5-7 atoms, where the said 5-7-member ring contains carbon atoms, where the said carbon atoms are optionally substituted with one or two heteroatoms selected from O and N, and the said atoms in the ring are optionally substituted with CO2R6; R4 represents H or halogen; R5 and R6 are each independently selected from a group consisting of H and lower alkyl; R7 and R8 each represents H. The invention also relates to a pharmaceutical composition for treating or controlling diseases progression of which can be enhanced by inhibiting cdk4, containing an effective amount of the disclosed compound as an active ingredient, to use of disclosed compounds for preparing medicinal agents and method of producing said compounds.

EFFECT: more effective treatment.

30 cl, 1 tbl, 142 ex

Organic compounds // 2382783

FIELD: chemistry.

SUBSTANCE: invention relates to a compound which is 1-[2-(2-ethyl-2H-tetrazol-5-yl)ethyl]-3-[5-(3-fluoro-4-methanesulfonylphenyl)-4-methylthiazol-2-yl]urea in free form or in form of a pharmaceutically acceptable salt.

EFFECT: composition has inhibitory activity on phosphatidylinositol-3-kinase, which contains the disclosed compound as an active ingredient, to use of the compound to prepare a pharmaceutical composition for treating diseases mediated by phosphatidylinositol-3-kinase and synthesis method thereof.

6 cl, 9 tbl, 154 ex

FIELD: chemistry.

SUBSTANCE: invention relates to benzothiazole derivatives with general formula and and their pharmaceutically acceptable acid-addition salts as adenosine receptor ligands and to a pharmaceutical preparation based on said compounds. The compounds can be used for treating and preventing diseases mediated by adenosine A2A receptors, for example Alzheimer's disease, certain depressive conditions, toxicomania and Parkinson's disease. In general formulae (IA) and (IB) R1, R2 independently represent lower alkyl or -(CH2)m-O-lower alkyl, or together with the N atom to which they are bonded form a 5-6-member heterocyclic ring which optionally contains 1 additional oxygen atom; R3 represents hydrogen or lower alkyl; R4 represents lower alkyl; hetaryl represents 3H-imidazole-2,4-diiyl or 1H-pyrazole-1,4-diiyl; n equals 1 or 2 and m equals 1 or 2.

EFFECT: more effective treatment.

12 cl, 36 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I: where A,Y,R and R2 assume values given in the description. The invention also relates to methods of producing compounds of formula I and their intermediate compounds, pharmaceutical compositions and methods of using the compounds and their pharmaceutical compositions for inhibiting caspase.

EFFECT: novel compounds have useful biological properties.

44 cl, 5 tbl, 66 ex

FIELD: chemistry.

SUBSTANCE: novel compound is N-(5-hydroxy-2,4-di-tert-butylphenyl)-4-oxo-1H-quinoline-3-carboxamide or its pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition.

EFFECT: obtaining a novel biologically active compound with CFTR activity modulation properties.

2 cl, 485 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula , where Qa is phenyl or heteroaryl, and Qa can possibly carry 1 or 2 substitutes selected from hydroxy, halogen, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino; R1 and R2 are each independently selected from hydrogen and (1-6C)alkyl; Qb is phenyl or heteroaryl, and Qb can possibly carry 1 or 2 substitutes selected from hydroxy, halogen, (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, (1-6C)alkoxycarbonyl, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulfinyl and (1-6C)alkylsulfonyl; where any of the substitutes Qa and Qb defined above, containing a CH2 group which is bonded to 2 carbon atoms, or a CH3 group bonded to a carbon atom, can possibly carry on each of the said CH2 or CH3 group one or more substitutes selected from hydroxy, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino; where heteroaryl is an aromatic 5- or 6-member monocyclic ring which can contain up to three heteroatoms selected from oxygen, nitrogen and sulphur, and can be condensed with a benzene ring or a five-member nitrogen-containing ring containing 2 nitrogen atoms; as well as pharmaceutically acceptable salts thereof. The invention also relates to a method of producing formula I compounds, a pharmaceutical composition and use of these compounds for treating conditions mediated by effect of TNF cytokines.

EFFECT: more effective treatment.

13 cl, 3 tbl, 46 ex

FIELD: chemistry.

SUBSTANCE: invention relates to benzothiazole derivatives with general formula (I) and their pharmaceutically acceptable acid addition salts, optically pure enantiomers, racemates and diastereomer mixtures as adenosine receptor ligands and to a pharmaceutical preparation based on said compounds. In general formula (I), R1 represents C3-7cycloalkyl substituted with a OR group, or 2-(7-oxa-bicyclo[2.2.1]hept-1-yl)-ethyl; R represents hydrogen or C(O)-lower alkyl; X represents -CHR'-; and R' represents hydrogen or lower alkyl.

EFFECT: compounds can be used for treating or preventing diseases mediated by adenosine A2A receptors, for example Alzheimer's disease, certain depressive conditions, toxicomania and Parkinson's disease.

8 cl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of diaryl compounds with formulae given below ,

.

, in which M is S(O)2, Rx represents alkyl, R1, R2, R3 and R4 are each independently selected from OH and -NR7S(O)2R8, R5 and R7 each independently represents hydrogen or alkyl, R8 is alkyl; and their pharmaceutically acceptable derivatives, as well as to pharmaceutical compositions containing said compounds and their use in making a medicinal agent with inhibitory activity on Aβ, IAPP amyloid fibrils or synuclein fibrils.

EFFECT: substituted n-arylbenzamide and related compounds for treating amyloid diseases and synucleinopathy are disclosed.

11 cl, 19 ex, 6 tbl

FIELD: chemistry.

SUBSTANCE: proposed phosphodiesterase 4 inhibitors are characterised by formulae II, III, V, VI, where X is CH or N; L is a single bond, -(CH2)nCONH-, -(CH2)nCON(CH2CH3)-, (CH2)nSO2, (CH2)nCO2 or alkylene, optionally substituted oxo or hydroxy; n assumes values from 0 to 3; R1 is optionally substituted alkyl; R3 - H, alkyl, cycloalkyl, alkoxyalkyl, optionally substituted phenyl, phenylalkyl, heterocyclyl, heterocyclylalkyl or cycloalkylalkyl; R4 and R5 represent alkyl; R6 - cycloalkyl, R7 is H; R8 is H, carboxy, alkoxycarbonyl, -CO-alkyl, optionally substituted alkyl.

EFFECT: new phosphodiesterase 4 inhibitors have improved properties.

55 cl, 30 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound N-(1-{(3R)-3-(3,5-difluorophenyl)-3-[1-(methylsulfonyl) piperidin-4-yl]propyl}piperidin-4-yl)-N-ethyl-2-[4- (methylsufonyl)phenyl]acetamide or its pharmaceutically acceptable salts. The invention also relates to a method for synthesis of the compound in paragraph 1, as well as to a pharmaceutical composition.

EFFECT: obtaining a novel biologically active compound with activity towards CCR5 (chemokine receptor 5).

6 cl, 6 ex, 2 tbl

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