1,1,1-trifluoro-2-hydroxy-3-phenylpropane derivatives

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I), where A is C-R1b; R1a, R1b, R1c, R1d, R1e, R2, R3, R4, R5 and n are as described in claim 1 of the invention, as well as pharmaceutically acceptable salts thereof. Described also is a pharmaceutical composition having activity as glucocorticoid receptor modulators.

EFFECT: novel compounds are obtained and described, which are glucocorticoid receptor antagonists and useful for treating and/or preventing diseases such as diabetes, dyslipidaemia, obesity, hyptension, cardiovascular diseases, adrenal gland malfunction or depression.

24 cl, 210 ex

 

The text descriptions are given in facsimile form.

1. Compounds of General formula:
,
where a represents C-R1b;
R1a, R , R1c, R1dand R1eindependently from each other selected from the group consisting of hydrogen, C1-7-alkyl, C3-7-cycloalkyl-C1-7-alkyl, halogen, halogen-C1-7-alkyl, halogen-C1-7-alkoxygroup, halogen-C1-7-alkylsulfonates, hydroxy-group, hydroxy-C1-7-alkyl, C1-7-alkoxygroup,1-7-alkoxy-C1-7-alkoxygroup, hydroxy-C1-7-alkoxygroup, amino-C1-7-alkoxygroup, ceanography, carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxygroup, C1-7-alkoxycarbonyl,1-7-alkoxycarbonyl-C1-7-alkoxygroup, C1-7-alkoxycarbonyl-C1-7-alkoxygroup,1-7-alkylcarboxylic-C1-7-alkoxygroup, aminocarbonyl-C1-7-alkoxygroup, di-C1-7-alkylamino, di-C2-7-alkenylamine, C1-7-alkylsulfonamides, phenylcarbonylamino, phenylsulfonylacetate, heteroaryl-C1-7-alkoxygroup, where heteroaryl ring selected from the group consisting of oxadiazolyl, isoxazolyl, thiadiazolyl and tetrazolyl, and is unsubstituted or substituted With1-7-alkyl, phenyloxy and phenyl-C1-7-alkoxygroup, and the indicated phenyl ring is unsubstituted or substituted one, two or three substituents, selected and from the group consisting of halogen, halogen-C1-7-alkyl, C1-7-alkyl, hydroxy-group, ceanography, C1-7-alkylsulfonyl, C1-7-alkoxygroup and halogen-C1-7-alkoxygroup;
or R1cand R1dor R1dand R1etogether are-CH=CH-CH=CH - with the formation of the phenyl ring together with carbon atoms to which they are attached;
R2selected from the group consisting of C1-7-alkyl, C3-7-cycloalkyl-C1-7-alkyl, carboxyl-C1-7-alkyl, C1-7-alkoxycarbonyl-C1-7-alkyl, triazolyl-C1-7-alkyl and phenyl, with the specified phenyl is unsubstituted or substituted one, two or three groups of halogen;
R3represents hydrogen or C1-7-alkyl;
or R2and R3together with the carbon atom to which they are attached, form a3-C5-cycloalkyl ring;
R4is a heteroaryl ring selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 2-oxo-1,2-dihydropyridine, chinoline, izochinolina, cinnoline, pyrazolyl, imidazolyl, thiazolyl, pyrazolo[1,5-a]pyridyl, imidazo[1,2-a] pyridyl, khinoksalinona, benzothiazolyl, benzotriazolyl, indolyl, indazole, 3,4-dihydro-1H-izochinolina and 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, and specified gets Roheline ring is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, ceanography,1-7-alkyl, C3-7-cycloalkyl-C1-7-alkyl, C1-7-alkoxygroup,1-7-alkoxy-C1-7-alkoxygroup, cyano-C1-7-alkoxygroup, hydroxy-C1-7-alkoxygroup, halogen-C1-7-alkoxygroup, carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7alkoxygroup,1-7-alkoxycarbonyl,1-7-alkoxycarbonyl-C1-7-alkyl, C1-7-alkoxycarbonyl-C1-7-alkoxygroup, R6R7N-carbonyl-C1-7-alkoxygroup, where R6and R7independently selected from hydrogen or C1-7-alkyl, or R6and R7together with the nitrogen atom to which they are attached, form a heterocyclic ring selected from pyrrolidine, piperidine, research or thiomorpholine; phenyl, and specified phenyl is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, C1-7-alkyl, hydroxy-group, ceanography, carboxyl,1-7alkoxycarbonyl and C1-7alkoxygroup; pyridyl; heterocyclyl selected from the group consisting of pyrrolidine and piperidine, and the specified heterocyclyl ring is unsubstituted or substituted carbon the sludge or 1-7-alkoxycarbonyl; phenyl-C1-7of alkyl, phenyloxy and phenyl-C1-7-alkoxygroup;
R5represents hydrogen or methyl;
n denotes 0 or 1;
and their pharmaceutically acceptable salts.

2. The compounds of formula I according to claim 1, where n denotes 0.

3. The compounds of formula I according to claim 1 or 2, where a represents C-R1b.

4. The compounds of formula I according to claim 1, where R1a, R1b, R1c, R1dand R1eindependently from each other selected from the group consisting of hydrogen, C1-7-alkyl, C3-7-cycloalkyl-C1-7-alkyl, halogen, halogen-C1-7-alkyl, halogen-C1-7-alkoxygroup, halogen-C1-7-alkylsulfonates, hydroxy-group, hydroxy-C1-7-alkyl, C1-7-alkoxygroup,1-7-alkoxy-C1-7-alkoxygroup, hydroxy-C1-7-alkoxygroup, amino-C1-7-alkoxygroup, ceanography, carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxygroup, C1-7-alkoxycarbonyl,1-7-alkoxycarbonyl-C1-7-alkoxygroup, C1-7-alkoxycarbonyl-C1-7-alkoxygroup,1-7-alkylcarboxylic-C1-7-alkoxygroup, aminocarbonyl-C1-7-alkoxygroup, di-C1-7-alkylamino, di-C2-7-alkenylamine,1-7-alkylsulfonamides, phenylcarbonylamino, peninsul is nilakshi; heteroaryl-C1-7-alkoxygroup, where heteroaryl ring selected from the group consisting of oxadiazolyl, isoxazolyl, thiadiazolyl and tetrazolyl, and is unsubstituted or substituted With1-7-alkyl; phenyloxy and phenyl-C1-7-alkoxygroup, and the indicated phenyl ring is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, C1-7-alkyl, hydroxy-group, ceanography,1-7-alkylsulfonyl,1-7-alkoxygroup and halogen-C1-7-alkoxygroup; and not more than three of R1a, R1b, R1c, R1dand R1erepresent hydrogen.

5. The compounds of formula I according to claim 1, where R1a, R1b, R1c, R1dand R1eselected from the group consisting of hydrogen, halogen, halogen-C1-7-alkyl, hydroxy-group, With1-7-alkoxygroup, ceanography, carboxyl,1-7-alkoxycarbonyl, di-C2-7-alkenylamine; heteroaryl-C1-7-alkoxygroup, where heteroaryl ring selected from the group consisting of oxadiazolyl, isoxazolyl, thiadiazolyl and tetrazolyl, and is unsubstituted or substituted With1-7-alkyl; phenyloxy and phenyl-C1-7-alkoxygroup, and the indicated phenyl ring is unsubstituted or substituted one, two is whether three substituents, selected from the group consisting of halogen, halogen-C1-7-alkyl, C1-7-alkyl, hydroxy-group, ceanography,1-7-alkylsulfonyl,1-7-alkoxygroup and halogen-C1-7-alkoxygroup.

6. The compounds of formula I according to claim 1, where R1arepresents a halogen.

7. The compounds of formula I according to claim 1, where R1arepresents halogen, and R1cselected from the group consisting of halogen, C1-7-alkoxygroup and phenyl-C1-7-alkoxygroup.

8. The compounds of formula I according to claim 1, where R2represents a C1-7-alkyl.

9. The compounds of formula I according to claim 1, where R3represents hydrogen.

10. The compounds of formula I according to claim 1, where R4is a heteroaryl ring selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 2-oxo-1,2-dihydropyridine, chinoline, izochinolina, cinnoline, pyrazolyl, imidazolyl, thiazolyl, pyrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, khinoksalinona, benzothiazolyl, benzotriazolyl, indolyl, indazole, 3,4-dihydro-1H-izochinolina and 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, and specified heteroaryl ring is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, ceanography,1-7-alkyl, C1-7-Ala is syrupy, cyano-C1-7-alkoxygroup, carboxyl-C1-7-alkoxygroup,1-7-alkoxycarbonyl, phenyl, pyridyl, pyrrolidinyl and phenyl-C1-7-alkoxygroup.

11. The compounds of formula I according to claim 1, where R4is a heteroaryl ring selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl and 2-oxo-1,2-dihydropyridine, and specified heteroaryl ring is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, ceanography,1-7-alkyl, C3-7-cycloalkyl-C1-7-alkyl, C1-7-alkoxygroup,1-7-alkoxy-C1-7-alkoxygroup, cyano-C1-7-alkoxygroup, hydroxy-C1-7-alkoxygroup, halogen-C1-7-alkoxygroup, carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxygroup,1-7-alkoxycarbonyl,1-7-alkoxycarbonyl-C1-7-alkyl, C1-7-alkoxycarbonyl-C1-7-alkoxygroup, R6R7N-carbonyl-C1-7-alkoxygroup, where R6and R7independently selected from hydrogen or C1-7-alkyl, or R6and R7together with the nitrogen atom to which they are attached, form a heterocyclic ring selected from pyrrolidine, piperidine, research or thiomorpholine; phenyl, with the specified eat phenyl is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, C1-7-alkyl, hydroxy-group, ceanography, carboxyl,1-7-alkoxycarbonyl and C1-7-alkoxygroup; pyridyl; heterocyclyl selected from the group consisting of pyrrolidine and piperidine, and the specified heterocyclyl ring is unsubstituted or substituted by carboxyla or1-7-alkoxycarbonyl; phenyl-C1-7-alkyl, phenyloxy and phenyl-C1-7-alkoxygroup.

12. The compounds of formula I according to claim 1, where R4represents pyridyl, and specified peregrinae ring is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, ceanography,1-7-alkyl, C3-7-cycloalkyl-C1-7-alkyl, C1-7-alkoxygroup,1-7-alkoxy-C1-7-alkoxygroup, cyano-C1-7-alkoxygroup, hydroxy-C1-7-alkoxygroup, halogen-C1-7-alkoxygroup, carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxygroup,1-7-alkoxycarbonyl,1-7-alkoxycarbonyl-C1-7-alkyl, C1-7-alkoxycarbonyl-C1-7-alkoxygroup; R6R7N-carbonyl-C1-7-alkoxygroup, where R6and R7independently selected from ogorodili 1-7-alkyl, or R6and R7together with the nitrogen atom to which they are attached, form a heterocyclic ring selected from pyrrolidine, piperidine, research or thiomorpholine; phenyl, and specified phenyl is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, C1-7-alkyl, hydroxy-group, ceanography, carboxyl, C1-7-alkoxycarbonyl and C1-7-alkoxygroup; pyridyl; heterocyclyl selected from the group consisting of pyrrolidine and piperidine, and the specified heterocyclyl ring is unsubstituted or substituted by carboxyla or1-7-alkoxycarbonyl; phenyl-C1-7-alkyl, phenyloxy and phenyl-C1-7-alkoxygroup.

13. The compounds of formula I according to claim 1, where R4represents pyridyl, substituted with one, two or three substituents selected from the group consisting of halogen, C1-7-alkyl, ceanography,1-7-alkoxygroup and carboxyl-C1-7-alkoxygroup.

14. The compounds of formula I according to claim 1, where R4is a heteroaryl ring selected from the group consisting of chinoline, izochinolina, cinnoline, pyrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, khinoksalinona, benzothiazolyl, benzotriazolyl, indolyl, indazole, 3,4-di is Idro-1H-izochinolina and 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, moreover, the specified heteroaryl ring is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, ceanography,1-7-alkyl, C3-7-cycloalkyl-C1-7-alkyl, C1-7-alkoxygroup,1-7-alkoxy-C1-7-alkoxygroup, cyano-C1-7-alkoxygroup, hydroxy-C1-7-alkoxygroup, halogen-C1-7-alkoxygroup, carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxygroup,1-7-alkoxycarbonyl, C1-7-alkoxycarbonyl-C1-7-alkyl, C1-7-alkoxycarbonyl-C1-7-alkoxygroup;
R6R7N-carbonyl-C1-7-alkoxygroup, where R6and R7independently selected from hydrogen or C1-7-alkyl, or R6and R7together with the nitrogen atom to which they are attached, form a heterocyclic ring selected from pyrrolidine, piperidine, research or thiomorpholine; phenyl, and specified phenyl is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, C1-7-alkyl, hydroxy-group, ceanography, carboxyl,1-7-alkoxycarbonyl and C1-7-alkoxygroup; pyridyl; heterocyclyl selected from the group consisting of pyrrolidine and piperid is on, moreover, the specified heterocyclyl ring is unsubstituted or substituted by carboxyla or C1-7-alkoxycarbonyl; phenyl-C1-7-alkyl, phenyloxy and phenyl-C1-7-alkoxygroup.

15. The compounds of formula I according to claim 1, where R4is chinoline, and specified hyalinella ring is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, ceanography,1-7-alkyl, C3-7-cycloalkyl-C1-7-alkyl, C1-7-alkoxygroup, halogen-C1-7-alkoxygroup, carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxygroup,1-7-alkoxycarbonyl, phenyl, pyridyl, pyrrolidinyl, fenoxaprop and phenyl-C1-7-alkoxygroup.

16. The compounds of formula I according to claim 1, where R4represents benzothiazolyl, and specified benzothiazoline ring is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, ceanography,1-7-alkyl, C3-7-cycloalkyl-C1-7-alkyl, C1-7-alkoxygroup, halogen-C1-7-alkoxygroup, carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxygroup,1-7-alkoxycarbonyl, phenyl, pyridyl, pyrrolidino the La, fenoxaprop and phenyl-C1-7-alkoxygroup.

17. The compounds of formula I according to claim 1, where R4is a heteroaryl ring selected from the group consisting of pyrazolyl, imidazolyl and thiazolyl, and specified heteroaryl ring is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, ceanography,1-7-alkyl, C3-7-cycloalkyl-C1-7-alkyl, C1-7-alkoxygroup,1-7-alkoxy-C1-7-alkoxygroup, cyano-C1-7-alkoxygroup, hydroxy-C1-7-alkoxygroup, halogen-C1-7-alkoxygroup, carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxygroup,1-7-alkoxycarbonyl, C1-7-alkoxycarbonyl-C1-7-alkyl, C1-7-alkoxycarbonyl-C1-7-alkoxygroup; R6R7N-carbonyl-C1-7-alkoxygroup, where R6and R7independently selected from hydrogen or C1-7-alkyl, or R6and R7together with the nitrogen atom to which they are attached, form a heterocyclic ring selected from pyrrolidine, piperidine, research or thiomorpholine, phenyl, and specified phenyl is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7 -alkyl, C1-7-alkyl, hydroxy-group, ceanography, carboxyl, C1-7-alkoxycarbonyl and C1-7-alkoxygroup; pyridyl, heterocyclyl selected from the group consisting of pyrrolidine and piperidine, and the specified heterocyclyl ring is unsubstituted or substituted by carboxyla or C1-7-alkoxycarbonyl, phenyl-C1-7-alkyl, phenyloxy and phenyl-C1-7-alkoxygroup.

18. The compounds of formula I according to claim 1, where R5represents hydrogen.

19. Compounds according to claim 1 of the formula:
,
where R1a, R1b, R1c, R1dand R1eindependently from each other selected from the group consisting of hydrogen, C1-7-alkyl, C3-7-cycloalkyl-C1-7-alkyl, halogen, halogen-C1-7-alkyl, halogen-C1-7-alkoxygroup, hydroxy-group, C1-7-alkoxygroup, carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxygroup, fenoxaprop and phenyl-C1-7-alkoxygroup, and the indicated phenyl ring is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, C1-7-alkyl, C1-7-alkoxygroup and halogen-C1-7-alkoxygroup;
R2selected from the group consisting of C1-7-alkyl, C3-7-cycloalkyl-C1-7 -alkyl and triazolyl-C1-7-alkyl;
R3represents hydrogen or C1-7-alkyl;
R4is a heteroaryl ring selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, chinoline, pyrazolyl, imidazolyl, thiazolyl, pyrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, khinoksalinona, benzothiazolyl, 3,4-dihydro-1H-izochinolina and 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, and specified heteroaryl ring is unsubstituted or substituted one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, C1-7-alkyl, C3-7-cycloalkyl-C1-7-alkyl, C1-7-alkoxygroup, halogen-C1-7-alkoxygroup, carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxygroup,1-7-alkoxycarbonyl, phenyl, pyridyl, pyrrolidinyl, fenoxaprop and phenyl-C1-7-alkoxygroup;
R5represents hydrogen or methyl;
and their pharmaceutically acceptable salts.

20. The compounds of formula I according to claim 1, selected from the group consisting of the following compounds:
3-(2-chloro-4-methoxyphenyl)-1,1,1-Cryptor-2-(5-methylpyrazine-2-yl)butane-2-ol,
1,1,1-Cryptor-2-(2-methylpyridin-4-yl)-3-phenylbutane-2-ol,
3-(2-chloro-4-methoxyphenyl)-1,1,1-Cryptor-2-(2-methylpyridin-4-yl)butane-2-ol,
3-(2-chloro-4-ethoxyphenyl)-11,1-Cryptor-2-(2-methylpyridin-4-yl)pentane-2-ol,
3-(2-chloro-4-propoxyphenyl)-1,1,1-Cryptor-2-(2-methylpyridin-4-yl)hexane-2-ol,
3-(2,3-dichloro-4-methoxyphenyl)-1,1,1-Cryptor-2-(2-methylpyridin-4-yl)butane-2-ol,
3-(2-chloro-5-methoxyphenyl)-1,1,1-Cryptor-2-(2-methylpyridin-4-yl)butane-2-ol,
3-(2,5-dichlorophenyl)-1,1,1-Cryptor-2-(2-methylpyridin-4-yl)butane-2-ol,
1,1,1-Cryptor-3-phenyl-2-pyridine-4-ivatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-pyridine-3-ivatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-pyridine-4-ivatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-pyridine-2-ivatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-pyridine-3-ingatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-pyridine-3-elexan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-pyridine-3-alpental-2-ol,
4-cyclopropyl-3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-pyridine-3-ivatan-2-ol,
3-(4-chloro-2-forfinal)-1,1,1-Cryptor-2-pyridine-3-ivatan-2-ol,
3-(2-chlorophenyl)-1,1,1-Cryptor-2-pyridine-3-ivatan-2-ol,
3-(3,4-dichlorophenyl)-1,1,1-Cryptor-2-pyridine-3-ivatan-2-ol,
3-(2,3-dichlorophenyl)-1,1,1-Cryptor-2-pyridine-3-ivatan-2-ol,
3-(3-chlorophenyl)-1,1,1-Cryptor-2-pyridine-3-ivatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(6-triptorelin-3-yl)butane-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-pyridin-3-yl-4-[1,2,4]triazole-1-ivatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-pyridine-4-elexan-2-ol,
3-(2-chloro-4-forfinal)-1,1,1-Cryptor-2-pyridine-4-elexan-2-ol,
1,1,1-Cryptor-3-(2-methoxyphenyl)-2-pyridine-4-elexan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-trip the PR-2-(2-methylpyridin-4-yl)butane-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(2-methylpyridin-4-yl)hexane-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-pyrazin-2-ivatan-2-ol,
1,1,1-Cryptor-3-(2-methoxyphenyl)-2-(2-methylpyridin-4-yl)butane-2-ol,
3-(2-chloro-5-triptoreline)-1,1,1-Cryptor-2-pyridine-4-ivatan-2-ol,
3-(2-chloro-6-forfinal)-1,1,1-Cryptor-2-pyridine-4-ivatan-2-ol,
1,1,1-Cryptor-2-pyridin-4-yl-3-o-toolbutton-2-ol,
3-(2-chloro-4-forfinal)-2-(2-chloropyridin-4-yl)-1,1,1-triptorelin-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-pyridazin-4-ivatan-2-ol,
1,1,1-Cryptor-3-(2-phenoxyphenyl)-2-pyridine-4-ivatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(2-methoxypyridine-4-yl)butane-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(5-methylpyrazine-2-yl)butane-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(6-methylpyridin-2-yl)butane-2-ol,
(2S,3S)-3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(6-methylpyridin-2-yl)butane-2-ol,
(2R,3R)-3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(6-methylpyridin-2-yl)butane-2-ol,
3-(2-chloro-4-forfinal)-2-(2-chloro-6-methoxypyridine-4-yl)-1,1,1-triptorelin-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(1-methyl-1H-pyrazole-4-yl)butane-2-ol,
2-(2-chloro-6-methylpyridin-4-yl)-3-(2,4-dichlorophenyl)-1,1,1-triptorelin-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-quinoline-3-ivatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-pyrimidine-4-ivatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(1-methyl-1H-imidazol-4-yl)butane-2-ol,
4-[2-(2,4-dichlorophenyl)-1-methoxy-1-cryptomaterial]pyridine,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-pyrazolo[1,5-a]pyridine-2-ivatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(1-methyl-1H-pyrazole-3-yl)butane-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-imidazo[1,2-a]pyridine-2-ivatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-quinoline-6-ivatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-cinoxacin-6-ivatan-2-ol,
2-(2-benzyloxypyridine-4-yl)-3-(2,4-dichlorophenyl)-1,1,1-triptorelin-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(6-methoxypyridine-3-yl)butane-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(5-methyl-1-phenyl-1H-pyrazole-4-yl)butane-2-ol,
2-benzothiazol-6-yl-3-(2,4-dichlorophenyl)-1,1,1-triptorelin-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-cinoxacin-2-ivatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(2-pyridin-4-iltiazem-4-yl)butane-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-thiazol-2-ivatan-2-ol,
tert-butyl ester of 7-[2-(2,4-dichlorophenyl)-1-hydroxy-1-cryptomaterial]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-pyrimidine-5-ivatan-2-ol,
2-(1-benzyl-1H-pyrazole-4-yl)-3-(2,4-dichlorophenyl)-1,1,1-triptorelin-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)butane-2-ol,
3-(2-chloro-4-forfinal)-1,1,1-Cryptor-2-quinoline-3-ivatan-2-ol,
3-(2-chloro-4-methoxyphenyl)-1,1,1-Cryptor-2-cinoxacin-2-ivatan-2-ol,
3-(2-chloro-4-forfinal)-1,1,1-Cryptor-2-quinoline-6-ivatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(6-pyrrolidin-1-espiridion-2-yl)butane-2-ol,
3-(2-chloro-4-forfinal)-1,1,1-Cryptor-2-(6-methylpyridin-2-yl)BU the EN-2-ol,
(2S,3S)-3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-quinoline-6-ivatan-2-ol,
(2R,3R)-3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-quinoline-6-ivatan-2-ol,
3-chloro-4-[3,3,3-Cryptor-2-hydroxy-1-methyl-2-(5-methylpyrazine-2-yl)propyl]phenol,
3-chloro-4-[3,3,3-Cryptor-2-hydroxy-1-methyl-2-(2-methylpyridin-4-yl)propyl]phenol,
3-(4-benzyloxy-2-chlorophenyl)-1,1,1-Cryptor-2-(2-methylpyridin-4-yl)butane-2-ol,
{4-[2-(2,4-dichlorophenyl)-1-hydroxy-1-cryptomaterial]pyridine-2-yloxy}acetic acid,
4-chloro-3-[3,3,3-Cryptor-2-hydroxy-1-methyl-2-(6-methylpyridin-2-yl)propyl]benzoic acid,
3-[2-chloro-4-(2-methoxyethoxy)phenyl]-1,1,1-Cryptor-2-(2-methylpyridin-4-yl)butane-2-ol,
tert-butyl ether ({3-chloro-4-[3,3,3-Cryptor-2-hydroxy-1-methyl-2-(2-methylpyridin-4-yl)propyl]phenoxy}acetic acid,
{3-chloro-4-[3,3,3-Cryptor-2-hydroxy-1-methyl-2-(2-methylpyridin-4-yl)propyl]phenoxy}acetic acid,
2-{3-chloro-4-[3,3,3-Cryptor-2-hydroxy-1-methyl-2-(5-methylpyrazine-2-yl)propyl]phenoxy}ndimethylacetamide,
3-{2-chloro-4-[2-(2-methoxyethoxy)ethoxy]phenyl}-1,1,1-Cryptor-2-(5-methylpyrazine-2-yl)butane-2-ol,
tert-butyl ether ({3-chloro-4-[3,3,3-Cryptor-2-hydroxy-1-methyl-2-(5-methylpyrazine-2-yl)propyl]phenoxy}acetic acid,
2-{3-chloro-4-[3,3,3-Cryptor-2-hydroxy-1-methyl-2-(5-methylpyrazine-2-yl)propyl]phenoxy}ethyl ester acetic acid,
tert-butyl ether (2-{3-chloro-4-[3,3,3-Cryptor-2-hydroxy-1-methyl-2-(5-methylpyrazine-2-yl)propyl]phenoxy}ethyl) - carbamino acid,
3[2-chloro-4-(2,2-diflorasone)phenyl]-1,1,1-Cryptor-2-(5-methylpyrazine-2-yl)butane-2-ol,
3-[2-chloro-4-(2-methoxyethoxy)phenyl]-1,1,1-Cryptor-2-(5-methylpyrazine-2-yl)butane-2-ol,
3-[2-chloro-4-([1,2,4]oxadiazol-3-ylethoxy)phenyl]-1,1,1-Cryptor-2-(5-methylpyrazine-2-yl)butane-2-ol,
3-[2-chloro-4-(5-methylisoxazol-3-ylethoxy)phenyl]-1,1,1-Cryptor-2-(5-methylpyrazine-2-yl)butane-2-ol,
3-[2-chloro-4-(2-hydroxyethoxy)phenyl]-1,1,1-Cryptor-2-(5-methylpyrazine-2-yl)butane-2-ol,
3-[4-(2-aminoethoxy)-2-chlorophenyl]-1,1,1-Cryptor-2-(5-methylpyrazine-2-yl)butane-2-ol,
3-[2-chloro-4-(1-methyl-1H-tetrazol-5-ylethoxy)phenyl]-1,1,1-Cryptor-2-(5-methylpyrazine-2-yl)butane-2-ol,
3-[2-chloro-4-(3-methyl-[1,2,4]thiadiazole-5-ylethoxy)phenyl]-1,1,1-Cryptor-2-(5-methylpyrazine-2-yl)butane-2-ol,
3-(2-chloro-4-forfinal)-1,1,1-Cryptor-2-(2-methoxypyridine-4-yl)butane-2-ol,
1,1,1-Cryptor-2-(5-methylpyrazine-2-yl)-3-naphthalen-1-ivatan-2-ol,
2-(6-chloropyrazine-2-yl)-3-(2,4-dichlorophenyl)-1,1,1-triptorelin-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-isoquinoline-5-ivatan-2-ol,
2-cinnolin-4-yl-3-(2,4-dichlorophenyl)-1,1,1-triptorelin-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-pyrazolo[1,5-a]pyridine-3-ivatan-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(1-phenethyl-1H-pyrazole-4-yl)butane-2-ol,
2-(6-chloropyridin-3-yl)-3-(2,4-dichlorophenyl)-1,1,1-triptorelin-2-ol,
5-[2-(2,4-dichlorophenyl)-1-hydroxy-1-cryptomaterial]pyridine-2-carbonitrile,
3-(2-chloro-4-penetrometer)-1,1,1-Cryptor-2-(2-methylpyridin-4-yl)butane-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(2-methoxypyridine-5-yl)butane-2-ol,
3-(2-chloro-4-label iphenyl)-1,1,1-Cryptor-2-pyridine-4-ivatan-2-ol,
3-chloro-4-(3,3,3-Cryptor-2-hydroxy-1-methyl-2-pyridine-4-ylpropyl)phenol,
3-(2-chloro-4-methoxyphenyl)-1,1,1-Cryptor-2-(3-isopropyl-3H-benzotriazol-5-yl)butane-2-ol,
3-(2-chloro-4-methoxyphenyl)-2-cinnolin-4-yl-1,1,1-triptorelin-2-ol,
3-chloro-4-(2-cinnolin-4-yl-3,3,3-Cryptor-2-hydroxy-1-methylpropyl " phenol,
3-(2-chloro-4-methoxyphenyl)-1,1,1-Cryptor-2-pyrazolo[1,5-a]pyridine-3-ivatan-2-ol,
3-chloro-4-(3,3,3-Cryptor-2-hydroxy-1-methyl-2-pyrazolo[1,5-a]pyridine-3-ylpropyl)phenol,
2-(2-chloropyridin-4-yl)-3-{2-chloro-4-[3-((1H)-tetrazol-5-yl)propoxy]phenyl}-1,1,1-triptorelin-2-ol,
3-(2-chloro-4-hydroxymethylene)-2-(2-chloropyridin-4-yl)-1,1,1-triptorelin-2-ol,
{3-chloro-4-[2-(2-chloropyridin-4-yl)-3,3,3-Cryptor-2-hydroxy-1-methylpropyl]phenyl}acetic acid,
3-{3-chloro-4-[2-(2-chloropyridin-4-yl)-3,3,3-Cryptor-2-hydroxy-1-methylpropyl]phenyl}propionic acid,
3-(2-chloro-5-methoxyphenyl)-2-(2-chloropyridin-4-yl)-1,1,1-triptorelin-2-ol,
4-chloro-3-[2-(2-chloropyridin-4-yl)-3,3,3-Cryptor-2-hydroxy-1-methylpropyl]phenol,
methyl ester of 3-(2,4-dichlorophenyl)-5,5,5-Cryptor-4-hydroxy-4-(6-methylpyridin-2-yl)pentanol acid,
3-(2,4-dichlorophenyl)-5,5,5-Cryptor-4-hydroxy-4-(6-methylpyridin-2-yl)pentane acid,
4-[2-(2,4-dichlorophenyl)-1-hydroxy-1-cryptomaterial]-1H-pyridine-2-it,
methyl ester {4-[2-(2,4-dichlorophenyl)-1-hydroxy-1-cryptomaterial]pyridine-2-yloxy}acetic acid,
methyl ester {4-[2-(2,4-dichlorophenyl)-1-hydroxy-1-trip ormerproblem]-2-oxo-2H-pyridin-1-yl}acetic acid,
{4-[2-(2,4-dichlorophenyl)-1-hydroxy-1-cryptomaterial]-2-oxo-2H-pyridin-1-yl}acetic acid,
2-{4-[2-(2,4-dichlorophenyl)-1-hydroxy-1-cryptomaterial]pyridine-2-yloxy}ndimethylacetamide,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-[2-(2-methoxyethoxy)pyridine-4-yl]butane-2-ol,
{4-[2-(2,4-dichlorophenyl)-1-hydroxy-1-cryptomaterial]pyridine-2-yloxy}acetonitrile,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-[2-(2-hydroxyethoxy)pyridine-4-yl]butane-2-ol,
2-{4-[2-(2,4-dichlorophenyl)-1-hydroxy-1-cryptomaterial]pyridine-2-yloxy}-1-morpholine-4-ylatason,
ethyl ester of 4-[2-(2,4-dichlorophenyl)-4,4,4-Cryptor-3-hydroxy-3-(6-methylpyridin-2-yl)butyl]benzoic acid
4-[2-(2,4-dichlorophenyl)-4,4,4-Cryptor-3-hydroxy-3-(6-methylpyridin-2-yl)butyl]benzoic acid,
methyl ether 4-chloro-3-[3,3,3-Cryptor-2-hydroxy-1-methyl-2-(6-methylpyridin-2-yl)propyl]benzoic acid
3-(2-chloro-4-methoxyphenyl)-2-(2-chloropyridin-4-yl)-1,1,1-triptorelin-2-ol,
3-chloro-4-[2-(2-chloropyridin-4-yl)-3,3,3-Cryptor-2-hydroxy-1-methylpropyl]phenol,
2-{3-chloro-4-[2-(2-chloropyridin-4-yl)-3,3,3-Cryptor-2-hydroxy-1-methylpropyl]phenoxy}-2-methylpropionamide,
methyl ether 3-chloro-4-[2-(2-chloropyridin-4-yl)-3,3,3-Cryptor-2-hydroxy-1-methylpropyl]benzoic acid
methyl ester 4-[2-(2-chloro-4-ethoxycarbonylphenyl)-1-hydroxy-1-cryptomaterial]pyridine-2-carboxylic acid,
3-chloro-4-[2-(2-chloropyridin-4-yl)-3,3,3-Cryptor-2-hydroxy-1-methylpropyl]benzoic Ki the lot,
4-[2-(4-carboxy-2-chlorophenyl)-1-hydroxy-1-cryptomaterial]pyridine-2-carboxylic acid,
3-(2-chloro-4-methoxyphenyl)-1,1,1-Cryptor-2-(2-yodellin-4-yl)butane-2-ol,
ethyl ester of 4-{4-[2-(2-chloro-4-methoxyphenyl)-1-hydroxy-1-cryptomaterial]pyridine-2-yl}benzoic acid,
4-(4-[2-(2-chloro-4-methoxyphenyl)-1-hydroxy-1-cryptomaterial]pyridine-2-yl}benzoic acid,
methyl ester of 3-{4-[2-(2-chloro-4-methoxyphenyl)-1-hydroxy-1-cryptomaterial]pyridine-2-yl}benzoic acid,
3-{4-[2-(2-chloro-4-methoxyphenyl)-1-hydroxy-1-cryptomaterial]pyridine-2-yl}benzoic acid,
3-(2-chloro-4-forfinal)-1,1,1-Cryptor-2-(2-yodellin-4-yl)butane-2-ol,
methyl ester of 3-{4-[2-(2-chloro-4-forfinal)-1-hydroxy-1-cryptomaterial]pyridine-2-yl}benzoic acid,
5-{4-[2-(2-chloro-4-forfinal)-1-hydroxy-1-cryptomaterial]pyridine-2-yl}-2-perbenzoate,
3-{4-[2-(2-chloro-4-forfinal)-1-hydroxy-1-cryptomaterial]pyridine-2-yl}benzoic acid,
ethyl ester of 4'-[2-(2-chloro-4-triftoratsetilatsetonom)-1-hydroxy-1-cryptomaterial]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid,
4'-[2-(2-chloro-4-hydroxyphenyl)-1-hydroxy-1-cryptomaterial]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid,
ethyl ester of 2-chloro-5-{4-[2-(2-chloro-4-forfinal)-1-hydroxy-1-cryptomaterial]pyridine-2-yl}benzoic acid,
ethyl ester of 5-{4-[2-(2-chloro-4-forfinal)--hydroxy-1-cryptomaterial]pyridine-2-yl}-2-fermenting acid,
5-{4-[2-(2-chloro-4-forfinal)-1-hydroxy-1-cryptomaterial]pyridine-2-yl}-2-Formentera acid,
2-chloro-5-{4-[2-(2-chloro-4-forfinal)-1-hydroxy-1-cryptomaterial]pyridine-2-yl}benzoic acid,
ethyl ester of 4'-[2-(2-chloro-4-methoxyphenyl)-1-hydroxy-1-cryptomaterial]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid,
4'-[2-(2-chloro-4-methoxyphenyl)-1-hydroxy-1-cryptomaterial]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid,
4'-[2-(2-chloro-4-ethoxyphenyl)-1-hydroxy-1-cryptomaterial]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carboxylic acid,
1,1,1-Cryptor-3-(6-methoxy-4-methylpyridin-3-yl)-2-pyridine-4-ivatan-2-ol,
1,1,1-Cryptor-2-pyridin-4-yl-3-quinoline-3-ivatan-2-ol,
3-(3,4-dichlorophenyl)-1,1,1-Cryptor-2-pyridine-4-ivatan-2-ol,
1,1,1-Cryptor-3-(4-methoxyphenyl)-2-pyridine-4-ivatan-2-ol,
1,1,1-Cryptor-3-(4-methoxy-2-were)-2-pyridine-4-ivatan-2-ol,
3-(2,4-differenl)-1,1,1-Cryptor-2-pyridine-4-ivatan-2-ol,
1,1,1-Cryptor-3-(2-methoxynaphthalene-1-yl)-2-pyridine-4-ivatan-2-ol,
1,1,1-Cryptor-3-naphthalen-2-yl-2-pyridin-4-ivatan-2-ol,
3-(2-chloro-4-diallylamine)-2-(2-chloropyridin-4-yl)-1,1,1-triptorelin-2-ol,
N-{3-chloro-4-[2-(2-chloropyridin-4-yl)-3,3,3-Cryptor-2-hydroxy-1-methylpropyl]phenyl}methanesulfonamide,
N-{3-chloro-4-[2-(2-chloropyridin-4-yl)-3,3,3-Cryptor-2-hydroxy-1-methylpropyl]phenyl}benzamide,
3-(2-chloro-4-forfinal)-2-(6-chloropyridin-3-yl)-1,1,1-triptorelin-ol,
5-[2-(2-chloro-4-forfinal)-1-hydroxy-1-cryptomaterial]pyridine-2-carboxylic acid,
4-[2-(2-chloro-4-forfinal)-1-hydroxy-1-cryptomaterial]pyridine-2-carboxylic acid,
3-(4-bromo-2-chlorophenyl)-1,1,1-Cryptor-2-(2-methylpyridin-4-yl)butane-2-ol,
1-[1-(4-chlorophenyl)cyclopropyl]-2,2,2-Cryptor-1-quinoline-3-retinol,
1-[1-(2,4-dichlorophenyl)cyclopropyl]-2,2,2-Cryptor-1-quinoline-3-retinol,
1-(2-chloropyridin-4-yl)-1-[1-(2,4-dichlorophenyl)cyclopropyl]-2,2,2-triptoreline,
2-(2-chloropyridin-4-yl)-3-(2,4-dichlorophenyl)-1,1,1-Cryptor-3-methylbutane-2-ol,
3-(4-chlorophenyl)-1,1,1-Cryptor-3-methyl-2-(2-methylpyridin-4-yl)butane-2-ol,
3-(2,6-dichloropyridine-3-yl)-1,1,1-Cryptor-2-(5-methylpyrazine-2-yl)butane-2-ol,
3-(2-chloro-4-methoxyphenyl)-1,1,1-Cryptor-2-quinoline-3-ivatan-2-ol,
3-chloro-4-(3,3,3-Cryptor-2-hydroxy-1-methyl-2-quinoline-3-ylpropyl)phenol,
3-[2-chloro-4-(4-methysulfonylmethane)phenyl]-1,1,1-Cryptor-2-quinoline-3-ivatan-2-ol,
3-chloro-4-(3,3,3-Cryptor-2-hydroxy-1-methyl-2-quinoline-3-ylpropyl)phenyl ether of benzosulfimide acid,
3-(2-chloro-4-methoxyphenyl)-1,1,1-Cryptor-2-isoquinoline-5-ivatan-2-ol,
3-chloro-4-(3,3,3-Cryptor-2-hydroxy-2-isoquinoline-5-yl-1-methylpropyl " phenol,
3-[2-(2-chloro-4-methoxyphenyl)-1-hydroxy-1-cryptomaterial]quinoline-6-carbonitrile,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(5-fluoro-1H-indol-3-yl)butane-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-(1-phenyl-1H-indazol-5-yl)butane-2-ol,
3-(2,4-dichlorophenyl)-1,1,1-tripto the-2-[1-(3-methoxyphenyl)-1H-indazol-5-yl]butane-2-ol,
3-{5-[2-(2,4-dichlorophenyl)-1-hydroxy-1-cryptomaterial]indazol-1-yl}phenol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-[1-(2-methoxyphenyl)-1H-indazol-5-yl]butane-2-ol,
2-{5-[2-(2,4-dichlorophenyl)-1-hydroxy-1-cryptomaterial]indazol-1-yl}phenol,
3-(2,4-dichlorophenyl)-1,1,1-Cryptor-2-[1-(4-methoxyphenyl)-1H-indazol-5-yl]butane-2-ol,
4-{5-[2-(2,4-dichlorophenyl)-1-hydroxy-1-cryptomaterial]indazol-1-yl}phenol,
3-(2-chloro-4-methoxyphenyl)-1,1,1-Cryptor-2-(6-methoxypyridine-3-yl)butane-2-ol,
5-[2-(2-chloro-4-methoxyphenyl)-1-hydroxy-1-cryptomaterial]-1H-pyridine-2-it,
5-[2-(2-chloro-4-methoxyphenyl)-1-hydroxy-1-cryptomaterial]-1-methyl-1H-pyridine-2-it,
5-[2-(2-chloro-4-hydroxyphenyl)-1-hydroxy-1-cryptomaterial]-1-methyl-1H-pyridine-2-it,
4-{3-chloro-4-[3,3,3-Cryptor-2-hydroxy-1-methyl-2-(1-methyl-6-oxo-1,6-dihydropyridines-3-yl)propyl]phenoxy}-3-perbenzoate,
3-chloro-4-{3-chloro-4-[3,3,3-Cryptor-2-hydroxy-1-methyl-2-(1-methyl-6-oxo-1,6-dihydropyridines-3-yl)propyl]phenoxy}benzonitrile,
5-{2-[2-chloro-4-(4-fluoro-3-methoxyphenoxy)phenyl]-1-hydroxy-1-cryptomaterial}-1-methyl-1H-pyridine-2-it,
5-{2-[2-chloro-4-(4-fluoro-3-hydroxyphenoxy)phenyl]-1-hydroxy-1-cryptomaterial}-1-methyl-1H-pyridine-2-it,
5-[2-(2,4-dichlorophenyl)-1-hydroxy-1-cryptomaterial]-1-methyl-1H-pyridine-2-it,
5-[2-(2,4-dichlorophenyl)-1-hydroxy-1-cryptomaterial]-1-ethyl-1H-pyridine-2-it,
5-[2-(4-bromo-2-chlorophenyl)-1-hydroxy-1-cryptomaterial]-1-methyl-1H-PI is one-2-it,
3-(4-bromo-2-chlorophenyl)-1,1,1-Cryptor-2-(6-methoxypyridine-3-yl)butane-2-ol,
5-[2-(4-bromo-2-chlorophenyl)-1-hydroxy-1-cryptomaterial]-1H-pyridine-2-it,
5-[2-(4-bromo-2-chlorophenyl)-1-hydroxy-1-cryptomaterial]-1-ethyl-1H-pyridine-2-it,
5-[2-(2-chloro-5-methoxyphenyl)-1-hydroxy-1-cryptomaterial]-1-methyl-1H-pyridine-2-it,
5-[2-(2,3-dichloro-4-methoxyphenyl)-1-hydroxy-1-cryptomaterial]-1-methyl-1H-pyridine-2-it,
5-[2-(2,3-dichloro-4-hydroxyphenyl)-1-hydroxy-1-cryptomaterial]-1-methyl-1H-pyridine-2-it,
5-[2-(2-chloro-5-fluoro-4-methoxyphenyl)-1-hydroxy-1-cryptomaterial]-1-methyl-1H-pyridine-2-it,
and their pharmaceutically acceptable salts.

21. Pharmaceutical composition having activity as modulators of glucocorticoid receptor, containing the compound according to any one of claims 1 to 20, as well as pharmaceutically acceptable carrier and/or adjuvant.

22. The pharmaceutical composition according to item 21 for the treatment and/or prevention of diseases associated with modulation of the glucocorticoid receptor.

23. Compounds according to claim 1, intended for use as therapeutically active substances for the treatment and/or prevention of diseases associated with modulation of the glucocorticoid receptor.

24. Compounds according to claim 1, intended for use as therapeutically active substances for the treatment and/or prevention of d is of Abete.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula (I) or to its stereoisomers, or to a pharmaceutically acceptable salt, wherein Ra represents H or (C1-C6)alkyl; Rb is specified in an optionally substituted group consisting of -(CH2)n-aryl, -CH(CH3)-aryl, -(CH2)n-arylaryl, -(CH2)n-arylheteroaryl, -(CH2)n-(C3-C8) cycloalkyl, -(CH2)n-heteroaryl, -(CH2)n-heterocyclyl and -(C3-C8) cycloalkylaryl; or Ra and Rb taken together with a nitrogen atom form 2,3-dihydro-1H-isoindolyl, decahydroisoquinolinyl, optionally substituted piperidinyl or optionally substituted pyrrolidinyl; Y is specified in an an optionally substituted group consisting of 5,6,7,8-tetrahydro[1,6]naphthyridinyl, -NH-(CH2)n-heterocyclyl, wherein NH is attached to carbonyl, and -heterocyclylaryl, wherein heterocyclyl is attached to carbonyl; and n is equal to 0, 1 or 2; wherein each heterocyclyl represents an independent non-aromatic ring system containing 3 to 12 ring atoms, and at least one ring atom specified in a group consisting of nitrogen, oxygen and sulphur; wherein each heteroaryl represents an independent non-aromatic ring system containing 3 to 12 ring atoms and at least one ring atom specified in a group consisting of nitrogen, oxygen and sulphur; and wherein the optional substitutes are independently specified in a group consisting of C1-C6-alkyl, C1-C6-alkoxy, halogen, CN, CF3, OCF3, NH2, NH(CH3), N(CH3)2, hydroxy, cyclohexyl, phenyl, pyrrolidinyl, -C(O)-piperidinyl, -N(H)-C(O)-C1-C6-alkyl and N(H)-S(O)2-C1-C6-alkyl. The invention also describes a pharmaceutical composition having chemokine receptor antagonist activity and a method of treating such diseases, such as rheumatoid arthritis, psoriasis, lupus, etc.

EFFECT: there are prepared and described new chemical compounds that can be used as chemokine receptor antagonists and, as such, may be used in treating certain pathological conditions and diseases, particularly inflammatory pathological conditions and diseases and proliferative disorders and conditions, eg rheumatoid arthritis, osteoarthritis, multiple sclerosis and asthma.

23 cl, 59 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a novel crystalline modification of para-methoxyanilide of 6-hydroxy-4-oxo-2,4-dihydro-1H-pyrrolo-[3,2,1-ij]quinoline-5-carboxylic acid of formula: (I) , which is obtained by crystallisation from ethyl acetate, where values of interplanar distance (d) and relative reflection intensities (Irel) are given in claim 1.

EFFECT: novel crystalline modification exhibits a high diuretic effect.

2 dwg, 9 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

,

where: A is CA1; E is CE1; W is (CH2)n; Y is (CH2)P; n and p are independently equal to 0 or 1; R1 is a phenyl which is substituted with a phenyl {which is optionally substituted with a halogen, hydroxy, CH(O), CO2H, C1-4alkyl, C1-4alkyl-(N(C1-4alkyl)2), C1-4alkyl(NH2), C1-4alkyl(NH(C1-4alkyl)), C1-4hydroxyalkyl, CF3, C1-4alkylthio, C1-4alkyl(heterocyclyl) or C1-4alkylNHC(O)O(C1-4alkyl)} or a heterocyclyl; and the heterocyclyl is optionally substituted with C1-6alkyl; R2 is NHC(O)R3; and R3 is C1-4alkyl {substituted with NR7R8 or a heterocyclyl}, C3-7cycloalkyl (optionally substituted with a NR43R44 group) or a heteroaryl; where R7, R8, R43 and R44 are as defined in claim 1; wherein the heteroaryl is optionally substituted with a halogen, C1-4alkyl, CF3, C1-4alkoxy, OCF3, heterocyclyl or an amino(C1-4alkyl) group; R7 and R8 are independently C1-6alkyl; A1, E1 and G1 are independently hydrogen or halogen; unless otherwise stated, the heterocyclyl is optionally substituted with C1-6alkyl; R25 is C1-6alkyl; R50 is hydrogen or C1-6alkyl (optionally substituted with a NR51R52 group); R30, R36, R40, R42 or R44 is independently hydrogen, C1-6alkyl(optionally substituted with hydroxy, C1-6alkoxy, C1-6alkylthio, C3-7cycloalkyl (which is optionally substituted with hydroxy) or NR45R46), C3-7cycloalkyl (optionally substituted with a hydroxy(C1-6alkyl) group) or a heterocyclyl (optionally substituted with C1-6alkyl); R29, R35, R39, R41, R43, R45, R46 and R51 are independently hydrogen or C1-6alkyl; where the heterocyclyl is a non-aromatic 5- or 6-member ring containing one or two heteroatoms selected from a group comprising nitrogen and oxygen; and where the aryl is phenyl or naphthyl; and where the heteroaryl is an aromatic 5- or 6-member ring, optionally condensed with another ring (which can be carbocyclic and aromatic or non-aromatic), having one or two heteroatoms selected from a group comprising nitrogen, or a pharmaceutically acceptable salt thereof. The invention also relates to a pharmaceutical composition based on said compounds.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine to treat a PDE4-mediated disease state.

10 cl, 81 dwg, 15 tbl, 375 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to novel tetrahydroisoquinolin-1-one derivatives of general formula or pharmaceutically acceptable salts thereof, where R1 is: lower alkylene-OH, lower alkylene-N(R0)(R6), lower alkylene-CO2R0, C5-6cycloalkyl, C6-10cycloalkenyl, aryl, heterocyclic group, -(lower alkylen, substituted OR0)-aryl or lower alkylene-heterocyclic group, where the lower alkylene in R1 can be substituted with 1-2 groups G1; cycloalkyl, cycloalkenyl and heterocyclic group in R1 can be substituted with 1-2 groups G2; aryl can be substituted with 1-2 groups G3; R0: identical or different from each other, each denotes H or a lower alkyl; R6: R0, or -S(O)2-lower alkyl, R2 is: lower alkyl, lower alkylene-OR0, lower alkylene-aryl, lower alkylene-O-lower alkylene-aryl, -CO2R0, -C(O)N(R0)2, -C(O)N(R0)-aryl, -C(O)N(R0)-lower alkylene-aryl, aryl or heterocyclic group, where the aryl in R2 can be substituted with 1-3 groups G4; R3 is: H or lower alkyl, or R2 and R3 can be combined to form C5-alkylene; R4 is: -N(R7)(R8), -N(R10)-OR7, -N(R0)-N(R0)(R7), -N(R0)-S(O)2-aryl or -N(R0)-S(O)2-R7, R7 is: lower alkyl, halogen-lower alkyl, lower alkylene-CN, lower alkylene-OR0, lower alkylene-CO2R0, lower alkylene-C(O)N(R0)2, lower alkylene-C(O)N(R0)N(R0)2, lower alkylene-C(=NOH)NH2, heteroaryl, lower alkylene-X-aryl or lower alkylene-X-heterocyclic group, where the lower alkylene in R7 can be substituted with 1-2 groups G1; aryl, heteroaryl and heterocyclic group in R7 can be substituted with 1-2 groups G6; X is: a single bond, -O-, -C(O)-, -N(R0)-, -S(O)p- or *-C(O)N(R0)-, where * in X has a value ranging from a bond to a lower alkylene, m is: an integer from 0 to 1, p is: is 2, R8 is: H, or R7 and R6 can be combined to form a lower alkylene-N(R9)-lower alkylene group, R9 is: aryl, R10 is: H, R5 is: lower alkyl, halogen, nitro, -OR0, -N(R0)2, or -O-lower alkylene-aryl, where the group G1 is: -OR0, N(R0)(R6) and aryl; group G2 is: lower alkyl, lower alkylene-OR0, -OR0, -N(R0)2, -N(R0)-lower alkylene-OR0, -N(R0)C(O)OR0, -N(R0)C(O)-lower alkylene-OR0, -N(R0)C(O)N(R0)2, -N(R0)C(=NR0)-lower alkyl, -N(R0)S(O)2-lower alkyl, -N(lower alkylene-CO2R0)-S(O)2-lower alkyl, -N(R0)S(O)2-aryl, -N(R0)S(O)2N(R0)2, -S(O)2-lower alkyl, -CO2R0, -CO2-lower alkylene-Si(lower alkyl)3, -C(O)N(R0)2, -C(O)N(R0)-lower alkylene-OR0, -C(O)N(R0)-lower alkylene-N(R0)2, -C(O)N(R0)-lower alkylene-CO2R0, -C(O)N(R0)-O-lower alkylene-heterocyclic group, -C(O)R0, -C(O)-lower alkylene-OR0, C(O)-heterocyclic group and oxo; under the condition that "aryl" in group G2 can be substituted with one lower alkyl; group G3 is: -OR0; group G4 is: halogen, CN, nitro, lower alkyl, -OR0, -N(R0)2) -CO2R0; group G5 is: halogen, -OR0, -N(R0)2 and aryl; group G6 is: halogen, lower alkyl which can be substituted with -OR0, halogen-lower alkyl which is substituted with -OR0, -OR0, -CN, -N(R0)2, -CO2R0, -C(O)N(R0)2, lower alkylene-OC(O)R0, lower alkylene-OC(O)-aryl, lower alkylene-CO2R0, halogen-lower alkylene-CO2R0, lower alkylene-C(O)]N(R0)2, halogen-lower alkylene-C(O)N(R0)2, -O-lower alkylene-CO2R0, -O-lower alkylene-CO2-lower alkylene-aryl, -C(O)N(R0)S(O)2-lower alkyl, lower alkylene-C(O)N(R0)S(O)2-lower alkyl, -S(O)2-lower alkyl, -S(O)2N(R0)2, heterocyclic group, -C(-NH)=NO-C(O)O-C1-10-alkyl, -C(=NOH)NH2, C(O)N=C(N(R0)2)2, -N(R0)C(O)R0, -N(R0)C(O)-lower alkylene-OR0, -N(R0)C(O)OR0, -C(aryl)3 and oxo; under the condition that the "heterocyclic group" in group G6 is substituted with 1 group selected from a group consisting of -OR0, oxo and thioxo (=S); where the "cycloalkenyl" relates to C5-10 cycloalkenyl, including a cyclic group which is condensed with a benzene ring at the site of the double bond; the "aryl" relates to an aromatic monocyclic C6-hydrocarbon group; the "heterocyclic group" denotes a cyclic group consisting of i) a monocyclic 5-6-member heterocycle having 1-4 heteroatoms selected from O, S and N, or ii) a bicyclic 8-9-member heterocycle having 1-3 heteroatoms selected from O, S and N, obtained via condensation of the monocyclic heterocycle and one ring selected from a group consisting of a monocyclic heterocycle, a benzene ring, wherein the N ring atom can be oxidised to form an oxide; the "heteroaryl" denotes pyridyl or benzimidazolyl; provided that existing compounds given in claim 1 of the invention are excluded. The invention also relates to a pharmaceutical composition based on the compound of formula (I), use of the compound of formula (I) and a method of treatment using the compound of formula (I).

EFFECT: obtaining novel tetrahydroisoquinolin-1-one derivatives which are useful as a BB2 receptor antagonist.

11 cl, 302 tbl, 59 ex

FIELD: chemistry.

SUBSTANCE: invention relates to complexes of lanthanides and organic ligands which are luminescent in the visible spectrum and are used in electroluminescent devices, means of protecting security paper and documents from falsification etc. Disclosed are novel luminescent coordination compounds of lanthanides of formula: where Ln is Eu3+, Tb3+, Dy3+, Sm3+, Gd3+.

EFFECT: said compounds have high luminescence intensity and considerable thermal tolerance of up to 400°C, which enables use thereof in modern production of light-emitting diodes.

4 dwg, 2 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to novel imidazopyridin-2-one derivatives of general formula or pharmacologically acceptable salts thereof, where (R1)n-A is a 1H-pyrrolo[2,3-b]pyridin-5-yl group, 3-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl group, 4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl group, 3-fluoro-1H-pyrrolo[2,3-b]pyridin-5-yl group, 4-fluoro-1H-pyrrolo[2,3-b]pyridin-5-yl group, 3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, 4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, 3,4-dimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, 3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group or 3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, B is a 3-6-member saturated or partially saturated monocyclic hydrocarbon group and can contain 1 or 2 oxygen atoms, a nitrogen atom and/or sulphonyl groups as ring components, B can have as substitutes identical or different R2 in amount of m, R2 is a substitute represented at a carbon atom or a nitrogen atom forming B, R2 is a substitute selected from a group consisting of a hydroxy group, a halogen atom, a cyano group, an oxo group, a C1-4alkyl group (where the C1-4 alkyl group can be substituted with 1 C1-4 alkoxy group) and a C1-4 alkoxy group, when R2 is a substitute represented at a carbon atom forming B, and R2 is a substitute selected from a group consisting of a C1-4 alkyl group and a C1-4 alkylcarbonyl group, when R2 is a substitute represented at a nitrogen atom forming B, m is any integer from 0 to 2, Q is a bond or a C1-4 alkylene group, R3 and R4 are identical or different and each denotes a hydrogen atom or a halogen atom, and R5 and R6 are identical or different and each denotes a hydrogen atom, a halogen atom or a C1-4 alkyl group. The invention also relates to specific compounds of formula (I), pharmacologically acceptable salts of compounds of formula (I), a pharmaceutical composition based on the compound of formula (I) and use of the compound of formula (I).

EFFECT: novel imidazopyridin-2-one derivatives, having mTOR inhibiting action, are obtained.

21 cl, 161 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new imidazo[4,5-b]pyrazine derivatives of general formula or to its pharmaceutically acceptable salt wherein: R1 represents either aryl unsubstituted or substituted by one of the groups: halogen, hydoxyl, C1-6alkyl, C1-6alkoxyl, NH2, NHC1-6alkyl, N(C1-6alkyl)2, NHC1-6alkylC1-6alkoxy, C1-6alkylhydroxy, -C(O)NH2, -C(O)OC1-6alkyl, -C(O)NH C1-6alkyl, cyano, carboxy, heteroaryl and heterocycloalkyl; or heteroaryl unsubstituted or substituted by one of the groups: C1-6alkoxy, hydroxy, -C1-6alkyl, NH2 and NHC1-6alkyl; heterocycloalkyl unsubstituted or substituted by one group =O; and R2 represents H; unsubstituted C3-4alkyl; C1-4alkyl substituted by C5-6cycloalkyl unsubstituted or substituted by one group specified in amino, hydroxyl, C1-6alkoxy, or heterocycloalkyl unsubstituted or substituted by 1-2 groups specified in =O, C1-6alkyl; or C5-6cycloalkyl substituted by one group specified in hydroxyl, C1-6alkoxyl, C1-6alkylC1-6alkoxy, C1-6alkylhydroxy, CONH2; or substituted ir unsubstituted heterocycloalkyl; wherein aryl represents an aromatic structure consisting of 6-10 carbon atoms containing one ring or two condensed rings; wherein heteroaryl represents a 5-10-member aryl ring system containing 1-2 heteroatoms specified in nitrogen, oxygen and sulphur; wherein heterocycloalkyl represents a 5-9-member nonaromatic cycloalkyl wherein 1-2 heteroatoms specified in nitrogen and oxygen; provided the compound does not represent 1,3-dihydro-5-phenyl-2H-imidazo[4,5-b]pyrazin-2-one. Also, the invention refers to the specific imidazo[4,5-b]pyrazine derivatives, to a based pharmaceutical composition, to a method of treating or preventing cancer, inflammatory conditions, immunological diseases, metabolic conditions, and to a method of kinase inhibition in a cell expressing said kinase.

EFFECT: there are produced new imidazo[4,5-b]pyrazine derivatives showing effective biological properties.

17 cl, 2 tbl, 210 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula

and

possessing the protein kinase inhibitor property, their pharmaceutically acceptable salts, solvates and hydrates, as well as to the use thereof and a based pharmaceutical composition. In general formula (1) X1 represents N, CRt1; X2 represents N, CRt2, X3 represents N, CRt3, X4 represents N, CH and wherein X1, X2, X3 and X4 are independently specified; Rt1 represents -H, halogen, -COOH, -CH3, -CH2CH3, -OH, -OCH3, -OCH2CH3, -CN, -CH3OH; Rt2 represents -H, halogen, -CH3, -CH2CH3, -OH, -OCH3, -OCH2CH3, -CN, CH2OH, -NH2; Rt3 represents -H, -S(O)rR4, halogen, -CN, -COOH, -CONH2, -COOCH3, -COOCH2CH3; the cycle A represents phenyl or a 6-member heteroaryl cycle, wherein heteroaryl contains 1-2 heteroatoms specified in N optionally substituted by 1-4 groups R'; the cycle B represents phenyl or a 5- or 6-member heteroaryl cycle, wherein heteroaryl contains 1-2 heteroatoms specified in N, S optionally substituted by 1-5 groups Rb; Ra and Rb are independently specified and represent -H, halogen, -CN, -R6, -OR4, -NR4R5, -C(O)YR4, -S(O)rR4, -SO2NR4R5, -NR4SO2NR4R5 wherein Y is independently specified and represents a chemical bond, -O-, -S-, -NR3-; L1 represents NR3C(O) or C(O)NR3; R3, R4 and R5 are independently specified and represent H, C1-C6-alkyl, and also the group NR4 R5 may represent a 5- or 6-member saturated or aromatic cycle; in each case R6 is independently specified and represents C1-C6-alkyl optionally substituted by C1-C6- alkyl or 5-6 merous heterocyclyl which may be substituted by C1-C6-alkyl; r is equal to 0; In general formula (II) Z represents CH; X, represents CRt1; X2 represents CRt2, X3 represents CRt3 X4 represents CH and wherein X1, X2, X3 and X4 are independently specified; Rt1 represents -H; Rt2 represents -H, -F; Rt3 represents -H, -F; the cycle A represents phenyl or 6-member heteroaryl cycle wherein heteroaryl contains 1-2 heteroatoms specified in N optionally substituted by 1-4 groups R3; the cycle B represents phenyl or a 5- or 6-member heteroaryl cycle wherein heteroaryl contains 1-2 heteroatoms specified in N, S optionally substituted by 1-5 groups Rb, Ra and Rb are independently specified and represent -H, halogen, -CN, -R6, -OR4, -NR4R5, -C(O)YR4, -S(O)rR4, -SO2NR4R5 wherein Y is independently specified and represents a chemical bond, -NR3-; L represents NR3C(O) or C(O)NR3; R4 and R5 are independently specified and represent H, C1-C6-alkyl, also the group NR4R3 may represent a 6-member saturated cycle; in each case R6 is independently specified and represents, C1-C6-alkyl optionally substituted by C1-C6-alkyl or 5-6 member heterocyclyl which may be substituted by C1-C6-alkyl; r is equal to 0; m is equal to 1; p is equal to 1.2.

EFFECT: preparing the compounds possessing the protein kinase inhibitor property.

16 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted N-phenylpyrrolidinyl methylpyrrolidine amides of formula , where R, R1, R2 and R3 are identical or different and independently denote H, (C1-C4)alkyl, CF3; R4 denotes phenyl, cyclohexyl, pyridinyl, furanyl, isoxazolyl, quinolinyl, naphthyridinyl, indolyl, benzoimidazolyl, benzofuranyl, chromanyl, 4-oxo-4H-chromenyl, 2,3-dihydrobenzofuranyl, benzo[1,3]dioxolyl and 2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[e]][1,4]diazepinyl; where said R4 is optionally substituted one to more times with a substitute selected from halogen, hydroxy, (C1-C4) alkyl, (C1-C4) alkoxy, CF3, hydroxymethyl, 2-hydroxyethylamino, methoxyethylamide, benzyloxymethyl, piperidinyl, N-acetylpiperidinyl, pyrrolyl, imidazolyl, 5-oxo-4,5-dihydropyrazolyl; or pharmaceutically acceptable salt thereof or enantiomer or diastereomer thereof.

EFFECT: compounds have modulating activity on histamine H3 receptor, which enables use thereof to prepare a pharmaceutical composition.

10 cl, 3 dwg, 29 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted N-phenylbipyrrolidine carboxamides of formula , where values of R, R1, R2, R3 and R4 are given in claim 1.

EFFECT: compounds have activity which binds to the H3 ligand, which allows use thereof in pharmaceutical compositions for treating sleep disorder.

10 cl, 1 tbl, 4 dwg, 153 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to novel tetrahydroisoquinolin-1-one derivatives of general formula or pharmaceutically acceptable salts thereof, where R1 is: lower alkylene-OH, lower alkylene-N(R0)(R6), lower alkylene-CO2R0, C5-6cycloalkyl, C6-10cycloalkenyl, aryl, heterocyclic group, -(lower alkylen, substituted OR0)-aryl or lower alkylene-heterocyclic group, where the lower alkylene in R1 can be substituted with 1-2 groups G1; cycloalkyl, cycloalkenyl and heterocyclic group in R1 can be substituted with 1-2 groups G2; aryl can be substituted with 1-2 groups G3; R0: identical or different from each other, each denotes H or a lower alkyl; R6: R0, or -S(O)2-lower alkyl, R2 is: lower alkyl, lower alkylene-OR0, lower alkylene-aryl, lower alkylene-O-lower alkylene-aryl, -CO2R0, -C(O)N(R0)2, -C(O)N(R0)-aryl, -C(O)N(R0)-lower alkylene-aryl, aryl or heterocyclic group, where the aryl in R2 can be substituted with 1-3 groups G4; R3 is: H or lower alkyl, or R2 and R3 can be combined to form C5-alkylene; R4 is: -N(R7)(R8), -N(R10)-OR7, -N(R0)-N(R0)(R7), -N(R0)-S(O)2-aryl or -N(R0)-S(O)2-R7, R7 is: lower alkyl, halogen-lower alkyl, lower alkylene-CN, lower alkylene-OR0, lower alkylene-CO2R0, lower alkylene-C(O)N(R0)2, lower alkylene-C(O)N(R0)N(R0)2, lower alkylene-C(=NOH)NH2, heteroaryl, lower alkylene-X-aryl or lower alkylene-X-heterocyclic group, where the lower alkylene in R7 can be substituted with 1-2 groups G1; aryl, heteroaryl and heterocyclic group in R7 can be substituted with 1-2 groups G6; X is: a single bond, -O-, -C(O)-, -N(R0)-, -S(O)p- or *-C(O)N(R0)-, where * in X has a value ranging from a bond to a lower alkylene, m is: an integer from 0 to 1, p is: is 2, R8 is: H, or R7 and R6 can be combined to form a lower alkylene-N(R9)-lower alkylene group, R9 is: aryl, R10 is: H, R5 is: lower alkyl, halogen, nitro, -OR0, -N(R0)2, or -O-lower alkylene-aryl, where the group G1 is: -OR0, N(R0)(R6) and aryl; group G2 is: lower alkyl, lower alkylene-OR0, -OR0, -N(R0)2, -N(R0)-lower alkylene-OR0, -N(R0)C(O)OR0, -N(R0)C(O)-lower alkylene-OR0, -N(R0)C(O)N(R0)2, -N(R0)C(=NR0)-lower alkyl, -N(R0)S(O)2-lower alkyl, -N(lower alkylene-CO2R0)-S(O)2-lower alkyl, -N(R0)S(O)2-aryl, -N(R0)S(O)2N(R0)2, -S(O)2-lower alkyl, -CO2R0, -CO2-lower alkylene-Si(lower alkyl)3, -C(O)N(R0)2, -C(O)N(R0)-lower alkylene-OR0, -C(O)N(R0)-lower alkylene-N(R0)2, -C(O)N(R0)-lower alkylene-CO2R0, -C(O)N(R0)-O-lower alkylene-heterocyclic group, -C(O)R0, -C(O)-lower alkylene-OR0, C(O)-heterocyclic group and oxo; under the condition that "aryl" in group G2 can be substituted with one lower alkyl; group G3 is: -OR0; group G4 is: halogen, CN, nitro, lower alkyl, -OR0, -N(R0)2) -CO2R0; group G5 is: halogen, -OR0, -N(R0)2 and aryl; group G6 is: halogen, lower alkyl which can be substituted with -OR0, halogen-lower alkyl which is substituted with -OR0, -OR0, -CN, -N(R0)2, -CO2R0, -C(O)N(R0)2, lower alkylene-OC(O)R0, lower alkylene-OC(O)-aryl, lower alkylene-CO2R0, halogen-lower alkylene-CO2R0, lower alkylene-C(O)]N(R0)2, halogen-lower alkylene-C(O)N(R0)2, -O-lower alkylene-CO2R0, -O-lower alkylene-CO2-lower alkylene-aryl, -C(O)N(R0)S(O)2-lower alkyl, lower alkylene-C(O)N(R0)S(O)2-lower alkyl, -S(O)2-lower alkyl, -S(O)2N(R0)2, heterocyclic group, -C(-NH)=NO-C(O)O-C1-10-alkyl, -C(=NOH)NH2, C(O)N=C(N(R0)2)2, -N(R0)C(O)R0, -N(R0)C(O)-lower alkylene-OR0, -N(R0)C(O)OR0, -C(aryl)3 and oxo; under the condition that the "heterocyclic group" in group G6 is substituted with 1 group selected from a group consisting of -OR0, oxo and thioxo (=S); where the "cycloalkenyl" relates to C5-10 cycloalkenyl, including a cyclic group which is condensed with a benzene ring at the site of the double bond; the "aryl" relates to an aromatic monocyclic C6-hydrocarbon group; the "heterocyclic group" denotes a cyclic group consisting of i) a monocyclic 5-6-member heterocycle having 1-4 heteroatoms selected from O, S and N, or ii) a bicyclic 8-9-member heterocycle having 1-3 heteroatoms selected from O, S and N, obtained via condensation of the monocyclic heterocycle and one ring selected from a group consisting of a monocyclic heterocycle, a benzene ring, wherein the N ring atom can be oxidised to form an oxide; the "heteroaryl" denotes pyridyl or benzimidazolyl; provided that existing compounds given in claim 1 of the invention are excluded. The invention also relates to a pharmaceutical composition based on the compound of formula (I), use of the compound of formula (I) and a method of treatment using the compound of formula (I).

EFFECT: obtaining novel tetrahydroisoquinolin-1-one derivatives which are useful as a BB2 receptor antagonist.

11 cl, 302 tbl, 59 ex

Amide compound // 2479576

FIELD: chemistry.

SUBSTANCE: compounds exhibit antagonistic activity towards the EP4 receptor, which enables use thereof as an active ingredient in a pharmaceutical composition for treating chronic kidney disease or diabetic nephropathy.

EFFECT: high efficiency of the compounds.

27 cl, 228 tbl, 86 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I or use thereof to prepare a medicine for treating depression, anxiety or both: or pharmaceutically acceptable salts thereof, where m is 0-3; n is 0-2; Ar is: optionally substituted indolyl; optionally substituted indazolyl; azaindolyl; 2,3-dihydro-indolyl; 1,3-dihydro-indol-2-one-yl; optionally substituted benzothiophenyl; benzothiazolyl; benzisothiazolyl; optionally substituted quinolinyl; 1,2,3,4-tetrahydroquinolinyl; quinolin-2-one-yl; optionally substituted naphthalenyl; optionally substituted pyridinyl; optionally substituted thiophenyl or optionally substituted phenyl; R1 is: C1-6alkyl; hetero-C1-6alkyl; halo-C1-6alkyl; halo-C2-6alkenyl; C3-7cycloalkyl; C3-7cycloalkyl-C1-6alkyl; C1-6alkyl-C3-6cycloalkyl-C1-6alkyl; C1-6alkoxy; C1-6alkylsulphonyl; phenyl; tetrahydropyranyl-C1-6alkyl; phenyl-C1-3alkyl, where the phenyl part is optionally substituted; heteroaryl-C1-3alkyl; R2 is: hydrogen or C1-6alkyl; and each Ra and Rb is independently: hydrogen; C1-6alkyl; C1-6alkoxy; halo; hydroxy or oxo; or Ra and Rb together form C1-2alkylene; under the condition that, when m is 1, n is 2, and Ar is an optionally substituted phenyl, then R1 is not methyl or ethyl, and where optionally substituted denotes 1-3 substitutes selected from alkyl, cycloalkyl, alkoxy, halo, haloalkyl, haloalkoxy, cyano, amino, acylamino, monoalkylamino, dialkylamino, hydroxyalkyl, alkoxyalkyl, pyrazolyl, -(CH2)q-S(O)rRf; -(CH2)q-C(=O)-NRgRh; -(CH2)q-N(Rf)-C(=O)-Ri or -(CH2)q-C(=O)-Ri; where q is 0, r is 0 or 2, each Rf, Rg and Rh is independently hydrogen or alkyl, and each Ri is independently alkyl, and where "heteroaryl" denotes a monocyclic radical having 5-6 ring atoms, including 1-2 ring heteroatoms selected from N or S, wherein the rest of the ring atoms are C atoms, "heteroalkyl" denotes an alkyl radical, including a branched C4-C7-alkyl, where one hydrogen atom is substituted by substitutes selected from a group consisting of -ORa, -NRbH, based on the assumption that the bonding of heteroalkyl radical occurs through a carbon atom, where Ra is hydrogen or C1-6alkyl, Rb is C1-6alkyl. Pharmaceutical compositions based on said compound are also disclosed.

EFFECT: obtaining novel compounds which can be used in medicine to treat depression, anxiety or both.

14 cl, 1 tbl, 28 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new derivatives of ((phenyl)imidazolyl)methylheteroaryl of formula wherein A represents pyridyl or thienyl having 0 or 1 substitute; B represents phenyl having 0, 1 or 2 substitutes; wherein each substitute independently represents alkyl having 1 to 8 carbon atoms, -F, -Cl, -Br or -CF3. Also, the invention refers to the use of the declared compounds for the purpose of preparing a therapeutic agent, a pharmaceutical composition on the basis of the declared compounds, and to a kit containing the pharmaceutical composition above.

EFFECT: there are prepared new derivatives of ((phenyl)imidazolyl)methylheteroaryl effective in pain management.

10 cl, 1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new indanone derivatives which may be preferentially used for treating and/or preventing a medical state for which cholinesterase inhibition is desired.

EFFECT: there are presented the new indanone derivatives which may be preferentially used for treating and/or preventing a medical state for which cholinesterase inhibition is desired.

11 cl, 36 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula

and

possessing the protein kinase inhibitor property, their pharmaceutically acceptable salts, solvates and hydrates, as well as to the use thereof and a based pharmaceutical composition. In general formula (1) X1 represents N, CRt1; X2 represents N, CRt2, X3 represents N, CRt3, X4 represents N, CH and wherein X1, X2, X3 and X4 are independently specified; Rt1 represents -H, halogen, -COOH, -CH3, -CH2CH3, -OH, -OCH3, -OCH2CH3, -CN, -CH3OH; Rt2 represents -H, halogen, -CH3, -CH2CH3, -OH, -OCH3, -OCH2CH3, -CN, CH2OH, -NH2; Rt3 represents -H, -S(O)rR4, halogen, -CN, -COOH, -CONH2, -COOCH3, -COOCH2CH3; the cycle A represents phenyl or a 6-member heteroaryl cycle, wherein heteroaryl contains 1-2 heteroatoms specified in N optionally substituted by 1-4 groups R'; the cycle B represents phenyl or a 5- or 6-member heteroaryl cycle, wherein heteroaryl contains 1-2 heteroatoms specified in N, S optionally substituted by 1-5 groups Rb; Ra and Rb are independently specified and represent -H, halogen, -CN, -R6, -OR4, -NR4R5, -C(O)YR4, -S(O)rR4, -SO2NR4R5, -NR4SO2NR4R5 wherein Y is independently specified and represents a chemical bond, -O-, -S-, -NR3-; L1 represents NR3C(O) or C(O)NR3; R3, R4 and R5 are independently specified and represent H, C1-C6-alkyl, and also the group NR4 R5 may represent a 5- or 6-member saturated or aromatic cycle; in each case R6 is independently specified and represents C1-C6-alkyl optionally substituted by C1-C6- alkyl or 5-6 merous heterocyclyl which may be substituted by C1-C6-alkyl; r is equal to 0; In general formula (II) Z represents CH; X, represents CRt1; X2 represents CRt2, X3 represents CRt3 X4 represents CH and wherein X1, X2, X3 and X4 are independently specified; Rt1 represents -H; Rt2 represents -H, -F; Rt3 represents -H, -F; the cycle A represents phenyl or 6-member heteroaryl cycle wherein heteroaryl contains 1-2 heteroatoms specified in N optionally substituted by 1-4 groups R3; the cycle B represents phenyl or a 5- or 6-member heteroaryl cycle wherein heteroaryl contains 1-2 heteroatoms specified in N, S optionally substituted by 1-5 groups Rb, Ra and Rb are independently specified and represent -H, halogen, -CN, -R6, -OR4, -NR4R5, -C(O)YR4, -S(O)rR4, -SO2NR4R5 wherein Y is independently specified and represents a chemical bond, -NR3-; L represents NR3C(O) or C(O)NR3; R4 and R5 are independently specified and represent H, C1-C6-alkyl, also the group NR4R3 may represent a 6-member saturated cycle; in each case R6 is independently specified and represents, C1-C6-alkyl optionally substituted by C1-C6-alkyl or 5-6 member heterocyclyl which may be substituted by C1-C6-alkyl; r is equal to 0; m is equal to 1; p is equal to 1.2.

EFFECT: preparing the compounds possessing the protein kinase inhibitor property.

16 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel isoquinolinone derivatives of formula (I) , wherein R1 is selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (CH2)a-X-Ar and (CR101R102)a-X-Ar, where said (C1-C6)alkyl is optionally substituted with 1, 2 or 3 groups independently selected from -(C1-C6)alkoxy, -halogen, -OH, -heterocycloalkyl, (C3-C7)cycloalkyl and -NR8R9; R2 is selected from H and (C1-C6)alkyl; R is selected from H, (C1-C6)alkyl and (CH2)d-Y; provided that when R3 is (CH2)d-Y, R2 is selected from H; R4 and R5 are independently selected from H, (C1-C6)alkyl and halogen; R is (C3-C7)cycloalkyl; R7 is H; Ar is phenyl or heteroaryl, optionally substituted with 1, 2 or 3 groups independently selected from -(C1-C6)alkyl, -(CH2)e-O-(C1-C6)alkyl, -(CH2)e-S(O)f(C1-C6)alkyl, -(CH2)e-N(R10)-(C1-C6)alkyl, -(CH2)e-Z-(C1-C6)alkyl, -halogen, heterocycloalkyl, -C(O)NR8R9, -NR8R9 and -C(O)OH, where (C1-C6)alkyl in each case is independently optionally substituted with 1, 2 or 3 groups, independently selected from -NRI2R13; X is selected from a single bond; Y is NR16R17, where R16 and R17 together with a nitrogen atom with which they are bonded form a 5-7-member ring, optionally containing an additional heteroatom NR27, where said ring is optionally substituted on the carbon atom with 1 or 2 substitutes independently selected from -(C1-C6)alkyl, where said -(C1-C6)alkyl is optionally substituted with -OH; and where R27 is selected from H and (C1-C6)alkyl, where said (C1-C6)alkyl is optionally substituted with -OH; Z is selected from C(O)N(R18); R8 and R9 are independently selected from H and (C1-C6)alkyl, where said (C1-C6)alkyl is optionally substituted with 1, 2 or 3 groups, independently selected from NR19R20; or R8 and R9 together with the nitrogen atom with which they are bonded form a 5-6-member ring, optionally containing an additional heteroatom, selected from NR21; R12 and R13 are independently selected from H and (C1-C6)alkyl, where said (C1-C6)alkyl is optionally substituted with -(C1-C6)alkoxy, -OH; or R12 and R13 together with the nitrogen atom with which they are bonded form a 5-6-member ring optionally containing an additional heteroatom selected from NR24; R10, R18, R19, R20, R21, R22, R23 and R24 are independently selected from H and (C1-C6)alkyl; a is selected from 1, 2, 3, 4, 5 and 6; d equals 0 or 1; e equals 0; f is independently selected from 1 and 2; where the heterocycloalkyl is a 5-6-member non-aromatic cyclic ring bonded at a C atom, having 1-2 NR28 atoms; optionally having one double bond; the heteroaryl is a 6-member aromatic ring containing 1 N atom; R is selected from H, (C1-C6)alkyl and -C(O)O-(C1-C6)alkyl; R101 is (C1-C6)alkyl; R102 is H; or pharmaceutically acceptable salts thereof or N-oxides. The invention also relates to methods of producing said compounds and use thereof as a p38 kinase inhibitor.

EFFECT: improved method.

13 cl, 4 dwg, 1 tbl, 128 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof: (I) where R1, R2 and R3, which are identical or different, denote H, lower alkyl; R4, R5, R6, R7 and R8, which are identical or different, denote H, lower alkyl, halogen, nitro, -X-OR0, -X-NR10R11, -X-NR0C(O)R10, -X-O-halogen lower alkyl, -X-O-X-phenyl; or R6 and R7 are combined to form -O-lower alkylene-O-; R, which is identical or different, denotes H, lower alkyl; R10, R11, which are identical or different, denote H, lower alkyl; X, which is identical or different, denotes a bond, lower alkylene.

EFFECT: compounds exhibit type 5 17βHSD inhibiting activity, which enables their use in producing a pharmaceutical composition and in a method of inhibiting type 5 17βHSD.

15 cl, 11 tbl, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to specific compounds of 1-substituted 3,4-tetrahydroisoquinoline derivative. Invention also relates to pharmaceutical composition based on claimed compounds, to blocker of N-type Ca2+- channel based on claimed compounds, to application of claimed compounds, as well as to method of prevention or treatment of some pathologic conditions.

EFFECT: obtained are novel 3,4-tetrahydroisoquinoline derivatives, having substituent in 1-position and possessing blocking action on N-type Ca2+- channels.

15 cl, 129 tbl, 17 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of dihydroquinone and dihydronaphthyridinone of formula (I) or to its pharmaceutically acceptable salts, in which X represents group CR11 or N; Y represents group -C(O)R3, oxazolyl or isoxazolyl; Z represents phenyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydropyranyl, pyridinyl, pyrimidinyl or pyrazolyl, and is substituted with groups R1 and R2; R1 and R2 each independently represents H, halogen, CN group, C1-6alkyl or group -Y1-Y2-Y3-R8, or R1 and R2 together form group -O(CH2)nO-, where n represents 1 or 2; Y1 represents group -O-, -C(O)-, -C(O)O-, -C(O)NR9-, -NR9C(O), -S-, -SO2- or bond; Y2 represents heterocycloalkylene, C1-6alkylene or bond, where heterocycloalkylene stands for cycloalkylene group, in which one, two carbon atoms are substituted with heteroatoms O or N, where heterocycloalkylene group also contains, at least, two carbon atoms and cycloalkylene represents ; Y3 represents group -O-, -C(O)-, -C(O)O-, -C(O)NR9-, -NR9C(O)-, -SO2- or bond; R8 represents H, C1-6alkyl, C1-6alkoxy, cyclohexyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, tetrahydropyranyl, or group -NR9R10, where R8, different from H, is optionally substituted with C1-6alkyl, halogen, group -CF3 or group -OH; R9 and R10 each independently represents H or C1-6alkyl; R3 represents OH, C1-6alkyl, C1-6alkoxy, (C1-6alkoxy)-C1-6alkoxy; R4 represents C1-6alkyl, phenyl, cyclopropyl, cyclobutyl, cyclobutyl, cyclohexyl, tetrahydropyranyl or tetrahydrothiophene 1,1 -dioxide, and is optionally substituted with C1-6alkyl, hydroxyl group, C1-6alkoxy, halogen, nitro group, amino group, cyano group or halo-lower alkyl; R5 and R6 each independently represents H, halogen, C1-6alkyl, group -CF3, C1-6alkoxy; R7 represents H; R11 represents H. Invention also re4lates to pharmaceutical composition based on formula (I) compound.

EFFECT: obtained are novel dihydroquinone and dihydronaphthyridinone derivatives, useful for treatment of disease mediated by JNK kinase.

9 cl, 4 tbl, 38 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof. In formula (I): X denotes a single bond or a binding group selected from -CO, -SO2-, -CS- or -CH2-; Y denotes a single bond or a divalent binding group obtained from a cyclic structure selected from benzene, pyridine, pyrimidine, pyrazole, imidazole, thiazole, thiophene, quinoline, benzoimidazole, benzothiazole, benzopyrazole, naphthalene and benzothiophene; X and Y are simultaneously single bonds; Z denotes a hydrogen atom or a substitute selected from a group A; m equals 1 or 2; n equals 0-3; in group A and group B, R, R' and R" can, respectively and independently, be identical or different and denote a hydrogen atom or -C1-6-alkyl; said -C1-6-alkyl can be substituted with a group selected from -OH, -O(C1-6-alkyl),-CONH2, -CONH(C1-6-alkyl), -CON(C1-6-alkyl)2, -NH2, -NH(C1-6-alkyl) and -N(C1-6-alkyl)2); Sus denotes a C3-C7 saturated or a C5-C10 unsaturated hydrocarbon ring or a nitrogen-containing C3-C7 heterocyclic ring containing 1-4 nitrogen atoms or containing an additional O, S atom; said C1-6 alkylene in groups A and B can be substituted in positions 1-3 with a -N(C1-6- alkyl)2 group, values of radicals R1, A1, T, B and Q are given in the claim. The invention also relates to a pharmaceutical composition containing said compounds, a PI3K inhibitor and a medicinal agent having PI3K inhibitor properties against a proliferative diseases such as a malignant tumour.

EFFECT: high efficiency of using the compounds.

21 cl, 645 ex

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