New piperidines as chemokine (ccr) modulators

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I) , where R1 is phenyl optionally substituted by halogen, cyano, C1-4alkyl or C1-4haloalkyl; R2 is hydrogen, C1-6alkyl or C3-6cycloalkyl; and R3 is a group with NH or OH and calculated or measured pKa from 1.0 to 8.0, selected out of: 2-oxo-thiazol-5-yl with C1-4fluoroalkyl, optionally substituted phenyl group, optionally substituted heterocyclyl group or CH2S(O)2(C1-4alkyl) group in position 4; 2-oxo-oxazol-5-yl with C1-4fluoroalkyl or CH2S(O)2(C1-4alkyl) in position 4; 1H-1,2,3-triazol-4-yl with C1-4alkyl, C3-6cycloalkyl, C1-4fluoroalkyl, S-R4 (where R4 is C1-4alkyl, C1-4fluoroalkyl or C3-6cycloalkyl), NHS(O)2(C1-4alkyl), N(C1-4alkyl)S(O)2(C1-4alkyl), phenyl group, heterocyclyl group or CH2S(O)2C1-4alkyl) group in position 5; 4-oxo-1H-1,4-dihydropyridine-3-yl with C1-4fluoroalkyl in position 2; 2,6-dioxo-1H-1,2,3,6-tetrahydropyrimidine-4-yl with C1-4alkyl, C3-6cycloalkyl or CH2(C1-3fluoroalkyl) in position 3 and optionally substituted in one or more other ring positions; 6-oxo-1H-1,6-dihydropyridine-3-yl with C1-4fluoroalkyl, cyano or phenyl in position 2 and/or in position 5 and optionally substituted in one or more other ring positions; 6-oxo-1H-1,6-dihydropyridine-3-yl with CH2CO2H at ring nitrogen atom and optionally substituted in one or more other ring positions; 2H-tetrazol-5-yl; CO2H, CH2CO2H or OCH2CO2H group at optionally substituted phenyl, optionally substituted CH2O phenyl or optionally substituted naphtyl ring or optionally substituted acylated dihydroisoquinolinyl ring; or group NHS(O)2(C1-4alkyl) at optionally substituted aromatic heterocyclic ring; or their tautomer where possible; in indicated positions where heterocyclyl ring in R3 can be optionally substituted, it can be optionally substituted by fluoro, chloro, bromo, C1-4alkyl, C3-6cycloalkyl, C1-4fluoroalkyl, S-R4 (where R4 is C1-4alkyl, C1-4fluoroalkyl or C3-6cycloalkyl), cyano, S(O)2(C1-4alkyl); in indicated positions where phenyl or naphtyl ring in R3 can be optionally substituted, it can be optionally substituted by halogen, cyano, C1-4alkyl, C1-4alkoxy, C1-4fluoroalkyl, OCF3, SCF3, nitro, S(C1-4alkyl), S(O)(C1-4alkyl), S(O)2(C1-4alkyl), S(O)2NH(C1-4alkyl), S(O)2N(C1-4alkyl)2, NHC(O)(C1-4alkyl) or NHS(O)2(C1-4alkyl); or its pharmaceutically acceptable salts. Also invention concerns compounds of formula (I), method of obtaining compounds of any of claims 1-12, as well as pharmaceutical composition.

EFFECT: obtaining novel bioactive compounds with chemokine receptor activity modulation effect.

16 cl, 51 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

where R1represents phenyl, possibly substituted with halogen, cyano, C1-4the alkyl or C1-4halogenoalkanes;

R2represents hydrogen, C1-6alkyl or C3-6cycloalkyl and

R3is a group with NH or HE, which has a calculated or measured pKa of 1.0 to 8.0, chosen from:

2-oxadiazol-5-yl having From1-4foralkyl, possibly substituted phenyl group, possibly substituted heterocyclyl group or the group CH2S(O)2C1-4alkyl) position 4;

2-oxohexanoyl-5-yl having From1-4foralkyl or CH2S(O)2(C1-4alkyl) position 4;

1H-1,2,3-triazole-4-yl, a1-4alkyl, C3-6cycloalkyl,1-4foralkyl, S-R4(where R4represents a C1-4alkyl, C1-4foralkyl or3-6cycloalkyl), NHS(O)2(C1-4alkyl), N(C1-4alkyl)S(O)2(C1-4alkyl), phenyl group, heterocyclyl group or the group CH2S(O)2(C1-4alkyl) at position 5;

4-oxo-1H-1,4-dihydropyridines-3-yl, With1-4foralkyl position 2;

2,6-dioxo-1H-1,2,3,6-tetrahydropyrimidin-4-yl, a1-4alkyl, C3-6cycloalkyl or CH2(C1-3foralkyl) position 3 and possibly substituted by one who does more than the other positions of the ring;

6-oxo-1H-1,6-dihydropyridines-3-yl, With1-4foralkyl, cyano or phenyl at position 2 and/or position 5 and possibly substituted by one or more other positions of the ring;

6-oxo-1H-1,6-dihydropyridines-3-yl having the CH2CO2N on the ring nitrogen atom and possibly substituted by one or more other positions of the ring;

2H-tetrazol-5-yl;

group CO2N, CH2CO2H or OCH2CO2N may be a substituted phenyl, possibly substituted CH2Finalnum, possibly substituted naftalina ring or possibly substituted acylated dihydroisoquinoline ring; or

group NHS(O)2(C1-4alkyl) may be substituted by an aromatic heterocyclic ring;

or, where possible, their tautomer;

where the above-indicated that heterocyclyl ring in R3may be substituted, it may be replaced with fluorescent, chloro, bromo, With1-4the alkyl, C3-6cycloalkyl,1-4perakyla, S-R4(where R4represents a C1-4alkyl, C1-4foralkyl or3-6cycloalkyl), cyano, S(O)2(C1-4alkyl) or S(O)2NH(C1-4alkyl);

where mentioned, which phenyl or naphtalene ring in R3may be substituted, it may be possible C is maseno halogen, cyano, C1-4the alkyl, C1-4alkoxy, C1-4perakyla, OCF3SCF3, nitro, S(C1-4alkyl), S(O)(C1-4alkyl), S(O)2(C1-4alkyl), S(O)2NH(C1-4alkyl), S(O)2N(C1-4alkyl)2, NHC(O)(C1-4alkyl) or NHS(O)2(C1-4alkyl);

or its pharmaceutically acceptable salt.

2. The compound of formula (I) according to claim 1, where R1represents phenyl substituted one, two or three of halogen, cyano, or C1-4the alkyl.

3. The compound of formula (I) according to claim 1 or 2, where R1represents phenyl, substituted by one or more chloro or stands and may additionally substituted with fluorescent.

4. The compound of formula (I) according to claim 1 or 2, where R1represents 3,4-dichlorophenyl, 2-methyl-4-chlorophenyl, 3-methyl-2,4-dichlorophenyl, 2-methyl-3,4-dichlorophenyl or 2-methyl-3-chloro-4-cyanophenyl.

5. The compound of formula (I) according to claim 1, where R2represents hydrogen.

6. The compound of formula (I) according to claim 1, where R3has heterocyclyl ring, which represents furyl, thienyl, pyrrolyl, 2,5-dihydropyrrole, thiazolyl, 2-oxo-2,3-dihydro-1,3-thiazolyl, isothiazolin, pyrazolyl, oxazolyl, isoxazolyl, imidazolyl, triazolyl, pyridinyl or pyrimidinyl.

7. The compound of formula (I) according to claim 1, where R3has heterocyclyl ring, which may be substituted with fluorescent, chloro, bromo is, With1-4the alkyl, C3-6cycloalkyl,1-4perakyla, S-R4(where R4represents a C1-4alkyl, C1-4foralkyl or3-6cycloalkyl), cyano, S(O)2(C1-4alkyl) or S(O)2NH(C1-4alkyl).

8. The compound of formula (I) according to claim 1, where R3represents:

2-oxohexanoyl-5-yl having From1-4foralkyl, phenyl group or heterocyclyl group on position 4, where phenyl and heterocyclyl ring possibly substituted, as set forth in claim 1;

1H-1,2,3-triazole-4-yl, a1-4alkyl, C1-4foralkyl, S-R4(where R4represents a C1-4alkyl or C1-4foralkyl), N(C1-4alkyl)S(O)2(C1-4alkyl) or phenyl group at position 5; or

6-oxo-1H-1,6-dihydropyridines-3-yl, With1-4foralkyl or cyano position 2 or position 5.

9. The compound of formula (I) according to claim 1, where R3represents:

2-oxadiazol-5-yl having CF3or C2F5position 4;

1H-1,2,3-triazole-4-yl having CF3C2F5SCF3, SCH2CF3or SC2F5no regulation 5; or

6-oxo-1H-1,6-dihydropyridines-3-yl having CF3or C2F5position 2.

10. The compound of formula (I) according to claim 9, where R3represents a 2-oxo-thiazol-5-yl having CF 3or C2F5in position 4, or its pharmaceutically acceptable salt.

11. The compound of formula (I) according to claim 1, where 2-hydroxy-group has the stereochemistry shown below:

12. The compound of formula (I), which represents:

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-6-oxo-2-(trifluoromethyl)-1,6-dihydropyridines-3-carboxamide;

N-{(2R)-3-[4-(2,4-Dichloro-3-methylphenoxy)piperidine-1-yl]-2-hydroxypropyl}-6-oxo-2-(trifluoromethyl)-1,6-dihydropyridines-3-carboxamide;

5-Bromo-N-{(2R)-3-[4-(3,4-dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-6-oxo-2-(trifluoromethyl)-1,6-dihydropyridines-3-carboxamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-2,3-dihydro-2-oxo-4-(trifluoromethyl)-5-thiazolecarboxamide;

N-{(2S)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-N-methyl-2-oxo-4-(trifluoromethyl)-2,3-dihydro-1,3-thiazole-5-carboxamide;

N-{(2S)-3-[4-(2,4-Dichloro-3-methylphenoxy)piperidine-1-yl]-2-hydroxypropyl}-N-methyl-2-oxo-4-(trifluoromethyl)-2,3-dihydro-1,3-thiazole-5-carboxamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-2-oxo-4-(pentafluoroethyl)-2,3-dihydro-1,3-thiazole-5-carboxamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-5-methyl-1H-1,2,3-triazole-4-carboxamide;

N-{(2R)-3-[4-(2,4-Dichloro-3-methylphenoxy)piperidine-1-yl]-2-g is droxidopa}-5-methyl-1H-1,2,3-triazole-4-carboxamide;

5-Cyano-N-{(2R)-3-[4-(3,4-dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-6-oxo-2-(trifluoromethyl)-1,6-dihydropyridines-3-carboxamide;

5-Cyano-N-{(2R)-3-[4-(2,4-dichloro-3-methylphenoxy)piperidine-1-yl]-2-hydroxypropyl}-6-oxo-2-(trifluoromethyl)-1,6-dihydropyridines-3-carboxamide;

5-Cyano-N-{(2R)-3-[4-(3,4-dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-6-oxo-2-phenyl-1,6-dihydropyridines-3-carboxamide;

5-Cyano-N-{(2R)-3-[4-(2,4-dichloro-3-methylphenoxy)piperidine-1-yl]-2-hydroxypropyl}-6-oxo-2-phenyl-1,6-dihydropyridines-3-carboxamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-3-methyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-carboxamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-2,6-dioxo-3-(2,2,2-triptorelin)-1,2,3,6-tetrahydropyrimidin-4-carboxamide;

5-Cyano-2-cyclopropyl-N-[(2R)-3-[4-(3,4-dichlorophenoxy)-1-piperidinyl]-2-hydroxypropyl]-1,6-dihydro-6-oxo-3-pyridinecarboxamide;

5-Cyano-2-cyclopropyl-N-[(2R)-3-[4-(2,4-dichloro-Z-methylphenoxy)-1-piperidinyl]-2-hydroxypropyl]-1,6-dihydro-6-oxo-3-pyridinecarboxamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-6-[(methylsulphonyl)amino]-4-(trifluoromethyl)nicotinamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-5-[(2,2,2-triptorelin)thio]-1H-1,2,3-triazole-4-carboxamide;

4-[({(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydro is sapropel}-amino)-carbonyl]-1-naphthoic acid;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-2-[(methylsulphonyl)amino]-4-(trifluoromethyl)-1,3-thiazole-5-carboxamide;

N-{(2R)-3-[4-(4-Chloro-2-methylphenoxy)piperidine-1-yl]-2-hydroxypropyl}-2-oxo-4-(trifluoromethyl)-2,3-dihydro-1,3-thiazole-5-carboxamide;

[5-[({(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}amino)carbonyl]-2-oxo-4-(trifluoromethyl)pyridine-1(2H)-yl]acetic acid;

N-{(2R)-3-[4-(3,4-Dichloro-2-methylphenoxy)piperidine-1-yl]-2-hydroxypropyl}-2-oxo-4-(trifluoromethyl)-2,3-dihydro-1,3-thiazole-5-carboxamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-4-(4-forfinal)-2-oxo-2,3-dihydro-1,3-thiazole-5-carboxamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-5-(4-forfinal)-1H-1,2,3-triazole-4-carboxamide;

N-{(2R)-3-[4-(3-Chloro-4-cianfrocca)piperidine-1-yl]-2-hydroxypropyl}-2-oxo-4-(trifluoromethyl)-2,3-dihydro-1,3-thiazole-5-carboxamide;

N-{(2S)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-2-oxo-4-(trifluoromethyl)-2,3-dihydro-1,3-thiazole-5-carboxamide;

N-{(2S)-3-[4-(3-Chloro-4-cianfrocca)piperidine-1-yl]-2-hydroxypropyl}-N-methyl-2-oxo-4-(trifluoromethyl)-2,3-dihydro-1,3-thiazole-5-carboxamide;

N-{(2R)-3-[4-(2,4-Dichloro-3-methylphenoxy)piperidine-1-yl]-2-hydroxypropyl}-2-oxo-4-(trifluoromethyl)-2,3-dihydro-1,3-thiazole-5-carboxamide;

N-{(2R)-3-[4-(3-Chloro-4-cianfrocca)piperidine-1-yl]-hydroxypropyl}-5-isopropyl-1H-1,2,3-triazole-4-carboxamide;

N-{(2S)-3-[4-(3-Chloro-4-cianfrocca)piperidine-1-yl]-2-hydroxypropyl}-5-isopropyl-N-methyl-1H-1,2,3-triazole-4-carboxamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-2-oxo-4-(2,2,2-triptorelin)-2,3-dihydro-1,3-thiazole-5-carboxamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-2-oxo-4-pyridin-2-yl-2,3-dihydro-1,3-thiazole-5-carboxamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-6-oxo-2-(pentafluoroethyl)-1,6-dihydropyridines-3-carboxamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-5-(methylthio)-1H-1,2,3-triazole-4-carboxamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-2-oxo-4-(trifluoromethyl)-2,3-dihydro-1,3-oxazol-5-carboxamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-5-(trifluoromethyl)-1H-1,2,3-triazole-4-carboxamide;

N-{(2R)-3-[4-(3,4-Dichlorophenoxy)piperidine-1-yl]-2-hydroxypropyl}-5-[methyl(methylsulphonyl)amino]-1H-1,2,3-triazole-4-carboxamide;

N-{(2R)-3-[4-(3-Chloro-4-cyano-2-methylphenoxy)piperidine-1-yl]-2-hydroxypropyl}-2-oxo-4-(trifluoromethyl)-2,3-dihydro-1,3-thiazole-5-carboxamide;

N-{(2R)-3-[4-(3-Chloro-4-cianfrocca)piperidine-1-yl]-2-hydroxypropyl}-5-(trifluoromethyl)-1H-1,2,3-triazole-4-carboxamide;

2-Chloro-5-[({(2R)-3-[4-(3,4-dichloro-2-methylphenoxy)piperidine-1-yl]-2-hydroxypropyl}amino)carbonyl]benzoic acid;

4-Chloro-3-[2-({(2R)-3-[4-(3,4-dichloro-2-methylphenoxy)piperidine-1-yl]-2-hydroxypropyl}amino)-2-oksidoksi]benzoic acid;

{2-Chloro-5-[({(2R)-3-[4-(3,4-dichloro-2-methylphenoxy)piperidine-1-yl]-2-hydroxypropyl}amino)carbonyl]phenoxy}acetic acid;

3-[2-({(2R)-3-[4-(3,4-Dichloro-2-methylphenoxy)piperidine-1-yl]-2-hydroxypropyl}amino)-2-oksidoksi]benzoic acid, or

{3-[({(2R)-3-[4-(3,4-Dichloro-2-methylphenoxy)piperidine-1-yl]-2-hydroxypropyl}amino)carbonyl]phenoxy}acetic acid;

or its pharmaceutically acceptable salt.

13. A method of obtaining a compound according to any one of claims 1 to 12, including the interaction of the compounds of formula (II)

where R1and R2are as defined in claim 1,

with the compound of the formula (III)

where L1represents a leaving group, and R3is such as defined in claim 1,

in the presence of a base, possibly in the presence of the agent combinations.

14. Pharmaceutical composition having activity as a modulator of the activity of chemokine receptors (CCR)containing the compound of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 12 and a pharmaceutically acceptable adjuvant, diluent or carrier for him.

15. The compound of formula (a) or its pharmaceutically acceptable salt according to any one of claims 1 to 12 for use in the treatment of painful conditions, mediated by receptor CCR3.

16. The compound of formula (I) or its pharmaceutically acceptable salt according to any claims 1 to 12 for the manufacture of a medicinal product for use in the treatment of painful conditions, mediated by receptor CCR3.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention claims derivatives of pyridazin-3(2H)-one of formula (I), where R1, R2 and R4 are organic radicals described in the claim 1, R3 is cyclic group described in the claim, and R5 is phenyl or heteroaryl group described in the claim. Compounds of formula (I) inhibit phosphodiesterase 4 (PDE-4) and can be applied in treatment of various diseases or pathological states alleviated by PDE-4 inhibition, and in medicine production for treatment of aforesaid diseases. Also invention claims method of obtaining these compounds and intermediate compounds for their obtainment.

EFFECT: obtaining compounds which can be used in treatment of various diseases or pathological states and in medicine production for treatment of aforesaid diseases.

25 cl, 28 tbl, 243 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to new compounds with formula I: , where L represents radical , in which R1 represents H, C1-4alkyl; n represents 0 or 1; or L represents radical , in which R1 represents H, C1-4alkyl; m equals 1; R represents H, halogen, C1-C4alkyl or C1-C4-alkoxy; Z represents a bond, -C(O)NH-, O or S; p is an integer from 1 to 5; Q represents a bond with the condition that, Z is not a bond, when p equals 1; or represents O, S or -C(O)NR6-, where R6 represents H, C1-4alkyl or C3-6cycloalkyl; or W and R6 together with a nitrogen atom, to which they are bonded, form or or Q represents -NR6-, or in the condition that, p is not equal to 1; W represents , , , , ,

, , ,

, , ,

, , , ,

, , , ,

, , , ,

, , , , ,

, , , , , and

.

EFFECT: obtaining compounds with agonistic activity towards PPAR receptors, which enables them to be used in pharmaceutical compositions and methods of treating conditions, mediated by these receptors.

12 cl, 7 ex

FIELD: chemistry, pharmaceutics.

SUBSTANCE: invention relates to compounds of formula 1 and their pharmaceutically acceptable salts as inhibitors of post-proline aminopepdidases, as well as to pharmaceutical composition based on them and application for manufacturing such composition, and to method of inhibition with their application. Compounds can be applied for treatment of diseases mediated by activity of post-proline aminopeptidases, such as type II diabetes and disturbed tolerance to glucose. In general formula 1 ,

either G1 represents -CH2-X2-(CH2)a-G3, and G2 represents H, or G2 represents -CH2-(CH2)a-G3, and G1 represents H; G3 is selected from group according to general formula 2 ,

group according to general formula 3

and group according to general formula 4 ;

a is 0, 1 or 2; b is 1 or 2; X1 is selected from CH2, S, CF2, CHF and O; X2 is selected from CH2; X3, X4 and X5 are selected from N; X6 is selected from NH; X7 is selected from NH; R1 is selected from H and CN; R2 represents H; R3 is selected from H, Cl, OH, NH2, NH-C1-C10alkyl and N(C1-C10alkyl)2; R4, R5, R6, R7 and R8 are independently selected from H, Br, Cl, F, OH, NO2; R9 represents H; R10, R11, R12, R13 and R14 are independently selected from H, Cl and CF3; R15 and R16 are independently selected from H, C1-C10alkyl, C1-C10alkenyl, C3-C10cycloalkyl, C3-C10cycloalkenyl, quinoline, naphtyl and -CH2-L-R17; R17 is selected from C1-C10alkyl, phenyl, naphtyl, quinolinyl and indolyl; L is selected from covalent bond, CH=CH and -C6H4-; on condition that when R15 and R16 both represent H, and b is 1, then X1 does not represent S or CH2.

EFFECT: obtaining compounds that can be applied for treatment of diseases mediated by activity of post-proline aminopeptidases, such as type II diabetes and disturbed tolerance to glucose.

58 cl, 10 tbl, 1705 ex

FIELD: chemistry.

SUBSTANCE: this invention refers to compounds of formula where one of R6, R7 or R8 means , and X, Y, substitutes of R1-R13 and n are as it is defined in item 1 of formula of invention, and to all their enantiomers, to pharmaceutically acceptable salts and/or esters.

EFFECT: production of compounds for treatment and/or prevention of diseases modulated by PPARδ and/or PPARα agonists.

26 cl, 1 tbl, 35 ex

FIELD: chemistry, pharmacology.

SUBSTANCE: claimed invention relates to methods of obtaining rosiglytasone, rosiglytasone, obtained by said methods, and its pharmacological compositions and methods of treatment using it.

EFFECT: obtaining of new crystalline modifications of rosiglytasone, which have useful biological properties.

58 cl, 4 dwg, 2 tbl, 9 ex

FIELD: chemistry, pharmacology.

SUBSTANCE: invention relates to novel compounds of formula (I), its pharmaceutically acceptable salts, possessing qualities of chemokine receptor modulators. Compounds can be applied for asthma, allergic rhinitis, COLD, inflammatory intestinal disease, irritated intestine syndrome, osteoarthritis, osteoporosis, rheumatoid arthritis, psoriasis or cancer. In compound of formula (I) , R1 represents group selected from C1-8alkyl, said group is possibly substituted with 1, 2 or 3 substituents, independently selected from -OR4 , -NR5R6 , phenyl, phenyl is possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4,-NR5R6,-SR10,C1-6alkyl and trifluoromethyl; R2 represents group selected from C1-8alkyl, said group is substituted with 1, 2 or 3 substituents, independently selected from hydroxy, amino, C1-6alkoxy, C1-6alkylamino, di(C1-6alkyl)amino, N-(C1-6alkyl)-N-(phenyl)amino; R3 represents hydrogen, R4 represents hydrogen or group selected from C1-6alkyl and phenyl, R5 and R6, independently, represent hydrogen or group selected from C1-6alkyl and phenyl, said group being probably substituted with 1, 2 or 3 substituents, independently selected from -OR14, -NR15R16, -COOR14,-CONR15R16, or R5 and R6 together with nitrogen atom, to which they are bound, form 4-7-member saturated heterocyclic ring system, possibly containing additional heteroatom, selected from oxygen and nitrogen atoms, ring possibly being substituted with 1, 2 or 3 substituents, independently selected from -OR14, -COOR14,-NR15R16,CONR15R16 and C1-6alkyl; R10 represents hydrogen or group selected from C1-6alkyl or phenyl; and each from R7, R8, R9, R14, R15, R16 independently represents hydrogen, C1-6alkyl or phenyl; X represents hydrogen, halogeno; Rx represents trifluoromethyl, -NR5 R6 , phenyl, naphtyl, heteroaryl, heteroring can be partly or fully saturated, and one or more ring carbon atoms can form carbonyl group, each phenyl or heteroaryl group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, cyano, -OR4, -NR5R6, -CONR5R6, -COR7, -COOR7, -NR8COR9, -SR10, -SO2R10, -SO2NR5R6, -NR8SO2R9, C1-6alkyl or trifluoromethyl; or Rx represents group selected from C1-6alkyl, said group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4, -NR5R6, phenyl or heteroaryl, where heteroaryl represents monocyclic or bicyclic aryl ring, containing from 5 to 10 ring atoms, from which 1, 2 or 3 ring atoms are selected from nitrogen, sulfur or oxygen. Invention also relates to methods of obtaining compounds, versions, pharmaceutical composition and application for manufacturing medications using compounds of invention.

EFFECT: obtaining novel compounds of formula (I), its pharmaceutically acceptable salts, possessing properties of chemokine receptor moduators.

25 cl, 138 ex

FIELD: chemistry.

SUBSTANCE: in novel compounds of formula (I) HetAr represents pyrimidinyl or thiadiasolyl; R1 and R2 represent H; A represents C1-C2-alkyl; B represents aryl(CH2)0-3-O-C(O)-or arylcyclopropyl-C(O)-, in which aryl can be substituted with 1-5 substituents, each substituent represents C1-C4-alkyl. Invention also relates to pharmaceutical composition and to application of compounds of item 1. Obtaining novel compounds, as well as pharmaceutical composition possessing NMDA/NR2B antagonist activity.

EFFECT: increase of composition efficiency.

13 cl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to new compounds with general formula: , where R is -(CH2)n-A, where A: where each of B and C independently represent phenyl or phenyl substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, -OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NH-C(O)-(C1-C6alkyl) and -NO2; or n equals an integer from 0 to 3; n1 equals an integer from 1 to 3; n2 equals an integer from 0 to 4; n3 equals an integer from 0 to 3; n4 equals an integer from 0 to 2; X1 is chosen from a chemical bond -S-, -S(O)2-, -NH-, -NHC(O)- and -C=C-, R1 is chosen from C1-C6alkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, tetrahydropyranyl, CN, -N(C1-C6alkyl)2, phenyl, pyridinyl, pyrimidinyl, furyl, thienyl, naphtyl, morpholinyl, triazolyl, pyrazolyl, piperidinyl, pyrrolidinyl, imidazolyl, piperizinyl, thiazolydinyl, thiomopholinyl, tetrazolyl, benzoxazolyl, imidazolidine-2-thionyl, 7,7-dimethylbicyclo[2.2.1]heptane-2-onyl, benzo[1.2.5]oxadiazolyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and pyrrolyl, each of which can be optionally substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NO2, -SO2(C1-C3alkyl), -SO2NH2, -SO2N(C1-C3alkyl)2, -COOH, -CH2-COOH, pyridyl, 2-methylazolyl, morpholino, 1-chloro-2-methylpropyl, phenyl, (optionally substituted with one or more halogens), benzyloxy, and , X2 selected from -O-, -CH2-, -S-, -SO-, -SO2-, -NH- and , R2 represents a ring group, chosen from a phenyl or thienyl group. Each ring group is substituted with a group with formula -(CH2)n4-CO2H; and besides that, the ring group can optionally be substituted with 1 or 2 extra substitutes, independently chosen from halogen, - C1-C6alkyl and -C1-C6alkoxy; R3 is chosen from H, halogen and -NO2; R4 is chosen from H, halogen and morpholino; or its salt form, used in pharmaceuticals. The invention also relates to pharmaceutical compositions, to methods of treatment, and to compounds with formula (A).

EFFECT: obtaining new biologically active compounds and pharmaceutical compositions based on them, which have inhibiting effect on cytosolic phospholipase A2.

45 cl, 300 ex

FIELD: medicine; pharmacology.

SUBSTANCE: subjects of invention are also pharmaceutical drugs or agents for prophylaxis and treatment of neuropathy, increase of production and treatment of the neurotrophic factor, for pain relief, for nerve protection, for prophylaxis and treatment of the neuropathic pain containing compound of the formula or of the formula . In the compounds of the formulas (I) and (II) symbols and radicals have the meanings mentioned in the invention formula. The specified agents have an excellent effect and low toxicity. There are also proposed ways of treatment and prophylaxis of the abovementioned conditions by means of the compounds of the formula (I) or (II) and application of these compounds for production of the abovementioned agents. Besides, one has proposed methods for production of the specified compounds and intermediate pyrazol compounds.

EFFECT: compound has an effect increasing production and secretion of the neurotrophic factor.

46 cl, 1 tbl, 233 ex

Carbonyl compounds // 2337099

FIELD: chemistry, pharmacology.

SUBSTANCE: claimed invention relates to novel compounds of general formula(I) , where D represents phenyl, pyridyl or tienyl, each of which is single-substituted or double-substituted with Hal; R1 represents H, =O, COOR3, OH, OA, NH2, alkyl, which has 1, 2, 3, 4, 5 or 6 carbon atoms, N3, ethinyl, vinyl, allyloxy, -OCOR3, NHCOA or NHSO2A; R2 represents H, =O, OH, OA or alkyl, which has 1, 2, 3, 4, 5 or 6 carbon atoms; R1 and R2 together alternatively represent spirocyclically linked 3-6-member carbocyclic ring, R3 represents H or A, R4 represents H or A; represents pyrrolidine-1,2-diyl, piperidine-1,2-diyl, oxazolidine-3,4 or 3,5-diyl, thiazolidine-3,4-diyl, 2,5-dihydro-1H-pyrrol-1,5-diyl, 1,3-dioxolane-4,5-diyl; G represents (CH2)n or (CH2)nNH-; X represents CONH; Y represents 1,3- or 1,4-phenylene, which is not substituted or is single-substituted with methyl, trifluoromethyl, ethyl, propyl, Cl or F; T represents morpholine-4-yl, which is single-substituted or double-substituted with carbonyl oxygen; A represents non-branched or branched alkyl, which has 1-10 carbon atoms and in which 1-7 hydrogen atoms can be substituted with F; Hal represents F, CI, Br or I, n represents 0, 1 or 2; and their pharmaceutically acceptable derivatives, solvates, salts or sterioisomers, including their mixtures in all ratios. Invention also relates to method of obtaining formula I compounds, to medication based on formula I compound and application of formula I compounds for preparation of medication, which has inhibiting activity with respect to coagulation factors Xa and VIla.

EFFECT: obtained novel compounds have inhibiting activity with respect to said coagulation factors.

11 cl, 1 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to compounds with formula (I) in which radicals and symbols assume values, defined in paragraph of the formula of invention. Formula (I) compounds have affinity to bonding with serotonin 5-HT6 receptor and can be used in therapeutic treatment of disorders, related to the 5-HT6 receptor or mediated by them.

EFFECT: design of a method of treating central nervous system disorders.

17 cl, 5 tbl, 128 ex

FIELD: chemistry.

SUBSTANCE: invention claims derivatives of pyridazin-3(2H)-one of formula (I), where R1, R2 and R4 are organic radicals described in the claim 1, R3 is cyclic group described in the claim, and R5 is phenyl or heteroaryl group described in the claim. Compounds of formula (I) inhibit phosphodiesterase 4 (PDE-4) and can be applied in treatment of various diseases or pathological states alleviated by PDE-4 inhibition, and in medicine production for treatment of aforesaid diseases. Also invention claims method of obtaining these compounds and intermediate compounds for their obtainment.

EFFECT: obtaining compounds which can be used in treatment of various diseases or pathological states and in medicine production for treatment of aforesaid diseases.

25 cl, 28 tbl, 243 ex

FIELD: chemistry.

SUBSTANCE: invention concerns method of obtaining heterocycles of formula I , where X, A, R10-R17 are as defined in point 1 of the claim, while a) isothiocyanate of formula II is transformed into thiourea of formula IV by interaction with primary amine of formula III, and b) thiourea of formula IV is transformed into compound of formula I by interaction with sulfochloride R6SO2Cl in the presence of a base, where A, X, n, m and R10 to R17 in compounds of formulae II, III and IV are as defined in formula I, and R6 is (C1-C4)-alkyl, trifluoromethyl or phenyl non-sustituted or substituted by methyl, trifluoromethyl, F, CI, Br or polymer carreir. The transportation is shown by combination formulae

EFFECT: new multipurpose synthesis technique for heterocyclic compounds of the general formula I.

8 cl, 31 ex

FIELD: chemistry, pharmaceutics.

SUBSTANCE: claimed invention relates to application of indazole derivatives of general formula (I) , in which: R stands for O; R3 stands for radical (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkinyl, said radicals being unsubstituted or substituted with one or several substitutes, given in item 1 of the formula; R4, R5, R6 and R7, independently on each other are selected from following radicals; hydrogen atom, halogen, CN, NO2, NH2, NHSO2R9, trifluoromethyl, trifluoromethoxygroup, (C1-C6)-alkyl, phenyl, phenyl-(C1-C6)-alkyl, pyridyl, possibly substituted with amino or hydroxygroup, thienyl, furanyl, morpholino, phenyl being unsubstituted or substituted with one or several substitutes, given in item 1 of the formula; R8, R9, R10, R11, independently on each other, stand for hydrogen atom, (C1-C6)-alkyl, phenyl possibly substituted with halogen; their racemates, enantiomers, diastereoisomers and their mixtures, their tautomers and their pharmaceutically acceptable salts for obtaining medication, inhibiting phosphorylation of Tau-protein. Invention also relates to novel compounds of formula (I), particular indazole derivatives, their racemates, enantiomers, tautomers and pharmaceutically acceptable salts, pharmaceutical composition and based on them medication which inhibits Tau-protein phosphorylation, as well as to method of obtaining compounds of formula (I).

EFFECT: obtaining medication based on indazole derivatives, inhibiting Tau-protein phosphorylation.

9 cl, 118 ex, 3 ex

FIELD: chemistry, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of general formula I , in which stands for thiophendiyl, phenylene or pyridindiyl; R1 represents alkyl, alkenyl, alkinyl, which optionally contain one or several substitutes, selected from group including halogen, cyano-, nitro- amino group, -NH-alkyl and N(alkyl)2; or -CH2-(O-CH2-CH2-)mO-alkyl; -(CH2)n-O-alkyl; -(CH2)n-C(O)-NH-alkyl; -(CH2)n-NH-C(O)-alkyl; -(CH2)n-C(O)alkyl; -(CH2)n-C(O)-O-alkyl; or -(CH2)n-O-C(O)-alkyl; or group -NR3R4, in which R3 and R4 independently represent hydrogen; alkyl, alkenyl or alkinyl, which optionally contain one or several substitutes, selected from group including halogen, cyano-, nitro- amino group, -NH-alkyl and N(alkyl) 2; or -CH2-(O-CH2-CH2-)mO-alkyl; -(CH2)n-(O)-alkyl; -(CH2)n-C(O)-NH-alkyl; -(CH2)n-NH-C(O)-alkyl; -(CH2)n-C(O)alkyl; -(CH2)n-C(O)-O-alkyl; or -(CH2)n-O-C(O)-alkyl; n is 1-6; m is 1-4; and to its pharmaceutically acceptable salts. Invention also relates to medication.

EFFECT: obtaining novel biologically active compounds, intended for inhibition tumor cell proliferation.

25 cl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns to new diamides of pyrimidine-4,6-dicarboxylic acid of I formula, selective inhibitors of collagenases possessing properties which concern to the metalloproteinase superfamily and the matrix metalloproteinases. The bonds render influence on hyperactivity of the matrix metalloproteinase-13 (MMP-13) and thus do not render influence on MMP-3 and MMP-8. In the formula I R1 means an atom of hydrogen, R2 means - (C1-C6)-alkyl where alkyl is unitary replaced by phenyl where phenyl is replaced 1) -(C0-C6)-alkyl-C(O)-N(R9)-(R10), where R9 and R10 identical or different and independently from each other mean i) atom of hydrogen or ii) - (C1-C6)-alkyl or R9 and R10 together with atom of nitrogen to which they are bound, form 5, 6-links the sated cycle, and instead of one or two other atoms of carbon there can be also a heteroatom from an oxygen row, sulphur and nitrogen, and in case of nitrogen atoms of nitrogen independently from each other can be unsubstituted or substituted with (C1-C6)-alkyl, 2) -(C0-C6)-alkyl-C(O)-NH-SN, 3) -O-(C0-C6)-alkyl-C(O)-N(R9)-(R10) where R9 and R10 have the specified above value, 4) -(C0-C6)-alkyl-C(O)-N (R8)-(C0-C6)-alkyl-N(R9)-(R10) where R8 means hydrogen, R9 and R10 have the specified above value, 5) -(C0-C6)-alkyl-C(O)-N(R8)-(C0-C6)-alkyl-Het, and R8 has the specified above value, and Het means the sated or nonsaturated monocyclic heterocyclic system with number of links from 3 to 6 which contains in a cycle of 1 or 2 identical or different heteroatoms from a number nitrogen, oxygen and sulphur and unsubstituted or one-, two- or triple independently from each other is replaced by halogen, b) hydroxy,) -(C1-C6)-alkyl, and alkyl is unsubstituted or one-, two- or triple is substituted by halogen, d)=0,e)-Het, R4 and R5 or R5 and R6 together with atom of Carboneum to which they are bound, independently from each other form 5 or 6-unit cycle which is sated and contains one or two heteroatoms from an oxygen row.

EFFECT: obtaining of bonds which can find application for treatment of degenerate diseases of joints, such as osteoarthritis, rheumatic disease.

7 cl, 3 tbl, 117 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention concerns to 3,4-disubstituted tsiklobuten-1,2-diones of the formula I or their pharmaceutically to comprehensible salts or solvates, . A is chosen from the group including

X=-O-, -NH-, -S-,

.

n=1-5

B is chosen from the group including

. The bonds can be used at treatment of mediated chemokine diseases, such as acute both chronic inflammatory diseases and a cancer. The pharmaceutical composition and application of bonds I are also described.

EFFECT: obtaining of bonds which can be used at treatment of mediated chemokine diseases, such as acute both chronic inflammatory diseases and cancer.

50 cl, 31 ex

FIELD: chemistry.

SUBSTANCE: compound of formula I , its diastereomers or salts, where dot line represents optional double bond, m and p independently stand for 0, 1, 2 or 3; R1 stands for H, -N(R8)-C(O)-NR6R7, -N(R8)-S(O)2-NR6R7, -N(R8)-C(O)-N(R8a)-S(O)2-NR6R7, etc.; R1a stands for H or group OH; or R1 or R1a together form oxo; or R1 and R1a together with carbon atom, to which they are bound, form optionally substituted oxo spiro-condensed heterocyclic group, representing fully saturated 5-member monocyclic group, containing 2 nitrogen atoms; R2 stands for heteroaryl, (heteroary)alkyl, representing 5-6-member aromatic ring, contaning 1 nitrogen atom and/or 1 atom of oxygen and/or sulphur, and optionally condensed with aryl ring; aryl, (aryl)alkyl, alkyl, alkenyl or cycloalkyl, representing partly or fully saturated C3-C6 monocyclic structure, any of which can be optionally, independently, substituted with one or more groups T1, T2 or T3; J stands for bond, C1-4 alkylene, R3 stands for -R5, -C(Z1)-R5, -N(R8a1)-C(Z1)-R5, -N(R8a1)-C(Z1)-O-R5, -N(R8a1)-S(O)2-R5; R4 stands for alkyl, halogenalkyl, cycloalkyl, aryl, which can be optionally condensed with heteroaryl 6-member ring, containing 1-2 heteroatoms, selected from group SO2, N, etc.; R5 stands for -NR6aR7a or heteroaryl, (heteroaryl)alkyl, representing 5-6-member aromatic ring, which contains 1-3 nitrogen atoms and/or 1 or 2 atoms of oxygen or sulphur, optionally condensed with heteroaryl ring, representing 6-member aromatic ring, containing 1 nitrogen atom, etc.; R6a, R7a independently represent H, alkyl, aryl, (aryl)alkyl, heteroaryl, representing 5-6-member aromatic ring, which contains 1-2 nitrogen atoms, optionally condensed with aryl or heteroaryl ring, representing 6-member aromatic ring with 1 nitrogen atom; any of which can be optionally, independently, substituted with one or more groups T1c, T2c or T3c; R6, R7, R8, R8a, R8a1 R8a2, and R9, independently, represent H, alkyl, hydroxy, alkoxy, (hydroxy)alkyl, (alkoxy)alkyl, (cyano)alkyl, (alkenyl)alkyl, -NR12R13, cycloalkyl, (cycloalkyl)alkyl, optionally condensed with aryl; aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, etc.; R10, R10a, R11 and R11a, independently, represent H, alkyl, aryl, (aryl)alkyl, , hydroxy, (hydroxy)alkyl; heteroaryl, (heteroaryl)alkyl, representing 5-member aromatic ring, which contains 2 nitrogen atoms, or R11 and R11a can together form oxogroup, or R10a can together with R11a form bond, or R10 can together with R9 form saturated 3-4-member cycle; R12 and R13, independently, represent H, alkyl; W represents =NR8a2, =N- CO2R8a2, =N- CN; X represents C(=O), C=N-CN; Z1represents =O, or =N-CN; RX represents one optional substituent, bound with any suitable carbon atom in cycle, independently selected from T1g, T2g or T3g. Compounds of formula I are applied for manufacturing medication for treatment of IKur-mediated disorders.

EFFECT: cycloalkyl compounds, useful as inhibitors of potassium channels function.

13 cl, 694 ex, 1 tbl

FIELD: chemistry, pharmacology.

SUBSTANCE: invention relates to novel compounds of formula (I), its pharmaceutically acceptable salts, possessing qualities of chemokine receptor modulators. Compounds can be applied for asthma, allergic rhinitis, COLD, inflammatory intestinal disease, irritated intestine syndrome, osteoarthritis, osteoporosis, rheumatoid arthritis, psoriasis or cancer. In compound of formula (I) , R1 represents group selected from C1-8alkyl, said group is possibly substituted with 1, 2 or 3 substituents, independently selected from -OR4 , -NR5R6 , phenyl, phenyl is possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4,-NR5R6,-SR10,C1-6alkyl and trifluoromethyl; R2 represents group selected from C1-8alkyl, said group is substituted with 1, 2 or 3 substituents, independently selected from hydroxy, amino, C1-6alkoxy, C1-6alkylamino, di(C1-6alkyl)amino, N-(C1-6alkyl)-N-(phenyl)amino; R3 represents hydrogen, R4 represents hydrogen or group selected from C1-6alkyl and phenyl, R5 and R6, independently, represent hydrogen or group selected from C1-6alkyl and phenyl, said group being probably substituted with 1, 2 or 3 substituents, independently selected from -OR14, -NR15R16, -COOR14,-CONR15R16, or R5 and R6 together with nitrogen atom, to which they are bound, form 4-7-member saturated heterocyclic ring system, possibly containing additional heteroatom, selected from oxygen and nitrogen atoms, ring possibly being substituted with 1, 2 or 3 substituents, independently selected from -OR14, -COOR14,-NR15R16,CONR15R16 and C1-6alkyl; R10 represents hydrogen or group selected from C1-6alkyl or phenyl; and each from R7, R8, R9, R14, R15, R16 independently represents hydrogen, C1-6alkyl or phenyl; X represents hydrogen, halogeno; Rx represents trifluoromethyl, -NR5 R6 , phenyl, naphtyl, heteroaryl, heteroring can be partly or fully saturated, and one or more ring carbon atoms can form carbonyl group, each phenyl or heteroaryl group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, cyano, -OR4, -NR5R6, -CONR5R6, -COR7, -COOR7, -NR8COR9, -SR10, -SO2R10, -SO2NR5R6, -NR8SO2R9, C1-6alkyl or trifluoromethyl; or Rx represents group selected from C1-6alkyl, said group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4, -NR5R6, phenyl or heteroaryl, where heteroaryl represents monocyclic or bicyclic aryl ring, containing from 5 to 10 ring atoms, from which 1, 2 or 3 ring atoms are selected from nitrogen, sulfur or oxygen. Invention also relates to methods of obtaining compounds, versions, pharmaceutical composition and application for manufacturing medications using compounds of invention.

EFFECT: obtaining novel compounds of formula (I), its pharmaceutically acceptable salts, possessing properties of chemokine receptor moduators.

25 cl, 138 ex

FIELD: chemistry.

SUBSTANCE: in compound of general formula I or its pharmaceutically acceptable salts or N-oxides R1 stands for , R2 stands for R3 stands for C0-4alkyl.

EFFECT: possibility to use compounds in elaboration of anti-cancer pharmaceutical preparations.

11 cl, 1 tbl, 20 ex

FIELD: chemistry.

SUBSTANCE: description is given of a derivative of propane-1,3-dione with general formula (I) and its pharmaceutical salt, in which symbols denote the following: ring A: benzol, which can be substituted, pyridine, which can be substituted or a thiophene ring; ring B: benzene or thiophene ring; R1: H or -CO-inferior alkyl; R2: H, -O-R5, -N(R6)R7, -N3, -S(O)m-inferior alkyl, pyridyl or imidazole, which can be substituted; R3: H or inferior alkyl; X: a bond, inferior alkylene, which can be substituted, or cycloalkanediyl. Description is also given of propane-1,3-dione derivatives with formulae (Ia) and (Ib) and a pharmaceutical composition. The proposed compounds are useful as GnRH receptor antagonists, can be used in curing diseases, which depend on sex hormones, such as prostate cancer, breast cancer, endometriosis, uterine leiomyoma and non-malignant hypertrophy of the prostate gland.

EFFECT: obtaining compounds, useful for curing diseases, which depend on sex hormones, such as prostate cancer, breast cancer, endometriosis, uterine leiomyoma and non-malignant hypertrophy of the prostate gland.

10 cl, 26 tbl, 23 ex

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