Tetrahydropyridoindole derivatives

FIELD: chemistry.

SUBSTANCE: invention relates to tetrahydropyridoindole derivatives of general formula , where R1, R2, R3 and R4 independently represent hydrogen; C1-C5alkyl, which can be optionally substituted and represents trifluoromethyl if C1-C5alkyl is substituted; C1-C3alkoxy or halogen, and R5 is C1-C6alkylcarbonyl, C1-C5alkylcarbamoyl, C1-C5alkoxycarbonyl, C2-C5alkenylcarbonyl, C3-C6cycloalkylcarbonyl, C3-C6cycloalkyl(C1-C3)alkylcarbonyl, C3-C6cycloalkylcarbamoyl, C3-C6cycloalkylthiocarbamoyl, phenylcarbonyl or phenyl(C1-C3)alkylcarbonyl, where the phenyl residue in these two groups contains one, two, three or four substitutes, independently selected from a group comprising C1-C4alkyl, C1-C3alkoxy, halogen, trifluoromethyl and trifluoromethoxy, monosubstituted with a C3-C6cycloalkyl group, or monosubstituted with a phenyl group which in turn is substituted with a C1-C3alkyl group; phenyl(C1-C3)alkoxycarbonyl, phenylcarbamoyl or phenylthiocarbamoyl (where these two groups are optionally independently monosubstituted with a C1-C5alkyl group or halogen atoms); phenyl(C1-C3)alkylcarbamoyl, phenyl(C1-C3)alkylthiocarbamoyl, biphenylcarbamoyl, naphthylcarbonyl, naphthyl(C1-C3)alkylcarbonyl or naphthylcarbamoyl (where the naphthyl residues in these three groups are optionally monosubstituted with substitutes independently selected from a group comprising C1-C3alkyl, C1-C3alkoxy and halogen); fluorenylcarbonyl, optionally substituted with an oxo group, fluorenyl(C1-C3)alkoxycarbonyl; or 5-9-member heteroarylcarbonyl groups containing one or two heteroatoms, independently selected from a group comprising oxygen, nitrogen and sulphur, where the said groups can be substituted with one or two groups independently selected from C1-C3alkyl and halogen, provided that if R1, R2, R3, R4 are hydrogen, R5 is not ethoxycarbonyl or tert-butoxycarbonyl, or salt thereof. The invention also relates to a pharmaceutical composition based on the compound of formula I and to use of the compound in preparing a medicinal agent.

EFFECT: obtaining novel tetrahydropyridoindole derivatives which have CRTH2 receptor antagonistic activity.

14 cl, 14 tbl, 171 ex

 

The text descriptions are given in facsimile form.

1. A compound selected from the group comprising derivatives of tetrahydropyridine General formula (I):

where R1, R2, R3and R4independently mean hydrogen; C1-C5alkyl which may be optionally substituted, and when With1-C5alkyl substituted, it represents trifluoromethyl; C1-C3alkoxy or halogen, and
R5means1-C5alkylsulphonyl,1-C5allylcarbamate, C1-C3alkoxycarbonyl,2-C5 alkenylboronic,3-C6cycloalkylcarbonyl,3-C6cycloalkyl(C1-C3)alkylsulphonyl,3-C6cycloalkylcarbonyl,3-C6cycloalkylcarbonyl, phenylcarbinol or phenyl(C1-C3)alkylsulphonyl, where the phenyl residue in the composition of these two groups contains one, two, three or four substituent, independently selected from the group comprising From1-C4alkyl, C1-C3alkoxy, halogen, trifluoromethyl, triptoreline, monosubstituted With3-C6cycloalkyl group, or a monosubstituted phenyl group, which, in turn, replaced by a group C1-C3alkyl; phenyl(C1-C3)alkoxycarbonyl, phenylcarbamoyl or phenylthiocarbamoyl (and these two groups are optionally independently monogamist group C1-C5alkyl or by halogen atoms); phenyl(C1-C3)allylcarbamate, phenyl(C1-C3)alkylthiomethyl, biphenylcarboxylic, afterburner, naphthyl(C1-C3)alkylsulphonyl or afterburner (and raftiline residues in the composition of these three groups are not necessarily monogamist substituents, independently selected from the group comprising C1-C3alkyl, C1-C3alkoxy and halogen); fluorenylmethyl, optionally substituted exography, fluorenyl(C1- 3)alkoxycarbonyl; or 5-9-membered heteroarylboronic group containing one or two heteroatoms, independently selected from the group comprising oxygen, nitrogen and sulfur, and the above-mentioned groups may be substituted by one or two groups independently selected from C1-C3of alkyl and halogen,
provided that if R1, R2, R3and R4mean hydrogen, R5does not mean etoxycarbonyl or tert-butoxycarbonyl,
or its salt.

2. The compound according to claim 1, in which R1, R2, R3and R4independently mean hydrogen; C1-C5alkyl which may be optionally substituted, and when With1-C5alkyl substituted, it represents trifluoromethyl; C1-C3alkoxy or halogen, and
R5means1-C5alkylsulphonyl,1-C5alkoxycarbonyl,2-C5alkenylboronic,3-C6cycloalkylcarbonyl,3-C6cycloalkyl(C1-C3)alkylsulphonyl, phenylcarbinol or phenyl(C1-C3)alkylsulphonyl, where the phenyl residue within the above groups may be independently substituted and contains one, two or three substituent selected from the group comprising From1-C4alkyl, C1-C3alkoxy, halogen, trifluoromethyl or triptoreline, or MONOSEM the puppy phenyl group, which, in turn, can be substituted by a group of C1-C3alkyl; afterburner, fluorenyl(C1-C3)alkoxycarbonyl; or five - or six-membered heteroarylboronic containing one or two heteroatoms, independently selected from the group comprising oxygen, nitrogen and sulfur, and the above-mentioned groups is substituted by one or two groups independently selected from the group comprising C1-C3alkyl and halogen,
if R1, R2, R3and R4mean hydrogen, R5does not mean etoxycarbonyl or tert-butoxycarbonyl,
or its salt.

3. The compound of formula (I) according to claim 1, in which R1, R2, R3and R4defined as in claim 1, and R5selected from the group comprising 2-cyclohexyl-2-phenylacetyl, 2-naphthalene-1-ylacetic, 2-naphthalene-2-ylacetic, 3-cyclopentylpropionyl, 3-phenylpropionyl, acetyl, diphenylacetyl, hexanol, (E)-but-2-enoyl, N-fluoren-9-ylmethoxycarbonyl, benzyloxycarbonyl, butoxycarbonyl, phenylacetyl, ethylcarbitol, 2-bromo-3-methylbenzoyl, 2-bromo-5-methylbenzoyl, 2-methoxybenzoyl, 3,4,5-trimethoxybenzoyl, 3,5-bis-trifloromethyl, 3,5-dimethoxybenzoyl, 3-chlorobenzoyl, 4-bromobenzoyl, 4-chlorobenzoyl, 4-methoxybenzoyl, 4-tert-butylbenzoyl, 4-trifloromethyl, 4-trifloromethyl, benzoyl, phenylcarbamoyl, 4'-ethylbiphenyl-4-carbonyl, biphenyl-2-ka is bonil, biphenyl-4-carbonyl, 2-methoxynaphthalene-1-carbonyl, 4-methoxynaphthalene-1-carbonyl, 2-ethoxynaphthalene-1-carbonyl, naphthalene-1-carbonyl, cyclohexanecarbonyl, cyclopropanecarbonyl, pyridine-3-carbonyl, 2-chloro-6-methylpyridin-4-carbonyl, pyridine-4-carbonyl, furan-2-carbonyl, furan-3-carbonyl, 2-methylfuran-3-carbonyl, 3-methylfuran-2-carbonyl, 5-bromofuran-2-carbonyl, pyrazin-2-carbonyl, benzo[b]thiophene-2-carbonyl, 5-chlorothiophene-2-carbonyl, 3-methylthiophene-2-carbonyl, 5-methylthiophene-2-carbonyl, thiophene-2-carbonyl and thiophene-3-carbonyl, or its salt.

4. The compound of formula (I) according to claim 1, in which R1, R2, R3and R4defined as in claim 1, and R5selected from the group comprising 2-naphthalene-1-ylacetic, 2-naphthalene-2-ylacetic, 3-cyclopentylpropionyl, 3-phenylpropionyl, acetyl, hexanoyl, (E)-but-2-enoyl, N-fluoren-9-ylmethoxycarbonyl, benzyloxycarbonyl, butoxycarbonyl, phenylacetyl, ethylcarbitol, 2-bromo-3-methylbenzoyl, 2-bromo-5-methylbenzoyl, 2-methoxybenzoyl, 3,4,5-trimethoxybenzoyl, 3,5-bis-trifloromethyl, 3,5-dimethoxybenzyl, 3-chlorobenzoyl, 4-bromobenzoyl, 4-chlorobenzoyl, 4-methoxybenzoyl, 4-tert-butylbenzoyl, 4-trifloromethyl, 4-trifloromethyl, benzoyl, phenylcarbamoyl, 4'-ethylbiphenyl-4-carbonyl, biphenyl-2-carbonyl, biphenyl-4-carbonyl, 2-methoxynaphthalene-1-carbonyl, naphthalene-1-carbonyl, cyclohexanecarbonyl, cyclopropanecarbonyl, PI is one-3-carbonyl, 2-chloro-6-methylpyridin-4-carbonyl, pyridine-4-carbonyl, furan-2-carbonyl, furan-3-carbonyl, 2-methylfuran-3-carbonyl, 3-methylfuran-2-carbonyl, 5-bromofuran-2-carbonyl, pyrazin-2-carbonyl, benzo[b]thiophene-2-carbonyl, 5-chlorothiophene-2-carbonyl, 3-methylthiophene-2-carbonyl, 5-methylthiophene-2-carbonyl, thiophene-2-carbonyl and thiophene-3-carbonyl, or its salt.

5. The compound according to any one of claims 1 to 4, in which R1, R2, R3and R4mean hydrogen, or its salt.

6. The compound according to any one of claims 1 to 4, in which R1, R2, R3and R4independently mean C1-C5alkyl which may be optionally substituted, and in the case when C1-C5alkyl substituted, it represents trifluoromethyl; C1-C3alkoxy or halogen, or its salt.

7. The compound according to any one of claims 1 to 4, in which one or two substituent selected from R1, R2, R3and R4independently denote methyl, trifluoromethyl, methoxy, fluorine, chlorine or bromine, or its salt.

8. The compound according to any one of claims 1 to 4, in which R2selected from methyl, trifloromethyl, fluorine, chlorine and bromine, R3denotes hydrogen or chlorine, and R1and R4both signify hydrogen, or its salt.

9. The compound according to claim 3, selected from the following compounds:
(2-benzyloxycarbonyl-4,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2 butoxycarbonyl the -1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-N-fluoren-9-ylmethoxycarbonyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-acetyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-phenylacetyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzoyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
[2-(3,4,5-trimethoxybenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
(2-cyclohexanecarbonyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
[2-(4-methoxybenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(furan-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
(2-pillpropranolol-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
[2-(naphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-methoxybenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4-trifloromethyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(3,5-bis-trifloromethyl)4,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(3-cyclopentylpropionyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(3-phenylpropionyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(biphenyl-4-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid which,
[2-(4-tert-butylbenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4-trifloromethyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-((E)-but-2-enoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4-chlorobenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(3,5-dimethoxybenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
(2-diphenylacetyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-hexanoyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
[2-(3-chlorobenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4-bromo-benzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(pyridine-3-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
(2-benzoyl-8-methoxy-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzoyl-7-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzoyl-8-bromo-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzoyl-8-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzoyl-6-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
[2-(pyrazin-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-bromo-3-methylbenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4'-ethylbiphenyl-4-carbonyl)-1,2,3,4-tet is hydroperiod[4,3-b]indol-5-yl]acetic acid,
[2-(2-bromo-5-methylbenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-chloro-6-methylpyridin-4-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(biphenyl-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(5-bromofuran-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(3-methylfuran-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-methylfuran-3-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(benzo[b]thiophene-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(5-chlorothiophene-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl] acetic acid,
[2-(furan-3-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-naphthalene-2-ylacetic)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(thiophene-3-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-naphthalene-1-ylacetic)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-cyclohexyl-2-phenylacetyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
(2-phenylcarbamoyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-ethylcarbamate-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
[2-(2-ethoxynaphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(3-methylthiophene-2-carb the Nile)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(5-methylthiophene-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid, and
[2-(pyridine-4-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
or its salt.

10. The compound of claim 9 selected from the group including:
[2-(naphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(3-chlorobenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4'-ethylbiphenyl-4-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-bromo-3-methylbenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
(2-benzoyl-8-bromo-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzoyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
[2-(4-bromobenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid, and
[2-(furan-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid
or its salt.

11. The compound according to claim 1, selected from the group including:
tert-butyl ester 5-carboxymethyl-7-chloro-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylic acid,
tert-butyl ester 5-carboxymethyl-8-chloro-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylic acid,
tert-butyl ester 5-carboxymethyl-6-chloro-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylic acid,
tert-butyl ester 5-carboxymethyl-7-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylic acid,
tert-bout levy ester of 5-carboxymethyl-8-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylic acid,
tert-butyl ester 8-bromo-5-carboxymethyl-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylic acid,
tert-butyl ester 5-carboxymethyl-8-fluoro-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylic acid,
[7-chloro-2-(3-chlorobenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-chloro-2-(3-chlorobenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[6-chloro-2-(3-chlorobenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(3-chlorobenzoyl)-7-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(3-chlorobenzoyl)-8-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-bromo-2-(3-chlorobenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(3-chlorobenzoyl)-8-fluoro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-chloro-2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[6-chloro-2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-bromo-2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-fluoro-2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[7-chloro-2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[7-methyl-2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-methyl-2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]UKS is SNA acid,
[8-fluoro-2-(2-methoxynaphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-fluoro-2-(4-methoxynaphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-chloro-2-(2-methoxynaphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-chloro-2-(4-methoxynaphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-methoxynaphthalene-1-carbonyl)-8-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4-methoxynaphthalene-1-carbonyl)-8-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
2-(2-methoxynaphthalene-1-carbonyl)-7-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-ethoxynaphthalene-1-carbonyl)-8-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-ethoxynaphthalene-1-carbonyl)-7-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4-methoxynaphthalene-1-carbonyl)-7-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-perbenzoic)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(3-perbenzoic)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(3,5-differentail)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(3,4,5-triterpenoid)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2,3,4,5-tetrafluorobenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic KIS the PTA,
(2-benzoyl-8-fluoro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzoyl-6-chloro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzoyl-8-isopropyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzoyl-8-chloro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzoyl-7,8-dichloro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzoyl-8-trifluoromethyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzoyl-8-tert-butyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzoyl-7-chloro-8-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzoyl-7,8-dimethyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzoyl-7-fluoro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
[7-chloro-2-(2-naphthalene-1-ylacetic)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-chloro-2-(2-naphthalene-1-ylacetic)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[7-methyl-2-(2-naphthalene-1-ylacetic)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-bromo-2-(2-naphthalene-1-ylacetic)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4'-ethylbiphenyl-4-carbonyl)-7-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-bromo-2-(4'-ethylbiphenyl-4-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4'-ethylbiphenyl-4-carbonyl)-8-f the PR-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[6-chloro-2-(4'-ethylbiphenyl-4-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[7-chloro-2-(4'-ethylbiphenyl-4-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-chloro-2-(4'-ethylbiphenyl-4-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4'-ethylbiphenyl-4-carbonyl)-8-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-methyl-2-(2-naphthalene-1-ylacetic)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[6-chloro-2-(2-naphthalene-1-ylacetic)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-chloro-2-(naphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[6-chloro-2- (naphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[7-methyl-2-(naphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-methyl-2-(naphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-bromo-2-(naphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-fluoro-2-(naphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-fluoro-2-(2-naphthalene-1-ylacetic)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-bromo-3-methylbenzoyl)-7-chloro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-bromo-3-methylbenzoyl)-8-chloro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-bromo-3-m is TELESOL)-6-chloro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-bromo-3-methylbenzoyl)-7-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-bromo-3-methylbenzoyl)-8-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-bromo-2-(2-bromo-3-methylbenzoyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-bromo-3-methylbenzoyl)-8-fluoro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-bromo-2-(2-ethoxynaphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido [4,3-b]indol-5-yl]acetic acid,
[2-(2-ethoxynaphthalene-1-carbonyl)-8-fluoro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[8-chloro-2-(2-ethoxynaphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4-methoxynaphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(5-does not depend-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4-methylnaphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-methylnaphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(biphenyl-3-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4-fornatale-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-methoxynaphthalene-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
2-(9-oxo-N-fluoren-2-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(N-fluore the-1-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(N-fluoren-4-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2,4,6-triterpenoid)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4-cyclohexylmethyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(1H-indol-4-carbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(2-tortenelmebol)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(3-tortenelmebol)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(4-tortenelmebol)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
(2-ortho-trikarbonil-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-meta-trikarbonil-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-para-trikarbonil-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzylcarbamoyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-phenetically-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
[2-(naphthalene-1-ylcarbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(naphthalene-2-ylcarbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
[2-(biphenyl-2-ylcarbonyl)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
(2-cyclohexylcarbonyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
[2-(2-chlorpheniramol)-1,2,3,4-tetrahydrate the IDO[4,3-b]indol-5-yl]acetic acid,
[2-(4-perpertrator)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
(2-phenylthiocarbamoyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-phenethyldithiocarbamoil-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-cyclohexanecarbonyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
(2-benzelstierna-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
[2-(2-chlorpheniramol)-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl]acetic acid,
(2-para-holistically-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid;
(2-meta-holistically-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid and
(2-ortho-holistically-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid,
or its salt.

12. The compound according to any one of claims 1, 3 or 9-11 or its pharmaceutically acceptable salt for use as a drug with activity of CRTH2 receptor antagonist.

13. Pharmaceutical composition having activity of CRTH2 receptor antagonist, comprising at least one compound according to any one of claims 1, 3 or 9-11 or its pharmaceutically acceptable salt and an inert carrier material and/or adjuvant.

14. The use of compounds according to any one of claims 1, 3 or 9-11 or its pharmaceutically acceptable salt for a medicinal product, the pre is scheduled for the prevention or treatment of disease, selected from the group comprising chronic and acute allergic/immune disease selected from the group consisting of allergic asthma, rhinitis, allergic nephritis, conjunctivitis, atopic dermatitis, bronchial asthma, food Allergy, anaphylactic shock, urtikarii, eczema, scabies and diseases associated with eosinophils, such as the syndrome of charge-Strauss and sinusitis.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel therapeutically suitable derivatives of pyridazin-3(2H)-one of formula and pharmaceutical compositions containing the said derivatives. These compounds are used for treating, preventing or inhibiting corresponding pathological conditions, diseases or disorders, mainly asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, atopic dermatitis, psoriasis or irritable colon syndrome.

EFFECT: obtaining compounds which are active and selective phosphodiesterase 4 (PDE4) inhibitors.

11 cl, 1 tbl, 182 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I), their N-oxide forms, pharmaceutically acceptable additive salts and stereochemically isomeric forms as 11-HSD1 inhibitors, to their use, a pharmaceutical composition based on the said compounds and method of obtaining the said compounds. In general formula (I) , X is C or N; Y is C or N; L is methyl or a single bond; Z1 is a single bond, C1-2alkyl or a radical of formula -CH=; Z2 is a single bond, C1-2alkyl; R1 is hydrogen, halogen, hydroxy; R2 is hydrogen, halogen or C1-4alkyloxy; A is phenyl or a monocyclic heterocycle selected from a group consisting of thiophenyl or pyrridinyl.

EFFECT: obtaining compounds which can be used for treating and preventing diseases mediated by 11-HSD1.

9 cl, 7 dwg, 2 tbl, 34 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrrolopyrimidine and pyrrolopyridine of general formula (I), substituted with a cyclic amino group (II), or their pharmaceutically acceptable salts having CRF antagonist properties. In general formula the cyclic amino group has formula , in which the cyclic amino group is a 6-member saturated cyclic amine, the said cyclic amine is substituted with a group of formula -(CH2)mX; in which X is -CO2H, -CONH2,-P(=O)(OH)2 or -S(=O)2OH; Y is N or CH; m is an integer selected from 1, 2 and 3; R4 is hydrogen; R5 is hydrogen; R6 is C1-5alkyl; R7 and R8 are identical or different and independently represent hydrogen, C1-5alkyl, Ar is phenyl which is unsubstituted or substituted with one or more substitutes which are identical or different and are selected from a group consisting of halogen, C1-5alkyl, C1-5alkoxy, C1-5alkylthio, trifluoromethyl and trifluoromethoxy.

EFFECT: compounds can be used for therapeutic or preventive treatment of diseases where CRF is considered to be involved, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension etc.

12 cl, 6 dwg, 1 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: invention provides novel pyrrolo[2,3-c]pyridine derivatives of formula (I), where radicals R1, R2, R3, R4 and R5 are as indicated in paragraph 1 of the formula of invention, or their pharmaceutically acceptable salts, as well as methods of producing the said compounds and a pharmaceutical composition having proton pump inhibiting effect.

EFFECT: novel compounds which exhibit excellent proton pump inhibiting effect and can have reversible proton pump inhibiting effect are obtained and described.

6 cl, 927 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: new compounds have formula (I) , where values of radicals R1 - R10 are as given in paragraph 1 of the formula of invention; n equals 2 or 3, --- denotes absence of substitution or a single bond; and denotes a single bond or a double bond, or to salts thereof. The invention also relates to a method of producing compounds of formula (Ic), to a NK2 receptor antagonist, to a pharmaceutical agent, to a method of antagonising the NK2 receptor, to a method of preventing or treating functional gastrointestinal diseases, as well as to use of compounds given in paragraph 1.

EFFECT: obtaining new biologically active compounds with antagonistic effect on the NK2 receptor.

31 cl, 331 ex, 7 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to the trihydrate of 8-cyano-1-cyclopropyl-7-(1S,6S-2,8-diazabicyclo-[4.3.0]nonan-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid of formula (I) .

EFFECT: novel compound is obtained, which is thermodynamically stable and has antibacterial activity.

1 cl, 3 tbl, 2 dwg, 3 ex

FIELD: chemistry.

SUBSTANCE: described are novel compounds with general formula , their stereoisomers and pharmaceutically acceptable salts or solvates, where the dashed line can represent a double bond (together with the present single bond); R represents phenyl or benzodioxolyl, each of which can be substituted; R1, R3 and R4 independently represent hydrogen or C1-C6alkyl; R5 represents C1-C6alkyl; R7 represents hydrogen; R12 represents R3 or -C(O)R2, where R2 represents C1-C4 alkyl; D and G represent -CH2 - or -CH- when they are bonded to each other by a double bond; m equals 1; a pharmaceutical composition containing said compounds, and use of the novel compounds in treating conditions mediated by corticotropin-releasing factor (CRF).

EFFECT: increased effectiveness of compounds.

11 cl, 13 ex, 11 tbl

FIELD: medicine.

SUBSTANCE: invention relates to compounds of general formula (I) and their pharmaceutically acceptable salts and pharmaceutically acceptable asters, possessing activity with respect to LXRα and/or LXRβ receptors. Compounds can be applied for treatment and prevention of diseases mediated by LXRα and/or LXRβ receptors, namely: increased level of lipids and cholesterol level, atherosclerotic diseases, diabetes, metabolic syndrome, dyslipidermia, sepsis, inflammatory diseases, pancreatitis, liver cholestasis/fibrosis, and diseases which include inflammatory component, such as Alzheimer's disease and reduced/improvable cognitive function. In general formula n represents integer number from 0 to 3; R1 is independently selected from group consisting of halogen, -CN, -NO2, -SO2Me, lower alkyl, -OR11, pyperidinyl and -N(R11)(R11), where R11 is independently selected from lower alkyl and H, X1, X2, X3 and X4 are independently selected from nitrogen and carbon, on condition that, not more than two of X1, X2, X3 and X4 can simultaneously represent nitrogen, and in case when two of X1, X2, X3 and X4 represent nitrogen, n represents 0,1 or 2; k represents integer number 0 or 1; R2 represents H; R3 represents H, lower alkyl or halogen; R4 represents aryl, heteroaryl, lower alkylaryl or lower alkylheteroaryl, each of which is optionally substituted with substituents in amount from one to five, which are independently selected from group consisting of halogen, lower alkyl, -OR41, lower alkinyl and NR42R43, where R41 represents lower alkyl, R42 and R43 independently on each other represent hydrogen or lower alkyl, or NR42R43 represents pyrrolidinyl, or R4 represents lower alkyl; R5 is selected from group, heteroaryl, consisting of and , said aryl and heteroaryl being optionally substituted in one or more positions with one or more substituents, independently selected from group consisting of H, halogen, lower alkyl and (CH2)VR53, where R51 is selected from group consisting of H, lower alkyl, lower alkenyl and lower alkylaryl, said lower alkylaryl is optionally substituted in one or more positions with one or more lower alkyl, -CN, halogen, group -COOR54 and group -CH2OR54, where R54 represents lower alkyl or H; R52 represents lower alkyl or -H; R53 represents H, lower alkyl, C3-C6-cycloalkyl, -COOR55, -N(R55)(R56), -CH2OH, -CN, CF3, -CONH2 or -CH2OR55, where R55 is independently selected from group consisting of lower alkyl, -H, -C(O)aryl or -C(O)-lower alkyl, and R56 is selected from group consisting of H, lower alkyl, -C(O)CF3, -C(O)aryl, -C(O)-lower alkyl and lower alkylaryl, and where said aryl and lower alkylaryl are optionally substituted in one or more positions with one or more lower alkyl, halogen, group COOR57 and group -CH2OR57, where R57 represents lower alkyl or -H, or R55 and R56 together with atom to which they are bound, form ring system; or R53 represents aryl, which can be optionally substituted with benzyloxy, carboxy, lower alkoxycarbonyl, hydroxy-(lower alkyl), halogen, carbamoyl, (lower alkyl)carbamoyl, di-(lower alkyl)carbamoyl, m represents integer number from 0 to 2; v represents integer number from 0 to 4; where term "lower alkyl" separately or in combination with other groups refers to branched or linear monovalent alkyl radical, containing from one to six carbon atoms, where term "aryl" separately or in combination with other groups refers to phenyl or naphthyl, and where term "hetyeroaryl" refers to aromatic 5- or 6-member ring, which can include 1-3 heteroatoms selected from nitrogen, oxygen and/or sulphur, and which can be condensed with phenyl group.

EFFECT: increase of compound application efficiency.

38 cl, 5 dwg, 137 ex

FIELD: medicine.

SUBSTANCE: there are described new compounds of general formula

where Xa represents 2 to 4 condensed cycloalkyl, aryl, heterocyclic rings containing 1 to 2 heteroatoms, chosen of N and O, and heteroaryl rings containing 1 to 4 heteroatoms, chosen of N, O or S where said rings can be additionally substituted. (Radical values R1-R4, R1, Y and n are specified in the patent claim), specific representatives of said compounds and a pharmaceutical composition containing them.

EFFECT: new compounds are effective in stimulation of endogenous development or release of growth hormone and can be used in treating obesity, osteoporosis and for increasing muscle bulk and muscle strength.

17 cl, 339 ex, 10 tbl

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: medicine.

SUBSTANCE: there are selected strains Lactobacillus capable to raise IL-10 level and simultaneously to reduce TGF-beta-2 level in human breast milk to be applied with the products containing cells of selected strains to improve human milk for breast feeding. Selected strains and said products containing cells of selected strains are applied to increase of levels of anti-inflammatory cytokine IL-10 in human breast milk and reduce risk of allergy development in a breast-fed infant, to improve anti-inflammatory activity of human breast milk and to reduce simultaneously causal factors.

EFFECT: invention provides decreased TGF-beta-2 level in milk that leads to reduced risk of mastitis development in a nursing mother.

22 cl, 1 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to chemical-pharmaceutical industry and concerns preparation of a solid dosage form for treating respiratory allergosis and arresting nasopharynx edema. There is offered a tableted medical product containing mixed active substance and excipient. As an active substance, it contains a corticosteroid preparation, and according to the invention, additionally contains an active substance presented with adrenaline or noradrenaline. The inside of a tablet contains the corticosteroid preparation, while the exterior contains adrenaline. As a corticosteroid preparation it contains dexamethasone, prednisolone or celestone. Also there is offered a tableted medical product that contains mixed active substance and excipient. As an active substance, it contains a corticosteroid preparation, and additionally contains active substances presented with adrenaline or noradrenaline, and also aminophylline and mesatone. The tablet is multilayered, its inside contains mesatone, the layer containing aminophylline adjoins the inside, then the layer containing the corticosteroid preparation is executed, and the exterior contains adrenaline or noradrenaline.

EFFECT: there is offered a tableted medical product.

4 cl, 3 ex

FIELD: medicine.

SUBSTANCE: external skin preparation contains as active components a ferrous compound and a compound chosen from 5-aminolevulin acid, salt of 5-aminolevulin acid, ester of 5-aminolevulin acids, ester of salt of 5-aminolevulin acids, N-acyl-5-aminolevulin acids, salts of N-acyl-5 aminolevulin acid and ester of N-acyl-5-aminolevulin acid. The ferrous compound is chosen from iron (II) citrate, sodium-iron citrate, ammonium-iron citrate, iron acetate, iron oxalate, iron (II) succinate, sodium-iron succinate and citrate, iron (II) pyrophosphate, iron (III) pyrophosphate, heme iron, iron dextrane, iron lactate, iron (II) gluconate, sodium-iron diethylene triaminepentaacetate, ammonium-iron diethylene triaminepentaacetate, ethylenediaminetetraacetate sodium-iron ethylene aminpentaacetate, ammonium-iron ethylene aminpentaacetate, iron triethylene tetraamine, sodium-iron dicarboxymehtyl glutamate and ammonium-iron dicarboxymehtyl glutamate.

EFFECT: improved skin look, prevention or reduction of roughness, dryness, wrinkles, flabbiness, and pigment spots, efficient for atopic dermatitis.

16 cl, 2 ex, 2 dwg

FIELD: medicine.

SUBSTANCE: there is described thiomorpholine compound presented by formula (I) wherein the ring A represents benzene ring; the ring B represents benzene ring; R1 represents hydrogen atom, R2 represents C1-6-alkyl group; R3a and R3b are identical or different, each representing hydrogen atom or C1-6-alkyl group, and n represents an integer equal to 2, or its pharmaceutically acceptable salt. There is also described method for making the compound of formula (1), a pharmaceutical composition and application of the compound of formula (1) for making a medical product used for treatment and prevention of the disease chosen from inflammation, allergic diseases, pain, migraine, neuralgia, itch, cough, central nervous system diseases, alimentary organ diseases, nausea, vomiting and urological disorders.

EFFECT: compounds exhibits affinity to neurokinine-1 receptor.

6 cl, 4 tbl, 16 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: 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: medicine.

SUBSTANCE: invention refers to pharmaceutical industry, particularly a preparation that is able to suppress an immune response underlying immunoglobulin-E-dependent allergic diseases. Application of water-soluble polysaccharides made of clover (Trifolium pretense L.), as a preparation able to suppress the immune response underlying immunoglobulin-E- dependent allergic diseases.

EFFECT: polysaccharides made of clover (Trifolium pretense L) exhibit effective antiallergic activity and affect the earliest stages of formation of Th2-dependent allergic reactions associated with development of immunoglobulins E and G1.

3 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: claimed invention relates to chemical-pharmaceutical industry and concerns pharmaceutical composition for prevention and treatment of diseases and disease states connected with metabolic pathways of cycloxygenase-2 (CG-2) and 5-lipooxygenase (5-LO), which contains mixture of extract obtained from Scutellariae and enriched with flavonoids with free B-ring, which include baicalein, and extract obtained from Acacia and enriched with flavans, which include catechine and epicatechine. Claimed invention also relates to method of body weight loss and control over glucose level in blood. Methods by claimed invention include introduction to person, who needs it, of efficient amount of composition by claimed invention together with pharmaceutically acceptable carrier. Claimed invention mainly relates to prevention and treatment of diseases and states connected with metabolic pathways of cycloxygenase-2 (CG-2) and 5-lipooxygenase (5-LO), including, but not confining to it, stopping discomfort and pain in joints, induced by such states as osteoarthritis, rheumatoid arthritis and other injuries caused by overload.

EFFECT: composition possesses high efficiency.

35 cl, 22 ex, 15 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to novel methods (versions) of producing N-acyl derivatives of amino acids of general formula , where n equals 2 or 3; and R is or their salts, using anhydrides of glutaric or succinic acid.

EFFECT: advantages of the proposed methods lie in simplicity of their realisation, easy extraction of the end product and high output of the end products.

2 cl, 27 tbl, 22 ex

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 novel substituted derivatives of N-(3-benzoylaminophenyl)-4-pyridyl-2-pyrimidine amine of general formula (I), with inhibitory activity towards protein kinase, method of producing said derivatives and pharmaceutical compositions based on the derivatives. In the compound of formula 1 R1 is hydrogen and R2 is NR5R6, or R1 is NR5R6 and R2 is hydrogen; R3 is trifluoromethyl; R4 is lower alkyl; and R5 and R6 are independently hydrogen, lower alkyl, di(lower alkyl)amino-lower alkyl, N-lower alkylpiperidinyl, N-lower alkylpyrrolidinyl, or lower alkyl, or NR5R6 together represent pyrrolidino, piperidino, morpholino, N-lower alkylpiperazino, 1N-imidazolyl, 1H-2-lower alkylimidazolyl, 1H-4-lower alkylimidazolyl or 1H-2,4-di-lower alkylimidazolyl, or a pharmaceutically acceptable salt of such a compound.

EFFECT: compounds can be used in treating diseases related to inhibition of protein kinase activity, such as neoplastic diseases or leukaemia.

13 cl, 21 ex

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