4,6,7,13-substituted derivatives of 1-benzylisoquinoline and pharmaceutical composition possessing inhibitory activity with respect to gfat

FIELD: organic chemistry, biochemistry.

SUBSTANCE: invention relates to compounds of the formula (I): wherein R1 means -lower alkyl, -CH2-aryl, -cycloalkyl, -(CH2)3, -OC(=O)CH3, -lower alcohol, -lower alkyl-R10, -CH2COOH or -CH2CH2OCH2CH3; R2 means -lower alkyl, -CH2-aryl, -lower alcohol, -CH2C(=O)-NH2 or lower alkyl-R10 wherein at least one radical among R1 or R2 means -CH3; R3 means -COOH, -lower alkyl-COOH, -lower alcohol, -CH2OCH2, -CH2NH2, -CHNHSO2R11, -C(=O)-R12, -(CH2)nNHC(=O)-R13, -(CH2)mC(=O)N-(R15)(R16), -C(=NH)-R17 or -(CH2)n-R18; R4 means hydrogen atom (-H), -lower alkoxy group, -O-C(R7R8)C(=O)-R19, -halogen atom, -SCH3, -C=CHC(=O)-R10, -CH2CH2C(=O)-R10, -O-lower alcohol, -OCH2CH(OH)CH2N=N±N-, -OCH2CH2OCH2CH2Cl, -NHC9=O)-CH2-lower alkyl, -O(CH2)n-cycloalkyl, -O-lower alkene or 5-membered unsaturated heterocyclic ring comprising one heteroatom representing sulfur (S) or oxygen (O) atom; R5 and R6 mean independently -H, -halogen atom or -lower alkoxy group; R7 and R8 mean independently -H or -CH3; R10 means 5-6-membered saturated heterocyclyl comprising 1 or 2 heteroatoms, such as N and O, and this group is bound with other moiety of molecule by a ring N atom; R11 means -CF3, -lower alkyl, -CH2Cl, -CH2CF3 or -R12; R12 means 5-6-membered saturated substituted or unsubstituted heterocyclic ring comprising 1 heteroatom, such as N, O and S wherein substituted ring represents heterocyclic ring substituted with -OH or -phenyl; R13 means -lower alkyl, -lower alkoxy group or -(CH2)nR14; R14 means 5-6-membered saturated or unsaturated heterocyclic ring comprising 1 and 2 heteroatoms, that are chosen from group comprising N and O; R15 means -H, -lower alkyl, -OH, -lower alkoxy group or -CH2COOCH2CH3; R17 means -lower alkoxy group, -NH2 or -N-lower alkyl; R18 means saturated or unsaturated 5-membered substituted or unsubstituted heterocyclic ring comprising from 1 to 4 heteroatoms, such as N, O and S wherein substituted ring represents heterocyclic ring that is substituted by one or two cyclic carbon atoms by =O, or it is substituted by cyclic N atom by -lower alcohol or -lower alkyl; R19 means -OH, -NHCH(CH3)2, -N(CH3)CH2-aryl, -N(CH3)-lower alkyl, 1-(aryl-(CH2)n-)-[1,4]-diazin-4-yl or 5-6-membered saturated heterocyclyl and optionally substituted with lower alkyl comprising 1 or 2 heteroatoms, such as N and O; m = 0, 1 or 2; n = 0 or 1, and their pharmaceutically acceptable salts and esters. Also, invention relates to a pharmaceutical composition possessing inhibitory activity with respect to GFAT and containing the effective amount of compound of the formula (I). Invention provides expanding assortment of agents possessing inhibitory activity with respect to GFAT. Proposed compounds can be used as inhibitors of GFAT, and pharmaceutical composition possessing inhibitory activity with respect to GFAT containing above said compound of the formula (I) also.

EFFECT: valuable biochemical properties of compounds and pharmaceutical composition.

25 cl, 134 ex

 

The text descriptions are given in facsimile form.

1. The compounds of formula (I)

in which R1means-ness. alkyl, -CH2-aryl, -cycloalkyl, -(CH2)3-OC(=O)CH3, -ness. alcohol-ness. alkyl-R10, -CH2COOH, or-CH2CH2OCH2CH3;

R2means-ness. alkyl, -CH2-aryl, -ness. alcohol, -CH2C(=O)NH2or nits. alkyl-R10where at least one of R1or R2denotes-CH3;

R3denotes-COOH, -ness. alkyl-COOH, -ness. alcohol, -CH2OCH2, -CH2NH2, -CH2NHSO2R11, -C(=O)R12, -(CH2)nNHC(=O)R13, -(CH2)mC(=O)N(R15)(R16), -C(=NH)-R17or -(CH2)n-R18;

R4denotes-H, -ness. alkoxygroup, -O-C(R7R8)C(=O)R19-halogen-SCH 3, -C=CHC(=O)-R10, -CH2CH2C(=O)-R10, -O-ness. alcohol-OCH2CH(OH)CH2N=N+=N-, -Och2CH2OCH2CH2Cl, -NHC(=O)CH2-ness. alkyl, -O(CH2)n-cycloalkyl, -O-ness. alkene, or a 5-membered unsaturated heterocyclic ring containing one heteroatom represents S or O;

R5and R6independently denote-H, -halogen, or-ness. alkoxygroup;

R7and R8independently represent-H or-CH3,

R10denotes a 5 - or 6-membered saturated heterocyclyl containing 1 or 2 heteroatoms, wherein each heteroatom selected from the group comprising N and O, and the group is associated with the rest of the molecule through a ring N atom;

R11means-CF3, -ness. alkyl, -CH2Cl, -CH2CF3or-R12;

R12denotes a 5 - or 6-membered saturated substituted or unsubstituted heterocyclic ring containing 1 heteroatom selected from the group comprising N, O and S, where the ring is substituted heterocyclic ring, substituted with-IT or-phenyl;

R13means-ness. alkyl, -ness. alkoxygroup, or -(CH2)nR14;

R14denotes a 5 - or 6-membered saturated or unsaturated heterocyclic ring containing 1 or 2 is heteroatom, selected from the group comprising N and O;

R15denotes-H or-CH3;

R16denotes-H, -ness. alkyl, -OH, -ness. alkoxygroup, or-CH2SOON2CH3;

R17means-ness. alkoxygroup-NH2or-N-ness. alkyl;

R18denotes a saturated or unsaturated 5-membered substituted or unsubstituted heterocyclic ring containing from 1 to 4 heteroatoms, which heteroatoms selected from the group comprising N, O and S, where the ring is substituted heterocyclic ring that is substituted by one or two cyclic carbon atoms with =O, or substituted by a cyclic atom N with-ness. alcohol or nits. of alkyl;

R19represents-OH, -NHCH(CH3)2, -N(CH3)CH2-aryl, -N(CH3)-ness. alkyl,

or 5 - or 6-membered saturated substituted or unsubstituted heterocyclyl containing 1 or 2 heteroatoms where each heteroatom selected from the group comprising N, O, where specified substituted heterocyclyl is heterocyclyl, substituted ness. by alkyl;

m is 0, 1 or 2;

n is 0 or 1;

and their pharmaceutically acceptable salts and esters.

2. Compounds according to claim 1, in which

R1and R2regardless about who appoints-ness. alkyl or-ness. alkyl-R10where at least one of R1or R2denotes-CH3;

R3denotes-COOH, -ness. alkyl-COOH, -(CH2)nNHC(=O)R13,

-CH2NHSO2R11or -(CH2)n-R18;

R4means-ness. alkoxygroup or-OC(R7R8)C(=O)R19;

R5and R6independently represent-H or-halogen,

R7, R8, R10, R11, R12, R13, R18, R19and n are as defined in claim 1, and their pharmaceutically acceptable salts and esters.

3. Compounds according to claim 1, in which R1means-ness. alkyl or-ness. alkyl-R10and R10denotes a 5 - or 6-membered saturated heterocyclyl containing 1 or 2 heteroatoms, wherein each heteroatom selected from the group comprising N and O, and the group is associated with the rest of the molecule through a ring atom N.

4. Compounds according to claim 1, in which R1denotes methyl or -(CH2)2-morpholinyl.

5. Compounds according to claim 1, in which R2means-ness. alkyl.

6. Compounds according to claim 1, in which R2denotes methyl.

7. Compounds according to claim 1, in which R3denotes-COOH, -ness. alkyl-COOH, -CH2NHSO2R11, -(CH2)nNHC(=O)R13or -(CH2)n-R18where R11about who appoints CF 3, R13means NISS. alkyl or 5 - or 6-membered saturated or unsaturated heterocyclic ring containing 1 or 2 heteroatoms, which are selected from the group comprising N and O, R18denotes a saturated or unsaturated 5-membered heterocyclic ring containing 1 to 4 heteroatoms, which heteroatoms selected from the group comprising N, O and S, and n is 0 or 1.

8. Compounds according to claim 1, in which R3denotes-COOH, -CH2-COOH, 4-methylpentanol acid, -CH2-NHC(=O)CH3, -CH2-NHC(=O)-pyridinyl, -CH2NHSO2CF3or tetrazolyl.

9. Compounds according to claim 1, in which R3represents -(CH2)n-R18and R18denotes an unsaturated 5-membered substituted or unsubstituted heterocyclic ring containing 2 to 4 heteroatoms, each of which is represented by N, where the substituted ring is a heterocyclic ring that is substituted on the ring N atom with-ness. the alkyl or-ness alcohol, and n is 0.

10. Compounds according to claim 9, in which R18denotes tetrazole or substituted tetrazole.

11. Compounds according to claim 1, in which R4denotes-O-ness. alkyl, -O-C(R7R8)C(=O)R19, -halogen, -SCH3, -C=CHC(=O)-R10, -CH2CH2C(=O)-R10, -O-ness. alcohol-OCH2CH(OH)CH2N=N+=N-, -Och2CH2 OCH2CH2Cl, -NHC(=O)CH2-R10, -NHC(=O)CH2-ness. alkyl, -O(CH2)n-cycloalkyl, -O-ness. alkene, or a 5-membered unsaturated heterocyclic ring containing one heteroatom represents S or O.

12. Compounds according to claim 1, in which R4means NISS. alkoxygroup or-O-C(R7R8)C(=O)R19, R7and R8denote SN3and R19means-NHCH(CH3)2.

13. Compounds according to claim 1, in which R5denotes a hydrogen or halogen.

14. Compounds according to claim 1, in which R5denotes hydrogen or fluorine.

15. Compounds according to claim 1, in which R6denotes a hydrogen or halogen.

16. Compounds according to claim 1, in which R6denotes hydrogen or fluorine.

17. Compounds according to claim 1, in which R4, R5and R6denote-H, and R1and R2denote-CH3,

18. Compounds according to claim 1, in which R4, R5and R6denote-H, and R3denotes-COOH.

19. Compounds according to claim 1, selected from the group including

2-[6,7-dimethoxy-1-(3-methoxybenzoyl)-isoquinoline-4-yl]-acetamide", she

3-[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-yl]-propionamide,

(4-aminomethyl-6,7-dimethoxyisoquinoline-1-yl)-(3-isopropoxyphenyl)-methanon,

2-[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-yl]-acetamide", she

(4-aminol the Il-6,7-dimethoxyisoquinoline-1-yl)-(2-fluoro-5-methoxyphenyl)-methanon,

1-(2,6-differentail)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

N-[1-(2,6-differentail)-6,7-dimethoxyisoquinoline-4-ylmethyl]-s,s-triftormetilfullerenov,

6,7-dimethoxy-1-[3-(3-oxo-3-pyrrolidin-1-ylpropyl)-benzoyl]-isoquinoline-4-carboxylic acid,

6,7-dimethoxy-1-{3-[(1-phenylethanol)-methoxy]-benzoyl}-isoquinoline-4-carboxylic acid,

6,7-dimethoxy-1-{3-[(1-phenylethanol)-methoxy]-benzoyl}-isoquinoline-4-carboxylic acid,

1-[3-(1-isopropylcarbamate-1 methylethoxy)-benzoyl]-6,7-dimethoxyisoquinoline-4-carboxylic acid,

1-(3-furan-2-aventyl)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

6,7-dimethoxy-1-(3-thiophene-3-aventyl)-isoquinoline-4-carboxylic acid,

(2-fluoro-5-isopropoxyphenyl)-[4-(2-hydroxyethyl)-6,7-dimethoxyisoquinoline-1-yl]-methanon,

7-benzyloxy-6-methoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carboxylic acid,

7-(2-hydroxyethoxy)-6-methoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carboxylic acid,

7 carbamoylphenoxy-6-methoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carboxylic acid,

6-methoxy-1-(3-methoxybenzoyl)-7-(2-pyrrolidin-1 ylethoxy)-isoquinoline-4-carboxylic acid,

6-benzyloxy-7-methoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carboxylic acid,

6 cyclopentyloxy-7-methoxy-1-(3-methoxybenzoyl)-isoquinoline-karbolovuju acid,

6-(3-acetoxypropionyl)-7-methoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carboxylic acid,

6-(3-hydroxypropoxy)-1-(3-isopropoxybenzoic)-7-methoxyethanol-4-carboxylic acid,

6 carboxymethoxy-1-(3-isopropoxybenzoic)-7-methoxyethanol-4-carboxylic acid,

6-(3-acetoxypropionyl)-1-(3-ethoxybenzoyl)-7-methoxyethanol-4-carboxylic acid,

1-(3-ethoxybenzoyl)-6-(2-ethoxyethoxy)-7-methoxyethanol-4-carboxylic acid,

1-(3-ethoxybenzoyl)-6-(2-hydroxyethoxy)-7-methoxyethanol-4-carboxylic acid,

6,7-dimethoxy-1-(3-methylsulfonylbenzoyl)-isoquinoline-4-carboxylic acid ethyl ester 1-(3-ethoxybenzoyl)-6,7-dimethoxyisoquinoline-4-carboxymethylate,

amide 1-(3-ethoxybenzoyl)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

1-(3-ethoxybenzoyl)-6,7-dimethoxyisoquinoline-4-carboxamide, (3-ethoxyphenyl)-[4-(aminomorpholine-4-ylmethyl)-6,7-dimethoxyisoquinoline-1-yl]-methanon,

1-(3-ethoxybenzoyl)-6,7-dimethoxy-N,N-dimethylethanol-4-carboxamide,

1-(3-ethoxybenzoyl)-6,7-dimethoxy-N,N-dimethylethanol-4-carboxamide,

rat-[3-(3-azido-2-hydroxypropoxy)-phenyl]-[6,7-dimethoxy-4-(1H-tetrazol-5-yl)-isoquinoline-1-yl]-methanon,

(3 cyclopentyloxy-4-methoxyphenyl)-[6,7-dimethoxy-4-(1H-tetrazol-5-yl)-isoquinoline-1-yl]-methanon,

(3-allyloxyphenyl)-[6,dimethoxy-4-(1H-tetrazol-5-yl)-isoquinoline-1-yl]-methanon,

(3-but-2-tyloxapol)-[6,7-dimethoxy-4-(1H-tetrazol-5-yl)-isoquinoline-1-yl]-methanon,

(3-cyclopentylacetyl)-[6,7-dimethoxy-4-(1H-tetrazol-5-yl)-isoquinoline-1-yl]-methanon,

(3-cyclopropylmethoxy)-[6,7-dimethoxy-4-(1H-tetrazol-5-yl)-isoquinoline-1-yl]-methanon,

(3-cycloheptylmethyl)-[6,7-dimethoxy-4-(1H-tetrazol-5-yl)-isoquinoline-1-yl]-methanon,

1-(3-hydroxyethoxyphenyl)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

1-{3-[2-(2-chloroethoxy)-ethoxy]-benzoyl}-6,7-dimethoxyisoquinoline-4-carboxylic acid,

1-(3,5-dimethoxybenzyl)-6,7-dimethoxyisoquinoline-4-carboxylic acid (2-morpholine-4-retil)-amide 6,7-dimethoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carboxylic acid,

(2-Tianeti)-amide 6,7-dimethoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carboxylic acid,

hydroxyamide 6,7-dimethoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carboxylic acid,

methoxime 6,7-dimethoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carboxylic acid,

methoxyethylamine 6,7-dimethoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carboxylic acid,

(4-hydroxymethyl-6,7-dimethoxyisoquinoline-1-yl)-(3-isopropoxyphenyl)-methanon,

6,7-dimethoxy-1-(3-methoxy-5-methylbenzoyl)-isoquinoline-4-carboxylic acid,

[4-(4-hydroxy-4-phenylpiperidine-1-carbonyl)-6,7-dimethoxyisoquinoline-1-yl]-(3-methoxyphenyl)-methane is,

ethyl ester {[6,7-dimethoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carbonyl]-amino}-acetic acid,

[4-(4-hydroxy-piperidine-1-carbonyl)-6,7-dimethoxyisoquinoline-1-yl]-(3-methoxyphenyl)-methanon,

amide 6,7-dimethoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carboxylic acid,

(4-hydroxymethyl-6,7-dimethoxyisoquinoline-1-yl)-(3-methoxyphenyl)-methanon,

(6,7-dimethoxy-4-methoxymethylethoxy-1-yl)-(3-methoxyphenyl)-methanon,

6,7-dimethoxy-1-[3-(2-morpholine-4-ylacetamide)-benzoyl]-isoquinoline-4-carboxylic acid,

6,7-dimethoxy-1-[3-(2-pyrrolidin-1 ylacetamide)-benzoyl]-isoquinoline-4-carboxylic acid,

1-(3-butylimidazole)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

1-(2,6-debtor-3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

1-(3-second-butoxybenzoyl)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

N-[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-acetamide", she

1-[3-(1-isopropylcarbamate-1 methylethoxy)-benzoyl]-6,7-dimethoxyisoquinoline-4-carboxylic acid,

With,With,With-Cryptor-N-[1-(2-fluoro-5-methoxybenzyl)-6,7-dimethoxyisoquinoline-4-ylmethyl]-methanesulfonamide,

6,7-dimethoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carboxylic acid,

[6,7-dimethoxy-4-(1H-tetrazol-5-yl)-isoquinoline-1-yl]-(3-ethoxyphenyl)-methanon,

2-[1-(2-fluoro-5-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-yl]-4-methylpentanol acid,

N-[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-nicotinamide,

[6,7-dimethoxy-1-(3-methoxybenzoyl)-isoquinoline-4-yl]-acetic acid,

1-(3-butoxybenzoyl)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

hydrochloride of 1-(3-ethoxybenzoyl)-7-methoxy-6-(2-morpholine-4-ylethoxy)-isoquinoline-4-carboxylic acid,

With,With,With-Cryptor-N-[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-methanesulfonamide,

6,7-dimethoxy-1-[3-(2-oxo-2-pyrrolidin-1 ylethoxy)-benzoyl]-isoquinoline-4-carboxylic acid,

6,7-dimethoxy-1-{3-[2-(4-methylpiperazin-1-yl)-2-oksidoksi]-benzoyl}-isoquinoline-4-carboxylic acid,

6,7-dimethoxy-1-[3-(2-morpholine-4-yl-2-oksidoksi)-benzoyl]-isoquinoline-4-carboxylic acid,

1-{3-[(benzylaminocarbonyl)-methoxy]-benzoyl}-6,7-dimethoxyisoquinoline-4-carboxylic acid,

1-{3-[2-(4-benzylpiperazine-1-yl)-2-oksidoksi]-benzoyl}-6,7-dimethoxyisoquinoline-4-carboxylic acid,

1-(3-carboxybenzoyl)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

N-[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-yl]-acetamide", she

[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-ylmethyl]-amide pyrazin-2-carboxylic acid,

N-[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-2-pyridine-3-ylacetamide,

3H-imidazole-4-carboxylic acid [1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-amide,

N-[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-isonicotinamide,

[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-amide morpholine-4-carboxylic acid,

N-[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-methanesulfonamide,

[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-amide econsultancy acid,

[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-yl]-acetic acid,

1-(2-fluoro-5-methoxybenzyl)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

N-[1-(2-fluoro-5-methoxybenzyl)-6,7-dimethoxyisoquinoline-4-ylmethyl]methanesulfonamide,

1-(2-fluoro-5-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

[1-(2-fluoro-5-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-yl]-acetic acid,

2-[1-(2-fluoro-5-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-yl]-propionic acid,

6,7-dimethoxy-1-[3-(3-oxo-3-pyrrolidin-1-ylpropyl)-benzoyl]-isoquinoline-4-carboxylic acid,

1-[3-(isopropylcarbamate)-benzoyl]-6,7-dimethoxyisoquinoline-4-carboxylic acid,

6,7-dimethoxy-1-[3-(2-oxo-2-thiomorpholine-ylethoxy)-benzoyl]-isoquinoline-4-carboxylic acid,

1-{3-[(ethylmethylamino)-methoxy]-benzoyl}-6,7-dimethoxyisoquinoline-4-carboxylic acid,

6,7-dimethoxy-1-{3-[2-oxo-2-(4-phenylpiperazin-1-yl)-ethoxy]-benzoyl}-isoquinoline-4-carboxylic acid,

1-(3-isobutoxide)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

1-[3-(1,1-dimethyl-2-oxo-2-pyrrolidin-1 ylethoxy)-benzoyl]-6,7-dimethoxyisoquinoline-4-carboxylic acid,

1-(3-butoxybenzoyl)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

2-[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-[1,2,4]oxadiazolidine-3,5-dione,

3-[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-thiazolidine-2,4-dione,

2-[1-(2-fluoro-5-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-yl]-4-methylpentanol acid,

1-(2,6-debtor-3-methoxybenzyl)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

[6,7-dimethoxy-4-(1H-tetrazol-5-ylmethyl)-isoquinoline-1-yl]-(2-fluoro-5-methoxyphenyl)-methanon,

7 butoxy-6-methoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carboxylic acid,

6 butoxy-7-methoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carboxylic acid,

hydrochloride of 1-(3-isopropoxybenzoic)-7-methoxy-6-(2-pyrrolidin-1 ylethoxy)-isoquinoline-4-carboxylic acid,

6-(3-acetoxypropionyl)-1-(3-ethoxybenzoyl)-7-methoxyethanol-4-carboxylic acid,

1-(3-ethoxybenzoyl)-6-isoprop the XI-7-methoxyethanol-4-carboxylic acid,

1-(3-ethoxybenzoyl)-7-methoxy-6-(2-morpholine-4-ylethoxy)-isoquinoline-4-carboxylic acid,

[1-(3-second-butoxybenzoyl)-6,7-dimethoxyisoquinoline-4-yl]-acetic acid,

1-(3-ethoxybenzoyl)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

(3-ethoxyphenyl)-{4-[1-(2-hydroxyethyl)-1H-tetrazol-5-yl]-6,7-dimethoxyisoquinoline-1-yl}-methanon,

(3-ethoxyphenyl)-{4-[2-(2-hydroxyethyl)-1H-tetrazol-5-yl]-6,7-dimethoxyisoquinoline-1-yl}-methanon,

[6,7-dimethoxy-4-(1-methyl-1H-tetrazol-5-yl)-isoquinoline-1-yl]-(3-ethoxyphenyl)-methanon,

[4-(4,5-dihydro-1H-imidazol-2-yl)-6,7-dimethoxyisoquinoline-1-yl]-(3-ethoxyphenyl)-methanon,

[6,7-dimethoxy-4-(1H-tetrazol-5-yl)-isoquinoline-1-yl]-[3-(2-hydroxyethoxy)-phenyl]-methanon,

[6,7-dimethoxy-4-(1H-tetrazol-5-yl)-isoquinoline-1-yl]-(3-isopropoxyphenyl)-methanon,

N-[1-(3-second-butoxybenzoyl)-6,7-dimethoxyisoquinoline-4-ylmethyl]-s,s-triftormetilfullerenov,

(6,7-dimethoxy-4-pyrrolidin-1-iletileceginden-1-yl)-(3-methoxyphenyl)-methanon,

N-[6,7-dimethoxy-1-(3-methoxybenzoyl)-isoquinoline-4-yl]-acetamide", she methyl ether [6,7-dimethoxy-1-(3-methoxybenzoyl)-isoquinoline-4-yl]-carbamino acid,

S-chloro-N-[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-methanesulfonamide,

[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-amituofo-2-sulfona the Oh of the acid, and

[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-amide 2,2,2-cryptgethashparam acid,

and their pharmaceutically acceptable salts and esters.

20. Compounds according to claim 1, selected from the group comprising 1-(2,6-debtor-3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

1-(3-second-butoxybenzoyl)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

N-[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-acetamide", she

1-[3-(1-isopropylcarbamate-1 methylethoxy)-benzoyl]-6,7-dimethoxyisoquinoline-4-carboxylic acid,

With,With,With-Cryptor-N-[1-(2-fluoro-5-methoxybenzyl)-6,7-dimethoxyisoquinoline-4-ylmethyl]-methanesulfonamide,

6,7-dimethoxy-1-(3-methoxybenzoyl)-isoquinoline-4-carboxylic acid,

[6,7-dimethoxy-4-(1H-tetrazol-5-yl)-isoquinoline-1-yl]-(3-ethoxyphenyl)-methanon,

2-[1-(2-fluoro-5-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-yl]-4-methylpentanol acid,

N-[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-nicotinamide,

[6,7-dimethoxy-1-(3-methoxybenzoyl)-isoquinoline-4-yl]-acetic acid, and

1-(3-butoxybenzoyl)-6,7-dimethoxyisoquinoline-4-carboxylic acid,

and their pharmaceutically acceptable salts and esters.

21. The connection is about to claim 1, in which the compound is 1-(3-ethoxybenzoyl)-7-methoxy-6-(2-morpholine-4-ylethoxy)-isoquinoline-4-carboxylic acid and its pharmaceutically acceptable salts and esters.

22. The compound according to claim 1 in which the compound is s,s,s, trifter-N-[1-(3-isopropoxybenzoic)-6,7-dimethoxyisoquinoline-4-ylmethyl]-methanesulfonamide and its pharmaceutically acceptable salts and esters.

23. Compounds according to any one of claims 1 to 22, intended for use as therapeutically active substances with inhibitory activity against GFAT.

24. Compounds according to any one of claims 1 to 22, intended for use as therapeutically active substances for the treatment and/or prevention of diseases mediated GFAT.

25. Pharmaceutical composition having inhibitory activity against GFAT comprising an effective amount of a compound according to any one of claims 1 to 22 and a pharmaceutically acceptable carrier and/or excipient.



 

Same patents:

FIELD: medicine.

SUBSTANCE: the present innovation deals with describing the efficient quantity of, at least, one heterocyclic compound of formula (I) or its salts, moreover, the compound of formula (I) should be chosen out of (i) the compounds of formula (III) or their salts, in which Z, Z' indicate O, X indicates S (thiazolidine dionic group), G indicates O or S; at least, one out of R2 and R3 indicates CF3, OR0 or COOR0, where R0 indicates H or saturated linear or branched C1-C20-alkyl and, preferably, C10-C10-alkyl, (ii) compounds (VI) or their salts: in which Z, Z' and G independently indicate O or S, at least, one out of R2 and R3 indicates hydrogen, CN, CF3, NO2, OR0, COOR0 or saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl, possibly substituted OR0, where R0 indicates H or saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl, (iii) compounds (VII) or their salts in which Z, Z' and G independently indicate O or S; R indicates saturated linear or branched C1-C10-alkyl; at least, one out of R2 and R3 indicates saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl, NO2, OR0, where R0 indicates H or saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl. The compounds in question reveal improved action upon stimulation of keratin fibers growth, particularly, human keratin fibers, that prevents their falling down and increases their density.

EFFECT: higher efficiency.

31 cl, 13 ex, 6 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel indolyl-derivatives of the formula (I): and their pharmaceutically acceptable salts and esters wherein R1 means phenyl optionally substituted with from one to three substitutes chosen independently from halogen atom, (C1-C8)-alkyl, (C1-C8)-alkoxy-group and (C1-C8)-alkyl substituted with from one to three halogen atoms; R2 means hydrogen atom, (C1-C8)-alkyl; R3 means (C1-C8)-alkoxy-group; R4 means hydrogen atom; A means oxygen atom or sulfur atom; n = 1,2 or 3. Synthesized compounds possess agonistic activity with respect to PPARα- and/or PPARγ-receptors. Also, invention relates to methods for their synthesis, a pharmaceutical composition based on thereof and their using for preparing medicinal agents, and to a method for treatment and/or prophylaxis of diseases.

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

29 cl, 1 tbl, 7 sch, 17 ex

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): wherein R1 means hydrogen atom or lower alkyl; R2 means substituted or unsubstituted thiazolinyl or oxazolinyl residue; each R5 and R6 means independently hydrogen atom or protective group; X means oxygen (O), sulfur atom (S) or -NR7 wherein in each case R7 means hydrogen atom or lower alkyl; RB means in each case independently hydrogen atom, (C1-C6)-alkyl, -CY3, -CHY2 or -CH2Y wherein Y means F, Br, Cl or J. Also, invention relates to a pharmaceutical composition containing compounds of the formula (I) and possessing cytotoxic activity, and using this compound in treatment of malignant tumor with multiple drug resistance.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

44 cl, 77 dwg, 13 ex

FIELD: organic chemistry, biochemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to novel diaminothiazoles of the formula (I) , their pharmaceutically acceptable salts and esters, and to a pharmaceutical composition based on thereof. Proposed compounds inhibit activity of cyclin-dependent kinase 4 (Cdk4), shows selectivity with respect to Cdk2 and Cdk1 and can be used in treatment against cancer, in particular, against solid tumors. In the general formula (I) R2 and R3 represent hydrogen atom; R4 is chosen from group comprising lower alkyl, (C3-C6)-cycloalkyl, O-lower alkyl, halogen atom, -NO2, S-lower alkyl, -CF3 and -CN; R5 is chosen from group comprising hydrogen atom, O-lower alkyl, lower alkyl, halogen atom and -OH, or, alternatively, R4 and R in common with two carbon atoms and a bond binding them belonging to benzene cycle (C) to which R4 and R5 are bound can form a cycle consisting of 5-6 atoms comprising one or two heteroatoms chosen from oxygen atom and optionally substituted with (C1-C4)-alkyl; R6 and R are chosen independently from group comprising hydrogen atom, lower alkyl and -COOR12, or, alternatively, group -NR6R7 can mean cycle consisting of 5-6 atoms optionally comprising heteroatom chosen from nitrogen or oxygen atoms; R8 and R9 are chosen independently from group comprising hydrogen atom and lower alkyl; R10 is chosen from group comprising hydrogen atom, lower alkyl, lower alkyl substituted with hydroxyl, and -COOR12; R11 is chosen from group comprising hydrogen atom, lower alkyl and -COOR12 wherein R12 means lower alkyl; m can mean 1 or 2; n can mean 0, 1 or 2 under condition that if m means 2 and R4 means fluorine atom then R5 is not hydrogen atom, and under condition if m means 1 and R4 means lower alkyl then R5 is not hydroxyl.

EFFECT: valuable biochemical and medicinal properties of compounds and pharmaceutical compositions.

20 cl, 6 sch, 3 tbl, 153 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to compound of the formula (I): wherein (a) each R1 is chosen independently from hydrogen atom and alkoxy-group; (b) R2 represents hydrogen atom; (c) each R3 and R4 is chosen independently of one another from hydrogen atom, alkyl, alkynyl, heteroalkyl group, aryl; or R3 and R4 in common with nitrogen atom bound with them form heteroaryl or heterocycloaryl substitute optionally substituted with one or more hydroxo-group, carboxyl group, keto-, thioketo-, phenyl group, alkyl, heteroalkyl group, heteroaryl, heterocycloalkyl, spirocycloalkyl and their combinations; (d) each R5 and R6 represents hydrogen atom; or optical isomers, diastereomers and enantiomers represented by above given formula, and their pharmaceutically acceptable salts also. Also, invention describes using compound of the formula (I) for preparing a pharmaceutical composition possessing antibacterial activity and antibacterial pharmaceutical composition containing the safety and effective amount of compound of the formula (I) and a pharmaceutically acceptable carrier. Invention provides synthesis of novel compounds possessing useful biological properties.

EFFECT: valuable properties of compounds and pharmaceutical composition.

7 cl, 37 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to alkylated (1H-benzimidazol-5-yl)-(-4-substituted phenyl)-amine derivatives, in particular compound of formula and pharmaceutically acceptable salts or solvates thereof, wherein R1, R2, and R9, are independently hydrogen, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluorimethoxy, azido, etc.; R7 is optionally substituted C1-C10-alkyl, C3-C10-cycloalkyl, etc.; A is-OR3 or NR4R3; R8 is hydrogen, -Cl, -Br, -F, cyano, nitro, etc.; and meanings of the rest substituents are as defined in specification. Also disclosed is composition for MEK inhibition and uses of benzinidazole compounds.

EFFECT: new compounds with value biological properties.

32 cl, 56 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: Described are derivatives of general formula I (all symbols are as described in specification), pharmaceutically acceptable salts thereof or cyclodextrin clathrates. Such compounds hardly bind of EP2 subtype of PGE receptor and are useful in prophylaxis of immune diseases, allergy, death of neuronal cells, liver or kidney insufficiency, etc.

EFFECT: new agent for prophylaxis of various diseases.

18 cl, 388 ex, 68 tbl, 3 dwg

Novel benzodioxols // 2304580

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of benzodioxol of the formula (I): wherein R1, R2, R3, R4, R5, R6, R7 and X are given in the description and the invention claim, and to their pharmaceutically acceptable salts. Also, invention relates to pharmaceutical compositions based on compounds of the formula (I) and their using for preparing medicinal agents used in treatment and/or prophylaxis of diseases associated with modulation of CB1 receptors.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

19 cl, 279 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds represented by the general formula (I): and their pharmaceutically acceptable salts and esters possessing agonistic activity with respect to peroxisome proliferator receptors PPARα and/or PPARγ, to a pharmaceutical composition based on thereof and their using for preparing medicines wherein R1 means thiophenyl or phenyl optionally substituted with from one to three substitutes chosen independently from halogen atom, (C1-C8)-alkoxy-group, (C1-C8)-alkyl and (C1-C8)-alkyl substituted with one-three halogen atoms; R2 means hydrogen atom or (C1-C8)-alkyl; R3 means phenoxy-, (C2-C8)-alkenyloxy- or (C1-C8)-alkoxy-group; R4 means hydrogen atom or (C1-C8)-alkyl wherein one of substitutes R5 and R6 means compound of the formula and another one means hydrogen atom and wherein the bond between carbon atoms Ca and Cb means a carbon-carbon simple or double bond; R7 means hydrogen atom or (C1-C8)-alkyl; R8 means hydrogen atom or (C1-C8)-alkyl being any of A and A1 means nitrogen atom and another means oxygen or sulfur atom; n means 1, 2 or 3.

EFFECT: valuable medicinal properties of compound and pharmaceutical composition.

30 cl, 1 tbl, 14 sch, 86 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of benzimidazole of the general formula (I): wherein A represents -CH2- or -C(O)-; Y represents -S- or -NH-; R1 and R2 represent independently hydrogen atom, (C1-C8)-alkyl, (C5-C9)-bicycloalkyl optionally substituted with one or some similar or different (C1-C6)-alkyl radicals, or radical of the formula -(CH2)n-X wherein X represents amino-group, (C3-C7)-cycloalkyl and other values of radicals also given in the invention claim; R3 represents -(CH2)p-W-(CH2)p'-Z3 wherein W3 represents a covalent bond, -CH(O)- or -C(O)-; Z3 represents (C1-C6)-alkyl, aryl radical, heteroaryl and other values of radical also; V3 represents -O-, -S-, -C(O)-, -C(O)-O-, -SO2- or a covalent bond; Y3 represents (C1-C6)-alkyl radical optionally substituted with one or some halogen-radicals, amino-group, di-((C1-C6)-alkyl)-amino-group, phenylcarbonylmethyl, heterocycloalkyl or aryl radicals; p, p' and p'' represent independently a whole number from 0 to 4; R4 represents radical of the formula: -(CH2)s-R''4 wherein R''4 represents heterocycle comprising at least one nitrogen atom and optionally substituted with (C1-C6)-alkyl or aralkyl, and other values of radicals given in the invention claim also. Also, invention relates to a pharmaceutical composition showing antagonistic property with respect to GnRH and based on these compounds. Also, using above proposed compounds for preparing a medicament is considered. Invention provides synthesis of novel compounds, preparing pharmaceutical composition and medicament based on thereof in aims for treatment of such diseases as endometriosis, fibroma, polycystic ovary, breast, ovary and endometrium cancer, gonadotropic hypophysis desensitization in medicinal stimulation of ovary in fertility treatment in females.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

18 cl, 2 tbl, 538 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds, namely, to N-substituted derivatives of piperidine of the formula (I): or their pharmaceutically acceptable salts, amides, esters wherein values R1, R, R3, m, X, n, W, Ar1 and Ar2 are disclosed in the invention claim. Also, invention relates to methods for inhibition of activity and methods for inhibition of activation of monoamine receptors. Methods involve contacting monoamine receptors or system comprising monoamine receptors with the effective amount of one or some compounds of the formula (I). Except for, invention relates to using compounds of the formula (I) in treatment of psychotic diseases.

EFFECT: valuable medicinal properties of compounds.

35 cl, 1 tbl

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to phthalimido-derivatives of the general formula (I): wherein X means -N= or -CH=; R1 means -CO-NR5R6, -CHR7-(CH2)n-CO-NR5R6, -(CH2)n-NR5R6, -(CH2)n-COOR8, -(CH2)n-CN, -CHR7-(CH2)n-CF3, -(CH2)n-NH-COR9, -(CH2)n-NH-COOR8, -(CH2)n-piperidinyl, -(CH2)n-morpholinyl, -(CH2)n-tetrahydrofuranyl, -(CH2)n-thiophenyl or -(CH2)n-isoxazolyl wherein a heterocyclic ring can be substituted with (C1-C6)-alkyl; -(CH2)n-phenyl wherein phenyl ring can be substituted with halogen atom or halogen-(C1-C6)-alkyl; -(CH2)p-OR8, -(CH2)p-SR8, -(CH2)p-SO-R9 or -(CH2)n-CS-NR5R6; R2 means hydrogen atom (H), (C1-C6)-alkyl, -(CH2)p-OR10, -(CH2)p-SR or benzyl; R3 means H, (C1-C6)-alkyl; R4 means halogen atom, halogen-(C1-C6)-alkyl, cyano-, (C1-C6)-alkoxy- or halogen-(C1-C6)-alkoxy-group; Each R5 and R6 means independently of one another H, (C1-C6)-alkyl; R7 means H, -OH, (C1-C6)-alkoxy-group; R8 means H, (C1-C6)-alkyl; R9 means (C1-C6)-alkyl; R10 means H, (C1-C6)-alkyl; m = 1, 2 or 3; n = 0, 1 or 2; p = 1 or 2, and their pharmaceutically acceptable salts. Compounds of the formula (I) inhibit activity of monoamine oxidase B (MAO B) that allows their using as a drug.

EFFECT: valuable medicinal and biochemical properties of compounds.

14 cl, 4 sch, 1 tbl, 53 ex

FIELD: medicine.

SUBSTANCE: the present innovation deals with describing the efficient quantity of, at least, one heterocyclic compound of formula (I) or its salts, moreover, the compound of formula (I) should be chosen out of (i) the compounds of formula (III) or their salts, in which Z, Z' indicate O, X indicates S (thiazolidine dionic group), G indicates O or S; at least, one out of R2 and R3 indicates CF3, OR0 or COOR0, where R0 indicates H or saturated linear or branched C1-C20-alkyl and, preferably, C10-C10-alkyl, (ii) compounds (VI) or their salts: in which Z, Z' and G independently indicate O or S, at least, one out of R2 and R3 indicates hydrogen, CN, CF3, NO2, OR0, COOR0 or saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl, possibly substituted OR0, where R0 indicates H or saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl, (iii) compounds (VII) or their salts in which Z, Z' and G independently indicate O or S; R indicates saturated linear or branched C1-C10-alkyl; at least, one out of R2 and R3 indicates saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl, NO2, OR0, where R0 indicates H or saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl. The compounds in question reveal improved action upon stimulation of keratin fibers growth, particularly, human keratin fibers, that prevents their falling down and increases their density.

EFFECT: higher efficiency.

31 cl, 13 ex, 6 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel indolyl-derivatives of the formula (I): and their pharmaceutically acceptable salts and esters wherein R1 means phenyl optionally substituted with from one to three substitutes chosen independently from halogen atom, (C1-C8)-alkyl, (C1-C8)-alkoxy-group and (C1-C8)-alkyl substituted with from one to three halogen atoms; R2 means hydrogen atom, (C1-C8)-alkyl; R3 means (C1-C8)-alkoxy-group; R4 means hydrogen atom; A means oxygen atom or sulfur atom; n = 1,2 or 3. Synthesized compounds possess agonistic activity with respect to PPARα- and/or PPARγ-receptors. Also, invention relates to methods for their synthesis, a pharmaceutical composition based on thereof and their using for preparing medicinal agents, and to a method for treatment and/or prophylaxis of diseases.

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

29 cl, 1 tbl, 7 sch, 17 ex

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): wherein R1 means hydrogen atom or lower alkyl; R2 means substituted or unsubstituted thiazolinyl or oxazolinyl residue; each R5 and R6 means independently hydrogen atom or protective group; X means oxygen (O), sulfur atom (S) or -NR7 wherein in each case R7 means hydrogen atom or lower alkyl; RB means in each case independently hydrogen atom, (C1-C6)-alkyl, -CY3, -CHY2 or -CH2Y wherein Y means F, Br, Cl or J. Also, invention relates to a pharmaceutical composition containing compounds of the formula (I) and possessing cytotoxic activity, and using this compound in treatment of malignant tumor with multiple drug resistance.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

44 cl, 77 dwg, 13 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention describes derivatives of aminotetraline of the formula (I) wherein R1 means (C1-C6)-alkyl; R2 means halogen atom or -OR'; R3 means hydrogen atom (H) or -OR' wherein R' means (C1-C6)-alkyl or -SO2R'' wherein R'' means phenyl, thienyl, isoxazolyl; R4 means (C1-C6)-alkyl, phenyl, piperidinyl, pyrrolidinyl, morpholinyl, piperazinyl, diazepinyl, furanyl, isoxazolyl, imidazolyl and pyrazolyl that can be substituted optionally, and pharmaceutical compositions containing derivatives of aminotetraline. Proposed compounds are selective antagonists of M2/M3 muscarinic receptors and designated for treatment and prophylaxis of diseases associated with smooth muscle disorder.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

23 cl, 1 tbl, 16 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to alkylated (1H-benzimidazol-5-yl)-(-4-substituted phenyl)-amine derivatives, in particular compound of formula and pharmaceutically acceptable salts or solvates thereof, wherein R1, R2, and R9, are independently hydrogen, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluorimethoxy, azido, etc.; R7 is optionally substituted C1-C10-alkyl, C3-C10-cycloalkyl, etc.; A is-OR3 or NR4R3; R8 is hydrogen, -Cl, -Br, -F, cyano, nitro, etc.; and meanings of the rest substituents are as defined in specification. Also disclosed is composition for MEK inhibition and uses of benzinidazole compounds.

EFFECT: new compounds with value biological properties.

32 cl, 56 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): wherein R means -C(O)R1 wherein R1 is chosen from the series: (C1-C6)-alkyl, -C=CH-COOH, -NHCH2-CH2R2, -N(CH2-CH2OH)CH2-CH2OH, -N(CH3)CH2-CH2-NHCH3, -N(CH3)CH2-CH2N(CH3)CH3, saturated 4-, 5- and 6-membered cycles and saturated and unsaturated 5- and 5-membered cycles comprising at least one heteroatom from a series sulfur (S), nitrogen (N) and oxygen (O), and optionally substituted with a group chosen from the series: (C1-C6)-alkyl, -C=O-R5, -OH, (C1-C6)-alkyl substituted with hydroxy-group optionally, (C1-C6)-alkyl substituted optionally with a group of the series: -NH2, -N-(C1-C6)-alkyl, -SO2CH3, =O, and 5- and 6-membered saturated cycles comprising at least one heteroatom chosen from N and O, and wherein R5 is chosen from the series: hydrogen atom (H), (C1-C6)-alkyl, (C1-C6)-alkyl substituted with hydroxy-group optionally, and (C1-C6)-alkyl substituted with NH2-group optionally; R2 is chosen from the series: -N(CH3)CH3, -NH2, morpholinyl and piperazinyl; X1, X2 and X3 are chosen independently from the series: -OH, (C1-C2)-alkyl, (C1-C6)-alkoxy-group, -Cl, -Br, -F, -CH2OCH3 and -CH2OCH2CH3, or one among X1, X2 or X3 means hydrogen atom, and two others are chosen independently from the series: hydroxy-group, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, -Cl, -Br, -F, -CF3, -CH2OCH3, -CH2OCH2CH3, -OCH2-CH2R3, -OCH2-CF3 and -OR4, morpholylmethyl, -N(CH3)CH3, -CH2OH, -COOH, or one among X1, X2 or X3 means hydrogen atom, and two others in common with two carbon atoms including bonds between them in benzene cycle to which they are bound optionally form 5- or 6-membered saturated cycle comprising at least one heteroatom chosen from S, N and O, and wherein R3 is chosen from the series: -F, -OCH3, -N(CH3)CH3, saturated 5-membered cycle comprising at least one heteroatom N; R4 means 3-5-membered saturated cycle, and each Y1 and Y2 is chosen independently from the series: -Cl, -Br, -NO2,-C≡N and C≡N, and compound of the formula (II) also given in the invention description. Also, invention relates to a pharmaceutical composition possessing anti-proliferative activity and based on these compounds. Invention provides preparing novel compounds possessing the useful biological properties.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

28 cl, 39 ex

Novel benzodioxols // 2304580

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of benzodioxol of the formula (I): wherein R1, R2, R3, R4, R5, R6, R7 and X are given in the description and the invention claim, and to their pharmaceutically acceptable salts. Also, invention relates to pharmaceutical compositions based on compounds of the formula (I) and their using for preparing medicinal agents used in treatment and/or prophylaxis of diseases associated with modulation of CB1 receptors.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

19 cl, 279 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to N3-alkylated benzimidazole derivatives for preparing a drug used in inhibition of MEK activity. Invention describes benzimidazole compound of the formula (I): and its pharmaceutically acceptable salts and solvates wherein R1, R2, R9 and R10 are chosen independently from hydrogen atom, halogen atom, trifluoromethyl group, difluoromethoxy-, trifluoromethoxy-, azido-group, -OR3, -C(O)R3, -C(O)OR3, -OC(O)R3, (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkylalkyl wherein each alkyl and cycloalkyl moiety is substituted possibly with groups in the amount from one to five and chosen independently from halogen atom, trifluoromethyl group, difluoromethoxy-, trifluoromethoxy-group; R3 is chosen from hydrogen atom, trifluormethyl group, (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkylalkyl wherein each alkyl and cycloalkyl group is substituted possibly with groups in the amount from one to five and chosen independently from halogen atom, trifluoromethyl group, difluoromethoxy-, trifluoromethoxy-group, -C(O)R', -C(O)OR', -OC(O)R' wherein R' is chosen independently from hydrogen atom, lower alkyl; R4 represents independently hydrogen atom or (C1-C6)-alkyl; R6 is chosen from trifluoromethyl group or (C1-C10)-alkyl, (C3-C10)-cycloalkyl wherein each alkyl and cycloalkyl moiety is substituted possibly with groups in the amount from one to five and chosen independently from halogen atom, trifluoromethyl group, difluoromethoxy-, trifluoromethoxy-group, -C(O)R', -C(O)OR', -OC(O)R', -OR'; R7 is chosen from (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkylalkyl wherein each alkyl and cycloalkyl moiety is substituted possibly with groups in the amount from one to five and chosen independently from halogen atom, trifluoromethyl group, difluoromethoxy-, trifluoromethoxy-group, -C(O)R3, -C(O)OR3, -OC(O)R3, -SO2R6, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl; W is chosen from -C(O)OR3, -C(O)NR3R4, -C(O)NROR3, -C(O)R4OR3, -C(O)(C3-C10)-cycloalkyl, -C(O)(C1-C10)-alkyl. Also, invention describes compositions used for inhibition of MEK activity, using such compounds for preparing a drug used in inhibition of MEK activity and preparing a drug used in cancer treatment.

EFFECT: valuable medicinal and biochemical properties of compounds and composition.

17 cl, 10 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

Up!