Indolyl derivatives as liver x-receptor modulators

FIELD: chemistry.

SUBSTANCE: invention relates to formula (I) compounds and to their use in treating diseases related to lipid storage disorders, such as atherosclerosis and diabetes. In R1 represents hydrogen, alkyl, halogen, formyl, hydroxyalkyl or trifluoromethyl, R2 represents hydrogen, alkyl or halogen, R3 represents hydrogen or alkyl, R4 represents hydrogen, alkyl, hydroxy or alkoxy, R5 and R6 are chosen from hydrogen, alkyl, phenylalkyl, hydroxyalkyl, alkoxycarbonyl and phenyl, A represents aryl or heterocyclyl, m equals 0-3, n equals 0-1, p equals 0-3, sum of m, n and p equals 1-4, the bond between carbon atoms Ca and Cb is a single or double carbon-carbon bond.

EFFECT: obtaining new biologically active compounds.

27 cl, 147 ex

 

The text descriptions are presented in facsimile form.

1. The compounds of formula (I)

where R1means hydrogen, alkyl, halogen, formyl, hydroxyalkyl or trifluoromethyl,
R2means hydrogen, alkyl or halogen,
R3means hydrogen or alkyl,
R4means hydrogen, alkyl, hydroxy or alkoxy,
R5and R6independently selected from the group comprising hydrogen, alkyl, phenylalkyl, hydroxyalkyl, alkoxycarbonyl and phenyl,
And means aryl selected from phenyl, biphenyl, naphthyl, benzhydryl, or heterocyclyl, which represents a 5-, 6-, 9-, 10-membered cycle, which contains one or two heteroatoms selected from nitrogen, oxygen and sulfur, where the phenyl, biphenyl, naphthyl, benzhydryl and heterocyclyl optionally substituted by 1-3 substituents, independently selected from the group comprising alkyl, halogen, amino, hydroxy, alkoxy, hydroxyalkyl, phenyl, tolyl, ethylphenyl, 4-fluoro-3-were, chlorophenyl, forfinal, triptoreline, tert-butylphenyl, isopropoxyphenyl, isopropylphenyl, methoxyphenyl, hydroxyphenyl hydroxyalkyloxy, carboxyphenyl, styryl, benzyl, phenylethyl, pyridinyl, triptoreline, fervency, alkoxycarbonyl, aminocarbonyl, carboxy, alkoxycarbonyl, alkoxycarbonylmethyl, aminoalkyl, trifluoromethyl, N,N-dimethylaminocarbonylmethyl, N,N-dimethylaminocarbonylmethyl, N-benzyl-N-methylaminomethyl, N-phenethyl-N-methylaminomethyl, N-phenylmethyl-N-methylaminomethyl, N-methyl-N-indolinecarboxylic, N-cyclohexyl-N-methylaminomethyl, N-pyridinylmethyl-N-methylaminomethyl, N-pyridinylmethyl-N-methylaminomethyl, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, alkoxycarbonylmethyl, indolealkylamines, morpholinylcarbonyl, morpholine-4-ylmethyl, aminocarbonyl, aminocarbonylmethyl, aminocarboxylate, alkoxycarbonyl, methoxycarbonylaminophenyl, pyridinedimethanol, aminocarboxylate, carboxyethyl, carboxylate, cycloalkylcarbonyl, morpholinylcarbonyl, morpholinylcarbonyl, pyrrolidinylcarbonyl, pyrrolidinylcarbonyl, piperidinylcarbonyl, piperazinylcarbonyl, pyridinyl, benzyloxyphenyl, methoxycarbonylaminophenyl, carboxymethoxy, ethoxycarbonylphenyl, N,N-dimethylaminocarbonylmethyl, aminocarbonylmethyl, aminocarbonylmethyl and piperidine-1-ylcarbonyl,
m is 0, 1, 2 or 3,
n ravno or 1,
p is 0, 1, 2 or 3, the sum of m, n and p is 1, 2, 3,or 4
where the bond between the carbon atoms Caand Cbrepresents a carbon-carbon single or double bond, and if the link between Caand Cbrepresents a carbon-carbon double bond, R3and R4no, the compound of formula I is 2-(1-benzyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexaferrite-2-ol, and pharmaceutically acceptable salts and pharmaceutically acceptable esters.

2. Compounds according to claim 1, where R1means hydrogen, alkyl, halogen, formyl, hydroxyalkyl or trifluoromethyl,
R2means hydrogen, alkyl or halogen,
R3means hydrogen or alkyl,
R4means hydrogen, alkyl, hydroxy or alkoxy,
R5and R6independently selected from the group comprising hydrogen, alkyl, phenylalkyl, hydroxyalkyl, alkoxycarbonyl and phenyl,
And means aryl selected from phenyl, biphenyl, naphthyl or benzhydryl, or heterocyclyl, which represents a 5-, 6-, 9-, 10-membered cycle, which contains one or two heteroatoms selected from nitrogen, oxygen and sulfur, where the phenyl, biphenyl, naphthyl, benzhydryl and heterocyclyl, optionally substituted by 1-3 substituents, independently selected from the group comprising alkyl, halogen, amino, hydroxyalkyl, phenyl, cryptometrics, alkoxy, Fe is ylmethyl, phenylethyl, alkoxycarbonyl, aminocarbonyl, carboxy, alkoxycarbonyl, alkoxycarbonylmethyl, aminoalkyl, trifluoromethyl, N-phenethyl-N-methylaminomethyl, N-phenylmethyl-N-methylaminomethyl, alkoxycarbonylmethyl, indolealkylamines, morpholinylcarbonyl, aminocarbonyl, aminocarbonylmethyl, aminocarboxylate, alkoxycarbonyl, N-pyridinylmethyl-N-methylaminomethyl, N-pyridinylmethyl-N-methylaminomethyl, methoxycarbonylaminophenyl, carboxymethoxy, N,N-dimethylaminocarbonylmethyl, aminocarbonyl, N,N-dimethylaminocarbonylmethyl, carboxyethyl, carboxylate, cycloalkylcarbonyl, morpholinylcarbonyl, morpholinylcarbonyl, benzyloxyphenyl, N,N-dimethylaminocarbonylmethyl, pyrrolidinylcarbonyl, pyrrolidinylcarbonyl, piperidinylcarbonyl, piperazinylcarbonyl, hydroxyalkyloxy and pyridinyl,
m is 0, 1, 2 or 3,
n is 0 or 1,
p is 0, 1, 2 or 3, the sum of m, n and p is 1, 2, 3,or 4
moreover, the connection does not mean 2-(1-benzyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexaferrite-2-ol,
and where the relationship between the carbon atoms Caand Cbrepresents a carbon-carbon single or double bond, and if the link between Caand Cbrepresents a carbon-carbon double the link, R3and R4no, and their pharmaceutically acceptable salts and pharmaceutically acceptable esters.

3. Compounds according to claim 1, where R1means methyl.

4. Compounds according to claim 1, where R2means hydrogen, alkyl or halogen.

5. Compounds according to claim 4, where R2means hydrogen.

6. Compounds according to claim 1, where R3means hydrogen.

7. Compounds according to claim 1, where R4means hydrogen.

8. Compounds according to claim 1, where m is 0 or 1.

9. Compounds according to claim 1, where n is equal to 0.

10. Compounds according to claim 1, where R is 0 or 1.

11. Compounds according to claim 1, where m is 1, n is 0 and p is 0.

12. Compounds according to claim 1, in which the bond between the carbon atoms Caand Cbis a simple carbon-carbon bond.

13. Compounds according to claim 1, in which the bond between the carbon atoms Caand Cbis a double carbon-carbon bond, and R3and R4no.

14. Compounds according to claim 1, where a represents phenyl, oxazolyl, chinoline, thiazolyl, naphthyl, benzothiophene, isoxazolyl, chinoline, pyridinyl, 2H-pyrazole-3-yl or isooxazolyl, and phenyl, oxazolyl, chinoline, thiazolyl, naphthalenyl, benzothiophene, isoxazolyl, chinoline, pyridinyl, 2H-pyrazole-3-yl or isooxazolyl optionally substituted by 1-3 substituents, independently selected from the group comprising alkyl, halogen, amino, hydroxyalkyl, f the Nile, cryptometrics, alkoxy, phenylmethyl, phenylethyl, alkoxycarbonyl, aminocarbonyl, carboxy, alkoxycarbonyl, alkoxycarbonylmethyl, aminoalkyl, trifluoromethyl, N-phenethyl-N-methylaminomethyl, N-phenylmethyl-N-methylaminomethyl, alkoxycarbonylmethyl, indolealkylamines, morpholinylcarbonyl, aminocarbonyl, aminocarbonylmethyl, aminocarboxylate, alkoxycarbonyl, N-pyridinylmethyl-N-methylaminomethyl, N-pyridinylmethyl-N-methylaminomethyl, methoxycarbonylaminophenyl, carboxymethoxy, N,N-dimethylaminocarbonylmethyl, aminocarbonyl, N,N-dimethylaminocarbonylmethyl, carboxyethyl, carboxylate, cycloalkylcarbonyl, morpholinylcarbonyl, morpholinylcarbonyl, benzyloxyphenyl, N,N-dimethylaminocarbonylmethyl, pyrrolidinylcarbonyl, pyrrolidinylcarbonyl, piperidinylcarbonyl.

15. Compounds according to claim 1, in which a represents phenyl, oxazol-2-yl or oxazol-4-yl, and phenyl, oxazol-2-yl and oxazol-4-yl optionally substituted by 1-3 substituents, independently selected from the group comprising alkyl, tolyl, ethylphenyl, triptoreline, forfinal, chlorophenyl, carboxymethoxy, aminocarbonylmethyl, carboxyphenyl, hydroxyphenyl, hydroxymethylene and aminocarbonylmethyl.

16. Compounds according to claim 1, where And who appoints phenyl.

17. Compounds according to claim 1, where a means oxazolyl substituted by one Deputy, which means alkyl, and the second Deputy, which means phenyl or pyridinyl, and phenyl substituted by hydroxyalkyl.

18. Connection 17, in which a represents 2-[4-(1-hydroxyethyl)phenyl]-5-methoxazole-4-ylmethyl, 2-[3-(1-hydroxyethyl)phenyl]-5-methoxazole-4-ylmethyl or 5-methyl-2-pyridin-3-isoxazol-4-ylmethyl.

19. Compounds according to claim 1, which is selected from the group comprising: 1,1,1,3,3,3-hexamer-2-[2-methyl-1-(5-methyl-2-meta-tolyloxy-4-ylmethyl)-1H-indol-5-yl]propan-2-ol,
2-(1-benzyl-3-chloro-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexaferrite-2-ol,
2-{1-[2-(4-ethylphenyl)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-{2-methyl-1-[5-methyl-2-(3-triptoreline)oxazol-4-ylmethyl]-1H-indol-5-yl}propane-2-ol,
2-(1-benzyl-3-fluoro-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-{1-[2-(2-forfinal)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(3-morpholine-4-iletileri)-1H-indol-5-yl]propan-2-ol,
methyl ester of 3-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]benzoic acid
2-[1-(3-dimethylaminomethylene)-2-methyl-1H-indol-5-yl]-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-{1-[2-(4-fluoro-3-were)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}about the EN-2-ol,
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(2-trifloromethyl-6-ylmethyl)-1H-indol-5-yl]propan-2-ol,
2-{1-[2-(3-chlorophenyl)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
2-{1-[2-(4-chlorophenyl)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-(2-methyl-1-quinoline-2-ylmethyl-1H-indol-5-yl)propan-2-ol,
1,1,1,3,3,3-hexamer-2-{2-methyl-1-[5-methyl-2-(4-triptoreline)oxazol-4-ylmethyl]-1H-indol-5-yl}propane-2-ol,
2-(1-benzyl-1H-indol-5-yl)-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-(2-methyl-1-phenethyl-1H-indol-5-yl)propan-2-ol,
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(5-methyl-2-phenyloxazol-4-ylmethyl)-1H-indol-5-yl]propan-2-ol,
2-(1-benzyl-2,3-dichloro-1H-indol-5-yl)-1,1,1,3,3,3-hexaferrite-2-ol,
2-{1-[2-(4-tert-butylphenyl)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
2-{1-[2-(4-chlorophenyl)-5-methylthiazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
2-(1-benzyl-2,3-diid-1H-indol-5-yl)-1,1,1,3,3,3-hexaferrite-2-ol,
1-benzyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-1H-indole-2-carbaldehyde,
2-(1-biphenyl-3-ylmethyl-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-(2-methyl-1-naphthalene-1-ylmethyl-1H-indol-5-yl)propan-2-ol,
2-(1-benzyl-3-iodine-1H-indol-5-yl)-1,1,1,3,3,3-hexaferrite-2-ol,
N-benzyl-N-methyl-3-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]ansamed,
methyl ester 4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]benzoic acid
N-methyl-3-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]-N-penicillinase,
ethyl ether (methyl-{3-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]benzoyl}amino)acetic acid,
3-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]benzoic acid,
N-[2-(1H-indol-3-yl)ethyl]-N-methyl-3-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]benzamide,
{3-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]phenyl}morpholine-4-ylmethanone,
N,N-dimethyl-3-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]benzamide,
N-methyl-3-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]-N-(2-pyridin-2-retil)benzamid,
N-methyl-3-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]-N-pyridin-2-ylmethylene,
2-[1-benzyl-2-(1-hydroxyethyl)-1H-indol-5-yl]-1,1,1,3,3,3-hexaferrite-2-ol,
1-[1-benzyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-1H-indol-2-yl]propan-1-ol,
1,1,1,3,3,3-hexamer-2-{1-[2-(4-isopropoxyphenyl)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-[1-(2-hydroxy-1-phenylethyl)-2-methyl-1H-indol-5-yl]propan-2-ol,
2-(1-benzyl-2-hydroxymethyl-1H-indol-5-yl)-1,1,1,3,3,3-hexaferrite-2-ol,
N-C is clohessy-N-methyl-3-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]benzamide,
2-[1-(5-chlorobenzo[b]thiophene-3-ylmethyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(5-methyl-3-phenylisoxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]propan-2-ol,
methyl ester 2-(2-chlorophenyl)-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-digidroid ol-1-ylmethyl]oxazole-5-carboxylic acid,
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(5-methyl-2-ortho-tolyloxy-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]propan-2-ol,
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(5-methyl-2-meta-tolyloxy-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]propan-2-ol,
2-(1-benzyl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexaferrite-2-ol,
2-{1-[2-(4-ethylphenyl)-5-methoxazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-[1-(3-hydroxymethylene)-2-methyl-2,3-dihydro-1H-indol-5-yl]propan-2-ol,
methyl ester of 3-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-ylmethyl]benzoic acid
1,1,1,3,3,3-hexamer-2-{1-[2-(2-forfinal)-5-methoxazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
2-{1-[2-(3-chlorophenyl)-5-methoxazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-{1-[2-(4-fluoro-3-were)-5-methoxazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-(2-methyl-1-phenethyl-2,3-dihydro-1H-indol-5-yl)propan-2-ol,
1,1,1,3,3,3-hexamer-2-{2-m is Teal-1-[5-methyl-2-(3-triptoreline)oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(5-methyl-2-phenyloxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]propan-2-ol,
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(2-trifloromethyl-6-ylmethyl)-2,3-dihydro-1H-indol-5-yl]propan-2-ol,
1,1,1,3,3,3-hexamer-2-{2-methyl-1-[5-methyl-2-(4-triptoreline)oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-(2-methyl-1-naphthalene-1-ylmethyl-2,3-dihydro-1H-indol-5-yl)propan-2-ol,
methyl ester [2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-yl]phenylacetic acid,
2-{1-[2-(4-chlorophenyl)-5-methoxazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-(2-methyl-1-quinoline-2-ylmethyl-2,3-dihydro-1H-indol-5-yl)propan-2-ol,
2-(1-biphenyl-3-ylmethyl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-{2-methyl-1-[4-(4-triptoreline)benzyl]-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
2-{1-[2-(4-tert-butylphenyl)-5-methoxazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
2-(1-benzhydryl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexaferrite-2-ol,
3-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-ylmethyl]benzoic acid,
methyl ester 4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-ylmethyl]benzoic acid
1,1,1,3,3,3-hexamer-2-[1-(2-hydroxy-1-phenylethyl)-2-methyl-2,3-dihydr what-1H-indol-5-yl]propan-2-ol,
2-{1-[2-(4-chlorophenyl)-5-methylthiazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-{1-[3-(4-pertenece)benzyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-{1-[2-(4-isopropoxyphenyl)-5-methoxazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-{2-methyl-1-[2-methyl-6-(4-triptoreline)pyridine-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
2-{1-[2-(2,5-diphenyloxazole-4-yl)ethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-{1-[2-(4-isopropylphenyl)-5-methoxazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-{1-[2-(2-methoxyphenyl)-5-methoxazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-{2-methyl-1-[5-methyl-2-(2-triptoreline)oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
2-{1-[2-(4-benzyloxyphenyl)-5-methoxazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
2-(1-benzyl-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-{2-methyl-1-[2-methyl-5-(4-triptoreline)-2H-pyrazole-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
2-{1-[2-ethyl-5-(4-triptoreline)-2H-pyrazole-3-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
methyl ester of (4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-digidroid the l-1-ylmethyl]oxazol-2-yl}phenoxy)acetic acid,
(4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-ylmethyl]oxazol-2-yl}phenoxy)acetic acid,
1,1,1,3,3,3-hexamer-2-{2-methyl-1-[2-(2-methyl-5-phenyloxazol-4-yl)ethyl]-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-{2-methyl-1-[4-methyl-2-(4-triptoreline)oxazol-5-ylmethyl]-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
N,N-dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-ylmethyl]oxazol-2-yl}phenoxy)ndimethylacetamide,
2-{1-[2-(3-benzyloxyphenyl)-5-methoxazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
methyl ester of 4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-ylmethyl]oxazol-2-yl}benzoic acid,
methyl ester of 3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-ylmethyl]oxazol-2-yl}benzoic acid,
3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-ylmethyl]oxazol-2-yl)benzoic acid,
4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-ylmethyl]oxazol-2-yl}benzoic acid,
methyl ester of 3-{4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-ylmethyl]oxazol-2-yl}benzoic acid,
2-{1-[2-(2,5-diphenyloxazole-4-yl)ethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexaplar--{1-[2-(4-isopropylphenyl)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-{1-[2-(2-methoxyphenyl)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-{2-methyl-1-[5-methyl-2-(2-triptoreline)oxazol-4-ylmethyl]-1H-indol-5-yl}propane-2-ol,
2-{1-[2-(4-benzyloxyphenyl)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenol,
4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenyl ether dimethylcarbinol acid,
1,1,1,3,3,3-hexamer-2-{2-methyl-1-[2-(5-methyl-2-phenyloxazol-4-yl)ethyl]-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-{2-methyl-1-[4-methyl-2-(4-triptoreline)oxazol-5-ylmethyl]-1H-indol-5-yl}propane-2-ol,
2-{1-[2-ethyl-5-(4-triptoreline)-2H-pyrazole-3-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-{2-methyl-1-[2-methyl-5-(4-triptoreline)-2H-pyrazole-3-ylmethyl]-1H-indol-5-yl}propane-2-ol,
methyl ester of (4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenoxy)acetic acid,
(4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenoxy)acetic acid,
2-{3-chloro-1-[2-(3-chlorophenyl)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-three is timetrail)indol-1-ylmethyl]oxazol-2-yl}phenyl ether pyrrolidin-1-carboxylic acid,
4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenyl ether morpholine-4-carboxylic acid,
2-(2-chlorophenyl)-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazole-5-carboxylic acid,
2-{1-[2-(2-chlorophenyl)-5-hydroxymethylimidazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
N,N-dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenoxy)ndimethylacetamide,
2-{1-[2-(3-benzyloxyphenyl)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenol,
3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenyl ether morpholine-4-carboxylic acid,
3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenyl ether dimethylcarbinol acid,
3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenyl ether pyrrolidin-1-carboxylic acid,
methyl ether (3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenoxy)acetic acid,
methyl ester of 3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}be what sainoi acid,
methyl ester of 4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}benzoic acid,
3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}benzoic acid,
1,1,1,3,3,3-hexamer-2-{1-[2-(3-hydroxymethylene)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}propane-2-ol,
4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}benzoic acid,
N,N-dimethyl-3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}benzamide,
(3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenoxy)acetic acid,
N,N-dimethyl-4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}benzamide,
1,1,1,3,3,3-hexamer-2-{1-[2-(4-hydroxymethylene)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}propane-2-ol,
2-[2,3-dimethyl-1-(5-methyl-2-phenyloxazol-4-ylmethyl)-1H-indol-5-yl]-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(5-methyl-2-ortho-tolyloxy-4-ylmethyl)-1H-indol-5-yl]propan-2-ol,
methyl ester 2-(2-chlorophenyl)-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazole-5-carboxylic acid,
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(5-methyl-3-phenylisoxazol-4-ylmethyl)-1H-indol-5-yl]propan-2-ol,
1,1,1,3,3,3-hexamer-2-{1-[3-(4-terfenol and)benzyl]-2-methyl-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-(2-methyl-1-naphthalene-2-ylmethyl-1H-indol-5-yl)propan-2-ol,
1,1,1,3,3,3-hexamer-2-(2-methyl-1-naphthalene-2-ylmethyl-2,3-dihydro-1H-indol-5-yl)propan-2-ol,
1,1,1,3,3,3-hexamer-2-{2-methyl-1-[2-methyl-6-(4-triptoreline)pyridine-3-ylmethyl]-1H-indol-5-yl}propane-2-ol and
{3-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]phenyl}piperidine-1-ylmethanone.

20. Compounds according to claim 1, selected from the group including:
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(5-methyl-2-meta-tolyloxy-4-ylmethyl)-1H-indol-5-yl]propan-2-ol,
2-(1-benzyl-3-chloro-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-{2-methyl-1-[5-methyl-2-(3-triptoreline)oxazol-4-ylmethyl]-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-{1-[2-(2-forfinal)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}propane-2-ol,
2-{1-[2-(3-chlorophenyl)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-(2-methyl-1-phenethyl-1H-indol-5-yl)propan-2-ol,
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(5-methyl-2-meta-tolyloxy-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]propan-2-ol,
2-{1-[2-(4-ethylphenyl)-5-methoxazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
2-{1-[2-(3-chlorophenyl)-5-methoxazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-(2-methyl-1-phenethyl-2,3-dihydro-1H-indol-5-yl)propan-2-ol,
1,1,1,3,3,3-hexamer-2-{2-IU the Il-1-[5-methyl-2-(3-triptoreline)oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
(4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-ylmethyl]oxazol-2-yl}phenoxy)acetic acid,
N,N-dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-ylmethyl]oxazol-2-yl}phenoxy)ndimethylacetamide,
3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-ylmethyl]oxazol-2-yl}benzoic acid,
4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-ylmethyl]oxazol-2-yl}benzoic acid,
4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenol,
(4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenoxy)acetic acid,
N,N-dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenoxy)ndimethylacetamide,
3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenol,
3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}benzoic acid,
1,1,1,3,3,3-hexamer-2-{1-[2-(3-hydroxymethylene)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}propane-2-ol,
4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}benzoic acid,
N,N-dimethyl-3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-triptime retil)indol-1-ylmethyl]oxazol-2-yl}benzamide,
(3-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}phenoxy)acetic acid,
N,N-dimethyl-4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)indol-1-ylmethyl]oxazol-2-yl}benzamide and
1,1,1,3,3,3-hexamer-2-{1-[2-(4-hydroxymethylene)-5-methoxazole-4-ylmethyl]-2-methyl-1H-indol-5-yl}propane-2-ol.

21. Compounds according to claim 1, selected from the group including:
TRANS-1,1,1,3,3,3-hexamer-2-[2-methyl-1-(5-methyl-2-storelocator-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]propan-2-ol,
2-[1-(2-benzyl-5-methoxazole-4-ylmethyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-1,1,1,3,3,3-hexaferrite-2-ol,
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(5-methyl-2-penetracion-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]propan-2-ol,
4-{5-methyl-4-[2-methyl-5-(2,2,2-Cryptor-1-hydroxy-1-trifloromethyl)-2,3-dihydroindol-1-ylmethyl]oxazol-2-yl}phenol,
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(5-methyl-2-penetracion-4-ylmethyl)-1H-indol-5-yl]propan-2-ol,
1,1,1,3,3,3-hexamer-2-{1-[2-(3-hydroxymethylene)-5-methoxazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-{1-[2-(4-hydroxymethylene)-5-methoxazole-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
1,1,1,3,3,3-hexamer-2-(1-{2-[4-(1-hydroxyethyl)phenyl]-5-methoxazole-4-ylmethyl}-2-methyl-1H-indol-5-yl)propan-2-ol,
1,1,1,3,3,3-hexamer-2-(1-{2-[3-(1-hydroxyethyl)phenyl]-5-methoxazole-4-ylmethyl}-2-methyl-1H-indol-5-yl)propan-2-ol,
(2R) ,1,1,3,3,3-hexamer-2-{2-methyl-1-[5-methyl-2-(3-triptoreline)oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}propane-2-ol,
(2S) 1,1,1,3,3,3-hexamer-2-{2-methyl-1-[5-methyl-2-(3-triptoreline)oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}propane-2-ol and
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(5-methyl-2-pyridin-3-isoxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]propan-2-ol and its pharmaceutically acceptable salts and pharmaceutically acceptable esters.

22. Compounds according to claim 1, selected from the group including:
1,1,1,3,3,3-hexamer-2-(1-{2-[4-(1-hydroxyethyl)phenyl]-5-methoxazole-4-ylmethyl}-2-methyl-1H-indol-5-yl)propan-2-ol,
1,1,1,3,3,3-hexamer-2-(1-{2-[3-(1-hydroxyethyl)phenyl]-5-methoxazole-4-ylmethyl}-2-methyl-1H-indol-5-yl)propan-2-ol and
1,1,1,3,3,3-hexamer-2-[2-methyl-1-(5-methyl-2-pyridin-3-isoxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]propan-2-ol and its pharmaceutically acceptable salts and pharmaceutically acceptable esters.

23. Compounds according to any one of claims 1 to 22 for use as therapeutically active substances.

24. Pharmaceutical composition having activity against elevated lipid levels, increased cholesterol levels, low levels of HDL cholesterol, elevated levels of LDL cholesterol, atherosclerotic diseases, diabetes, non-insulin-dependent diabetes mellitus, metabolic syndrome, dyslipidemia, sepsis, inflammatory diseases, skin diseases, colitis, pancreatitis, cholestasis of the liver, liver fibrosis, macular degeneration or disease Alch is imera, comprising the compound according to any one of claims 1 to 22 and a therapeutically inert carrier.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention covers thaizole derivatives of formula (I) and to their pharmaceutically acceptable salts. In formula I: X1 and X2 differ from each other and represent sulphur atom or carbon atom; R1 represents phenyl group; phenyl group substituted by 1-2 members chosen from the group including halogen atoms, alkoxygroup with 1-6 carbon atoms, hydroxygroup, phenylalkoxygroup with 7-12 carbon atoms; phenyl group fused with 5-7-membered heteroaromatic or nonaromatic ring with at least one heteroatom consisting of N, O and S; pyridyl group; R2 represents hydrogen atom, halogen atom, alkyl group with 1-6 carbon atoms, alkyl group with 1-6 carbon atoms substituted by 1-5 halogen atoms, alkoxygroup with 1-6 carbon atoms, or hydroxyalkyl group with 1-5 carbon atoms; A represents group which is presented by formula or . Also, the invention concerns ALK5 inhibitor containing compound of the invention as an active component, stimulators of hair follicles proliferation and hair growth, and also to thiazole derivative of formula where A1 represents .

EFFECT: higher efficiency.

12 cl, 2 tbl, 50 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: invented compounds have antagonist properties towards CB1 receptors. In formula (I) , R1 is a lower alkoxy, (lower alkyl amino)-(lower alkoxy) or -N(Ra)Rb; Ra is hydrogen, lower alkyl, carbamoyl-(lower alkyl), hydroxy-(lower alkyl), dihydroxy-(lower alkyl), lower alkynyl, lower alkoxy, (lower alkoxy)-(lower alkyl), di-(lower alkylamino)-(lower alkyl), C3-6cycloalkyl; or Ra is a phenyl-(lower alkyl) group, where the phenyl fragment can be optionally mono-substituted, independently, by lower alkyl, lower alkoxy or halogen; or Ra is a 5- or 6-member heteroaromatic ring system, containing one or two nitrogen atoms in the ring, where the said heteroaromatic ring system is bonded to the remaining part of the molecule by lower alkylene; or Ra is a 5-, 6- or 7-member saturated heterocyclic ring system, containing one nitrogen heteroatom, where the said heterocyclic ring system is optionally mono-substituted by lower alkyl; Rb is hydrogen, lower alkyl or (lower alkoxy)-(lower alkyl); or Ra and Rb together with a nitrogen atom to which they are bonded, for a 4-, 5- or 6-member saturated or partially unsaturated heterocyclic ring system, optionally containing an extra heteroatom, which is chosen from nitrogen, oxygen or sulphur, where the said heterocyclic ring system is optionally mono- or disubstituted, independently, by lower alkyl, hydroxy group, hydroxy-(lower alkyl), lower alkoxy, (lower alkoxy)-(lower alkyl) group, cyano group, halogen, phenyl and/or benzyl; R2 is hydrogen or lower alkyl; R3 is phenyl, mono- or disubstituted, independently, by lower alkoxy, halogen, or perfluoro-(low alkoxy) group; and R4 is phenyl, which is mono- or disubstituted with a halogen.

EFFECT: new compounds have useful biological properties.

18 cl, 195 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds with general formula (I) or pharmaceutically acceptable salts thereof, where R1 is chosen from a group containing optionally substituted C1-C6alkyl, lower alkoxy group, (lower)alkoxy(lower)alkyl, cycloalkyoxy(lower)alkyl, lower thioalkyl, (lower)alkylthio(lower)alkyl, cycloalkyl, cycloalkyl(lower)alkyl; R2 is chosen from a group containing optionally substituted (lower)alkyl, cycloalkyl, cycloalkyl(lower)alkyl; R3 is chosen from a group containing halogen, cyano group, optionally substituted (lower alkyl, lower thioalkyl, aryl, aryl(lower)alkyl, lower alkenyl, lower alkynyl); R4 is chosen from a group containing hydrogen, halogen, cyano group, hydroxyl group, optionally substituted (lower alkyl, lower alkoxy group, aryl, pyridyl, aryl(lower)alkyl, heteroaryl, which is an aromatic mono- or bicyclic hydrocarbon, containing from 5 to 9 ring atoms, from which one or more is a heteroatom, chosen from O, N or S, and an amino group) and a group, with formula R8-Z-(CH2)n-; where Z is a single bond or chosen from a group consisting of O, NH, CH2, CO, SO, SO2 or S; where R8 is chosen from a group containing optionally substituted (aryl, pyridyl); and where n=0, 1 or 2; R5 represents hydrogen; R6 is chosen from a group containing halogen, optionally substituted lower alkoxy group; R7 is one or more substitutes, independently chosen from a group containing hydrogen, optionally substituted lower alkoxy group; where the optional substitute or substitutes when R1-R8 are independently chosen from a group containing halogen, hydroxyl group, lower alkyl, mono- or di(lower)alkylamino group, aminocarbonyl, sulfinyl, sulfonyl, sulfanyl, mono- or di(lower)alkylaminocarbonyl, amino group, carboxyl group, lower alkoxy group, C3-C12cycloalkyl, (lower)alkylcarbonyl, (lower)alkoxycarbonyl, nitrile, aryl; all of which, except halogen, are independently optionally substituted with one or more substitutes, chosen from a group containing halogen, hydroxyl group, lower alkyl, sulfinyl, sulfonyl, sulfanyl, amino group, carboxyl group, lower alkoxy group, carbamoyl. Invention also relates to formula (I'), to a pharmaceutical composition, as well as use of formula (I) compounds given in paragraph 1.

EFFECT: obtaining new biologically active compounds, for preventing or treating bone diseases, associated with very low or resorption of calcium.

6 cl, 151 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new compounds with formula I where R1, R2, R3 and Y together with a formula I residue, are compounds, chosen from a group given in the formula of invention, or to their pharmaceutically used and split esters, or to their acid-additive salts, which promote release of parathyroid hormone.

EFFECT: compounds can be used for making medicinal agents, with antagonistic properties towards calcium sensitive parathyroid gland receptor for treating diseases mediated by effect of parathyroid hormone.

7 cl, 179 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of general formula (I): (I) where: R1 represents either direct or branched (C1-C7)alkyl, or (C2-C4)alkenyl; R2 represents piridinyl, thienyl, thiazol; R3 represents one or more substitutes chosen from halogen atoms and following groups; trifluoromethyl, direct or branched (C1-C6)alkyl; as free base or additive salt with acid. Additionally, the invention concerns medical product, pharmaceutical composition, and application.

EFFECT: production of new biologically active compounds active to specific inhibitors of glycine glyt 1 and/or glyt 2 carriers.

6 cl, 2 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: present invention pertains to mew compounds with formula (I), their pharmaceutical salts and ester derivatives. In general formula (I) n equals 0 or an integer from 1 to 4; Z is -(CHR8)m-, -(CH2)mO(CHR8)r-, -(CH2)mS(CHR8)r- or -(CH2)mNR9(CHR8)r-, L3 is -(CHR)S-, where R is represents hydrogen and s equals 1, Q2 is oxygen, X and Y independently represent CH or nitrogen; or -X=Y- represents sulphur, oxygen. Description of the rest of the radicals is given in the summary of invention.

EFFECT: invented compounds have inhibiting effects on PTPase.

12 cl, 3 dwg, 51 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I) and pharmaceutically acceptable salts. Claimed compounds have modulation effect on CB cannabinoid receptor. In the general formula (I) , R and R1 are the same or different and are phenyl optionally substituted by 1-3 substitutes Y, where Y is substitute selected out of group including chlorine, iodine, bromine, fluorine, on condition that X is not a sub-group (ii); or one of R and R1 radicals is phenyl group, while the other radical is formed or linear C2-8-alkyl group or benzyl group; X is one of the sub-groups (i) or (ii). Also invention concerns application of the compounds in obtaining pharmaceutical composition, pharmaceutical composition with modulation effect on CB cannabinoid receptor, and compound of the general formula (IV) with radical values as indicated in the claim.

EFFECT: enhanced efficiency of composition and treatment method.

5 cl, 1 tbl, 25 ex

FIELD: chemistry.

SUBSTANCE: invention concerns compounds with inhibition effect on thrombocyte aggregation, their pharmaceutically acceptable salts, particularly compounds of general formula (I) (where R1 is C1-C6 alkyl etc., R2 is hydrogen, C2-C7 alkanoyl, C7-C11 arylcarbonyl, group of formula R4-(CH2)1- etc., R3 is C6-C10 aryl etc., X1, X2, X3, X4 and X5 are independently hydrogen, halogen etc., and n is an integer from 0 to 2), its pharmaceutically acceptable salts. Invention claims pharmaceutical compositions inhibiting thrombocyte activation and containing claimed compounds as agent.

EFFECT: obtaining compounds applicable as media of prevention and treatment of diseases related to thrombo- or embologenesis.

26 cl, 272 ex, 8 tbl

FIELD: medicine; pharmacology.

SUBSTANCE: compounds of this invention possess properties of protein kinase inhibitors. In the general formula p means integer within 0 to 2; R and R1 mean O; A1 and A2 mean single bond, (C1-C6)alkyl; B2 means monocyclic or bicyclic, saturated or unsaturated heterocyclic radical including 1 to several identical or different heteroatoms, chosen among O, S, N and NR7, probably substituted with one or several identical or different substitutes.

EFFECT: inhibiting effect on protein kinase, effective application of compounds of formula for medical products.

49 cl, 1 tbl, 6 dwg, 334 ex

FIELD: chemistry.

SUBSTANCE: described are 2,6-substituted pyridine-3-carbonyl derivatives of formula (I) , in which A stands for alkandiyl, is necessary disrupted by oxygen; X stands for halogen, alkylsulfonyl with 1-6 carbon atoms; Y stands for heterocycle and, if necessary, heterocycle can contain SO2-group or oxo-group (C=O), possibly substituted by alkyl, alkoxy, alkylthio with 1-6 carbon atoms in alkyl groups; Z stands for group of formula: or . Also described are intermediate derivatives of formulas (II) and (IV) .

EFFECT: extension of range of substituted pyridylketones with herbicidal activity.

3 cl, 3 tbl, 49 ex

Cynnamide compound // 2361872

FIELD: chemistry.

SUBSTANCE: invention relates to a compound with formula (I) , where Ar1 is an imidazolyl group, which can be substituted with 1-3 substitutes; Ar2 is a pyridinyl group, pyrimidinyl group or phenyl group, which can be substituted with 1-2 substitutes; X1 is (1) -C≡C- or (2) double bond etc., which can be substituted, R1 and R2 are, for example, C1-6-alkyl group or C3-8-cycloalkyl group, which can be substituted; or to a pharmacologically acceptable salt of the said compound and pharmaceutical drugs for lowering production of Aβ42, containing formula (I) compound as an active ingredient.

EFFECT: wider field of use of the compounds.

26 cl, 1119 ex, 31 tbl

FIELD: chemistry.

SUBSTANCE: present invention pertains to new compounds with formula (I): where R1 and R2 each independently represents a hydrogen atom, C1-8 alkyl or a halogen atom; R3 represents C1-8 alkyl, which can be substituted with 1-3 halogen atom(s) or phenyl; R4 represents a hydrogen atom or C1-8 alkyl; R5 and R6 each independently represents a hydrogen atom; X represents a sulphur atom or oxygen atom; ring A is 4-(trifluoromethyl)piperidin-1-yl, 2,2-difluoro-1,3- benzodioxol-5-yl or 3,4-dihydro-1H-isoquinolin-2-yl. The invention also relates to salts or solvates of this derivative, as well as medicinal preparation, pharmaceutical composition, method of preventing and/or treating diseases, caused by PPAR, and use of this derivative.

EFFECT: obtaining new biologically active compounds, which can be used for preventing and/or treating diseases caused by PPARδ.

8 cl, 39 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I) and their pharmaceutically acceptable salts. Claimed compounds have antibacterial effect. In formula (I) , X is ; R1 is i) hydrogen, ii) (CH2)nNR5R6, iv) NRCO2R, v) (C1-6alkyl)CN, CN, (CH2)pOH; Y is NR*, O or S(O)p; is phenyl or 5-6-member heteroaryl with N or S as heteroatoms; R3 is NR(C=X2)R12, NR*R12, or -(O)n-5-6-member heteroaryl with 1-3 heteroatoms selected out of N, O, which can be linked over either carbon atom or heteroatom; the indicated 5-6-member heteroaryl can be optionally substituted by 1-3 groups of R7; R4, R4a, R4b and R4c are independently i) hydrogen, ii) halogen; other radicals are defined in the claim.

EFFECT: pharmaceutical composition containing effective volume of the claimed compound.

13 cl, 1 dwg, 194 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compound of the formula (I): wherein R1 represents azido, -OR4, -NHR4 wherein R4 represents hydrogen atom or unsubstituted groups chosen from acyl, thioacyl, (C1-C6)-alkoxycarbonyl, (C3-C6)-cycloalkoxythiocarbonyl, (C2-C6)-alkenyloxycarbonyl, (C2-C6)-alkenylcarbonyl, (C1-C6)-alkoxythiocarbonyl, (C2-C6)-alkenyloxythiocarbonyl, -C(=O)-C(=O)-(C1-C6)-alkoxy, -C(C=S)-S-(C1-C6)-alkyl, -(C=S)-NH2, -(C=S)-NH-(C1-C6)-alkyl, -C(=S)-N-((C1-C6)-alkyl)2, -C(=S)-NH-(C2-C6)-alkenyl, -C(C=S)-(C=O)-(C1-C6)-alkoxy, thiomorpholinylthiocarbonyl; R2 and R3 can be similar or different and represent independently hydrogen atom, halogen atom, (C1-C6)-alkyl group, halogen-(C1-C6)-alkyl; heterocyclic moiety represents 5-membered heterocycle wherein Z represents sulfur (S), oxygen (O) atom or -NRb wherein Rb represents hydrogen atom or unsubstituted (C1-C6)-alkyl, (C3-C6)-cycloalkyl, aryl or aryl-(C1-C6)-alkyl; Y1 represents group =O or =S ; Y2 and Y3 represent independently hydrogen atom, and if Y2 and Y3 present in common on adjacent carbon atoms then they form 6-membered aromatic cyclic structure substituted if necessary with (C1-C6)-alkyl, or to its pharmaceutically acceptable salt. Also invention relates to a pharmaceutical composition possessing antibacterial activity and containing as an active compound the compound of the formula (I) taken in the effective dose and a pharmaceutically acceptable carrier, diluting agent, excipient. Also, invention relates to method for synthesis of compound of the formula (I). Method for synthesis of compound of the formula (I) wherein R1 represents group -NHR4 wherein R4 means acyl, (C1-C6)-alkoxycarbonyl, (C2-C6)-alkenyloxycarbonyl, (C2-C6)-alkenylcarbonyl, -C(=O)-C(=O)-(C1-C6)-alkoxy and -(C=S)-S-(C1-C6)-alkyl involves acetylation of compound of the formula (I) wherein R1 represents -NHR4 group wherein R4 represents hydrogen atom and all symbols are given above and using halide. Method for synthesis of compound of the formula (I) wherein R1 represents -NHR4 group wherein R4 means thioacyl, (C3-C6)-cycloalkoxythiocarbonyl, (C1-C6)-alkoxythiocarbonyl, (C2-C6)-alkenyloxythiocarbonyl involves the following steps: (i) conversion of compound of the formula (I) wherein R1 represents -NHR4 wherein R4 represents hydrogen atom, and all symbols are given above to compound of the formula (I) wherein R1 represents isothiocyanate group by reaction with thiophosgene, and (ii) conversion of compound of the formula (I) wherein R1 represents isothiocyanate group to compound of the formula (I) wherein R1 represents -NHR4 wherein R4 represents -C(=S)-OR4d wherein R4d represents (C1-C6)-alkyl, (C3-C6)-cycloalkyl, (C2-C6)-alkenyl, and all symbols are given above, in reaction with alcohol. Compounds of the formula (I) are used in treatment of bacterial infection that involves administration of compound of the formula (I) in a patient needing in this treatment. Invention provides synthesis of oxazolidinone compounds possessing antibacterial activity.

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

7 cl, 1 tbl, 144 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel pyrrolidine-2-ones of the formula (I): , wherein R1 means group chosen from the following formulae:

wherein each of them comprises optionally additional nitrogen (N) atom as a heteroatom; Z means optional substitute halogen atom, -CH2NH2, -NRaRb or -CN; Z' means optional substitute halogen atom, -CH2NH2 or -CN; alk means alkylene or alkenylene; T means sulfur atom (S), oxygen atom (O); R2 means hydrogen atom (H), -(C1-C3)-alkyl-CONRaRb, -(C1-C3)-alkyl-CO2-(C1-C4)-alkyl, -(C1-C3)-alkylmorpholino-group, -CO2-(C1-C4)-alkyl or -(C1-C3)-alkyl-CO2H; X means phenyl or 5- or 6-membered aromatic or nonaromatic heterocyclic group comprising one or two heteroatoms chosen from O, N or S wherein each of them is substituted optionally with 0-2 groups chosen from halogen atom, -CN, -(C1-C4)-alkyl, -(C2-C4)-alkenyl, -CF3, -NRaRb, -NO2, -N-(C1-C4)-alkyl-(CHO), -NHCO-(C1-C4)-alkyl, -NHSO2Rc, -(C0-C4)-alkyl-ORd, -C(O)Rc, -C(O)NRaRb, -S(O)nRc and -S(O)2NRaRb; Y means: (i) a substitute chosen from H, halogen atom, -CN, -(C1-C4)-alkyl, -(C2-C4)-alkenyl, -CF3, -NRaRb, -NO2, -N-(C1-C4)-alkyl-(CHO), -NHCO-(C1-C4)-alkyl, -NHSO2Rc, -(C0-C4)-alkyl-ORd, -C(O)Rc, -C(O)NRaRb, -S(O)nRc and -S(O)2NRaRb, or (ii) phenyl or 5- or 6-membered aromatic or nonaromatic heterocyclic group comprising one or two heteroatoms, chosen from O, N or S and wherein each of them is substituted optionally with 0-2 groups chosen from halogen atom, -CN, -(C1-C4)-alkyl, -(CH2)nNRaRb, -(CH2)nN+RaRbCH2CONH2, -(C0-C4)-alkyl-ORd, -C(O)Rc, -C(O)NRaRb, -S(O)nRc, -S(O)2NRaRb, =O, oxide at N atom in cycle, -CHO, -NO2 and -N-(Ra)(SO2Rc) wherein Ra and Rb mean independently H, -(C1-C6)-alkyl; Rc means -(C1-C6)-alkyl; Rd means H, -(C1-C6)-alkyl; n means 0-2, and to their pharmaceutically acceptable salts or solvates. Compounds inhibit Xa factor that allows their using as components of pharmaceutical composition.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

10 cl, 144 ex

FIELD: organic chemistry, medicine, endocrinology.

SUBSTANCE: invention relates to novel compounds representing C-glycoside derivatives and their salts of the formula: wherein ring A represents (1) benzene ring; (2) five- or six-membered monocyclic heteroaryl ring comprising 1, 2 or 4 heteroatoms chosen from nitrogen (N) and sulfur (S) atoms but with exception of tetrazoles, or (3) unsaturated nine-membered bicyclic heterocycle comprising 1 heteroatom representing oxygen atom (O); ring B represents (1) unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (2) saturated or unsaturated five- or six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (3) unsaturated nine-membered bicyclic carbocycle, or (4) benzene ring; X represents a bond or lower alkylene wherein values for ring A, ring B and X correlate so manner that (1) when ring A represents benzene ring then ring B is not benzene ring, or (2) when ring A represents benzene ring and ring B represents unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O and comprising benzene ring or unsaturated nine-membered bicyclic carbocycle comprising benzene ring then X is bound to ring B in moiety distinct from benzene ring comprised in ring B; each among R1-R4 represents separately hydrogen atom, -C(=O)-lower alkyl or lower alkylene-aryl; each R5-R11 represents separately hydrogen atom, lower alkyl, halogen atom, -OH, =O, -NH2, halogen-substituted lower alkyl-sulfonyl, phenyl, saturated six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N and O, lower alkylene-OH, lower alkyl, -COOH, -CN, -C(=O)-O-lower alkyl, -O-lower alkyl, -O-cycloalkyl, -O-lower alkylene-OH, -O-lower alkylene-O-lower alkyl, -O-lower alkylene-COOH, -O-lower alkylene-C(=O)-O-lower alkyl, -O-lower alkylene-C(=O)-NH2, -O-lower alkylene-C(=O)-N-(lower alkyl)2, -O-lower alkylene-CH(OH)-CH2(OH), -O-lower alkylene-NH, -O-lower alkylene-NH-lower alkyl, -O-lower alkylene-N-(lower alkyl)2, -O-lower alkylene-NH-C(=O)-lower alkyl, -NH-lower alkyl, -N-(lower alkyl)2, -NH-lower alkylene-OH or NH-C(=O)-lower alkyl. Indicated derivatives can be used as inhibitor of co-transporter of Na+-glucose and especially as a therapeutic and/or prophylactic agent in diabetes mellitus, such as insulin-dependent diabetes mellitus (diabetes mellitus 1 type) and non-insulin-dependent diabetes mellitus (diabetes mellitus 2 type), and in diseases associated with diabetes mellitus, such as insulin-resistant diseases and obesity.

EFFECT: valuable medicinal properties of compounds.

11 cl, 41 tbl, 243 ex

FIELD: organic chemistry, chemical technology, biology.

SUBSTANCE: invention relates to a method for synthesis of compound of the formula (11): wherein X2 represents a leaving group; R3 and R4 represent substitutes chosen independently from group consisting of hydrogen atom, aromatic group and aliphatic group, or taken in common -NR3R4 form 4-11-membered aliphatic ring, but R3 and R4 can't means hydrogen atom simultaneously. Method involves interaction of compound of the formula (10): wherein X1 represents a leaving group with amine of the formula (3): (HNR3R4) in the presence of Lewis acid and a non-nucleophilic base and wherein groups X1 and X2 are similar. Compounds of the formula (11) can be used in treatment of anomalous growth of cells.

EFFECT: improved method of synthesis, valuable biological property of compound.

14 cl, 5 sch, 2 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formulae (I) and (II) and their pharmaceutically acceptable salts and esters wherein each Z1, Z2 and Z3 is chosen from series of (C1-C6)-alkoxy-group, -CH2OCH3 and -CH2OCH2CH3, or one Z1, Z2 or Z3 means hydrogen atom, and each of two others is chosen independently from series (C1-C6)-alkyl, (C1-C6)-alkoxy-group, -Cl, -Br, -F, -CF3, -CH2OCH3, -CH2OCH2CH3, -OCH2CH2R1, -CH2-morpholino, -OR2, -OCH2CF3, -OCH(CH3)CH2OH and -COOQ wherein Q is chosen from series hydrogen atom and (C1-C6)-alkyl, or one of Z1, Z2 or Z3 means hydrogen atom, and two others in common with carbon atoms and in combination with bonds between them and benzene cycle to which they are bound for a cycle chosen from 5- and 6-membered unsaturated cycles and 5- and 6-membered saturated cycles that comprise at least one oxygen atom as heteroatom, and wherein R1 is chosen from series -F, -OCH3, -N(CH3)2 and unsaturated 5-membered cycles comprising at least one nitrogen or oxygen atom as heteroatom, and wherein R2 means 3-6-membered saturated cycle, and each Y1 and Y2 is chosen independently from series -Cl, -Br, -NO2, -C≡N and -C≡CH, and their pharmaceutically acceptable salts and esters and wherein Z4 is chosen from series (C1-C2)-alkyl, (C1-C6)-alkoxy-group, -OH, -SCH3, -CF3, -NO2, -COOQ2, -N(CH3)2, -OCH2-phenyl, -Cl, -Br, -F, -OCH2COQ1, saturated 5- and 6-membered cycles comprising at least one heteroatom wherein heteroatom is chosen from nitrogen (N) and oxygen (O) atom, and wherein Q1 is chosen from series, -OH, -NH2 and -O(C1-C6)-alkyl; Q2 is chosen from series hydrogen atom and (C1-C6)-alkyl; Y1 and Y2 are chosen independently from series -Cl, -Br, -NO2, -C≡N and -C≡CH under condition that if both Y1 and Y2 means -Cl then Z4 doesn't means -Cl, and if both Y1 and Y2 mean -NO2 then Z4 doesn't mean -NO2, and if both Y1 and Y2 mean -CN then Z4 doesn't mean -CN. Also, invention relates to a pharmaceutical composition possessing inhibitory activity with respect to MDM2. Invention provides synthesis of novel biologically active compounds and preparing pharmaceutical compositions based on thereof possessing inhibitory activity with respect to MDM2.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

14 cl, 50 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): their pharmaceutically acceptable salts or solvates, or stereoisomers possessing properties of agonists of β2-adrenoreceptors, to pharmaceutical composition based on thereof, using the claimed compounds in manufacturing a medicinal agent, and to a method for modulation of β2-adrenergic receptors. In the formula (I) each among R1-R5 is chosen independently from group comprising hydrogen atom, (C1-C4)-alkyl and Ra wherein alkyl is substituted optionally with substituted chosen from Rb; or R4 and R5 are combined to form group of the formula: -NRdC(=O)C(Rd)=C(Rd)-; R6, R7 and R8 represent hydrogen atom; R9 represents (C1-C4)-alkyl; R10 represents hydrogen atom or (C1-C4)-alkyl; each among R11, R12 and R13 is chosen independently from group including hydrogen atom, (C1-C4)-alkyl, vinyl, cyclohexyl, phenyl, halogen atom, -CO2Rd, -ORd, -S(O)mRd, -N(NRdRe)Rd or -S(O)2NRdRe, 5-6-membered monocyclic heteroaryl comprising 1 or 2 heteroatoms chosen from nitrogen (N), sulfur (S) atoms, 9-membered bicyclic heteroaryl comprising N as a heteroatom and 5-membered heterocycle comprising N as a heteroatom; or R11 and R12 in common with atoms to which they are bound form 6- or 7-membered heterocyclic ring comprising oxygen (O) atom as a heteroatom and wherein for R11-R13 each phenyl or heteroaryl is substituted optionally with 1 or 2 substitutes chosen independently from Rc, and each heterocyclyl is substituted optionally with 1 or 2 substitutes chosen from Rb and Rc; alkyl is substituted optionally with substitute chosen from Rb, and vinyl is substituted optionally with substitute chosen from Rm; w = 0, 1, 2, 3 or 4. Values Ra, Rb, Rc, Rd, Rm and m are given in the invention claim.

EFFECT: improved method for modulation, valuable medicinal properties of compounds and pharmaceutical composition.

22 cl, 225 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivative compound of carboxylic acid represented by the formula (I): , wherein each X and Y represents independently (C1-C4)-alkylene; Z means -O-; each R1, R2, R3 and R4 means independently hydrogen atom or (C1-C8)-alkyl; R5 means (C2-C8)-alkenyl; A means -O- or -S-; D means D1, D2, D3, D4 or D5 wherein D1 means (C1-C8)-alkyl; D2 means compound of the formula: wherein ring 1 represents saturated 6-membered monoheteroaryl comprising one nitrogen atom and, optionally, another one heteroatom chosen from oxygen, sulfur and nitrogen atoms; D3 means compound of the formula: wherein ring 2 represents (1) completely saturated (C3-C10)-monocarboxylic aryl, or (2) optionally saturated 5-membered monoheteroaryl comprising 3 atoms chosen from nitrogen and sulfur atoms, or completely saturated 6-membered monoheteroaryl comprising 1 heteroatom representing oxygen atom; D4 means compound of the formula: ; D5 means compound of the formula: ; R6 represents (1) hydrogen atom, (2) (C1-C8)-alkyl, (3) -NR7R8 wherein R7 or R8 represent hydrogen atom or (C1-C8)-alkyl, or R7 and R8 taken in common with nitrogen atom to which they are added form saturated 5-6-membered monoheteroaryl comprising one nitrogen atom and, optionally, another one heteroatom representing oxygen atom; E means -CH or nitrogen atom; m means a whole number 1-3, or its nontoxic salt. Invention relates to a regulator activated by peroxisome proliferator receptor, agent used in prophylaxis and/or treatment of diseases associated with metabolism disorders, such as diabetes mellitus, obesity, syndrome X, hypercholesterolemia or hyperlipoproteinemia, hyperlipidemia, atherosclerosis, hypertension, diseases coursing with circulation disorder, overeating or heart ischemic disease, and to an agent that increases cholesterol level associated with HDL, reduces cholesterol level associated with LDL and/or VLDL, eliminates risk factor in development of diabetes mellitus and/or syndrome X and comprising a compound represented by the formula (I) or its nontoxic salt as an active component and a carrier, excipient or solvent optionally. Invention proposes derivative compounds of carboxylic acid possessing the modulating activity with respect to peroxisome proliferator receptor (PPAR).

EFFECT: valuable medicinal properties of compounds.

15 cl, 5 tbl, 48 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds with general formula (I) or pharmaceutically acceptable salts thereof, where R1 is chosen from a group containing optionally substituted C1-C6alkyl, lower alkoxy group, (lower)alkoxy(lower)alkyl, cycloalkyoxy(lower)alkyl, lower thioalkyl, (lower)alkylthio(lower)alkyl, cycloalkyl, cycloalkyl(lower)alkyl; R2 is chosen from a group containing optionally substituted (lower)alkyl, cycloalkyl, cycloalkyl(lower)alkyl; R3 is chosen from a group containing halogen, cyano group, optionally substituted (lower alkyl, lower thioalkyl, aryl, aryl(lower)alkyl, lower alkenyl, lower alkynyl); R4 is chosen from a group containing hydrogen, halogen, cyano group, hydroxyl group, optionally substituted (lower alkyl, lower alkoxy group, aryl, pyridyl, aryl(lower)alkyl, heteroaryl, which is an aromatic mono- or bicyclic hydrocarbon, containing from 5 to 9 ring atoms, from which one or more is a heteroatom, chosen from O, N or S, and an amino group) and a group, with formula R8-Z-(CH2)n-; where Z is a single bond or chosen from a group consisting of O, NH, CH2, CO, SO, SO2 or S; where R8 is chosen from a group containing optionally substituted (aryl, pyridyl); and where n=0, 1 or 2; R5 represents hydrogen; R6 is chosen from a group containing halogen, optionally substituted lower alkoxy group; R7 is one or more substitutes, independently chosen from a group containing hydrogen, optionally substituted lower alkoxy group; where the optional substitute or substitutes when R1-R8 are independently chosen from a group containing halogen, hydroxyl group, lower alkyl, mono- or di(lower)alkylamino group, aminocarbonyl, sulfinyl, sulfonyl, sulfanyl, mono- or di(lower)alkylaminocarbonyl, amino group, carboxyl group, lower alkoxy group, C3-C12cycloalkyl, (lower)alkylcarbonyl, (lower)alkoxycarbonyl, nitrile, aryl; all of which, except halogen, are independently optionally substituted with one or more substitutes, chosen from a group containing halogen, hydroxyl group, lower alkyl, sulfinyl, sulfonyl, sulfanyl, amino group, carboxyl group, lower alkoxy group, carbamoyl. Invention also relates to formula (I'), to a pharmaceutical composition, as well as use of formula (I) compounds given in paragraph 1.

EFFECT: obtaining new biologically active compounds, for preventing or treating bone diseases, associated with very low or resorption of calcium.

6 cl, 151 ex

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