Amide derivatives carrying cyclopropylaminocarbonyl substitute, suitable as cytokine inhibitors

FIELD: chemistry.

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

EFFECT: more effective treatment.

13 cl, 3 tbl, 46 ex

 

The text descriptions are given in facsimile form.

(57) 1. The compound of the formula I

where Qarepresents phenyl or heteroaryl, very lovely and q aperhaps you may bear 1 or 2 substituent selected from hydroxy, halogeno, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino;
R1and R2each independently selected from hydrogen and (1-6C)alkyl; and
Qbrepresents phenyl or heteroaryl, and Qbperhaps you may bear 1 or 2 substituent selected from hydroxy, halogeno, (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, (1-6C)alkoxycarbonyl, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulfonyl and (1-6C)alkylsulfonyl;
and where any of the substituents on Qaor Qbdefined above, containing the group CH2that is attached to 2 carbon atoms, or a group CH3that is attached to the carbon atom, may possibly carry on each specified group of CH2or CH3one or more than one Deputy, selected from hydroxy, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino;
where heteroaryl represents an aromatic 5 - or 6-membered monocyclic ring, which may contain up to three heteroatoms selected from oxygen, nitrogen and sulfur, and may be condensed with benzene ring or five-membered nitrogen-containing to ICOM, containing 2 nitrogen atom;
or its pharmaceutically acceptable salt.

2. The compound of formula I according to claim 1,
where Qarepresents phenyl, pyridyl, pyrimidinyl or pyrazinyl, and Qaperhaps you may bear 1 or 2 substituent selected from halogeno, (1-6C)alkyl and (1-6C)alkoxy;
R1and R2each independently selected from hydrogen and (1-6C)alkyl; and
Qbrepresents phenyl or heteroaryl, and Qbperhaps you may bear 1 or 2 substituent selected from hydroxy, halogeno, (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, (1-6C)alkoxycarbonyl, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulfonyl and (1-6C)alkylsulfonyl;
and where any of the substituents on Qaor Qbdefined above, containing the group CH2that is attached to 2 carbon atoms, or a group CH3that is attached to the carbon atom, may possibly carry on each specified group of CH2or CH3one or more than one Deputy, selected from hydroxy, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino;
or its pharmaceutically acceptable salt.

3. The compound of formula I according to claim 1,
where Qarepresents phenyl, pyridyl, Pirim denil or pyrazinyl, and Qaperhaps you may bear 1 or 2 substituent selected from hydroxy, halogeno, (1-6C)alkyl and (1-6C)alkoxy;
or its pharmaceutically acceptable salt.

4. The compound of formula I according to claim 1,
where Qbrepresents phenyl, pyridyl, pyrimidinyl, pyridazinyl, thiazolyl, thiadiazolyl, imidazolyl, isoxazolyl, furanyl, benzimidazolyl, ethenolysis, chinoline, benzothiazolyl or pyrido[1,2-a] imidazolyl, and Qbperhaps you may bear 1 or 2 substituent selected from hydroxy, halogeno, (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, (1-6C)alkoxycarbonyl, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulfonyl and (1-6C)alkylsulfonyl;
and where any of the substituents on Qbcontaining the group CH2that is attached to 2 carbon atoms, or a group CH3that is attached to the carbon atom, may possibly carry on each specified group of CH2or CH3one or more than one Deputy, selected from hydroxy, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino;
or its pharmaceutically acceptable salt.

5. The compound of formula I according to claim 1,
where Qarepresents phenyl, pyridyl, pyrimidinyl or pyrazinyl, and Qawho is you can carry 1 or 2 substituent, selected from halogeno, (1-6C)alkyl and (1-6C)alkoxy;
each R1and R2independently selected from hydrogen and (1-6C)alkyl; and
Qbrepresents phenyl, pyridyl, pyrimidinyl, pyridazinyl, thiazolyl, thiadiazolyl, imidazolyl, isoxazolyl, furanyl, benzimidazolyl, ethenolysis, chinoline, benzothiazolyl or pyrido[1,2-a]imidazolyl, and Qbperhaps you may bear 1 or 2 substituent selected from hydroxy, halogeno, (1-6C)alkyl, (3-6C)nikolkina, (1-6C)alkoxy, (1-6C)alkoxycarbonyl, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulfonyl and (1-6C)alkylsulfonyl;
and where any of the substituents on Qbcontaining the group CH2that is attached to 2 carbon atoms, or a group CH3that is attached to the carbon atom, may possibly be worn for each specified group of CH2or CH3one or more than one Deputy, selected from hydroxy, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl] amino;
or its pharmaceutically acceptable salt.

6. The compound of formula I according to claim 1, selected from
3-{[4-(benzyloxy)benzoyl]amino}-N-cyclopropyl-4-methylbenzamide;
3-{[3-(benzyloxy)benzoyl]amino}-N-cyclopropyl-4-methylbenzamide;
4-(Ben is yloxy)- N-{5-[(cyclopropylamino)carbonyl]-2-were}-3-methylbenzamide;
4-(benzyloxy)-3-fluoro-N-{5-[(cyclopropylamino)carbonyl]-2-were}benzamide;
4-(benzyloxy)-3-chloro-N-{5-[(cyclopropylamino)carbonyl]-2-were}benzamide;
N-cyclopropyl-4-methyl-3-{[4-(pyridine-2-ylethoxy)benzoyl] amino}-benzamide;
N-cyclopropyl-4-methyl-3-{[4-(1,3-thiazol-4-ylethoxy)benzoyl]amino}-benzamide;
N-cyclopropyl-4-methyl-3-{[4-(pyridine-3-ylethoxy)benzoyl]amino} -benzamide;
N-cyclopropyl-4-methyl-3-({4-[(5-methylisoxazol-3-yl)methoxy]benzoyl}-amino)benzamide;
3-({4-[(5-chloro-1,2,3-thiadiazolyl-4-yl)methoxy]benzoyl}amino)-N-cyclopropyl-4-methylbenzamide;
N-cyclopropyl-3-{[4-(imidazo[1,2-a]pyridine-2-ylethoxy)benzoyl]-amino}-4-methylbenzamide;
N-cyclopropyl-4-methyl-3-({4-[(2-methyl-1,3-thiazol-4-yl)methoxy]benzoyl}-amino)benzamide;
N-cyclopropyl-3-({4-[(3,5-dimethylisoxazol-4-yl)methoxy]benzoyl}-amino)-4-methylbenzamide;
N-cyclopropyl-4-methyl-3-{[4-(1,2,5-thiadiazolyl-3-ylethoxy)benzoyl]-amino}benzamide;
methyl-5-({4-[({5-[(cyclopropylamino)carbonyl]-2-were}amino)-carbonyl]phenoxy}methyl)-2-furoate;
3-({4-[(2-chloro-1,3-thiazol-5-yl)methoxy]benzoyl}amino)-N-cyclopropyl-4-methylbenzamide;
4-(benzyloxy)-N-{5-[(cyclopropylamino)carbonyl]-2-were}-3-methoxybenzamide;
N-{5-[(cyclopropylamino)carbonyl]-2-methylp the Nile}-3-methoxy-4-(pyridine-2-ylethoxy)benzamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-3-methoxy-4-(1,3-thiazol-4-ylethoxy)benzamide;
N-cyclopropyl-4-methyl-3-{[3-methyl-4-(pyridine-2-ylethoxy)benzoyl]-amino}benzamide;
N-cyclopropyl-4-methyl-3-{[3-methyl-4-(1,3-thiazol-4-ylethoxy)benzoyl]-amino}benzamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-3-fluoro-4-(pyridine-2-ylethoxy)benzamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-3-fluoro-4-[(2-methyl-1,3-thiazol-4-yl)methoxy]benzamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-4-[(3,5-dimethylisoxazol-4-yl)methoxy]-3-fermentated;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-3-fluoro-4-(1,2,5-thiadiazolyl-3-ylethoxy)benzamide;
N-cyclopropyl-4-methyl-3-{[3-(1,3-thiazol-4-ylethoxy)benzoyl]amino}-benzamide;
N-cyclopropyl-4-methyl-3-({3-[(2-methyl-1,3-thiazol-4-yl)methoxy]benzoyl}-amino)benzamide;
N-cyclopropyl-4-methyl-3-{[3-(pyridine-2-ylethoxy)benzoyl]amino}-benzamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-3-fluoro-4-(1,3-thiazol-4-ylethoxy)benzamide;
N-cyclopropyl-4-methyl-3-({3-methyl-4-[(2-methyl-1,3-thiazol-4-yl)methoxy]-benzoyl}amino)benzamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-4-[(3,5-dimethylisoxazol-4-yl)methoxy]-3-methylbenzamide;
N-cyclopropyl-4-methyl-3-{[3-methyl-4-(1,2,5-thiadiazolyl-3-ylethoxy)benzoyl]amino}benzamide;
methyl-5-({4-[({5-[(cyclopropylamino)carbonyl]-2-were}amino)carbonyl-2-methylphenoxy}methyl)-2-furoate;
3-chloro-N-{5-[(cyclopropylamino)carbonyl]-2-were}-4-(pyridine-2-ylethoxy)benzamide;
3-chloro-N-{5-[(cyclopropylamino)carbonyl]-2-were}-4-(1,3-thiazol-4-ylethoxy)benzamide;
N-cyclopropyl-3-({3-[(3,5-dimethylisoxazol-4-yl)methoxy]benzoyl}-amino)-4-methylbenzamide;
N-cyclopropyl-4-methyl-3-{[3-(1,2,5-thiadiazolyl-3-ylethoxy)benzoyl]amino}benzamide;
3-({3-[(2-chloro-1,3-thiazol-5-yl)methoxy]benzoyl}amino)-N-cyclopropyl-4-methylbenzamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-3-fluoro-4-(imidazo[1,2-a]pyridine-2-ylethoxy)benzamide;
N-cyclopropyl-3-({4-[(4-methoxypyridine-2-yl)methoxy]benzoyl}amino)-4-methylbenzamide;
N-cyclopropyl-4-methyl-3-{[4-(1-pyridine-2-ylethoxy)benzoyl]amino}benzamide;
N-cyclopropyl-3-({3-[(4-methoxypyridine-2-yl)methoxy]benzoyl}amino)-4-methylbenzamide;
N-cyclopropyl-3-[(4-{[5-(hydroxymethyl)pyridine-2-yl]methoxy}benzoyl)amino]-4-methylbenzamide;
N-temporaril-3-[(4-{[5-(1-hydroxy-1-methylethyl)pyridine-2-yl]methoxy}benzoyl)amino]-4-methylbenzamide;
N-cyclopropyl-3-{[4-({5-[(isopropylamino)methyl]pyridine-2-yl}methoxy)-benzoyl]amino}-4-methylbenzamide;
N-cyclopropyl-3-{[4-({5-[(dimethylamino)methyl]pyridine-2-yl}methoxy)benzoyl]amino}-4-methylbenzamide;
methyl-6-({4-[({5-[(cyclopropylamino)carbonyl]-2-were}amino)-carbonyl]phenoxy}methyl)nicotinate;
N-cyclopropyl-3-{[4-({5-[2-(dimethylamino)ethoxy]pyridine-2-yl}methoxy)-benzoyl]amino}--methylbenzamide;
N-cyclopropyl-3-({4-[(5-hydroxypyridine-2-yl)methoxy]benzoyl}amino)-4-methylbenzamide;
methyl-6-({4-[({5-[(cyclopropylamino)carbonyl]-2-were}amino)-carbonyl]phenoxy}methyl)pyridine-2-carboxylate;
N-cyclopropyl-3-[(4-{[6-(hydroxymethyl)pyridine-2-yl]methoxy}benzoyl)amino]-4-methylbenzamide;
N-cyclopropyl-3-[(4-{[6-(1-hydroxy-1-methylethyl)pyridine-2-yl]methoxy}benzoyl)amino]-4-methylbenzamide;
N-cyclopropyl-3-({4-[(6-{[2-(diethylamino)ethoxy]methyl}pyridine-2-yl)methoxy]benzoyl}amino)-4-methylbenzamide;
N-cyclopropyl-3-({4-[(6-{[2-(dimethylamino)ethoxy]methyl}pyridine-2-yl)methoxy]benzoyl}amino)-4-methylbenzamide;
N-cyclopropyl-4-methyl-3-({4-[(1-oxidability-2-yl)methoxy]benzoyl}-amino)benzamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-2-(imidazo[1,2-a]pyridine-2-ylethoxy)pyrimidine-5-carboxamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-2-(1,3-thiazol-2-ylethoxy)pyrimidine-5-carboxamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-2-(pyrimidine-2-ylethoxy)pyrimidine-5-carboxamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-2-[(1-methyl-1H-imidazol-2-yl)methoxy]pyrimidine-5-carboxamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-2-[(1,5-dimethyl-1H-pyrazole-3-yl)methoxy]pyrimidine-5-carboxamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-2-[(1,3-dimethyl-1H-pyrazole-5-yl)methoxy]pyrimidine-5-carboxamide;
N-{5-[(cyclopropylamino)Carbo is Il]-2-were}-2-[(3-methylpyridin-2-yl)methoxy]pyrimidine-5-carboxamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-2-[(1-methyl-1H-benzimidazole-2-yl)methoxy]pyrimidine-5-carboxamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-2-(isoquinoline-1-ylethoxy)pyrimidine-5-carboxamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-2-(quinoline-2-ylethoxy)pyrimidine-5-carboxamide;
2-(1,3-benzothiazol-2-ylethoxy)-N-{5-[(cyclopropylamino)carbonyl]-2-were}pyrimidine-5-carboxamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-2-(1-pyridine-2-ylethoxy)pyrimidine-5-carboxamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-2-(1,3-thiazol-4-ylethoxy)pyrimidine-5-carboxamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-2-(pyridine-2-ylethoxy)pyrimidine-5-carboxamide;
N-cyclopropyl-3-({4-[(5-cyclopropyl-1,3,4-thiadiazolyl-2-yl)methoxy]benzoyl}amino)-4-methylbenzamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-6-(pyridine-2-ylethoxy)nicotinamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-5-(pyridine-2-ylethoxy)pyrazin-2-carboxamide;
3-({4-[(6-bromopyridin-2-yl)methoxy]benzoyl}amino)-N-cyclopropyl-4-methylbenzamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}is 3.5-debtor-4-(pyridine-2-ylethoxy)benzamide;
N-cyclopropyl-4-methyl-3-({4-[(6-methylpyridin-2-yl)methoxy]benzoyl}-amino)benzamide;
N-cyclopropyl-4-methyl-3-({4-[(3-methylpyridin-2-yl)methoxy]benzoyl}-amino)benzamide;
N-cyclopropyl-4-methyl-3-{[4-(feast of midin-2-ylethoxy)benzoyl]amino}benzamide;
N-cyclopropyl-4-methyl-3-{[4-(pyridazin-3-ylethoxy)benzoyl]amino}benzamide;
N-cyclopropyl-3-{[4-({6-[(2-methoxyethyl)amino]pyridine-2-yl}methoxy)-benzoyl]amino}-4-methylbenzamide;
N-cyclopropyl-3-({4-[(6-{[2-(dimethylamino)ethyl]amino}pyridine-2-yl)methoxy]benzoyl}amino)-4-methylbenzamide;
5-(benzyloxy)-N-{5-[(cyclopropylamino)carbonyl]-2-were}-pyridine-2-carboxamide;
N-{5-[(cyclopropylamino)carbonyl]-2-were}-5-(pyridine-2-ylethoxy)pyridine-2-carboxamide; and
N-cyclopropyl-4-methyl-3-[(4-{[4-(methylsulphonyl)benzyl]oxy}benzoyl)-amino]benzamide;
or its pharmaceutically acceptable salt.

7. The method of obtaining the compounds of formula I according to claim 1 or its pharmaceutically acceptable salt, including
the interaction of the acid of formula IV or its activated derivative

with an aniline of the formula VI

in standard conditions of formation of amide linkages, where Qa, Qb, R1and R2such as defined in claim 1 or 2, and where any functional group could be protected, and:
(1) removing any protective groups;
(2) may form pharmaceutically acceptable salts.

8. The method of obtaining the compounds of formula I according to claim 1 or its pharmaceutically acceptable salt, where the substituents on Qaor Qbrepresents (1-6C)alkoxy or substituted (1-6C)alkoxy, (1-C)alkylamino, di-[(1-6C)alkyl]amino or substituted (1-6C)alkylamino, including
alkylation of amide derivative of the formula I where the substituents on Qaor Qbrepresents a hydroxy or amino.

9. Pharmaceutical composition having the properties of an inhibitor of the production of tumor necrosis factor (TNF) and enzyme inhibitor R kinase containing an effective amount of a compound of formula I according to any one of claims 1 to 6, or its pharmaceutically acceptable salt in combination with a pharmaceutically acceptable diluent or carrier.

10. The compound of formula I according to any one of claims 1 to 6, or its pharmaceutically acceptable salt having the properties of an inhibitor of the production of tumor necrosis factor (TNF) and enzyme inhibitor R kinase.

11. The compound of formula I according to any one of claims 1 to 6, or its pharmaceutically acceptable salt for the manufacture of a medicinal product having the properties of an inhibitor of the production of tumor necrosis factor (TNF) and enzyme inhibitor R kinase.

12. The compound of formula I according to any one of claims 1 to 6, or its pharmaceutically acceptable salt for the manufacture of a medicine for treating conditions mediated by the action of the cytokines TNF.

13. The use of the compounds of formula I according to any one of claims 1 to 6, or its pharmaceutically acceptable salts in the manufacture of a medicine for the treatment of rheumatoid and is TRITA, asthma, chronic obstructive pulmonary disease, inflammatory bowel disease, multiple sclerosis, AIDS, septic shock, congestive heart failure, ischaemic heart disease or psoriasis.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel deazapurines of formula (I): and pharmaceutically acceptable salts thereof, where n = 0; R1 is H, -NH2, -NHCH3, -NH-Ac, -OH, F, -OCH3, -CN, -NH(C=O)OC2H5; R2 is H, -NRARB, -ORA, C1-20alkyl, C1-20halogenalkyl, C6-10aryl, where RA and RB each independently represents H, C1-20alkyl, where C6-10aryl can be independently unsubstituted or substituted with one or more substitutes selected from a group consisting of C1-20alkyl, C1-20alkoxy and C1-20thioalkyl; each R3 independently represents H, halogen, CN, C1-20alkyl, C1-20alkoxy, C1-20thioalkyl, a -G-RC group, where G is absent or represents CH2-, -(CH2)2-, -CH=CH-CH2-, -CH-CH-, -OC-, -O- or (C=O) and where RC is H, -NRF-RG , -ORF, -SRF, -S(=O)RF, -S(=O)2RF, C1-20alkyl, C1-20alkenyl, C1-20alkynyl, C3-10cycloalkyl, C3-10cycloalkenyl, tert-butyl dimethyl silyloxy, heterocycle, C6-10aryl, C5-14heteroaryl with one N atom as a heteroatom, where RF and RG each independently represents H, C1-20alkyl, C1-20alkenyl, C1-20alkynyl, C3-10cycloalkyl, C3-10cycloalkenyl, C6-10aryl, 6-member heterocycle with one O atom as a heteroatom, where RF and RG together form a 3-, 4-, 5-, 6-, 7- or 8-member cycloalkyl, cycloalkenyl, where the said heterocycle relates to a non-aromatic 5-, 6-, 7-member ring or bi- or tri-cyclic group containing condensed 6-member rings with 1-2 heteroatoms independently selected from O, S, N; where each of the said alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycle, heteroaryl can be independently unsubstituted or substituted with one or more substitutes selected from a group consisting of O, halogen, OH, -CN, C1-20halogenalkyl, -CH2CF3, C1-20alkyl, C1-20alkoxy, C3-6cycloalkyl, C6-10aryl, 5- or 6-member heterocycle with one or two N atoms as heteroatoms, NHRh, NRhRi, N-ORh, ORh, C(=O)Rh, S(=O)Rh, S(=O)2Rh, =CR4R5, =NR4, where Rh and Rj present C1-20alkyl, C6-10aryl, and each of R4, R5 independently represents H, OH, ORx or C1-6alkyl, where Rx is C1-6alkyl, where the said aryl can be independently further unsubstituted or substituted with one or more substitutes selected from a group consisting of halogen, C1-20alkyl or C1-20alkoxy.

EFFECT: compounds can inhibit cytokine induced expression of adhesion molecules with endothelial cells, which enables their use in pharmaceutical compositions.

54 cl

Organic compounds // 2379309

FIELD: chemistry.

SUBSTANCE: invention describes compounds of formula (I) in free or salt form, where Q is a bond, R1 and R2 independently represent H or C1-C8alkyl, or R3 is C1-C8alkyl, R4 and R5 independently represent halogen, C1-C8alkyl, C1-C8haloalkyl, C3-C15carbocyclic group, nitro group, cyano-group, C1-C8alkylsulphonyl group, R6 is H or C1-C8alkyl; W is a group of formula (Wa1) or (Wa2), where A independently represents C or N, or W represents a group of formula (Wb); where Y independently represents C or N; and Z represents N, O or S, or W represents a group of formula (Wc), where Y independently represents C or N; and Z represents O or S; X represents -SO2-, -CH2-, -CH(C1-C8alkyl)- or a bond; m and n each independently represents an integer from 0 to 3; and p is 1, to a pharmaceutical composition with CRTh2 antagonist activity, as well as to use thereof as a medicinal agent and production method thereof.

EFFECT: new compounds which can be used in medicine are obtained and described.

10 cl, 153 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: invention concerns compounds of general formula I or to their pharmaceutically acceptable salts, where X1 - CH; X2 - N or CH; Q1 represents ,

where X11 - CH or C-halogen; X12 - CH, C-halogen or C-CF3; X13 - CH; X14 - C-E11, and E11 represents C0-10alkyl or C0-10alkoxy; X15 - CH or N; X16 - N or N+ -0; G1 - phenyl or 5-6-members unsaturated ring containing one heteroatom N or S; R1 - C0-10alkyl, cycloC3-10alkyl or piperidinyl, any of which is optionally substituted with 1-2 independent substitutes G11, or R1 represents phenyl; G11 is chosen from: OR21 where R21 represents C0-10alkyl; -oxo; -cycloC3-8alkyl; -C0-10alkyl optionally substituted with group N(C0-10alkyl)(C0-10alkyl) wherein C0-10alkyl is optionally substituted with group N(C0-10alkyl)C(O)C0-10alkyl; group OR2221, where R2221 - C0-10alkyl; group N(C0-10alkyl)C(O)C0-10alkyl; group N(C0-10alkyl)SO2(C0-10alkyl); group -N(C0-10alkyl)C(O)N(C0-10alkyl)(C0-10alkyl); group -N(C0-10alkyl)C(=O)R3331, where R3331 - C1-10alkoxy C1-10alkyl or tetrahydrofuranyl; -N(R21)R31 where R21 and R31 independently represent C0-10alkyl optionally substituted with thiophenyl, morphlinyl, furanyl; cycloC3-8alkyl; C1-10alkoxyC1-10alkyl; tetrahydropyranyl; piperidylC0-10alkyl; or piperidyl optionally substituted with C0-10alkyl; or R21 and R31 optionally taken together with nitrogen atom whereto attached, form 3-10-members saturated ring optionally substituted with one or more independent substitutes G1111, and optionally including one or more heteroatoms different from nitrogen whereto R21 and R31 are attached; where G1111 - C0-10alkyl optionally substituted with group OR77 where R77 - C0-10alkyl, or G1111 represents C1-10alkoxyC1-10alkyl, pirimidinyl, pyrazinyl, imidazolylmethyl; C(O)N(R21)R31 where R21 and R31 independently represent C0-10alkyl; -C(O)O(C0-10alkyl); -C(O) C0-10alkyl optionally substituted with N(C0-10alkyl)(C0-10alkyl) or halogen; -heterocyclylC0-10alkyl where heterocyclyl represents 4-6-members saturated ring containing 1 or 2 heteroatoms, independently chosen from N, O or S optionally substituted with a substitute chosen from: 1) OR2221, where R2221 - pyrimidinyl or C0-10lkyl; 2) C(O)OR2221, where R2221 - C0-10alkyl or phenyl-C0-10alkyl; 3) C(O)C0-10alkyl optionally substituted with N(C0-10alkyl)(C0-10alkyl) or C1-10alkoxy C1-10alkyl; 4) C(O)N(C0-10alkyl)(C0-10alkyl); 5) S(O)2C0-10alkyl; 6) SO2N(C0-10alkyl)(C0-10alkyl); 7) -NR2221R3331, where R2221 and R3331 taken together with nitrogen atom whereto attached, form pyrrolidinyl; or G11 represents C, which taken together with carbon whereto attached, forms C=C double bond substituted with R5 and G111 where R5 and G111 are hydrogens. The invention also specifically concerns cys-3-[8-amino-1-(2-phenylquinoline-7-yl)-imidazo[1,5-α]pyrazine-3-yl]-1-methl-cyclobutanole or its pharmaceutically acceptable salt. The specified compounds and their pharmaceutically acceptable salts are applicable in treatment of conditions mediated by activity IGF-1R proteinkinase, particularly angiogenesis, vascular permeability, immune response, cell apoptosis, tumour growth or inflammation. The invention also concerns a pharmaceutical composition.

EFFECT: improved efficiency of the composition and method of treatment.

14 cl, 3 tbl, 171 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel cyclic amine compounds of formula (1) or pharmaceutically acceptable salts thereof: . In formula (1), X is O, S, NR2 (where R2 is H, C1-C12 alkyl); when X is O, S, then R1 is H, CN, COOH, C2-C13 alkoxycarbonyl, carbamoyl group; and when X is NR2 (where R2 assumes values given above), R1 is CN; Ar1 and Ar2 are identical or different and each represents an aryl which can be substituted with 1-3 halogens; or Ar1 and Ar2 together with neighbouring carbon atoms to which they are bonded form a group with formula (b): (where ring S and ring T are identical and each is a benzene ring; Y is O); ring B is a benzene ring which can be substituted with 1-3 substitutes independently selected from a group comprising halogen, C1-C12 alkyl, C1-C8 halogenalkyl, C1-C12 alkoxy, C1-C8 halogenalkoxy group; n is an integer from 1 to 10; p, q are identical or different and each is an integer equal to 1 or 2. Formula (1) compounds are bonding inhibitors of the α2C-adrenoreceptor.

EFFECT: possibility of using compounds in pharmaceutical compositions.

7 cl, 1 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel pyrrolo[3,2-c]pyridine derivatives of formula (I) or their pharmaceutically acceptable salts in which R1 is hydrogen; straight or branched C1-C6alkyl group optionally substituted with one or more substitutes selected from a group consisting of C1-C5alkoxy, hydroxyl, C3-C7 cycloalkyl, C1-C3 alkylthiazolyl and 1,3-dioxolanyl; straight or branched C2-C6 alkenyl group; straight or branched C2-C6 alkynyl group; C3-C7cycloalkyl group; or benzyl group optionally substituted with one or more substitutes selected from a group consisting of halogen, C1-C3alkyl and C1-C3alkoxy, R2 is a straight or branched C1-C6 alkyl group, R3 is hydrogen; straight or branched C1-C6 alkyl group; straight or branched C2-C6alkenyl group; or a benzyl group optionally substituted with one or more halogens, and R4 is 1,2,3,4-tetrahydroisoquinolinyl group; a benzyloxy group optionally substituted with one or more halogens; or an amine group substituted with one or two substitutes selected from a group consisting of hydrogen, straight or branched C1-C5alkylcarbonyl, phenoxycarbonyl, benzyl, optionally substituted with one or more halogens, and benzoyl, optionally substituted with one or more halogens, as well as to method of producing said compounds and a pharmaceutical composition with inhibitory effect on a proton pump containing these compounds.

EFFECT: new compounds are obtained and described, which exhibit excellent inhibitory effect on a proton pump and can provide reversible inhibitory effect on a proton pump.

7 cl, 82 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to 4-{[1-(aminocarbonyl)-4-piperidinyl]amino}-H-[(3,4-dimethylphenyl)methyl]-1-ethyl-1H-pyrazole[3,4-b]pyridine-5-carboxamide, which is a compound of formula or its pharmaceutically acceptable salt, as well as to a method of producing said compounds. The invention also relates to use of the said compound or its pharmaceutically acceptable salt as phosphodiesterase IV (PDE4) inhibitor, for example in treatment and/or prevention of inflammatory and/or allergic disease, cognitive impairment or depression in mammals. The invention particularly pertains to use of the compound or its pharmaceutically acceptable salt in treating and/or preventing atopic dermatitis in mammals, for example via external local administration to a mammal, for example a human being.

EFFECT: pharmaceutical compositions are also provided, which contain the said compound or its pharmaceutically acceptable salt, particularly suitable for external local administration.

35 cl, 1 tbl, 19 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a quinazoline compound of formula or its pharmaceutically acceptable salts, used as inhibitors of potential-dependant sodium and calcium channels, where R1, R2, R3, R5a, R5, y and x are defined in the formula of invention. The invention also relates to a pharmaceutical composition containing the disclosed compound and to methods of inhibiting one or more of NaV1.2, NaV1.3, NaV1.8, or CaV2.2.

EFFECT: 4-aminoquinazoline antagonists of selective sodium and calcium ion channels.

17 cl, 3 tbl, 1 ex

FIELD: pharmacology.

SUBSTANCE: present invention refers to compounds of formula (I) , to its N-oxides, salts, stereoisomer forms where n is equal 1, 2 or 3; R1 means cyano group; X means bivalent radical NR2 or O; R2 means hydrogen or C1-10alkyl, each Q1 independently stands for direct coupling, -CH2- or -CH2-CH2-; each R4 independently means hydrogen or C1-4alkyl; each R5a, R5b, R5c independently means hydrogen, C1-4alkyl or arylC1-4alkyl; each R5e, R5f independently means hydrogen, C1-4alkyl or arylC1-4alkyl, or R5e and R5f together can form bivalent alkandiyl radical of formula -CH2-CH2- or -CH2-CH2-CH2-; R11 means aryl, arylC1-4alkyl, C1-4alkylcarbonyl, arylcarbonyl, arylC1-4alkylcarbonyl, C1-4alkyloxycarbonyl, arylC1-4alkyloxycarbonyl, R5aR5bN-carbonyl, hydroxyC1-4alkyl, C1-4alkyloxyC1-4alkyl, arylC1-4alkyloxyC1-4alkyl, aryloxyC1-4alkyl, pyridyl; -a1=a2-a3=a4- means a bivalent radical of formula -CH=CH-CH=CH- (c-1); where one or two hydrogen atoms in (c-1) are substituted by radical C1-6alkyl, C1-4alkoxy, halogen, hydroxy group, (R5g)(R5h)N-(C1-4alkandiyl)-O-trifluoromethyl, cyano group, radical -COOR4, (R5a)(R5b)N-sulphonyl, pyrrolidinyl-sulphonyl, piperidinyl sulphonyl, radical N(R5a)(R5b), radical (a-1), (a-7), morpholinyl, (R5g)(R5h)N-(C1-4alkandiyl)-N(R5c)-, C1-6alkylcarbonylamino, C1-6alkyloxycarbonylamino, C1-6alkylsulphonylamino, (R5a)(R5b)N-C1-4alkyl; R20 means hydrogen, spiro (C2-4alkylenedioxy), spiro (diC1-4alkyoxy) or -NR5gR5h; each R5g or R5h independently means either hydrogen, or C1-4alkyl, or R5g and R5h together with nitrogen atom whereto attached form pyrrolidinyl, piperidinyl or morpholinyl; R3 means nitro group, cyano group, amino group, halogen, hydroxy group or C1-4alkoxy; aryl means phenyl optionally substituted with one or more substitutes chosen from the group consisting of C1-6alkyl, C1-4alkoxy, halogen, hydroxy, amino and trifluoromethyl. Besides it relates to the pharmaceutical composition with antiviral activity, and method for making said compounds.

EFFECT: there are prepared and described new compounds with antiviral activity.

9 cl, 15 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: present invention is related to new crystalline forms of salt of mesylate2,3-dimethyl-8-(2,6-dimethylbenzylamino)-N-hydroxyethyl-imidaso[1,2-a]pyridine-6-carboxamide and to their mixture. Besides the present invention is also related to methods of their preparation, application and pharmaceutical composition for inhibition of gastric acid secretion, which contains them. Production of new salt of 2,3-dimethyl-8-(2,6-dimethylbenzylamino)-N-hydroxyethyl-imidaso[1,2-a]pyridine-6-carboxamide and its crystalline forms for production of medicinal agent for use in treatment or prophylaxis of gastrointestinal disorders such as gastritis, gastric ulcer, duodenal ulcer, peptic ulcerous diseases, reflux-esophagitis, Zollinger-Ellison syndrome, ulcerogenic adenomas of pancreas, acute bleeding from upper compartments of gastrointestinal tract.

EFFECT: wider area of compounds application.

33 cl, 1 tbl, 12 dwg, 8 ex

FIELD: medicine.

SUBSTANCE: invention is related to new derivatives of aryl and heteroarylpiperidinecarboxylates, of formula (I): , where: type means integer numbers from 1 to 3, such that m+n is integer number from 2 to 5; p means integer number from 1 to 7; A means simple connection or is selected from one or several groups X, Y; X means -CH2-; Y means C2-alkynilene group; R1 means group R5, substituted with one or several groups R6 and/or R7; R2 means H, F, OH; R3 means H; R4 means H, C1-6-alkyl; R5 means group selected from phenyl, pyridinyl, pyrimidinyl, pyrrolyl, imidazolyl, thiazolyl, pyrazolyl, isoxazolyl, oxadiazolyl, naphthyl, chinolynyl, tetrahydrochinolinyl, isochinolinyl, tetrahydroisochinolinyl, indolyl, indolinyl, isoindolyl, benzimidazolyl, benzoxazolyl, benzizoxazolyl, benzothiazolyl, benzithiazolyl, benzotriazolyl, benzoxadiazolyl, pyrrolopyridinyl; R6 means halogen, CN, C1-6-alkyl, C3-7-cycloalkyl, C1-6-alkoxy, OH, C1-6-fluoroalkyl, C1-6-fluoroalkoxy, or cycle selected from pyrrolidine and piperidine cycle, besides this cycle is unnecessarily substituted with C1-6-alkyl group; R7 means phenyl group, besides group or groups R7 may be substituted with one or several groups R6, identical or differing from each other, selected from halogen, C1-6-alkyl and C1-6-fluoroalkyl, C1-6-alkoxy, in the form of pharmaceutically acceptable base or acid-additive salt.

EFFECT: compounds are applicable as inhibitors of FAAH ferment.

10 cl, 1 tbl, 7 ex

FIELD: chemistry.

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

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

8 cl, 8 ex

FIELD: chemistry.

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

.

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

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

11 cl, 19 ex, 6 tbl

FIELD: chemistry.

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

EFFECT: new phosphodiesterase 4 inhibitors have improved properties.

55 cl, 30 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrrolidine-3,4-dicarboxamide derivatives of formula (I): , where: X is N or C-R6; R1 is C1-7alkyl, C3-10cycloalkyl, C3-10cycloalkyl-C1-7alkyl, fluoro-C1-7alkyl, hydroxy-C1-7alkyl, CN-C1-7alkyl, R10C(O), R10OC(O)-, N(R11,R12)C(O)-; R10OC(O)C1-7alkyl, N(R11,R12)C(O)-C1-7alkyl, R10SO2, R10-SO2-C1-7alkyl, N(R11, R12)-SO2, N(R11,R12)-SO2-C1-7alkyl, aryl-C1-7alkyl, 5-member monocyclic heteroaryl containing a nitrogen atom, where the ring carbon atom can be substituted with a carbonyl group, heteroaryl-C1-7alkyl, where the term "heteroaryl" represents an aromatic -member monocyclic ring with 1 S atom or a 6-member monocyclic ring with 1 N atom, C1-7alkoxy-C1-7alkyl, C1-7alkoxycarbonyl-C3-10cycloalkyl-C1-7alkyl or halogen substituted 4-member heterocyclyl-C1-7alkyl with one O atom; R2 is H, C1-7alkyl; R3 is aryl, aryl-C1-7alkyl, heteroaryl, heteroaryl-C1-7alkyl, where the term "heteroaryl" represents a 5-member monocyclic ring with 1 S atom, a 6-member monocyclic ring with 1 or 2 N atoms, 9-, 10-member bicyclic system with 1 or 2 N atoms in one ring; R4 is H, C1-7alkyl, OH; R5, R6, R7, R8 are independently selected from a group consisting of H, halogen, C1-7alkyl, C1-7alkoxy, flouro-C1-7alkyl, fluoro-C1-7alkyloxy; R9 is aryl, heterocyclyl, heteroaryl, heterocyclyl-C(O)-; R10 is H, C1-7alkyl, C3-10cycloalkyl, C3-10cycloalkyl-C1-7alkyl, fluro-C1-7alkyl, heteroaryl, heteroaryl-C1-7alkyl, where the term "heteroaryl" represents a 5-member monocyclic ring with 4 N atoms, a 5-member heterocyclyl with 1 N atom; R11, R12 are independently selected from a group consisting of H, C1-7alkyl, C3-10cycloalkyl, C3-10cycloalkyl-C1-7 alkyl; and pharmaceutically acceptable salts thereof; where the term "aryl" represents a phenyl group which can be optionally substituted with 1 to 5 substitutes which are independently selected from a group consisting of the following: halogen, CF3, NH2, C1-7alkylsulphonyl, C1-7alkoxy, fluoro-C1-7alkyl, fluoro-C1-7 alkoxy; the term "heterocyclyl" represents a nonaromatic monocyclic 5-, 6-member heterocyclic group with 1, 2 N atoms, or with 1 N atom and 1 O atom, where the heterocyclyl group can be substituted as indicated with respect to the term "aryl", and one carbon atom of the ring system of the heterocyclyl group can be substituted with a carbonyl group; the term "heteraryl" represents an aromatic 5- or 6-member monocyclic ring system which can have 1, 2, 3 N atoms, or 1 N atom and 1 S atom, where the heteroaryl group can be substituted as indicated with respect to the term "aryl", and one carbon atom of the ring system of the heteroaryl group can be substituted with a carbonyl group. Formula I compounds have inhibitory activity towards coagulation factor Xa.

EFFECT: possibility of using said compounds in a pharmaceutical composition and for preparing a medicinal agent.

27 cl, 90 ex

FIELD: pharmacology.

SUBSTANCE: invention deals with formula I compounds and their sals pharmaceutically relevant in the capacity of phosphatidylinositol 3-kinase inhibitors, their preparation method as well as their application for production of a pharmaceutical preparation, a pharmaceutical compounds based thereon and a therapy method envisaging their application. In a formula compound R1 is represented by aminocarbonyl, non-obligatorily displaced with nitrile, or R1 is represented by C1-C8-alkylcarbonyl that is non-obligatorily displaced with hydroxi, carboxi, C1-C8-alcoxicarbonyl, nitrile, phenyl, C1-C8-halogenalkyl or C1-C8-alkyl, non-obligatorily displaced with hydroxi or R1 is represented by C1-C8-alkyl aminocarbonyl alkylcarbonyl that is non-obligatorily displaced with halogen, hydroxi, C1-C8-alkylanimo, di(C1-C8-alkyl)amino, carboxi, C1-C8-alcoxicarbonyl, nitrile, C1-C8-halogenalkyl or C1-C8-alkyl, non-obligatorily displaced with hydroxi or R1 is represented by C1-C8-alkylaminocarbonyl, non-obligatorily displaced with C1-C8-cycloalkyl or R1 is represented by C1-C8-alkylcarbonyl or C1-C8-alkylaminocarbonyl, each of them non-obligatorily displaced with C1-C8-alcoxi, non-obligatorily displaced with hydroxi or R1 is represented by C1-C8-alkylaminocarbonyl, displaced with phenyl, additionally displaced with hydroxi or R1 is represented by C1-C8-alkylcarbonyl that is non-obligatorily displaced with a 5- or 6-membered heterocyclic ring that has 1-4 cyclic nitrogen heteroatom(s) where the ring is non-obligatorily displaced with C1-C8-alkyl on condition that the 6-membered heterocyclic ring is no 1-piperidyl or R1 is represented by C1-C8-alkylaminocarbonyl that is non-obligatorily displaced with a 5- or 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatom(s) selected from among the group consisting of oxygen and nitrogen where the ring is non-obligatorily displaced with C1-C8-alkyl or R1 is represented by -(C=O)-(NH)a-Het, where a stands to denote 0 or 1 and Het stands to denote a 4-, 5- or 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatom(s) where the ring is non-obligatorily displaced with hydroxi, C1-C8-alkyl, C1-C8-alcoxi or a 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatom(s) selected from among the group consisting of oxygen and nitrogen or R1 is represented by -(C=O)-(NH)b-T, where b stands to denote 0 or 1 and T stands to denote C3-C8-cycloalkyl that is non-obligatorily displaced with hydroxi or C1-C8-alkyl displaced with hydroxi or R1 is represented by -(C=O)-(NH)b-T, where b stands to denote 1 and T stands to denote phenyl that is non-obligatorily displaced with C1-C8-alkyl or C1-C8-alkyl displaced with hydroxi, R2 is represented by C1-C3-alkyl; one of R3 and R4 is represented by R6 while the other is represented by R7; R5 is represented by hydrogen or a halogen; R6 is represented by hydrogen, hydroxi, amino, -SOR8, -SO2R8, -SO2NH2, -SO2NR9R10, -COR8, -CONHR8, -NHSO2R8, nitrile, carboxi, -OR8 or C1-C8-halogenalkyl; R7 is represented by hydrogen, R11, -OR11, halogen, -SO2R8, ciano or C1-C8-halogenalkyl or, when R4 is represented by R7, R7 may equally be represented by -NR12R13; R8 and R11 are independently represented by C1-C8-alkyl or C3-C8-cycloalkyl, non-obligatorily displaced with hydroxi, nitrile, amino, C1-C8-alkylamino or di(C1-C8-alkyl)amino; any R9 is represented by C1-C8-alkyl or C3-C8-cycloalkyl, non-obligatorily displaced with hydroxi, C1-C8-alcoxi, nitrile, amino, C1-C8-akrylamino, di(C1-C8-alkyl)amino or 5- or 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatom(s) selected from among the group consisting of oxygen and nitrogen where the ring where the ring is non-obligatorily displaced with C1-C8-alkyl, and R10 is represented by hydrogen or C1-C8-alkyl or R9 and R10 together with the nitrogen atom they are connected to form a 5- or 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatoms where the ring is non-obligatorily displaced with C1-C8-alkyl; any R12 is represented by C1-C8-alkyl or C3-C8-cycloalkyl, non-obligatorily displaced with amino, C1-C8-alkylamino or di(C1-C8-alkyl)amino and R13 is represented by halogen or C1-C8-alkyl or R12 and R13 together with the nitrogen atom they are connected to form a 5- or 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatoms where the ring is non-obligatorily displaced with C1-C8-alkyl.

EFFECT: proposed compounds are to be utilised for treatment of diseases mediated by phosphatidilinozitol 3-kinase such as allergy, psoriasis, diabetes, atherosclerosis, diabetes, cancer.

19 cl, 3 tbl, 181 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a quinazoline compound of formula or its pharmaceutically acceptable salts, used as inhibitors of potential-dependant sodium and calcium channels, where R1, R2, R3, R5a, R5, y and x are defined in the formula of invention. The invention also relates to a pharmaceutical composition containing the disclosed compound and to methods of inhibiting one or more of NaV1.2, NaV1.3, NaV1.8, or CaV2.2.

EFFECT: 4-aminoquinazoline antagonists of selective sodium and calcium ion channels.

17 cl, 3 tbl, 1 ex

FIELD: pharmacology.

SUBSTANCE: invention refers to compounds of formula (I) as inhibitor of phosphotyrosinphosphotase 1B, and to application thereof for making a based medical product. In general formula (I) X represents C-R2; Y represents O, R1 represents phenyl, 5-merous heterocycle with one sulphur atom with phenyl residue, and heterocyclic residue being mono-, twice- or trisubstituted with halogen, CN, -OH, -CF3, -(C1-C6)alkyl, -COOH, -(CH2)-COOH, phenyl, -O-phenyl with phenyl ring being substituted with halogen; R2, R3, R4, R5, R6, R7 and R8 represent H.

EFFECT: compounds can find application in treating adipose and carbohydrate metabolic disorders, including for controlling blood glucose.

3 cl, 2 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: there are described derivatives of 1,3,4-oxadiazol-2-one of formula I and their pharmaceutically acceptable salts wherein ARYL represents phenyl which can have one substitute chosen from halogen; W represents chain or (CH2)m where m designates an integer 1 to 4; Z represents -O(CH2)n-, -(CH2)n-Y-(CH2)n- where Y designates O, n independently means an integer 1 to 5; X represents O or S; R1 represents C1-6 alkyl; R2 represents substituted phenyl where substitutes are chosen from the group including C1-6alkyl, C1-4perfluoralkyl. There are also described pharmaceutical composition, and method of treating a disease in mammal wherein said disease can be modulated by PPAR-delta receptor binding activity.

EFFECT: compounds possess agonist or antagonist activity with respect to PPAR-delta receptor.

9 cl, 2 tbl, 34 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to compounds of formula (I), their R and S isomers; or a mixture of R and S isomers; or pharmaceutically acceptable salts. Disclosed compounds can be used as a medicinal agent with agonist properties towards PPAR. In formula (I) and L represents (II) or (III); R1, R2, R3, Ya, R4a, R", Yb, R4b are hydrogen; R and R' are independently hydrogen, C1-C4alkoxy; n equals 0, 1 or 2; m equals 0, 1 or 2; X1 is a -Z-(CH2)P-Q-W group; X2 is -CH2-, -C(CH3)2-, -O- or -S-.

EFFECT: invention relates to a pharmaceutical composition, which contains the disclosed compound, to use of the pharmaceutical composition as a medicinal agent, to use of the disclosed compound in making the pharmaceutical composition.

13 cl, 35 ex

FIELD: chemistry.

SUBSTANCE: object of present invention is the following compounds: thiazol-2-ylamide 2-(3,4-dichlorophenoxy) hexanoic acid, 2-(4-fluorophenoxy)-N-1,3-thiazol-2-ylhexaneamide, 2-(4-methoxyphenoxy)-N-1,3-thiazol-2-ylhexaneamide, 2-(4-methoxyphenoxy)-K-pyridin-2-ylhexaneamide, 2-(3,4-dichlorophenoxy)-4-methyl-N,3-thiazol-2-ylpentaneamide, 2-(1,1'-biphenyl-4-yloxy)-N-1,3-thiazol-2-ylhexaneamide, 2-(4-isopropylphenoxy)-N-1,3-thiazol-2-ylhexaneamide, 2-(3-methoxyphenoxy)-N-1,3-thiazol-2-ylhexaneamide, and others, named in the formula of invention. Present invention also relates to a pharmaceutical composition, which contains the invented compound as an active ingredient and use of compounds in preparing a medicinal agent which increases activity of glucose. The invention also pertains to a compound of formula (I) where G is -C(O)-; L1 is a direct bond, A is >N-, X is a direct bond, R1 is cyclohexyl, R3 is cyclohexyl, substituted with R34, R4 is hydrogen; R5 is thiazol-5-yl, substituted with R48.

EFFECT: obtaining compounds which can be used for preparing a medicinal agent which can be used for treating diseases caused by glucokinase deficiency, for preparing a medicinal agent for treating diseases where increased activity of glucokinase is favourable.

6 cl, 143 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a crystalline salt of 1,2-ethanedisulfonic acid 1-[2-(2-chloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinoline-5-yl)ethylamino]methyl} -5- methoxyphenylcarbamoyl)ethyl]piperadin-4-yl ether biphenyl-2-ylcarbamic acid or its solvate. The invention also relates to a pharmaceutical composition containing such a salt, a combination containing the salt in paragraph 1 and a steroid anti-inflammatory agent, a method of treating pulmonary disorder, a method of producing the salt in paragraph 1 and use of the salt in paragraph 1 in making a medicinal agent.

EFFECT: novel crystalline salt of the compound given above, having useful biological properties, is obtained.

34 cl, 6 dwg, 19 ex

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