2,3,4,9-tetrahydro-1h-carbazole derivatives as crth2 receptor antagonists

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds selected from a group comprising 2,3,4,9-tetrahydro-1H-carbazoles of formula I

,

where R1, R2, R3 and R4 independently denote hydrogen, alkyl, alkoxy, halogen, nitro, cyano, trifluoromethyl or formyl, R5 denotes hydrogen, alkyl or -CF3, R6 denotes alkoxy, arylalkoxy, selected from benzyloxy and 1-phenylethoxy, or -NR7R8, R7 and R8 independently denote hydrogen, alkyl, cyanoalkyl, alkenyl, where alkenyl is ethenyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4-pentenyl or 5-hexenyl; aryl, where aryl is a phenyl or naphthyl radical, where said radicals can optionally be monosubstituted with a halogen, alkyl, alkoxy, -CF3, -OCF3, phenylalkyl or phenylcarbonyl; or disubstituted with a substitute independently selected from halogen, alkoxy and phenyl; arylalkyl, where arylalkyl is phenylalkyl, where the alkyl group can optionally be substituted with phenyl; phenylalkyl, where the phenyl ring can optionally be substituted with methylenedioxy; phenylalkyl which is disubstituted with a halogen; phenylalkyl which is monosubstituted with a halogen, -CF3, -OCHF2, alkyl or alkylsulfanyl; or naphthylalkyl; phenylcarbonyl; cycloalkyl, where cycloalkyl is a cyclopentyl or cyclohexyl radical, where said radicals can optionally be substituted with a condensed benzene ring; pyridylalkyl; thienylalkyl; or R7 and R8 together with a nitrogen atom to which they are bonded form a heterocyclic 5-, 6-, 7- or 8-member ring system containing 1-3 heteroatoms selected from nitrogen, oxygen and sulphur atoms, wherein said cyclic system can optionally be substituted with (1) one or two condensed benzene rings, where the benzene rings are unsubstituted or substituted with one or two substitutes independently selected from a group comprising C1-C4alkyl, C1-C4alkoxy, halogen, -CF3 and -OCF3; (2) unsubstituted phenyl ring, (3) mono- or disubstituted phenyl ring, where the substitutes are independently selected from a group comprising halogen, C1-C4alkyl, C1-C4alkoxy, -CF3 and -OCF3; or (4) phenylalkyl, where the alkyl group is substituted with phenyl; where the term "alkyl", separately or in any combination, denotes a saturated straight or branched hydrocarbon chain containing 1-7 carbon atoms; where the said alkyl group is unsubstituted unless stated otherwise; or to pharmaceutically acceptable salts thereof. Invention also relates to a pharmaceutical composition and to use of compounds in claim 1.

EFFECT: obtaining novel biologically active compounds having CRTH2 receptor antagonist activity.

13 cl, 5 tbl

 

The text descriptions are given in facsimile form.

1. A compound selected from the group comprising 2,3,4,9-tetrahydro-lH-carbazole formula I

where R1, R2, R3and R4independently mean hydrogen, alkyl, alkoxy, halogen, nitro, cyano, trifluoromethyl or formyl,
R5means hydrogen, alkyl or-CF3,
R6means alkoxy, Allakaket selected from benzyloxy and 1-phenylethane, or-NR7R8,
R7and R8independently mean
hydrogen, alkyl, cianelli;
alkenyl, where alkenyl is an ethynyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4-pentenyl or 5-hexenyl;
aryl, where aryl represents phenyl or nattily radical, where these radicals may not necessarily be monogamist halogen, alkyl, alkoxy, -CF3, -OCF3, phenylalkyl or phenylcarbonylamino or tizamidine Deputy, independently selected from halogen, alkoxy and phenyl;
arylalkyl where arylalkyl is phenylalkyl, where the alkyl group optionally may be substituted by phenyl; phenylalkyl, where the phenyl ring may not necessarily be the Deputy who placed methylendioxy; phenylalkyl that Disaese halogen; phenylalkyl that monogamist halogen, -CF3, -OCHF2, alkyl or alkylsulfonyl;
or nafcillin;
phenylcarbinol;
cycloalkyl where cycloalkyl is cyclopentyl or tsiklogeksilnogo radical, where these radicals optionally may be substituted condensed benzene ring;
pyridylethyl; tanisaki; fornelli or imidazolylalkyl;
or R7and R8together with the nitrogen atom to which they are attached, form a heterocyclic 5-, 6-, 7 - or 8-membered ring system containing one to three heteroatoms selected from nitrogen atoms, oxygen and sulfur, and the specified cyclic system optionally can be substituted
(1) one or two condensed benzene ring cycles, where benzene cycles unsubstituted or substituted by one or two substituents, independently selected from the group comprising From1-C4alkyl, C1-C4alkoxy, halogen, -CF3and-OCF3;
(2) unsubstituted phenyl cycle
(3) mono - or disubstituted phenyl cycle, where the substituents independently selected from the group including halogen, C1-C4alkyl, C1-C4alkoxy, -CF3and-OCF3; or
(4) phenylalkyl, where the alkyl group substituted by phenyl;
where the term "alkyl" by itself is whether in any combination, means a saturated straight or branched hydrocarbon chain, containing 1-7 carbon atoms; where this alkyl group is unsubstituted, unless approved by the other;
or its pharmaceutically acceptable salt.

2. The compound according to claim 1, where R1, R2, R3and R4mean1-C4alkyl, C1-C4alkoxy, halogen, nitro, cyano or trifluoromethyl, or its pharmaceutically acceptable salt.

3. The compound according to claim 1, where R1, R2, R3and R4means methyl, trifluoromethyl, methoxy, fluorine, chlorine, bromine or iodine, or its pharmaceutically acceptable salt.

4. The compound according to claim 1, where R7means of alkenyl, alkyl, aryl(C1-C4)alkyl, cycloalkyl, thienyl(C1-C4)alkyl, furanyl(C1-C4)alkyl, pyridyl(C1-C4)alkyl or imidazolyl(C1-C4)alkyl and R8means hydrogen, aryl, aryl(C1-C4)alkyl, furanyl(C1-C4)alkyl, pyridyl(C1-C4)alkyl or thienyl(C1-C4)alkyl,
or its pharmaceutically acceptable salt.

5. The compound according to claim 1, where R7means hydrogen, allyl, 2-cyanoethyl, methyl, butyl, ethyl, isopropyl, benzyl, 1-phenylethyl, 2-phenylethyl, phenylpropyl, cyclohexyl or thiophene-3-ylmethyl and R8means phenyl, 2-benzylphenol, 2-methoxyphenyl, 2-were 2-triptoreline, 3,4-dichlorophenyl, 3-benzoylphenyl, 3-chlorophenyl, 2-forfinal, 3-terphenyl, 4-chlorophenyl, 4-Forfar, 4-methoxybiphenyl-3-yl, 4-trifloromethyl, 5-chloro-2-methoxyphenyl, naphthalene-1-yl, benzo[1,3]dioxol-5-ylmethyl, benzyl, diphenylmethyl, 1-phenylethyl, 2-phenylethyl, 2-pyridine-2-retil, 4-pentylbenzoyl, 3,4-dichlorobenzyl, 2,4-dichlorobenzyl, deformational, 2-Chlorobenzyl, 4-Chlorobenzyl, 2-methylsulfonylbenzoyl, 2-tormentil, 3-tormentil, 4-tormentil, 2-trifloromethyl, 3-trifloromethyl, 2,4-diferensial, 2.5-diferensial, 2,6-diferensial, 3,5-diferensial, 4-chloro-2-tormentil, (2-forfinal)ethyl, (3-forfinal)ethyl, (4-forfinal)ethyl, (4-chlorophenyl)ethyl, (2,6-dichlorophenyl)ethyl, naphthalene-1-ylmethyl, 1,2,3,4-tetrahydronaphthalen-1-yl, indan-2-yl or 2,2-diphenylether,
or its pharmaceutically acceptable salt.

6. The compound according to claim 1, where R7and R8together with the nitrogen atom to which they are attached, form dihydrobenzo[b,f]Asotin, dihydroindol, dihydroisoquinoline, dihydroquinoline or dibenzazepine,
or its pharmaceutically acceptable salt.

7. The compound according to claim 1, where R7and R8together with the nitrogen atom to which they are attached, form a heterocyclic system selected from the group comprising 11,12-dihydro-6N-dibenzo[b,f]Asotin-5-yl, 2,3-dihydroindol-1-yl, 3,4-dihydro-1 H-isoquinoline-2-yl, 3,4-dihydro-2H-quinoline-1-yl, 4-(4-forfinal)piperazine-1-yl, 6,11-dihydrobenzo[b,e]azepin-5-yl, 6,7-dimethoxy-3,4-dihydro-1H-eskinol the h-2-yl, 7-trifluoromethyl-3,4-dihydro-2H-quinoline-1-yl, dibenzo[b,f]azepin-5-yl, 1H,3H-benzo[d,e]isoquinoline-2-yl, 4-benzhydrylpiperazine-1-yl and Asotin-1-Il,
or its pharmaceutically acceptable salt.

8. The compound according to claim 1, where R6means (R)-1-phenylethylene or benzyloxy, or its pharmaceutically acceptable salt.

9. The compound according to claim 1, selected from the group including:
[3-methyl-3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[(3-chlorophenyl)methylcarbamoyl]-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(2,3-dihydroindol-1-carbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-methyl-3-(phenylthiophene-3-letiltasaval)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(benzylpenicilloyl)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[(4-forfinal)methylcarbamoyl]-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(6,11-dihydrobenzo[b,e]azepin-5-carbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(benzylpenicilloyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[phenyl(3-phenylpropyl)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(2,3-dihydroindol-1-carbonyl)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[(3,4-dichlorophenyl)methylcarbamoyl]-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(allylfentanyl)-3-methyl,2,3,4-tetrahydrocarbazole-9-yl]acetic acid,
{3-[benzyl((S)-1-phenylethyl)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
{3-[methyl(2-triptoreline)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(methylphenylcarbinol)-6-trifluoromethyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-methyl-3-(methyl-o-trikarbonil)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(2-benzylpenicilloyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(dibenzo[b,f]azepin-5-carbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(ethylnaphthalene-1-ylcarbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(benzylaminocarbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-methyl-3-[phenyl-(3-phenylpropyl)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl} acetic acid,
[3-(ethylenically)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(phenylthiophene-3-letiltasaval)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(benzylidenemalonate)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[4-(4-forfinal)piperazine-1-carbonyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(benzylpenicilloyl)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(3,4-dihydro-2H-quinoline-1-carbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(cyclohexyloxycarbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-methyl-3-(penicillinallergic)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(2-methoxyphenylacetyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(allylfentanyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(benzylpenicilloyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(penicillinallergic)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(methyl-o-trikarbonil)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid
{3-[benzyl((R)-1-phenylethyl)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(methylphenylcarbinol)-6-nitro-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(7-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(3,4-dihydro-2H-quinoline-1-carbonyl)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[(4-forfinal)methylcarbamoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(4-methoxybiphenyl-3-ylcarbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[6-fluoro-3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[7-chloro-3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[6-chloro-3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[methyl-(2-pyridin-2-retil)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl} acetic acid,
{3-[(4-chloroformmethanol]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
{(R)-3-[(4-chlorophenyl)methylcarbamoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(isopropylaminocarbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[(3,4-dichlorophenyl)methylcarbamoyl]-1,2,3,4-tetrahydrocarbazol-9-yl} acetic acid,
[3-(benzylaminocarbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[6-cyano-3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[benzyl((R)-1-phenylethyl)carbarnoyl]-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl} acetic acid,
[3-(2-benzylpenicilloyl)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[6-isopropyl-3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[6-methyl-3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(11,12-dihydro-6N-dibenzo[b,f]Asotin-5-carbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[6-bromo-3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(3-benzylpenicilloyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
(3-dibenzylamino-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
[3-(ethylnaphthalene-1-ylcarbonyl)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[(3-forfinal)methylcarbamoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
{3-[benzyl(2-cyan is ethyl)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
(3-phenylcarbamoyl-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
[3-(isopropylaminocarbonyl)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
(3-definitional-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
[3-(benzylaminocarbonyl)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(5-chloro-2-methoxyphenylacetyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(butylphenylmethyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[ethyl(4-trifloromethyl)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[6-iodine-3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[6-methoxy-3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
(R)-1-phenethyl ester 9-carboxymethyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid;
{(S)-3-[(4-chlorophenyl)methylcarbamoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(6,11-dihydrobenzo[b,e]azepin-5-carbonyl)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[8-chloro-3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
benzyl ether 9-carboxymethyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid,
[3-(3,4-dihydro-1H-isoquinoline-2-carbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(6,7-is metoxi-3,4-dihydro-1H-isoquinoline-2-carbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[(benzo[1,3]dioxol-5-ylmethyl)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid, and
[3-(cyclohexyloxycarbonyl)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid.

10. The compound according to claim 1, selected from the group including:
{3-[benzyl((R)-1-phenylethyl)carbarnoyl]-6-fluoro-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(benzylaminocarbonyl)-6-fluoro-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[benzyl((S)-1-phenylethyl)carbarnoyl]-6-fluoro-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(benzylpenicilloyl)-6-fluoro-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(2,3-dihydroindol-1-carbonyl)-6-fluoro-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(benzylidenemalonate)-6-fluoro-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(Asotin-1-carbonyl)-6-fluoro-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
(3-phenylcarbamoyl-3-propyl-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
[3-(methylphenylcarbinol)-3-propyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[6-fluoro-3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{6-fluoro-3-[4-(4-forfamilies-1-carbonyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(4-tortenelmebol)-3-propyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{6-fluoro-3-[4-(4-forfinal)piperazine-1-carbonyl]-1,2,3,4-tetrahydrocarbazol-9-yl} uksusno the acid,
[3-(benzylaminocarbonyl)-6-fluoro-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
(3-{benzyl[2-(2,6-dichlorophenyl)ethyl]carbarnoyl}-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
{3-[benzyl((S)-1-phenylethyl)carbarnoyl]-6-fluoro-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(3-tortenelmebol)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(3,5-diferenzierbarer)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(3-tortenelmebol)-3-propyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(3-tortenelmebol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(2,3-dihydroindol-1-carbonyl)-3-ethyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-ethyl-3-(3-tortenelmebol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-ethyl-3-(4-tortenelmebol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(2-chlorobenzylamino)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(benzylpenicilloyl)-6-fluoro-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-methyl-3-(2-methylsulfonylbenzoyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
(3-ethyl-3-phenylcarbamoyl-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
{3-[benzyl((R)-1-phenylethyl)carbarnoyl]-6-fluoro-1,2,3,4-tetrahydrocarbazol-9-yl} acetic acid,
[3-ethyl-3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]uksosn the Yu acid,
[3-(2-tortenelmebol)-3-propyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(2-tortenelmebol)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-methyl-3-[(naphthalene-1-ylmethyl)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
{3-[benzyl(2-cyanoethyl)carbarnoyl]-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(benzylmethylamine)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(4-tortenelmebol)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(4-tortenelmebol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(2,4-dichloraniline)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[benzyl(4-terbisil)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(benzylidenemalonate)-6-fluoro-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(2-differentoccasions)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(2-tortenelmebol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(benzylaminocarbonyl)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
(3-methyl-3-phenylcarbamoyl-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
[3-ethyl-3-(2-tortenelmebol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(4-chlorobenzylamino)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
(3-{Benz is l[2-(4-forfinal)ethyl]carbarnoyl}-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
[3-methyl-3-(4-pentylbenzoyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[benzyl(4-chloro-2-terbisil)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(Asotin-1-carbonyl)-6-fluoro-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(2-verbesserbar)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(3,4-dichloraniline)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
(3-{benzyl[2-(4-chlorophenyl)ethyl]carbarnoyl}-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
[3-(2,4-diferenzierbarer)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(benzylaminocarbonyl)-3-propyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{8-chloro-3-[4-(4-forfinal)piperazine-1-carbonyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[8-chloro-3-(2,3-dihydroindol-1-carbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(2,6-diferenzierbarer)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[benzyl(3-terbisil)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(benzylaminocarbonyl)-8-chloro-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(benzylaminocarbonyl)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[benzyl(3-trifloromethyl)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(benzylaminocarbonyl)-3-ethyl-1,2,3,4-tetrahydro carbazol-9-yl]acetic acid,
[3-(4-verbesserbar)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
(3-{benzyl[2-(3-forfinal)ethyl]carbarnoyl}-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
[3-(benzylidenemalonate)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[benzyl(3,5-diferensial)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
(3-{benzyl[2-(2-forfinal)ethyl]carbarnoyl}-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
{3-[benzyl(2-trifloromethyl)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
{3-[benzyl(4-terbisil)carbarnoyl]-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(1H,3H-benzo[d,e]isoquinoline-2-carbonyl)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[benzyl(2.5-diferensial)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
{3-[benzyl(3-terbisil)carbarnoyl]-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
{3-methyl-3-[(R)-(1,2,3,4-tetrahydronaphthalen-1-yl)carbarnoyl]-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
{3-[benzyl-(3,5-diferensial)carbarnoyl]-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(benzylaminocarbonyl)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
(3-{benzyl[2-(4-chlorophenyl)ethyl]carbarnoyl}-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
(3-{benzyl[2-(4-forfinal)ethyl]carbarnoyl}-3-methyl-1,2,3,4-tetrahydrocarbazol the ol-9-yl)acetic acid,
[8-chloro-3-(2,2-diphenylethanol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[benzyl(3-trifloromethyl)carbarnoyl]-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl} acetic acid,
[3-(4-benzhydrylpiperazine-1-carbonyl)-8-chloro-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
{3-[benzyl(4-chloro-2-terbisil)carbarnoyl]-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[3-(benzylaminocarbonyl)-8-chloro-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(2,3-dihydroindol-1-carbonyl)-3-propyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
(3-{benzyl[2-(3-forfinal)ethyl]carbarnoyl}-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
(3-{benzyl[2-(2,6-dichlorophenyl)ethyl]carbarnoyl}-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
{3-[benzyl(2-trifloromethyl)carbarnoyl]-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
{3-[benzyl(2.5-diferensial)carbarnoyl]-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl}acetic acid,
[8-chloro-3-(indan-2-ylcarbonyl)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
(3-{benzyl[2-(2-forfinal)ethyl]carbarnoyl}-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl)acetic acid,
[6-fluoro-3-((R)-1-phenylethanol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[6-fluoro-3-((R)-1-phenylethanol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
[3-(benzylcarbamoyl)-3-methyl-1,2,3,4-tetrahydrocarbazol the-9-yl]acetic acid,
[3-(2,3-dichloraniline)-3-methyl-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid, and
[7-methyl-3-(methylphenylcarbinol)-1,2,3,4-tetrahydrocarbazol-9-yl]acetic acid,
or its pharmaceutically acceptable salt.

11. Pharmaceutical composition having antagonistic activity against the CRTH2 receptor comprising a compound according to claim 1 or its pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier.

12. The compound according to claim 1, or its pharmaceutically acceptable salt, or a composition according to claim 11 for use as a medicinal product, which has antagonistic activity against receptor CRTH2.

13. The use of compounds according to claim 1 or its pharmaceutically acceptable salt to obtain a pharmaceutical composition intended for the prevention and/or treatment of diseases selected from the group comprising chronic and acute allergic diseases or immune disorders, including allergic asthma, rhinitis, chronic obstructive pulmonary disease (COPD), dermatitis, inflammatory bowel disease, rheumatoid arthritis, allergic nephritis, conjunctivitis, atopic dermatitis, bronchial asthma, food Allergy, systemic mastocytosis, anaphylaxis, urticaria, eczema, itching, inflammation, damage due to ischemia/reperfusion, Serebrov the molecular violations pleurisy, ulcerative colitis, and eosinophil-associated diseases such as syndrome it continues-Strauss and sinusitis, and basophil-associated diseases, such as basophilic leukemia and basophilic leukocytosis.



 

Same patents:

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: invention is related to new compounds of common formula IC1: , where A represents cyano; B represents hydrogen; R1, R2, R3 and R4 independently represent hydrogen; alkyl; halogen or nitro; R5 and R6 independently represent hydrogen; alkyl; cycloalkyl; cycloalkylalkyl; heteroaryl; heteroarylalkyl; alkenyl; carboxyalkyl; cyanoalkyl; diphenylalkyl; aryl, arylalkoxyaryl, arylalkyl, arylalkylaryl, arylcarbonylaryl or aryloxyaryl, or R5 and R6, together with atom of nitrogen, to which they are connected, create heterocyclic ring system; or to salts of such compound; at the same time "heteroaryl" used separately or in combination, is related to mono-, bi- or tricyclic aromatic ring system, which contains up to 14 atoms included in ring, in which at least one ring contains at least one heteroatom, independently chosen from nitrogen, oxygen or sulfur, besides specified heteroaryl group may be unsubstituted or substituted with one to three substituents, independently selected from alkyl and alkoxy; "diphenylalkyl" is related to alkyl group, where each of two atoms of hydrogen is substituted with unsubstituted phenyl group; "aryl" is related to carbocyclic group, selected from group, which consists of phenyl, biphenyl, 1,2,3,4-tetrahydronaphthyl, naphthyl, antryl, phenantryl, fluorenyl, indanyl, 2,3-dihydrobenzo[1,4]dioxynyl and benzo[1,3]dioxolyl group, besides specified aryl group may be unnecessarily substituted with functional groups in number from one to three, which are separately and independently selected from alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, cyano, halogen, halogenlkoxy, halogenalkyl and nitro groups, where in certain specific cases, if aryl group represents condensed system from several rings, in which not all the rings are aromatic, one of carbon atoms of which is not included into aromatic ring may be in oxidised condition, and according fragment of ring -CH2- will be substituted by fragment-C(O); "arylalkoxy", used separately or in combination, is related to aryl group, which is connected to initial molecular fragment via alkoxygroup, where aryl group is unsubstituted; "arylalkyl", used separately or in combination, is related to aryl group, which is connected to initial molecular fragment via alkyl group, where aryl group may be unsubstituted or substituted with 1-3 substituents, independently selected from group, which consists of halogen; "aryloxy", used separately or in combination, is related to aryl group, which is connected to initial molecular fragment via oxygen bridge, where aryl group may be unsubstituted or substituted with 1-3 substituents, independently selected from group, which consists of halogen; "arylcarbonyl", used separately or in combination, is related to aryl group, which is connected to initial molecular fragment via carbonyl group, where aryl group is unsubstituted; "heterocyclic ring system", used separately or in combination, is related to monocyclic, bicyclic or polycyclic ring system, which contains up to 15 atoms included into ring, at least one of which represents heteroatom, independently selected from nitrogen, oxygen or sulfur, besides specified ring system may be saturated, partially unsaturated, unsaturated or aromatic, where specified heterocyclic fragment may be unnecessarily substituted with one or more substituents, every of which separately and independently is selected from group made of halogen and halogenalkyl, excluding the following compounds: {3-[(E)-2-cyano-2-(4-fluorophenylcarbamoyl)vinyl]indole-1-yl}acetic acid; [3-((E)-2-cyano-2-m-tolylcarbamoylvinyl)indole-1-yl]acetic acid; (3-[(E)-2-(3-bromophenylcarbamoyl)-2-cyanovinyl]indole-1-yl}acetic acid; [3-((E)-2-cyano-2-phenylcarbamoylvinyl)indole-1-yl]acetic acid; [3-((E)-2-benzylcarbamoyl-2-cyanovinyl)indole-1-yl]acetic acid; [3-((E)-2-cyano-2-o-tolylcarbamoylvinyl)indole-1-yl]acetic acid; [3-((E)-2-cyano-2-t-tolylcarbamoylvinyl)indole-1-yl]acetic acid; (3-[(E)-2-(4-bromophenylcarbamoyl)-2-cyanovinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(4-ethylphenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(4-methoxyphenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2~cyano-2-(4- ethoxyphenylcarbamoyl)vinyl]indole-1-yl}acetic acid; [3-((E)-2-cyano-2-isopropylcarbamoylvinyl)indole-1-yl]acetic acid; {3-[(E)-2-cyano-2-(3-etoxyphenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-3-[[2-(1H-indole-3-yl)ethyl]amino]-3-oxo-1-propenyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(4-chlorophenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-3-(4-methyl-piperidine-1-yl)-3-oxopropenyl]indole-1-yl}acetic acid; {3-[(E)-2-(3-chloro-4-methylphenylcarbamoyl)-2-cyanovinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(3-phenylpropylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(2,3-dichlorophenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-(5-chloro-2-methylphenylcarbamoyl)-2-cyanovinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(4-methoxybenzylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(2-fluorophenylcarbamoyl)vinyl]indole-1-yl}acetic acid; and {3-[(E)-2-cyano-3-oxo-3-(4-phenyl-piperazine-1-yl)propenyl]indole-1-yl}acetic acid. Invention is also related to pharmaceutical composition, and also to application of compounds of clause 1.

EFFECT: production of biologically active compounds, which have activity of antagonist coupled with G-protein of chemoattractant receptor of molecules homologue released by Th2-cells.

11 cl, 156 ex, 8 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to the methods for preparation of X-ray amorphous carvedilol [(+)-1-(9H-carbazole-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amine}propane-2-ol] modification and can be used in pharmaceutical industry. Method involves the evaporation of carvedilol parent drug in vacuum device at temperature 80-200oC, residual pressure 5 - 5×10-4 Torr in a inert gas flow fed with the rate from 10 to 100 ml/min with following condensation at -196 - +25oC. The process results in obtaining of powder of X-ray amorphous carvedilol [(±)-1-(9H-carbazole-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amine}propane-2-ol] modification with particle size less than 5 mcm.

EFFECT: enhancing of bioactivity.

7 ex, 8 dwg

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of tetrahydrocarbazole of the formula (I): wherein n = 0, 1 or 2; X represents -NH or oxygen atom (O); each R is a similar or different radical and chosen independently from group consisting of halogen atom, halogenalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -R10-cycloalkyl, -OR2, -R10OR2, -R10C(O)R2, -C(O)R2, -CO2R2, -R10CO2R2, -R10SO2R2, -S(O)mR2, cyano- or nitro-group; each R1 is a similar or different radical and chosen independently from group consisting of halogen, halogenalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -R10-cycloalkyl, -OR2, -R10OR2, -R10C(O)R2, -C(O)R2, -CO2R2, -R10CO2R2, -R10SO2R2, -S(O)mR2, cyano- or nitro-group and wherein each m means 2 independently; each R10 is a similar or different radical and chosen independently from alkylene; each p and q is chosen independently from 0, 1, 2, 3, 4 or 5; each R2 is a similar or different radical and chosen independently from group consisting of hydrogen atom (H), alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -R10-cycloalkyl and -R10OH; ring A represents phenyl, naphthyl or heteroaryl wherein heteroaryl represents monocyclic 5-7-membered aromatic ring or condensed bicyclic aromatic ring system consisting of two such aromatic rings that comprise one or two nitrogen atoms and/or sulfur atoms, and to their pharmaceutically acceptable salts, solvates, esters and amides. Compounds of the formula (I) possess effect against disorders caused by HPV-infection and useful in treatment of human papilloma. Also, invention relates to a pharmaceutical composition based on compounds of the formula (I) and its using in preparing drugs for their using in treatment and prophylactic of states or disorders caused by HPV-infection.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

FIELD: pharmaceuticals, in particular composition for treatment or prophylaxis of heart diseases.

SUBSTANCE: invention relates to pharmaceutically acceptable composition containing crystalline form IV of (±)-1-(4-carbazolyloxy)-3-[2-(2-methoxyphenoxy)ethylamine]-2-propanol hemihydrate (carvediol) having melt temperature of 94-96°C or pharmaceutically acceptable salts thereof and pharmaceutically acceptable carrier and/or adjuvant having no surfactant properties, which has melt temperature 120°C or lower and is selected from polyethylene glycol and/or isomalt; and/or nonionic surfactant such as polyoxyethylene and polyoxypropylene copolymer. Claimed composition is obtained by melting of crystalline form of (±)-1-(4-carbazolyloxy)-3-[2-(2-methoxyphenoxy)ethylamine]-2-propanol (carvediol) having melt temperature of 123-126°C or 114-115°C or pharmaceutically acceptable salts thereof in abovementioned adjuvant and/or nonionic surfactant followed by fast cooling and addition of pharmaceutically acceptable carrier.

EFFECT: new pharmaceutical composition for treatment or prophylaxis of heart diseases.

15 cl, 7 dwg, 14 ex

FIELD: organic chemistry, chemical technology, pharmacy.

SUBSTANCE: invention relates to a new method for preparing 1-(9H-carbazole-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amine}-2-propanol of the formula (I):

and its pharmaceutical salts of acids addition. Method involves interaction of secondary amine of the formula (V):

with epichlorohydrine and synthesized chlorine-containing compound of the formula (VI):

reacts with 4-hydroxy-9H-carbazole of the formula:

and synthesized benzyl-carvedilol of the formula (VIII):

is debenzylated by the catalytic hydrogenation reaction. If necessary, the synthesized compound is subjected for reaction with inorganic or organic acid for preparing its pharmaceutically acceptable salt of acid addition.

EFFECT: improved preparing method.

8 ex

The invention relates to a thermodynamically stable form (R)-3[[(4-forfinal)sulfonyl] amino] -1,2,3,4-tetrahydro-N-carbazole-9-propanoic acid (ramatroban) formula

< / BR>
with a melting point of 151oWith, which is characterized by the fact that its infrared spectrum has a peak maxima at 3338 cm-1, 1708 cm-1and 1431 cm-1for its preparation, which is that the modification of ramatroban II with a melting point of 137oWith suspended in water or inert organic solvents, introducing a seed crystal sustainable modifications I and carry out the conversion at 20-50oWith up until the desired degree of conversion will not be achieved
The invention relates to an improved method for producing 4-hydroxy-N-carbazole by dehydrogenation of 1,2,3,4-tetrahydro-4-exacerbate in an aqueous alkali solution in the presence of a catalyst and as a catalyst using palladium on coal and the dehydrogenation is carried out at a temperature of about 100oWith

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to allergology, and can be applied for treatment of allergic rhinitis of domestic etiology. For this purpose in treatment included is allergen-specific immunotherapy with sublingual introduction of cause-significant allergen. Simultaneously hirudotherapy with application of medical leech on skin in region of oral cavity bottom projection is carried out. Procedures are carried out 2 times per week, starting from 0.1 ml 10-6 degree of dissolving of cause-significant allergen and bringing up to 0.5 ml of undissolved allergen, which after that is introduced 1 time per 2 weeks during 3 years.

EFFECT: invention allows to increase treatment efficiency due to increase of cause-significant allergen penetration into system of organs of mucosal immunity of upper airways.

1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to allergology, and can be used for treating angioedemas. For this purpose introduced are antihistamine preparations, membrane-stabilisers, as well as pulmicort as glucocorticosteroid preparation. Pulmicort is introduced in amount 10 drops per 2 ml of physiological solution by inhalations through nebuliser during 3 minutes. Introduction of pulmicort is carried out daily during 1-3 days.

EFFECT: invention allows fast reduction of gullet and pharynx angioedemas due to direct impact on mucous membranes by said glucocorticosteroid in dose and mode of introduction specially designed for this purpose.

2 ex

FIELD: medicine.

SUBSTANCE: invention refers to new compounds of formula I in the form of salt where J means a C1-C2 alkylene; R1 means cyclopentane, cyclohexyl, phenyl or thiophenes; R2 means hydroxy; R3 means a cyclopentane, cyclohexyl, phenyl or thiophenes; with R1 and R3 are not identical, or -CR1R2R3 together form a group of the formula , where Ra means a chemical bond, and Rb means hydroxy; R4 means methyl; R5 means C1 alkyl substituted with -CO-NH-R6; R6 means 5- or 6-membered heterocyclic group that contains in a cycle at least one heteroatom selected from nitrogen, oxygen and sulfur; or J means C1-C2 alkylene; R1 and R3 both mean phenyl; R2 means hydroxy; R4 means methyl, R5 means C1 alkyl substituted with -CO-NH-R9; and R9 means 5- or 6-membered heterocyclic group that contains in a cycle at least one heteroatom selected from nitrogen, oxygen and sulfur. The invention also refers to pharmaceutical composition, to application of compound according to any of clauses 1-3, as well as to method for obtaining a compound of formula I according to clause 1.

EFFECT: obtaining new biologically active compounds having antagonistic activity against muscarinic receptor M3.

7 cl, 21 ex

FIELD: chemistry.

SUBSTANCE: novel 1,2,4-triazole derivatives - protein kinase inhibitors of formula (I) are described, where X - N; Y - CH2, NH, NR or 0; R1 and R2 each independently denote hydrogen; R3 is phenyl, substituted with -CN, 6-member heteroaryl containing 1-2 N atoms, possibly substituted with a 7-member heterocyclyl containing 2 nitrogen atoms, which in turn is substituted with C1-6alkylcarbonyl; R4 is hydrogen; R5 is hydrogen or -CN; and R is a C1-6alkyl group, C1-6alkylcarbonyl group substituted with -CN, or a C3-6cycloalkyl group, a method of inhibiting FLT-3 or c-KIT protein kinase.

EFFECT: obtaining novel compounds and their use in making a medicinal agent for treating or relieving acute myelogenic leucosis.

11 cl, 1 tbl, 13 ex

FIELD: medicine, veterinary science.

SUBSTANCE: agent for treating inflammatory and allergic skin disease in cats and dogs contains Polcortolon as a glucocorticosteroid, Levomycetin and Metronidazole as an antibiotic, excipients - lidocaine hydrochloride, dimethyl formamide, dimethyl sulphoxide, isopropyl alcohol and polyethylene glycol 400, additionally contains calendula extract and Metronidazole, in the following ratio, wt %: Polcortolon 0.01-3.0; Levomycetin 0.1-3.0; lidocaine hydrochloride 0.1-6.0; dimethyl formamide 10.0-15.0; dimethyl sulphoxide 10.0-15.0; calendula extract 0.1-4.0; Metronidazole 0.1-5.0; polyethylene glycol 400 10.0-15.0; isopropyl alcohol - the rest.

EFFECT: invention provides reduced recovery time of allergic and inflammatory functional condition of skin in an animal.

3 ex

FIELD: chemistry.

SUBSTANCE: benzamide derivatives are presented by the formula [1] or its salt, where Z is -O-, -NR5-, -S-, -SO-; 1 is 0 or 1; m is 0 or 1; R1 is hydrogen atom, C1-6-alkyl group, R2 is hydrogen atom, hydroxylic group, C1-6- alkyl group, carboxyl group, C1-6-alkoxycarbonyl group or -CONR10R11, or R2 and R1 together form =O; R3 is hydrogen atom or C1-6-alkyl group; R4 is hydrogen atom or halogen atom; V is direct bond or -(CR21R22)n-; P1 and P2 rings are the same or different, and each is aromatic or saturated carbocyclic group, or 5-10-member saturated or unsaturated heterocyclic group containing 1-3 heteroatoms selected out of N, O, S.

EFFECT: obtainment of compound with excellent inhibition effect on vanilloid receptor type 1 activity, efficiency in treatment of diseases involving vanilloid receptor type 1 activity.

17 cl, 56 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: invention belongs to medicine, notably to hepatology, and relates to viral hepatitis A treatment in children with food allergy in acute phase of disease. On admission to hospital patient receives usual complex therapy of hepatitis, complemented with antihistaminic drugs - suprastin or tavegil, and enzymatic drugs - pancreatin or mesym - forte. Suprastin or tavegil is administered ј - 1 tablet after meal two times a day during 7-10 days. Pancreatin or mezym-forte is administered Ѕ-1 tablet 3 times a day during 14-18 days.

EFFECT: method fastens children recovery and reduces frequency of disease residual effects.

1 ex, 6 tbl, 4 dwg

FIELD: chemistry.

SUBSTANCE: present invention relates to phenylalanine derivatives and their pharmaceutically acceptable salts. In formula (1) R11 is a hydroxyl group, an alkoxyl group having 1-6 carbon atoms, which can be substituted with a methoxy group, cycloalkoxyl group having 3-6 carbon atoms, or a benzyloxy group; R12 and R13 each independently represents a hydrogen atom, alkyl group having 1-6 carbon atoms, cycloalkyl group having 3-6 carbon atoms, acetyl group or methyloxycarbonyl group, or N(R12)R13 is a 1-pyrrolidinyl group, 1-piperidinyl group, 4-morpholinyl group; R14 is a methyl group; R1' is a hydrogen atom, fluorine atom; X1 is -CH(R1a)-, -CH(R1a)CH(R1b)-, -CH(R1a)CH(R1b)CH(R1c)-, -N(R1a)CH(R1b)CH(R1c)-, -OCH(R1a)CH(R1b)-, -OCH(R1a)CH(R1b)CH(R1c)- or 1,3-pyrrolidinylene, where R1a, R1b, each independently represents a hydrogen atom or a methyl group, and R1c is a hydrogen atom; Y11 and Y12 represent any of the combinations (CI, Cl), (CI, Me), (CI, F). Invention also relates to phenylalanine derivatives of formulae (2)-(14), given in the formula of invention.

EFFECT: obtaining a pharmaceutical composition having antagonistic effect on α4-integrin, containing a phenylalanine derivative as an active ingredient, a α4-integrin antagonist and a therapeutic agent.

65 cl, 51 tbl, 244 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I) capable of bonding with S1P receptor (specifically EDG-6, preferably EDG-1 and EDG-6), its non-toxic water-insoluble salts or its methyl or ethyl ester.

EFFECT: obtaining compounds which can be used in preventing and/or treating graft rejection, graft-versus-host diseases, autoimmune diseases and allergic diseases.

11 cl, 66 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and concerns a complex containing mequitazine, cyclodextrin and a reaction agent where the molar ration within the system mequitazine/cyclodextrin/the reaction agent and mequitazine/the reaction agent is 1/1 - 1/10 and water-dissolution rate of mequitazine being a part of the complex measured for an aqueous solution with mequitazine concentration 2 g/l at 35°C after 15 minutes of stirring, makes more than 50% at pH 9, to a method for preparing said complex and a based pharmaceutical composition.

EFFECT: invention provides improved solubility of mequitazine.

20 cl, 1 dwg, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry. Vitamin E, ocimum basilicum oil, coconut oil, cloves oil, lemon oil and eucalyptus oil are mixed in the ratio, wt %: vitamin E 0.0001-0.001; ocimum basilicum oil 1.0-10.0; pine oil 1.0-20.0; coconut oil 1.0-15.0; cloves oil 1.0-10.0; lemon oil 1.0-10.0; eucalyptus oil - the rest, Cremophor is added to the prepared mixture in the ratio 1:(0.8-1.2) respectively. Then iron sulphate, alanine, tryptophan, isoleucine and water are mixed in the following ratio, wt %: iron sulphate 0.1-3.0; alanine 0.1-0.5; tryptophan 0.1-0.5; isoleucine 0.1-0.5; water - the rest. The mixed vitamin E, vegetable oils and Cremophor are combined connect in continual stirring at room temperature with the composition containing iron sulphate, alanine, tryptophan, isoleucine and water in the ratio 1:(1-500), respectively.

EFFECT: invention allows higher effectiveness of the composition.

3 cl, 13 ex, 2 tbl

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