Substituted hydantoins

FIELD: chemistry.

SUBSTANCE: described are compounds of formula (I)

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

EFFECT: compounds are highly efficient.

16 cl, 27 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

where R1represents unsubstituted phenyl or phenyl substituted by a Deputy selected from the group consisting of hydroxyl; lower alkyl; lower alkoxygroup; substituted by hydroxyl low alkoxygroup; -P(O)(O-lower alkyl)2; -N(lower alkyl)2; piperidinyl, substituted-HE; morpholinyl; -S(O)2-lower alkyl; -NHC(O)-lower alkyl; -N(CH3)(C2H4OCH3); 3,4-Ethylenedioxy; -O-alkyl, where the alkyl group is substituted by one or two substituents selected from the group N(lower alkyl)2piperidinyl, morpholinyl, -O-lower alkyl, -COOH, -COO-lower alkyl, -C(O)-heterocyclyl selected from morpholinyl, pyrrolidinyl, azetidine, -C(O)-N(lower alkyl)2; C(O)-NH-lower alkyl, where the alkyl group is optionally replaced by-O-stands; -C(O)NH2, -P(O)(O-lower alkyl)2;
R2denotes hydrogen;
R3denotes a lower alkyl group;
R4selected from the group consisting of substituted with halogen or lower alkoxygroup or unsubstituted phenyl group, hydroxyl, lower CNS, benzyl, optionally substituted with halogen, or lower and Kilroy groups;
R5selected from the group consisting of COOR, COR, CON(R7)2, CHOHR or S(O)nR, where n=0-2, and where R denotes lower alkyl or lower alkyl, substituted lower alkoxygroup; C3-7-cycloalkyl;
R6and R7selected from hydrogen or lower alkyl groups,
not necessarily in the form of its diastereoisomers,
or its pharmaceutically acceptable salt.

2. The compound according to claim 1, where R1denotes phenyl or phenyl substituted by a Deputy selected from the group consisting of hydroxyl; lower alkoxygroup; -P(O)(O-lower alkyl)2; -N(lower alkyl)2; piperidinyl, substituted-HE; morpholinopropan; -S(O)2is lower alkyl; NHC(O)-lower alkyl; -O-alkyl, where the alkyl group is substituted by one or two substituents selected from the group N(lower alkyl)2, hydroxyl, piperidinyl, morpholinopropan, -O-lower alkyl, C(O)-heterocyclyl selected from morpholinopropan, pyrrolidinyl, -C(O)-N(lower alkyl)2-C(O)-NH-lower alkyl, where the alkyl group is optionally replaced by-O-stands, -C(O)-NH2.

3. The compound according to claim 1, where R1indicates 2,3-dihydrobenzo[1,4]dioxin-6-yl.

4. The connection according to one of claims 1 to 3, where R3denotes a methyl group.

5. The connection according to one of claims 1 to 3, where R4denotes a substituted or unsubstituted phenyl.

6. The connection according to one of claims 1 to 3, where R5 denotes the COR, and R denotes methyl or ethyl.

7. The connection according to one of claims 1 to 3, where R5denotes cyclopropyl.

8. The connection according to one of claims 1 to 3, where R6denotes hydrogen.

9. The compound of formula II

where R8denotes lower alkyl; With3-7-cycloalkyl; -O-lower alkyl; N(lower alkyl)2;
R9denotes lower alkyl, preferably methyl;
R10denotes hydrogen or halogen, and the halogen is preferably selected from fluorine;
R11selected from the group consisting of hydroxyl; lower alkoxygroup; -P(O)(O-lower alkyl)2; -N(lower alkyl)2; piperidinyl, substituted by-OH; morpholinopropan; -S(O)2-lower alkyl; -NHC(O)-lower alkyl; -O-alkyl, where the alkyl group is substituted by one or two substituents selected from the group of-N(lower alkyl)2, hydroxyl, piperidinyl, morpholinopropan, -O-lower alkyl; -COOH; -C(O)-heterocyclyl selected from morpholinopropan, pyrrolidinyl, -C(O)-N(lower alkyl)2; -C(O)-NH-lower alkyl, where the alkyl group is optionally replaced by-O-stands, or-C(O)NH2;
not necessarily in the form of its diastereoisomers,
or its pharmaceutically acceptable salt.

10. The compound according to claim 1 or 9, selected from the group including:
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-[(R)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-tanilba aramid;
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-[(R)-4-(4-hydroxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide;
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-{(R)-4-[4-(2-hydroxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide;
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide;
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-((R)-4-{4-[2-(2-methoxyethoxy)ethoxy]phenyl}-2,5-dioxoimidazolidin-1-yl)-3-phenylbutyramide;
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-{(R)-4-[4-(2-ethoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide;
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-{(R)-4-[4-(2-dimethylaminoethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide;
connection with triperoxonane acid
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-{(R)-4-[4-(2-diethylaminoethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide;
connection with triperoxonane acid
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-[(R)-4-(4-ethoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide;
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-{(5)-4-[4-(2-dimethylaminoethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide;
connection with triperoxonane acid
Diethyl ether (4-{1-[(1S,2S)-1-(4-acetylthiazole-2-ylcarbonyl)-2-phenylpropyl]-2,5-dioxoimidazolidin-4-yl}phenyl)phosphonic acid;
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-[4-(4-dimethylaminophenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide;
(4-Acetylthiazole-2-yl)-amide (2S,3S)-2-[(R)-4-(4-methodology Setenil)-2,5-dioxoimidazolidin-1-yl]-3-phenylpentane acid;
(2S,3S)-2-[(R)-4-(4-Methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-[(R)-4-(2,3-Dihydrobenzo[1,4]dioxin-6-yl)-2,5-dioxoimidazolidin-1-yl]-3-phenyl-M-(4-propositional-2-yl)butyramide;
(2S,3S)-2-[(R)-4-(4-Ethoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-[(R)-4-(4-Hydroxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenyl-H-(4-propositional-2-yl)butyramide;
(2S,3S)-2-{(R)-4-[4-(2-Methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenyl-R-(4-propositional-2-yl)butyramide;
(2S,3S)-2-{(S)-4-[4-(2-Methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-{(R)-4-[4-(2-Hydroxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-((R)-4-{4-[2-(2-Methoxyethoxy)ethoxy]phenyl}-2,5-dioxoimidazolidin-1-yl)-3-phenyl-N-(4-propositional-2-yl)butyramide and
(2S,3S)-2-{(R)-4-[4-(2-Ethoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenyl-N-(4-propositional-2-yl)butyramide.

11. The compound according to claim 1 or 9, selected from the group including:
(2S,3S)-2-{(R)-4-[4-(2-Ethoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-{(R)-4-[4-(2-Dimethylaminoethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenyl-N-(4-propositional-2-yl)butyramide;
connection with triperoxonane acid
Dimethyl ether (4-{(R)-2,5-dioxo-1-[(1S,2S)-2-phenyl-1-(4-propioni the thiazole-2-ylcarbonyl)propyl]imidazolidin-4-yl}phenoxymethyl)phosphonic acid;
(2S,3S)-N-(4-Isobutylthiazole-2-yl)-2-{4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide;
(2S,3S)-N-(4-Isobutylthiazole-2-yl)-2-[(R)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide;
(2S,3S)-2-{(3)-4-[4-(2-Dimethylaminoethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenyl-N-(4-propositional-2-yl)butyramide;
connection with triperoxonane acid;
(2S,3S)-2-{2,5-Dioxo-4-[4-(2-piperidine-1-ylethoxy)phenyl]imidazolidin-1-yl}-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-{4-[4-(2-Morpholine-4-ylethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-3-(3-Forfinal)-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-[(R)-4-(4-Methoxy-3-were)-2,5-dioxoimidazolidin-1-yl]-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-{(S)-4-[4-(2-Hydroxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-((R)-2,5-Dioxo-4-phenylimidazoline-1-yl)-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-[4-(4-Dimethylaminophenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-[4-(4-(Morpholine-4-ylphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-{4-[4-(4-Hydroxypiperidine-1-yl)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-(4-{4-[(2-Metakit the l)methylamino]phenyl}-2,5-dioxoimidazolidin-1-yl)-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-N-(4-Cyclopropanecarbonyl-2-yl)-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide;
(4-Propositional-2-yl)amide (2S,3S)-2-{4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-methylpentanoic acid;
(2S,3R)-3-Benzyloxy-2-{(R)-4-[4-(2-methoxyethoxy)-phenyl]-2,5-dioxoimidazolidin-1-yl}-N-(4-propositional-2-yl)-butyramide;
(2S,3S)-N-[4-(2-Methoxyacetyl)thiazol-2-yl]-2-[(R)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide;
Methyl ester 2-{(2S,3S)-2-[(R)-4-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide}thiazole-4-carboxylic acid and
Methyl ester 2-[(2S,3S)-2-((R)-2,5-dioxo-4-phenylimidazoline-1-yl)-3-phenylbutyramide]thiazole-4-carboxylic acid.

12. The compound according to claim 1 or 9, selected from the group including:
Methyl ester 2-{(2S,3S)-2-[(R)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide}thiazole-4-carboxylic acid;
Methyl ester 2-{(2S,3S)-2-[(R)-4-(4-hydroxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide}thiazole-4-carboxylic acid;
Methyl ester of 2-((2S,3S)-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide)thiazole-4-carboxylic acid;
Methyl ester of 2-((2S,3S)-2-{(R)-4-[4-(2-hydroxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide)thiazole-4-carboxylic acid;
Methyl ester 2-{(2S,3S)-2-[(R)-4-(4-isopropoxyphenyl)-2,5-deok imidazolidin-1-yl]-3-phenylbutyramide}thiazole-4-carboxylic acid;
Methyl ester 2-{(2S,3S)-2-[(R)-4-(4-methoxy-3-were)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide}thiazole-4-carboxylic acid;
Methyl ester of 2-((2S,3S)-2-{(R)-4-[4-(diethoxyphosphoryloxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide)thiazole-4-carboxylic acid;
Methyl ester 2- {(2S,3S)-3-(2-methoxyphenyl)-2-[4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]bucillamine}thiazole-4-carboxylic acid;
Methyl ester of 2-((2S,3S)-3-(4-forfinal)-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}bucillamine)thiazole-4-carboxylic acid;
Methyl ester 2-{(2S,3S)-2-[(R)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-methylpentylamino}thiazole-4-carboxylic acid;
Methyl ester 2-[(2S,3S)-2-((R)-2,5-dioxo-4-phenylimidazoline-1-yl)-3-methylpentylamino]thiazole-4-carboxylic acid;
Methyl ester of 2-((2S,3S)-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-methylpentylamino)thiazole-4-carboxylic acid;
Methyl ester 2-{(2S,3R)-3-hydroxy-2-[(R)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]bucillamine}thiazole-4-carboxylic acid;
Methyl ester of 2-((2S,3R)-3-hydroxy-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}bucillamine)thiazole-4-carboxylic acid;
Methyl ester of 2-((2S,3R)-3-tert-butoxy-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}bucillamine)thiazole-4-carboxylic acid;
Methyl ester 2-{(2S,R)-3-methoxy-2-[(R)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]bucillamine}thiazole-4-carboxylic acid;
Methyl ester of 2-((2S,3R)-3-methoxy-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}bucillamine)thiazole-4-carboxylic acid;
Methyl ester of 2-((2S,3R)-3-benzyloxy-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}bucillamine)thiazole-4-carboxylic acid;
Methyl ester of 2-((2S,3R)-3-(4-chlorobenzoyloxy)-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}bucillamine)thiazole-4-carboxylic acid;
Methyl ester 2-{(2S,3R)-2-[(R)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-methylpentylamino}thiazole-4-carboxylic acid;
Methyl ester of 2-((2S,3R)-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-methylpentylamino)thiazole-4-carboxylic acid;
Methyl ester of 2-((2S,3R)-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-methylpentylamino)thiazole-4-carboxylic acid;
Methyl ester 2-{(2S,3S)-2-[4-(4-methanesulfonyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide} thiazole-4-carboxylic acid and
Methyl ester 2-{(S)-2-[(R)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-methyl-3-phenylbutyramide}thiazole-4-carboxylic acid.

13. The compound according to claim 1 or 9, selected from the group including:
Methyl ester 2-{(2S,3R)-2-[(R)-4-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide}thiazole-4-carboxylic acid;
Methyl ester 2-{(2S,3S)-2-[(R)-4-(4-acetylaminophenol)-2,5-dioxoimidazolidin the-1-yl]-3-phenylbutyramide}thiazole-4-carboxylic acid;
N-[4-(1-Hydroxy-1-methylethyl)thiazol-2-yl]-2-[(R)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide;
(2S,3S)-2-[(R)-4-(2,3-Dihydrobenzo[1,4]dioxin-6-yl)-2,5-dioxoimidazolidin-1-yl]-N-[4-(1-hydroxypropyl)thiazole-2-yl]-3-phenylbutyramide;
(2S,3S)-N-[4-(1-Hydroxyethyl)thiazol-2-yl]-2-[(R)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide;
Dimethylamide 2-{(2S,3S)-2-[(R)-4-(4-methoxyphenyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide}thiazole-4-carboxylic acid;
(2S,3S)-N-(4-Ethylsulfanyl-2-yl)-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide;
(2S,3S)-N-(4-Atonalities-2-yl)-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide;
(2S,3S)-N-(4-Econsultation-2-yl)-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide;
(2S,3S)-N-(2-Hydroxyacyl)thiazol-2-yl]-2-{(R)-4-[4-(2-methoxyethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide;
Methyl ester of (4-{(R)-1-[(1S,2S)-1-(4-acetylthiazole-2-ylcarbonyl)-2-phenylpropyl]-2,5-dioxoimidazolidin-4-yl}phenoxy)acetic acid;
Methyl ester of (4-{(R)-2,5-dioxo-1-[(1S,2S)-2-phenyl-1-(4-propositional-2-ylcarbonyl)propyl]imidazolidin-4-yl}phenoxy)acetic acid;
(4-{2,5-Dioxo-1-[(1S,2S)-2-phenyl-1-(4-propositional-2-ylcarbonyl)propyl]imidazolidin-4-yl}phenoxy)acetic acid;
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-[(R)-4-(4-dimethylcarbamodithioato the l)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide;
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-[(R)-4-(4-methylcarbamoylmethyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide;
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-[(R)-4-(4-carbamoylmethyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide and
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-((R)-4-{4-[(2-methoxyethanol)methoxy]phenyl}-2,5-dioxoimidazolidin-1-yl)-3-phenylbutyramide.

14. The compound according to claim 1 or 9, selected from the group including:
(2S,3S)-N-Acetylthiazole-2-yl)-2-((R)-4-{4-[(2-methoxyethanol)methoxy]phenyl}-2,5-dioxoimidazolidin-1-yl)-3-phenylbutyramide;
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-{(R)-4-[4-(2-morpholine-4-yl-2-oksidoksi)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenylbutyramide;
(2S,3S)-N-(4-Acetylthiazole-2-yl)-2-{(R)-2,5-dioxo-4-[4-(2-oxo-2-pyrrolidin-1 ylethoxy)phenyl]imidazolidin-1-yl}-3-phenylbutyramide;
(2S,3S)-2-[(R)-4-(4-Dimethylcarbamoyl)-2,5-dioxoimidazolidin-1-yl]-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-[(R)-4-(4-Methylcarbamoylmethyl)-2,5-dioxoimidazolidin-1-yl]-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-((R)-4-{4-[(2-Methoxyethanol)methoxy]phenyl}-2,5-dioxoimidazolidin-1-yl)-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-{(R)-4-[4-(2-Morpholine-4-yl-2-oksidoksi)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenyl-N-(4-propositional-2-yl)butyramide;
(2S,3S)-2-{(R)-2,5-Dioxo-4-[4-(2-oxo-2-pyrrolidin-1 ylethoxy)phenyl]imidazolidin-1-yl}-3-phenyl-N-(4-propositional-2-yl)butir the MFA;
(2S,3S)-2-{(R)-4-[4-(2-Azetidin-1-yl-2-oksidoksi)phenyl]-2,5-dioxoimidazolidin-1-yl}-3-phenyl-N-(4-propositional-2-yl)butyramide and
(2S,3S)-N-(4-Cyclopropanecarbonyl-2-yl)-2-[(R)-4-(4-methylcarbamoylmethyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylbutyramide.

15. Pharmaceutical composition, in particular for use in disease-mediated MEK 1/2, comprising the compound according to claim 1 or 9 and a pharmaceutically acceptable carrier.

16. The compound according to claim 1 or 9 for use as therapeutically active substance, in particular for use in disease-mediated MEK 1/2.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula

or

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

EFFECT: compounds are highly effective.

40 cl, 48 tbl, 191 ex

FIELD: chemistry.

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

EFFECT: more effective treatment.

30 cl, 1 tbl, 142 ex

FIELD: chemistry.

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

EFFECT: novel compounds have useful biological properties.

44 cl, 5 tbl, 66 ex

FIELD: chemistry.

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

EFFECT: increased effectiveness of using said compounds.

8 cl, 1 tbl, 6 dwg, 12 ex

FIELD: chemistry.

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

EFFECT: increased effectiveness of using said compounds.

13 cl, 37 ex

FIELD: chemistry.

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

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

8 cl, 8 ex

FIELD: chemistry.

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

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

10 cl, 3 tbl, 5 ex

FIELD: chemistry.

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

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

1 cl, 5 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention refers to compounds of formula I or formula II, to their pharmaceutically acceptable salts, enantiomers and diastereoisomers as metalloprotease inhibitors, and also to a pharmaceutical composition based thereon and to versions of application thereof. Said compounds can find application in treatment of the diseases mediated by activity of metalloproteases, Her-2 SHEDDASE, ADAM-10 and ADAM-17, such as arthritis, cancer, cardiovascular disorders, skin diseases, inflammatory and allergic conditions, etc. In general formula I or II: A represents CWNHOH; B represents CH2; G represents CH2; D represents oxygen; X represents CH2NRb; Y represents CH2; M represents C; U is absent or represents NRb; V is absent or represents phenyl, or 4-10-members heterocyclyl containing 1-2 heteroatoms chosen from N and S, substituted with 0-5 groups Re; U' is absent or represents C1-10alkylene, O or combinations thereof; V' represents H, C1-8alkyl, NRbRc, C6-10carbocyclyl substituted with 0-3 groups Re, or 5-14-members heterocyclyl containing 1-3 heteroatoms chosen from N, O and C substituted with 0-4 groups Re; Ra and Re, independently represents H, T, C1-8alkylene-T, C(O)NRa'(CRb'Rc')r-T, (CRb'Rc')r-O-(CRb'Rc')r-T, OH, Cl, F, CN, NO2, NRIRII, COORIV, ORIV, CONRIRII, C1-8halogenalkyl, C3-13carbocyclyl; Rb and Rc independently represents H, T, C1-6alkylene-T, C(O)O(CRb'Rc')r-T, C(O)(CRb'Rc')r-T, S(O)p(CRb'Rc')r-T; T represents H, C1-10alkyl substituted with 0-1 groups Rb'; C3-6carbocyclyl, 5-6-members heterocyclyl containing one oxygen atom; Ra' Rb' and Rc' independently represents H, ORIV or phenyl; R1 represents hydrogen; R2 represents hydrogen; R3 represents: (i) C1-10alkyl; (ii) 4-14-members heterocyclyl containing 1-3 nitrogen atoms optionally substituted with one or two substitutes chosen from C1-6alkyl, OR13, 5-10-members heterocyclyl containing 1-3 heteroatoms chosen from N O and C, or phenyl; (iii) NR16R17; R4 represents H; R4' represents H; R5' represents H; W represents oxygen; R13 represents C1-C6alkyl; R16 and R17 independently represents C1-C10alkyl or phenyl where each is optionally substituted with one C1-4alkyl; RI and RIIindependently represents H or C1-6alkyl; RIV represents C1-6alkyl; i is equal to 0; p is equal to 1 or 2 and r is equal to 0, 1 or 2; provided that a) a spiro ring represents a stable chemical base unit and b) NR8 and NRb do not contain neither N-N, nor N-O bonds.

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

54 cl, 1 tbl, 9 dwg, 284 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing new 3,4-dithienyl-substituted maleic anhydrides or maleimides of general formula I: , where X=O, or NR1; R1 and R2=alkyl C1-C4; R3=alkyl C1-C4, or nitrogen- and/or sulphur-containing heterocyclic substitute. The method involves reacting the corresponding 2,5-disubstituted 3-thienyl-acetic acid with the corresponding 2,5-disubstituted 3-halogen acetythiophenes while heating in the presence of a base in a medium of inert organic solvent in atmospheric oxygen with subsequent separation of the end product of general formula I, where X=O, or, if necessary, the latter is converted to a compound of general formula I, where X=NR1, where R1 assumes values given above, by treating it with the corresponding amine. These compounds can be used as photochromes, which are widely used as optical switches in high-capacity data carriers used for recording, processing and storing data.

EFFECT: versatility of the method, ie possibility of obtaining compounds with and without equivalent heterocyclic substitutes using readily available thienyl-acetic acid and halogen ketones of the thiophene family, which considerably widens the assortment of organic photochromic dithienylethenes.

4 cl, 5 ex

FIELD: chemistry.

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

EFFECT: more effective treatment.

30 cl, 1 tbl, 142 ex

Organic compounds // 2382783

FIELD: chemistry.

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

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

6 cl, 9 tbl, 154 ex

FIELD: chemistry.

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

EFFECT: more effective treatment.

12 cl, 36 ex

FIELD: chemistry.

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

EFFECT: novel compounds have useful biological properties.

44 cl, 5 tbl, 66 ex

FIELD: chemistry.

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

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

2 cl, 485 ex, 3 tbl

FIELD: chemistry.

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

EFFECT: more effective treatment.

13 cl, 3 tbl, 46 ex

FIELD: chemistry.

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

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

8 cl, 8 ex

FIELD: chemistry.

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

.

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

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

11 cl, 19 ex, 6 tbl

FIELD: chemistry.

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

EFFECT: new phosphodiesterase 4 inhibitors have improved properties.

55 cl, 30 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 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: medicine.

SUBSTANCE: invention relates to pharmaceutical composition, which contains ZD6474 or its pharmaceutically acceptable salt, fragile thinner and second thinner, which is practically insoluble and possesses compression plasticity. Fragile thinner represents calcium hydrophosphate, and second thinner, which is practically insoluble and possesses compression plasticity, represents microcrystalline cellulose.

EFFECT: good bioavailability for active substance.

5 cl, 7 tbl, 5 ex, 2 dwg

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