Derivatives of indole-1-ylacetic acid

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

 

The text descriptions are given in facsimile form.

1. The compound of General formula IC1

where a represents cyano;
Represents a hydrogen;
R1, R2, R3and R4independently represent hydrogen; alkyl; halogen or nitro;
R5and R6independently represent hydrogen; alkyl; cycloalkyl; cycloalkenyl; heteroaryl; heteroaromatic; alkenyl; carboxyethyl; cianelli; divanillyl; aryl, arielcoceres, arylalkyl, arylalkyl, arylcarboxylic or aryloxyalkyl, or R5and R6together with the nitrogen atom to which they are attached, form a heterocyclic ring system;
or a salt of such a compound;
thus heteroaryl, IP is olshey individually or in combination, refers to mono-, bi - or tricyclic aromatic ring system containing up to 14 members of the ring atoms in which at least one ring contains at least one heteroatom independently selected from nitrogen, oxygen or sulfur, with the specified heteroaryl group can be unsubstituted or substituted from one to three substituents, which option is selected from alkyl and alkoxy;
divanillyl refers to an alkyl group where each of the two hydrogen atoms is substituted by an unsubstituted phenyl group;
aryl refers to carbocyclic group selected from the group consisting of phenyl, biphenyl, 1,2,3,4-tetrahydronaphthyl, naphthyl, Anttila, financila, fluorenyl, indanyl, 2,3-dihydrobenzo[1,4]dioxine and benzo[1,3]dioxolane group, and mentioned aryl group may be optionally substituted by functional groups in the amount of from one to three, which are individually and independently selected from alkoxy, alkoxycarbonyl, alkyl, alkylsulphonyl, cyano, halogen, halogenoalkane, halogenoalkane and nitro groups, where in some specific cases, if the aryl group is a condensed a system of several rings, in which not all of the rings are aromatic, one of the carbon atoms of which is not included in the aromatic ring may be oxidized in the second state, and the relevant portion of the ring-CH2- will be replaced with the fragment-C(O);
Allakaket used individually or in combination, refers to an aryl group attached to the original molecular fragment through alkoxygroup, where the aryl group is unsubstituted;
arylalkyl used individually or in combination, refers to an aryl group attached to the original molecular fragment through an alkyl group, where the aryl group can be unsubstituted or substituted by 1-3 substituents, independently selected from the group consisting of halogen;
aryloxy used individually or in combination, refers to an aryl group that is attached to the original molecular fragment through an oxygen bridge, where the aryl group can be unsubstituted or substituted by 1-3 substituents, independently selected from the group consisting of halogen;
arylcarbamoyl used individually or in combination, refers to an aryl group that is attached to the original molecular fragment through a carbonyl group, where the aryl group is unsubstituted;
heterocyclic ring system, used separately or in combination, refers to monocyclic, bicyclic or polycyclic ring system containing up to 15 WMO who yaschih in ring atoms, at least one of which is a heteroatom independently selected from nitrogen, oxygen or sulfur, with the specified ring system may be saturated, partially unsaturated, unsaturated or aromatic, where the specified heterocyclyl fragment can be optionally substituted by one or more Deputy, each of which is individually and independently selected from the group consisting of halogen and halogenoalkane, except for the following compounds:
{3-[(E)-2-cyano-2-(4-tortenelmebol)vinyl]indol-1-yl}acetic acid;
[3-((E)-2-cyano-2-m-tolylmorpholine)indol-1-yl]acetic acid;
{3-[(E)-2-(3-bromoresorcinol)-2-cyanovinyl]indol-1-yl} acetic acid;
[3-((E)-2-cyano-2-phenylcarbamoyl)indol-1-yl]acetic acid;
[3-((E)-2-benzylcarbamoyl-2-cyanovinyl)indol-1-yl]acetic acid;
[3-((E)-2-cyano-2-o-tolylmorpholine)indol-1-yl]acetic acid;
[3-((E)-2-cyano-2-n-tolylmorpholine)indol-1-yl]acetic acid;
{3-[(E)-2-(4-bromoresorcinol)-2-cyanovinyl]indol-1-yl} acetic acid;
{3-[(E)-2-cyano-2-(4-ethylenically)vinyl]indol-1-yl} acetic acid;
{3-[(E)-2-cyano-2-(4-methoxyphenylacetyl)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(4-ethoxyphenylurea)vinyl]indol-1-yl}acetic acid;
[3-((E)-2-cyano-2-isopropylaniline)indol-1-yl]acetic KIS the PTA;
{3-[(E)-2-cyano-2-(3-ethoxyphenylurea)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-3-[[2-(1H-indol-3-yl)ethyl]amino]-3-oxo-1-propenyl] indol-1-yl} acetic acid;
{3-[(E)-2-cyano-2-(4-chlorpheniramol)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-3-(4-methyl-piperidine-1-yl)-3-oxopropyl] indol-1-yl} acetic acid;
{3-[(E)-2-(3-chloro-4-methylphenylcarbinol)-2-cyanovinyl]indol-1-yl} acetic acid;
{3-[(E)-2-cyano-2-(3-phenylpropionyl)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(2,3-dichlorophenylamino)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(5-chloro-2-methylphenylcarbinol)-2-cyanovinyl]indol-1-yl} acetic acid;
{3-[(E)-2-cyano-2-(4-methoxybenzylidene)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(2-tortenelmebol)vinyl]indol-1-yl}acetic acid; and
{3-[(E)-2-cyano-3-oxo-3-(4-phenyl-piperazine-1-yl)propenyl]indol-1-yl} acetic acid.

2. The compound according to claim 1, where
And represents cyano;
Represents a hydrogen;
R1, R2, R3and R4all represent hydrogen atoms or one of the radicals R1,
R2, R3and R4represents a halogen, while all other radicals are hydrogen; and R5selected from the group consisting of heteroaromatic; diphenylamine; aryl, which is unsubstituted or substituted 1 or 2 times replace the s, independently selected from the group consisting of halogen, alkoxy, halogenoalkane and alkylcarboxylic; allakariallak; arylalkyl; arylalkylamine; arylcarboxylic and aryloxyalkyl, and R6selected from the group consisting of alkyl; alkenyl; cycloalkyl; aryl, which is unsubstituted or substituted 1 or 2 times with substituents independently selected from the group consisting of halogen, alkoxy, halogenoalkane and alkylcarboxylic; arylalkyl and zainoulline; or R5and R6together with the nitrogen atom to which they are attached, form the following ring system is dihydrofinasteride, dihydrouridine, dehydrodimerization, dihydrobenzofuran, dihydroindol, dihydroquinoline, dibenzoxazepines, phenothiazines, oxazolobenzodiazepines, dihydroisoquinoline, which may be unsubstituted or substituted by one Deputy, selected from halogen and trifloromethyl;
or a salt of such compounds.

3. Compounds according to claim 1, where
And represents cyano;
Represents a hydrogen;
one of R2and R3represents a halogen, while the other radicals R1and R4represent hydrogen; or a salt of such compounds.

4. The compound according to claim 1, where the groups of R5and R6do not form a heterocyclic ring system together with the nitrogen atom to which they are attached; or with the ü of such compounds.

5. The compound according to claim 4, where R5represents aryl, and R6selected from the group consisting of alkyl, cycloalkyl, alkenyl, cyanoalanine, diphenylamine, heteroallyl, arylalkyl and aryl, or a salt of such compounds.

6. The compound according to claim 4, where R5is arylalkyl, and R6selected from the group consisting of alkyl, aryl and arylalkyl, or salt of such compounds.

7. The compound according to claim 1, where the group R5and R6together with the nitrogen atom to which they are attached, form a heterocyclic ring system, or a salt of such compounds.

8. The compound according to claim 1, which is chosen from the group consisting of the following compounds:
{3-[(E)-2-cyano-2-(cyclohexyloxycarbonyl)vinyl]indol-1-yl}acetic acid;
[3-((E)-2-cyano-2-fenetylline)indol-1-yl]acetic acid;
[3-((E)-2-cyano-2-profilerviewer)indol-1-yl]acetic acid;
[3-((E)-2-cyano-2-cyclohexylcarbonyl)indol-1-yl]acetic acid
{3-[(E)-2-cyano-2-(3-methylbutanoyl)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(benzylpenicilloyl)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(4-cyanophenylacetic)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(4-phenoxyphenylacetic)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(naphthalene-2-ylcarbonyl)vinyl]indol-1-yl)acetic acid;
3-[(E)-2-cyano-2-(2-isopropylaminocarbonyl)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(4-isopropylaminocarbonyl)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(3-methoxyphenylacetyl)vinyl indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(3-tortenelmebol)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(N-fluoren-2-ylcarbonyl)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(4-propylenecarbonate)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(biphenyl-4-ylcarbonyl)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(3,2'-dimethylbiphenyl-4-ylcarbonyl)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(4-tert-butylphenylmethyl)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(2-benzylpenicilloyl)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(4-butylphenylmethyl)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(2-acetylpenicillamine)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(indan-5-ylcarbonyl)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(4-second-butylphenylmethyl)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(2-propylpentanoic)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(3-phenoxyphenylacetic)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(3-ethylenically)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(2-ethoxyphenylurea)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(3-benzyloxycarbonyl)-2-lanov the Nile]indol-1-yl} acetic acid;
{3-[(E)-2-cyano-2-(4-idgenerator)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(3-idgenerator)vinyl]indol-1-yl}acetic acid;
(3-{(E)-2-cyano-2-[(4-forfinal)methylcarbamoyl]vinyl}indol-1-yl)acetic acid;
(3-{(E)-2-cyano-2-[(4-methoxyphenyl)methylcarbamoyl]vinyl}indol-1-yl)acetic acid;
{3-[(E)-2-cyano-2-(methylphenylcarbinol)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-3-(3,4-dihydro-2H-quinoline-1-yl)-3-oxopropyl]indol-1-yl} acetic acid;
{3-[(E)-2-cyano-2-(methyl-n-trikarbonil)vinyl]indol-1-yl}acetic acid;
(3-{(E)-2-cyano-2-[2-(2,4-dichlorphenoxy)phenylcarbamoyl]vinyl}indol-1-yl)acetic acid;
{3-[(E)-2-cyano-2-(2,5-dimethylphenylcarbamate)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(9-ethyl-N-carbazole-3-ylcarbonyl)vinyl]indol-1-yl} acetic acid;
{3-[(E)-2-(3,5-bis-cryptomaterial)-2-cyanovinyl] indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(5-methoxy-2-methylphenylcarbinol)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(3-benzylpenicilloyl)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(4-benzyloxycarbonyl)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(3-nitrophenylamino)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(9-oxo-N-fluoren-2-ylcarbonyl)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(4-methoxy-biphenyl-3-ylcarbonyl)vinyl]indol-1-yl}at Sosna acid;
{3-[(E)-2-cyano-2-(2-methoxy-dibenzofuran-3-ylcarbonyl)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(9-oxo-N-fluoren-4-ylcarbonyl)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(9-oxo-N-fluoren-1-ylcarbonyl)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(2-benzylpenicilloyl)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(3-chloro-4-methoxyphenylacetyl)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(5-chloro-2-methoxyphenylacetyl)-2-cyanovinyl]indol-1-yl}acetic acid;
methyl ester of 3-[(E)-3-(1-carboxymethyl-1H-indol-3-yl)-2-cyano-acrylamido]-4-methylbenzoic acid;
methyl ester 2-[(E)-3-(1-carboxymethyl-1H-indol-3-yl)-2-cyano-acrylamido]benzoic acid;
{3-[(E)-2-cyano-2-(4-triftormetilfullerenov)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(3,5-dimethylphenylcarbamate)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(3-bromo-4-methylphenylcarbinol)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(4-bromo-3-methylphenylcarbinol)-2-cyanovinyl]indol-1-yl}acetic acid;
ethyl ester of 4-[(E)-3-(1-carboxymethyl-1H-indol-3-yl)-2-cyano-acrylamido]benzoic acid;
methyl ester of 3-[(E)-3-(1-carboxymethyl-1H-indol-3-yl)-2-cyano-acrylamido]benzoic acid;
{3-[(E)-2-cyano-2-(4-cryptomaterial)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(3,5-dimethoxycinnamoyl)Winnie the]indol-1-yl}acetic acid;
{3-[(E)-2-(4-bromo-3-chlorpheniramol)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(4-bromo-2-methylphenylcarbinol)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(4-acetylpenicillamine)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(2-bromo-4-methylphenylcarbinol)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(benzo[1,3]dioxol-5-ylcarbonyl)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(penicillinallergic)vinyl]indol-1-yl)acetic acid;
{3-[(E)-2-cyano-3-(11,12-dihydro-6N-dibenzo[b,f]Asotin-5-yl)-3-oxopropyl]indol-1-yl}acetic acid;
[3-((E)-2-cyano-2-diphenylcarbinol)indol-1-yl]acetic acid;
[3-((E)-2-cyano-3-dibenzo[b,f]azepin-5-yl-3-oxopropyl)indol-1-yl]acetic acid;
(3-{(E)-2-[(4-chlorophenyl)methylcarbamoyl]-2-cyanovinyl}indol-1-yl)acetic acid;
{3-[(E)-2-cyano-3-(6,11-dihydrobenzo[b,e]azepin-5-yl)-3-oxopropyl]indol-1-yl}acetic acid;
[3-((E)-2-cyano-2-definitionmonoamine)indol-1-yl]acetic acid;
{3-[(E)-2-cyano-3-(10,11-dihydrobenzo[b,f]azepin-5-yl)-3-oxopropyl]indol-1-yl}acetic acid;
(3-{(E)-2-cyano-2-[methyl-((R)-1-phenylethyl)carbarnoyl]vinyl}indol-1-yl)acetic acid;
{3-[(E)-2-(benzylaminocarbonyl)-2-cyanovinyl]indol-1-yl}acetic acid;
(3-{(E)-2-[(4-acetylphenyl)methylcarbamoyl]-2-cyanovinyl}indol-1-yl)acetic acid;
(3-{(E)-2-[(4-acetylphenyl)furan-2-ylmethyl carbamoyl]-2-cyanovinyl} indol-1-yl)acetic acid;
{3-[(E)-2-(benzylcarbamoyl)-2-cyanovinyl]indol-1-yl}acetic acid;
3-{benzyl-[(E)-3-(1-carboxymethyl-1H-indol-3-yl)-2-cyano-acryloyl]amino}propionic acid;
{3-[(E)-2-cyano-3-(2,3-dihydroindol-1-yl)-3-oxopropyl]indol-1-yl}acetic acid;
{3-[(E)-2-(carboxymethylaminomethyl)-2-cyanovinyl]indol-1-yl}acetic acid;
(3-{(E)-2-cyano-2-[(2-cyanoethyl)phenylcarbamoyl]vinyl}indol-1-yl)acetic acid;
(3-{(E)-2-[(3-chlorophenyl)methylcarbamoyl]-2-cyanovinyl}indol-1-yl)acetic acid;
{3-[(E)-2-(allylfentanyl)-2-cyanovinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(cyclohexyloxycarbonyl)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(methyl-o-trikarbonil)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(ethylenically)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-(butylphenylmethyl)-2-cyanovinyl]indol-1-yl}acetic acid;
[5-bromo-3-((E)-2-cyano-2-phenylcarbamoyl)indol-1-yl]acetic acid;
[3-((E)-2-cyano-2-phenylcarbamoyl)-5-Florinda-1-yl]acetic acid;
[3-((E)-2-cyano-2-phenylcarbamoyl)-5-methylindol-1-yl]acetic acid;
[3-((E)-2-cyano-2-phenylcarbamoyl)-6-Florinda-1-yl]acetic acid;
[3-((E)-2-cyano-2-phenylcarbamoyl)-6-nitroindole-1-yl]acetic acid;
[3-((E)-2-cyano-2-phenylcarbamoyl)-7-methylindol-1-yl]acetic acid;
{3-[(E)-3-(2-chlorophenothiazine-10-is)-2-cyano-3-oxopropyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(phenylthiophene-3-letiltasaval)vinyl]indol-1-yl}acetic acid;
(3-{(E)-2-cyano-2-[(2,2-diphenylether)phenylcarbamoyl]vinyl}indol-1-yl)acetic acid;
(3-{(E)-2-cyano-2-[phenyl-(3-phenylpropyl)carbarnoyl]vinyl}indol-1-yl)acetic acid;
[3-((E)-2-cyano-2-{[2-(4-forfinal)ethyl]-phenylcarbamoyl}vinyl)indol-1-yl]acetic acid;
{3-[(E)-2-cyano-3-(11N-10-oxa-5-sediment[a,d]cyclohepten-5-yl)-3-oxopropyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(isopropylaminocarbonyl)vinyl]indol-1-yl}acetic acid;
(3-{(E)-2-cyano-2-[(3,4-dichlorophenyl)methylcarbamoyl]vinyl}indol-1-yl)acetic acid;
(3-{(E)-2-cyano-2-[ethyl-(4-trifloromethyl)carbarnoyl]vinyl}indol-1-yl)acetic acid;
{3-[(E)-2-(benzylaminocarbonyl)-2-cyanovinyl]indol-1-yl}acetic acid;
(3-{(E)-2-cyano-2-[methyl-(2-trifloromethyl)carbarnoyl]-vinyl}indol-1-yl)acetic acid;
{3-[(E)-2-cyano-2-(2,4-differencemaker)vinyl]indol-1-yl}acetic acid;
(3-{(E)-2-cyano-2-[methyl-(4-trifloromethyl)carbarnoyl]vinyl}indol-1-yl)acetic acid;
{3-[(E)-2-cyano-2-(ethylnaphthalene-1-ylcarbonyl)vinyl]indol-1-yl}acetic acid;
(3-{(E)-2-cyano-2-[(2,4-differenl)methylcarbamoyl]vinyl}indol-1-yl)acetic acid;
{3-[(E)-2-cyano-2-(2,4,6-triptoreline)vinyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(2,3,4-triptoreline)vinyl]indol-1-yl}acetic acid the same;
{3-[(E)-2-cyano-3-(3,4-dihydro-1H-isoquinoline-2-yl)-3-oxopropyl]indol-1-yl}acetic acid;
{3-[(E)-2-cyano-3-oxo-3-(7-trifluoromethyl-3,4-dihydro-2H-quinoline-1-yl)propenyl]indol-1-yl}acetic acid;
(3-{(E)-2-cyano-2-[(3-forfinal)methylcarbamoyl]vinyl}indol-1-yl)acetic acid;
[3-((E)-2-cyano-3-dibenzo[b,f]azepin-5-yl-3-oxopropyl)-5-Florinda-1-yl]acetic acid;
{3-[(E)-2-cyano-3-(6,11-dihydrobenzo[b,e]azepin-5-yl)-3-oxopropyl]-5-Florinda-1-yl}acetic acid;
{3-[(E)-2-(benzylpenicilloyl)-2-cyanovinyl]-5-Florinda-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(yclohexanol)vinyl]-5-Florinda-1-yl}acetic acid;
{3-[(E)-2-(butylphenylmethyl)-2-cyanovinyl]-5-Florinda-1-yl}acetic acid;
(3-{(E)-2-cyano-2-[(4-forfinal)methylcarbamoyl]vinyl}-5-Florinda-1-yl)acetic acid;
(3-{(E)-2-cyano-2-[(3-forfinal)methylcarbamoyl]vinyl}-5-Florinda-1-yl)acetic acid;
(3-{(E)-2-cyano-2-[(3,4-dichlorophenyl)methylcarbamoyl]vinyl}-5-Florinda-1-yl)acetic acid;
(3-{(E)-2-cyano-2-[methyl-(2-triptoreline)carbarnoyl]vinyl}-5-Florinda-1-yl)acetic acid;
(3-{(E)-2-cyano-2-[(2,4-differenl)methylcarbamoyl]vinyl}-5-Florinda-1-yl)acetic acid;
{3-[(E)-2-cyano-2-(phenylthiophene-3-letiltasaval)vinyl]-5-Florinda-1-yl}acetic acid;
{3-[(E)-2-cyano-3-oxo-3-(7-trifluoromethyl-3,4-dihydro-2H-quinoline-1-yl)propenyl]-5-Florinda-1-yl}acetic acid to the slot;
(3-{(E)-2-cyano-2-[ethyl-(4-trifloromethyl)carbarnoyl]vinyl}-5-Florinda-1-yl)acetic acid;
{3-[(E)-2-cyano-3-(3,4-dihydro-1H-isoquinoline-2-yl)-3-oxopropyl]-5-Florinda-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(penicillinallergic)vinyl]-5-Florinda-1-yl}acetic acid;
[3-((E)-2-cyano-3-dibenzo[b,f]azepin-5-yl-3-oxopropyl)-6-methylindol-1-yl]acetic acid;
{3-[(E)-2-cyano-3-(6,11-dihydrobenzo[b,e]azepin-5-yl)-3-oxopropyl]-6-methylindol-1-yl}acetic acid;
{3-[(E)-2-cyano-3-(10,11-dihydrobenzo[b,f]azepin-5-yl)-3-oxopropyl]-6-methylindol-1-yl}acetic acid;
{3-[(E)-2-(benzylpenicilloyl)-2-cyanovinyl]-6-methylindol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(cyclohexyloxycarbonyl)vinyl]-6-methylindol-1-yl}acetic acid;
(3-{(E)-2-cyano-2-[(4-forfinal)methylcarbamoyl]vinyl}-6-methylindol-1-yl)acetic acid;
{3-[(E)-2-(butylphenylmethyl)-2-cyanovinyl]-6-methylindol-1-yl}acetic acid;
{3-[(E)-2-cyano-2-(cyclohexyloxycarbonyl)vinyl]-7-methylindol-1-yl} acetic acid; and
(3-{(E)-2-cyano-2-[(4-forfinal)methylcarbamoyl]vinyl}-7-methylindol-1-yl)acetic acid,
or a salt of such compounds.

9. The compound according to claim 1, where the compound of the formula IC1is a compound of the formula IC2

where a represents cyano;
Represents a hydrogen;
R1, R2, R 3and R4independently represent hydrogen; alkyl; halogen or nitro;
R5and R6independently represent hydrogen; alkyl; cycloalkyl;
cycloalkenyl; heteroaryl; heteroaromatic; alkenyl; carboxyethyl;
cianelli; divanillyl; aryl, arielcoceres, arylalkyl, arylalkyl, arylcarboxylic or aryloxyalkyl, or R5and R6together with the nitrogen atom to which they are attached, form a heterocyclic ring system;
under the condition that must be performed, at least one of the following provisions:
one of the radicals R1, R2, R3and R4is other than a hydrogen atom; or in the case when R5and R6are such that they do not form a heterocyclic ring system together with the nitrogen atom to which they are attached, then both radical R5and R6are other than hydrogen and one of the radicals R5and R6is other than alkyl; or
in the case when R5and R6are such that they form a heterocyclic ring system together with the nitrogen atom to which they are attached, then the specified heterocyclic ring system is not a substituted or unsubstituted piperidine or substituted or unsubstituted piperazine;
or a salt of such compounds.

10. Pharma is eticeskaja composition, having antagonist activity associated with G-protein chemoattractant receptor homologue molecules secreted by Th2 dysbalance-cells containing as active ingredient at least one compound according to claim 1 or a pharmaceutically acceptable salt of such compounds, and pharmaceutically acceptable carrier.

11. The use of compounds according to claim 1 or pharmaceutically acceptable salts of such compounds for obtaining a medicinal product intended for the prevention and treatment of chronic or acute allergic immune disorders, or disorders, including allergic asthma, rhinitis, chronic obstructive pulmonary disease (COPD), dermatitis, inflammatory disease of the gastrointestinal tract, rheumatoid arthritis, allergic nephritis, conjunctivitis, atopic dermatitis, bronchial asthma, food Allergy, systemic disorders and disorders associated with fat cells, anaphylactic shock, urticaria, eczema, itching, inflammation, damage associated with ischemia-reperfusion injury, cerebrovascular disturbances and disorders, pleuritis, ulcerative colitis, diseases, mediated by eosinophils, including syndrome Cerca-Strauss and sinusitis, diseases, mediated by basophils, including basophilic leukemia and basophilic leukocytosis.



 

Same patents:

FIELD: pharmacology.

SUBSTANCE: invention concerns indazol derivatives of general formulae (I) or (II) , where radicals and groups are defined as shown in cl. 1 of invention claim, and their pharmaceutically acceptable salts. Also invention claims medicine, method of medicine obtainment and application of claimed compounds in treatment and/or prevention of fatty acid metabolism derangement and glucose assimilation disorders.

EFFECT: inhibition of hormone-sensitive lipases.

13 cl, 1 tbl, 103 ex

FIELD: chemistry.

SUBSTANCE: invention relates to formula (I) compounds and to their use in treating diseases related to lipid storage disorders, such as atherosclerosis and diabetes. In R1 represents hydrogen, alkyl, halogen, formyl, hydroxyalkyl or trifluoromethyl, R2 represents hydrogen, alkyl or halogen, R3 represents hydrogen or alkyl, R4 represents hydrogen, alkyl, hydroxy or alkoxy, R5 and R6 are chosen from hydrogen, alkyl, phenylalkyl, hydroxyalkyl, alkoxycarbonyl and phenyl, A represents aryl or heterocyclyl, m equals 0-3, n equals 0-1, p equals 0-3, sum of m, n and p equals 1-4, the bond between carbon atoms Ca and Cb is a single or double carbon-carbon bond.

EFFECT: obtaining new biologically active compounds.

27 cl, 147 ex

FIELD: medicine.

SUBSTANCE: invention covers thaizole derivatives of formula (I) and to their pharmaceutically acceptable salts. In formula I: X1 and X2 differ from each other and represent sulphur atom or carbon atom; R1 represents phenyl group; phenyl group substituted by 1-2 members chosen from the group including halogen atoms, alkoxygroup with 1-6 carbon atoms, hydroxygroup, phenylalkoxygroup with 7-12 carbon atoms; phenyl group fused with 5-7-membered heteroaromatic or nonaromatic ring with at least one heteroatom consisting of N, O and S; pyridyl group; R2 represents hydrogen atom, halogen atom, alkyl group with 1-6 carbon atoms, alkyl group with 1-6 carbon atoms substituted by 1-5 halogen atoms, alkoxygroup with 1-6 carbon atoms, or hydroxyalkyl group with 1-5 carbon atoms; A represents group which is presented by formula or . Also, the invention concerns ALK5 inhibitor containing compound of the invention as an active component, stimulators of hair follicles proliferation and hair growth, and also to thiazole derivative of formula where A1 represents .

EFFECT: higher efficiency.

12 cl, 2 tbl, 50 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: invented compounds have antagonist properties towards CB1 receptors. In formula (I) , R1 is a lower alkoxy, (lower alkyl amino)-(lower alkoxy) or -N(Ra)Rb; Ra is hydrogen, lower alkyl, carbamoyl-(lower alkyl), hydroxy-(lower alkyl), dihydroxy-(lower alkyl), lower alkynyl, lower alkoxy, (lower alkoxy)-(lower alkyl), di-(lower alkylamino)-(lower alkyl), C3-6cycloalkyl; or Ra is a phenyl-(lower alkyl) group, where the phenyl fragment can be optionally mono-substituted, independently, by lower alkyl, lower alkoxy or halogen; or Ra is a 5- or 6-member heteroaromatic ring system, containing one or two nitrogen atoms in the ring, where the said heteroaromatic ring system is bonded to the remaining part of the molecule by lower alkylene; or Ra is a 5-, 6- or 7-member saturated heterocyclic ring system, containing one nitrogen heteroatom, where the said heterocyclic ring system is optionally mono-substituted by lower alkyl; Rb is hydrogen, lower alkyl or (lower alkoxy)-(lower alkyl); or Ra and Rb together with a nitrogen atom to which they are bonded, for a 4-, 5- or 6-member saturated or partially unsaturated heterocyclic ring system, optionally containing an extra heteroatom, which is chosen from nitrogen, oxygen or sulphur, where the said heterocyclic ring system is optionally mono- or disubstituted, independently, by lower alkyl, hydroxy group, hydroxy-(lower alkyl), lower alkoxy, (lower alkoxy)-(lower alkyl) group, cyano group, halogen, phenyl and/or benzyl; R2 is hydrogen or lower alkyl; R3 is phenyl, mono- or disubstituted, independently, by lower alkoxy, halogen, or perfluoro-(low alkoxy) group; and R4 is phenyl, which is mono- or disubstituted with a halogen.

EFFECT: new compounds have useful biological properties.

18 cl, 195 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds with general formula (I) or pharmaceutically acceptable salts thereof, where R1 is chosen from a group containing optionally substituted C1-C6alkyl, lower alkoxy group, (lower)alkoxy(lower)alkyl, cycloalkyoxy(lower)alkyl, lower thioalkyl, (lower)alkylthio(lower)alkyl, cycloalkyl, cycloalkyl(lower)alkyl; R2 is chosen from a group containing optionally substituted (lower)alkyl, cycloalkyl, cycloalkyl(lower)alkyl; R3 is chosen from a group containing halogen, cyano group, optionally substituted (lower alkyl, lower thioalkyl, aryl, aryl(lower)alkyl, lower alkenyl, lower alkynyl); R4 is chosen from a group containing hydrogen, halogen, cyano group, hydroxyl group, optionally substituted (lower alkyl, lower alkoxy group, aryl, pyridyl, aryl(lower)alkyl, heteroaryl, which is an aromatic mono- or bicyclic hydrocarbon, containing from 5 to 9 ring atoms, from which one or more is a heteroatom, chosen from O, N or S, and an amino group) and a group, with formula R8-Z-(CH2)n-; where Z is a single bond or chosen from a group consisting of O, NH, CH2, CO, SO, SO2 or S; where R8 is chosen from a group containing optionally substituted (aryl, pyridyl); and where n=0, 1 or 2; R5 represents hydrogen; R6 is chosen from a group containing halogen, optionally substituted lower alkoxy group; R7 is one or more substitutes, independently chosen from a group containing hydrogen, optionally substituted lower alkoxy group; where the optional substitute or substitutes when R1-R8 are independently chosen from a group containing halogen, hydroxyl group, lower alkyl, mono- or di(lower)alkylamino group, aminocarbonyl, sulfinyl, sulfonyl, sulfanyl, mono- or di(lower)alkylaminocarbonyl, amino group, carboxyl group, lower alkoxy group, C3-C12cycloalkyl, (lower)alkylcarbonyl, (lower)alkoxycarbonyl, nitrile, aryl; all of which, except halogen, are independently optionally substituted with one or more substitutes, chosen from a group containing halogen, hydroxyl group, lower alkyl, sulfinyl, sulfonyl, sulfanyl, amino group, carboxyl group, lower alkoxy group, carbamoyl. Invention also relates to formula (I'), to a pharmaceutical composition, as well as use of formula (I) compounds given in paragraph 1.

EFFECT: obtaining new biologically active compounds, for preventing or treating bone diseases, associated with very low or resorption of calcium.

6 cl, 151 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new compounds with formula I where R1, R2, R3 and Y together with a formula I residue, are compounds, chosen from a group given in the formula of invention, or to their pharmaceutically used and split esters, or to their acid-additive salts, which promote release of parathyroid hormone.

EFFECT: compounds can be used for making medicinal agents, with antagonistic properties towards calcium sensitive parathyroid gland receptor for treating diseases mediated by effect of parathyroid hormone.

7 cl, 179 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of general formula (I): (I) where: R1 represents either direct or branched (C1-C7)alkyl, or (C2-C4)alkenyl; R2 represents piridinyl, thienyl, thiazol; R3 represents one or more substitutes chosen from halogen atoms and following groups; trifluoromethyl, direct or branched (C1-C6)alkyl; as free base or additive salt with acid. Additionally, the invention concerns medical product, pharmaceutical composition, and application.

EFFECT: production of new biologically active compounds active to specific inhibitors of glycine glyt 1 and/or glyt 2 carriers.

6 cl, 2 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: present invention pertains to mew compounds with formula (I), their pharmaceutical salts and ester derivatives. In general formula (I) n equals 0 or an integer from 1 to 4; Z is -(CHR8)m-, -(CH2)mO(CHR8)r-, -(CH2)mS(CHR8)r- or -(CH2)mNR9(CHR8)r-, L3 is -(CHR)S-, where R is represents hydrogen and s equals 1, Q2 is oxygen, X and Y independently represent CH or nitrogen; or -X=Y- represents sulphur, oxygen. Description of the rest of the radicals is given in the summary of invention.

EFFECT: invented compounds have inhibiting effects on PTPase.

12 cl, 3 dwg, 51 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I) and pharmaceutically acceptable salts. Claimed compounds have modulation effect on CB cannabinoid receptor. In the general formula (I) , R and R1 are the same or different and are phenyl optionally substituted by 1-3 substitutes Y, where Y is substitute selected out of group including chlorine, iodine, bromine, fluorine, on condition that X is not a sub-group (ii); or one of R and R1 radicals is phenyl group, while the other radical is formed or linear C2-8-alkyl group or benzyl group; X is one of the sub-groups (i) or (ii). Also invention concerns application of the compounds in obtaining pharmaceutical composition, pharmaceutical composition with modulation effect on CB cannabinoid receptor, and compound of the general formula (IV) with radical values as indicated in the claim.

EFFECT: enhanced efficiency of composition and treatment method.

5 cl, 1 tbl, 25 ex

FIELD: chemistry.

SUBSTANCE: invention concerns compounds with inhibition effect on thrombocyte aggregation, their pharmaceutically acceptable salts, particularly compounds of general formula (I) (where R1 is C1-C6 alkyl etc., R2 is hydrogen, C2-C7 alkanoyl, C7-C11 arylcarbonyl, group of formula R4-(CH2)1- etc., R3 is C6-C10 aryl etc., X1, X2, X3, X4 and X5 are independently hydrogen, halogen etc., and n is an integer from 0 to 2), its pharmaceutically acceptable salts. Invention claims pharmaceutical compositions inhibiting thrombocyte activation and containing claimed compounds as agent.

EFFECT: obtaining compounds applicable as media of prevention and treatment of diseases related to thrombo- or embologenesis.

26 cl, 272 ex, 8 tbl

FIELD: medicine.

SUBSTANCE: compounds can be used for treatment and prevention of diseases associated with activity of specified enzyme, such as diabetes, obesity, diseases associated with food intake, dyslipidemia and hypertension. In general formula (I) , R1 represents methyl, ethyl, cyclopropyl, cyclobutyl, isopropyl, tert-butyl, methoxymethyl, cyclopropyl methoxymethyl, 2-methyl thiazolyl, morpholinyl methyl or phenyl; R2 represents hydrogen, C1-4alkyl or phenyl; R3 represents hydrogen, C1-4alkyl or phenyl; R4 represents phenyl, naphthyl, thiophenyl, quinolyl or piperidyl where phenyl, naphthyl, thiophenyl, quinolyl and piperidyl are optionally substituted with one to three substitutes independently chosen of C1-4alkyl, halogen, C1-4alkoxy, cyano, trifluoromethyl, phenyl, phenyls C1-4alkyl, phenyloxy, oxasolyl and pyridinyl; R5 represents hydrogen, C1-4alkyl, phenyl-C1-4alkyl, C3-6dicloalkyl-C1-4alkyl or aminocarbonylC1-4alkyl.

EFFECT: higher clinical effectiveness.

17 cl, 2 dwg, 72 ex

FIELD: chemistry.

SUBSTANCE: invention relates to formula (I) compounds and to their use in treating diseases related to lipid storage disorders, such as atherosclerosis and diabetes. In R1 represents hydrogen, alkyl, halogen, formyl, hydroxyalkyl or trifluoromethyl, R2 represents hydrogen, alkyl or halogen, R3 represents hydrogen or alkyl, R4 represents hydrogen, alkyl, hydroxy or alkoxy, R5 and R6 are chosen from hydrogen, alkyl, phenylalkyl, hydroxyalkyl, alkoxycarbonyl and phenyl, A represents aryl or heterocyclyl, m equals 0-3, n equals 0-1, p equals 0-3, sum of m, n and p equals 1-4, the bond between carbon atoms Ca and Cb is a single or double carbon-carbon bond.

EFFECT: obtaining new biologically active compounds.

27 cl, 147 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds with general formula (I) or pharmaceutically acceptable salts thereof, where R1 is chosen from a group containing optionally substituted C1-C6alkyl, lower alkoxy group, (lower)alkoxy(lower)alkyl, cycloalkyoxy(lower)alkyl, lower thioalkyl, (lower)alkylthio(lower)alkyl, cycloalkyl, cycloalkyl(lower)alkyl; R2 is chosen from a group containing optionally substituted (lower)alkyl, cycloalkyl, cycloalkyl(lower)alkyl; R3 is chosen from a group containing halogen, cyano group, optionally substituted (lower alkyl, lower thioalkyl, aryl, aryl(lower)alkyl, lower alkenyl, lower alkynyl); R4 is chosen from a group containing hydrogen, halogen, cyano group, hydroxyl group, optionally substituted (lower alkyl, lower alkoxy group, aryl, pyridyl, aryl(lower)alkyl, heteroaryl, which is an aromatic mono- or bicyclic hydrocarbon, containing from 5 to 9 ring atoms, from which one or more is a heteroatom, chosen from O, N or S, and an amino group) and a group, with formula R8-Z-(CH2)n-; where Z is a single bond or chosen from a group consisting of O, NH, CH2, CO, SO, SO2 or S; where R8 is chosen from a group containing optionally substituted (aryl, pyridyl); and where n=0, 1 or 2; R5 represents hydrogen; R6 is chosen from a group containing halogen, optionally substituted lower alkoxy group; R7 is one or more substitutes, independently chosen from a group containing hydrogen, optionally substituted lower alkoxy group; where the optional substitute or substitutes when R1-R8 are independently chosen from a group containing halogen, hydroxyl group, lower alkyl, mono- or di(lower)alkylamino group, aminocarbonyl, sulfinyl, sulfonyl, sulfanyl, mono- or di(lower)alkylaminocarbonyl, amino group, carboxyl group, lower alkoxy group, C3-C12cycloalkyl, (lower)alkylcarbonyl, (lower)alkoxycarbonyl, nitrile, aryl; all of which, except halogen, are independently optionally substituted with one or more substitutes, chosen from a group containing halogen, hydroxyl group, lower alkyl, sulfinyl, sulfonyl, sulfanyl, amino group, carboxyl group, lower alkoxy group, carbamoyl. Invention also relates to formula (I'), to a pharmaceutical composition, as well as use of formula (I) compounds given in paragraph 1.

EFFECT: obtaining new biologically active compounds, for preventing or treating bone diseases, associated with very low or resorption of calcium.

6 cl, 151 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new compounds with formula I where R1, R2, R3 and Y together with a formula I residue, are compounds, chosen from a group given in the formula of invention, or to their pharmaceutically used and split esters, or to their acid-additive salts, which promote release of parathyroid hormone.

EFFECT: compounds can be used for making medicinal agents, with antagonistic properties towards calcium sensitive parathyroid gland receptor for treating diseases mediated by effect of parathyroid hormone.

7 cl, 179 ex

FIELD: chemistry.

SUBSTANCE: described are derivatives of pyridinecarboxamides with formula (I), where the descriptions of radicals are given in the formula of the invention and its salts.

EFFECT: compounds exhibit insecticide activity.

7 cl, 5 tbl, 21 ex

FIELD: chemistry.

SUBSTANCE: invention relates to (Z)-methyl-16-(5-oxo-2-phenyl-oxazol-4-ilidenmethyl)-15,16-epoxy-8(17),13(16),14-labdatrien-18-oate of formula (I) (I). Compound (I) possesses high antioxidative, hepatoprotective and hemostimulatng activity and can be used for correction of side effects, arising with introduction of highly toxic medications used in anti-tumor therapy.

EFFECT: obtaining compound, which possesses high antioxidative, hepatoprotective and hemostimulatng activity.

1 cl, 4 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel compound represented by formula I, where R1 and R2 are similar or different and each represents: (I) C1-10alkyl group optionally substituted with 1-3 substituents selected from C3-10cycloalkyl group, C1-6alkoxycarbonyl group b C1-6alkoxygroup; (2) C6-14aryl group optionally substituted with 1-3 substituents selected from halogen atom, carboxyl group, C1-6alkoxycabonyl group b carbamoyl group; or (3) C7-13aralkyl group; R3 represents C6-14aryl group optionally substituted with 1-3 substituents selected from C1-6alkyl group, optionally substituted with 1-3 halogen atoms, halogen atom, C1-6alkoxycarbonyl group, carboxyl group, hydroxy group, C1-6alkoxygroup, optionally substituted with 1-3 halogen atoms; R4 represents amino group; L represents C1-10alkylene group; Q represents bond, C1-10alkylene group or C2-10alkenylene group; and X represents: (1) hydrogen atom; (2) cyanogroup; (3) (3a) carboxyl group; (3b) carbamoyl group; and further as presented in invention formula. Invention also describes medication for treating diabetes, peptidase inhibitor, application of formula I compound, method of prevention or treatment of diabetes, method of peptidase inhibiting and method of obtaining formula I compounds.

EFFECT: obtaining novel compounds which have peptidase-inhibiting activity and are useful as medication for prevention and treatment of diabetes.

16 cl, 433 ex, 6 tbl

FIELD: chemistry.

SUBSTANCE: claimed invention relates to compounds of formula (I), their obtaining and application as elastase inhibitors, and can be applied in medicine, where Y = CH; R№ represents H or alkyl; RІ represents phenyl or 5-6-memner heteroaryl, G1 represents phenyl; R5 represents H, halogen, alkyl, CN or fluorinated alkyl; n=1-3; R4 = H; L represents bond, O, NR29 or alkyl; or R4 and L are bound together in such way that group -NR4L- represents 5-7-member asacyclic ring; G2 represents phenyl, 5-6-member heteroaryl, cycloalkyl, C4-7-heterocycle, bicycle from two condensed, bound with direct bond or separated with O atom rings, selected from phenyl, 5-6-member heteroaryl, cycloalkyl or C4-7-heterocycle; or when L does not represent bond, G2 represents H; s = 0-2; R25 represents H, alkyl or cycloalkyl; R29 represents H or alkyl.

EFFECT: obtaining novel biologically active compounds.

10 cl, 95 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: present invention pertains to a new piperidine derivative, with the following general formula (I) where R1 - R4 each stands for any of the univalent groups, indicated below: R1 stands for a hydrogen atom, halogen atom, inferior alkyl, which can be substituted with a halogen atom or OH; -O-inferior alkyl, which can be substituted with a halogen atom; -O-aryl, aryl, -C(=O)-inferior alkyl, COOH, -C(=O)-O-inferior alkyl, -C(=O)-NH2, -C(=O)NH-inferior alkyl, -C(=O)N-(inferior alkyl)2, OH, -O-C(=O)-inferior alkyl, NH2, -NH-inferior alkyl, -N-(inferior alkyl)2, NH-C(=O)- inferior alkyl, CN or NO2; R2 and R3 each stands for a hydrogen atom; and R4 stands for any of the univalent groups (a), (b) and (c), shown below in formula 2 where in the above indicated groups (a), (b) and (c), A stands for a pyrrolidine, piperidine, morpholine, piperizine or oxazepane ring; B stands for a pyrrolidine or piperidine ring; R5 and R8-R11 can be identical or different from each other and each stands for a hydrogen atom, -C(=O)-O-inferior alkyl, cycloalkyl or tetrahydropyrane; R6 stands for a hydrogen atom, -C(=O)-O-inferior alkyl, OH, -inferior alkylene-OH or -C(=O)-pyridine; and R7 stands for a hydrogen atom. The invention also pertains to pharmaceutical salts of the piperidine derivative, as well as medicinal compositions.

EFFECT: obtaining new biologically active compounds and a medicinal composition, based on these compounds, which is a sodium channel inhibitor.

10 cl, 91 ex, 22 tbl

FIELD: chemistry.

SUBSTANCE: invention concerns compounds with inhibition effect on thrombocyte aggregation, their pharmaceutically acceptable salts, particularly compounds of general formula (I) (where R1 is C1-C6 alkyl etc., R2 is hydrogen, C2-C7 alkanoyl, C7-C11 arylcarbonyl, group of formula R4-(CH2)1- etc., R3 is C6-C10 aryl etc., X1, X2, X3, X4 and X5 are independently hydrogen, halogen etc., and n is an integer from 0 to 2), its pharmaceutically acceptable salts. Invention claims pharmaceutical compositions inhibiting thrombocyte activation and containing claimed compounds as agent.

EFFECT: obtaining compounds applicable as media of prevention and treatment of diseases related to thrombo- or embologenesis.

26 cl, 272 ex, 8 tbl

FIELD: medicine.

SUBSTANCE: compounds can be used for treatment and prevention of diseases associated with activity of specified enzyme, such as diabetes, obesity, diseases associated with food intake, dyslipidemia and hypertension. In general formula (I) , R1 represents methyl, ethyl, cyclopropyl, cyclobutyl, isopropyl, tert-butyl, methoxymethyl, cyclopropyl methoxymethyl, 2-methyl thiazolyl, morpholinyl methyl or phenyl; R2 represents hydrogen, C1-4alkyl or phenyl; R3 represents hydrogen, C1-4alkyl or phenyl; R4 represents phenyl, naphthyl, thiophenyl, quinolyl or piperidyl where phenyl, naphthyl, thiophenyl, quinolyl and piperidyl are optionally substituted with one to three substitutes independently chosen of C1-4alkyl, halogen, C1-4alkoxy, cyano, trifluoromethyl, phenyl, phenyls C1-4alkyl, phenyloxy, oxasolyl and pyridinyl; R5 represents hydrogen, C1-4alkyl, phenyl-C1-4alkyl, C3-6dicloalkyl-C1-4alkyl or aminocarbonylC1-4alkyl.

EFFECT: higher clinical effectiveness.

17 cl, 2 dwg, 72 ex

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