Novel cyclic derivative of aminobenzoic acid

FIELD: chemistry.

SUBSTANCE: present invention relates to cyclic derivatives of aminobenzoic acid and to their pharmaceutically acceptable salts of general formula , in which ring Ar is a phenyl group, a 5-member aromatic heterocyclic group containing 1-2 heteroatoms selected from nitrogen, sulphur and oxygen, or a benzothiazolyl group; where the said groups can have 1-2 substitutes selected from a group comprising lower alkyl; a phenyl group; a phenyl group substituted with 1-2 halogens; a phenyl group substituted with a lower alkoxy group; a phenyl group substituted with a halogen-substituted lower alkyl group; a phenoxy group substituted with a halogen; a halogen; Z is an oxygen atom or -(CH2)-n (where n equals 0, 1 or 2); Y is C1-C4 alkylene, C2-C4 alkenylene or general formula (2) -T-A-U- (2) in which T is a single bond, C1-C4 alkylene or C2-C4 alkenylene; U is single bond, C1-C4 alkylene; values of the rest of radicals are given in the formula of invention.

EFFECT: obtaining a PPARα, agonist which contains an active ingredient in form of at least one cyclic derivative of aminobenzoic acid, and an agent which reduces the level of lipids which contains an active ingredient in form of at least one cyclic derivative of aminobenzoic acid.

12 cl, 16 tbl, 184 ex

 

The text descriptions are given in facsimile form.

1. Cyclic derivative of aminobenzoic acid represented by the General formula (1)
[Chemical formula 1]

in which cycle Ar represents a phenyl group, a 5-membered aromatic heterocyclic group, sotiriadou the 1-2 heteroatoms, selected from nitrogen, sulfur and oxygen, or benzothiazolyl group; and these groups may have 1-2 substituent selected from the group of lower alkyl; phenyl group; phenyl groups substituted by 1-2 halogen; phenyl groups, substituted lower alkoxygroup; phenyl groups, substituted halogen-substituted group of the lower alkyl; fenoxaprop, substituted with halogen; halogen;
Y represents a C1-C4alkylen,2-C4albaniles
or the General formula (2)
[Chemical formula 2]

in which T represents a single bond, C1-C4alkylen or2-C4albaniles;
U is an ordinary link1-C4alkylen;
Rather it represents a carbonyl group, oxygen atom, sulfur atom, -NR1- (R1represents a hydrogen atom or a group of the lower alkyl),
or a group having the General formula (3)
[Chemical formula 3]

in which L1represents a single bond or the group-NR1-, a R1has the values listed above;
or the General formula (4)
[Chemical formula 4]

in which L2represents a single bond, a R1has the values listed above;
Z represents an oxygen atom is whether -(CH 2)-n(where n represents 0, 1 or 2);
X represents a hydrogen atom, halogen atom, lower alkoxygroup, the nitro-group, amino group, benzyloxy;
R represents a hydrogen atom or a group of the lower alkyl and the group-COOR substituted in the ortho - or meta-position loop W;
or its pharmaceutically acceptable salt.

2. Cyclic derivative of aminobenzoic acid according to claim 1, wherein in the General formula (1) Y represented by the General formula (2A)
[Chemical formula 5]

in which T1represents a single bond, C1-C4alkylen or2-C4albaniles; U1represents ordinary communication or1-C4alkylen; and1represents an oxygen atom, a sulfur atom,
or the General formula (3)
[Chemical formula 6]

in which L1represents a single bond or-NR1-, a R1matter mentioned above,
or the General formula (4)
[Chemical formula 7]

in which L2represents a single bond, a R1has the values specified above; or its pharmaceutically acceptable salt.

3. Cyclic derivative of aminobenzoic acid according to claim 1, wherein in the General formula (1) Y presents the General formula is y (2b)
[Chemical formula 8]

in which T1represents a single bond, C1-C4alkylen or2-C4albaniles; U1represents ordinary communication or1-C4alkylen; And2represents an oxygen atom, a sulfur atom,
or the General formula (3A)
[Chemical formula 9]

in which Rlarepresents a hydrogen atom or a lower alkyl group, or the General formula (4A)
[Chemical formula 10]

in which Rlahas the above values;
or its pharmaceutically acceptable salt.

4. Cyclic derivative of aminobenzoic acid according to claim 1, wherein in the General formula (1) Y represented by the General formula (2C)
[Chemical formula 11]

in which T1represents a single bond, C1-C4alkylen or2-C4albaniles; U2is an ordinary bond or methylene; And3represented by the General formula (3A)
[Chemical formula 12]

in which Rlarepresents a hydrogen atom or a lower alkyl group; or the General formula (4A)
[Chemical formula 13]

in which Rlahas the value pointed to by the e above;
or its pharmaceutically acceptable salt.

5. Cyclic derivative of aminobenzoic acid according to claim 1, wherein in the General formula (1) Z is an oxygen atom or a methylene; or its pharmaceutically acceptable salt.

6. Cyclic derivative of aminobenzoic acid according to claim 1, wherein in the General formula (1) Z is a methylene; or its pharmaceutically acceptable salt.

7. Cyclic derivative of aminobenzoic acid according to claim 1, wherein in the General formula (1), X represents a hydrogen atom, halogen atom, lower alkoxygroup, the amino group; or its pharmaceutically acceptable salt.

8. Cyclic derivative of aminobenzoic acid according to claim 1, wherein in the General formula (1) cycle Ar represents a 5-membered aromatic heterocyclic group containing 1-2 heteroatoms selected from nitrogen, sulfur, oxygen, and these groups may have 1-2 substituent selected from the group of lower alkyl; phenyl group; phenyl groups substituted by 1-2 halogen; phenyl groups, substituted lower alkoxygroup; phenyl groups, substituted halogen-substituted group of the lower alkyl; or its pharmaceutically acceptable salt.

9. Cyclic derivative of aminobenzoic acid according to claim 1, wherein in the General formula (1) cycle Ar presented the Yong General formula (5)
[Chemical formula 14]

in which R2represents a phenyl group, phenyl group, substituted by 1-2 halogen; phenyl group, a substituted lower alkoxygroup; or phenyl group, substituted halogen-substituted group of the lower alkyl;
R3represents a hydrogen atom, or a group of the lower alkyl; G represents an oxygen atom or a sulfur atom; or its pharmaceutically acceptable salt.

10. Cyclic derivative of aminobenzoic acid according to claim 1, characterized in that the compound of General formula (1) is:
2-[3-[[2-(4-chlorophenyl)-4-methylthiazole-5-yl]methoxymethyl]piperidine-1-yl]benzoic acid
3-[3-[[2-(4-chlorophenyl)-4-methylthiazole-5-yl]methoxymethyl]piperidine-1-yl]benzoic acid
3-[3-[[2-(4-chlorophenyl)-4-methylthiazole-5-yl]methoxy]piperidine-1-yl]benzoic acid
2-[3-[[2-(4-chlorophenyl)-4-methylthiazole-5-yl]carbonylmethyl]piperidine-1-yl]benzoic acid
3-[3-[[2-(4-chlorophenyl)-4-methylthiazole-5-yl]carbonylmethyl]piperidine-1-yl]benzoic acid
3-[3-[[2-(4-chlorophenyl)-4-methylthiazole-5-yl]carbonylmethyl]piperidine-1-yl]benzoic acid
2-[3-[N-[[2-(4-chlorophenyl)-4-methylthiazole-5-yl]methyl]carbarnoyl]piperidine-1-yl]benzoic acid
(S)-2-[3-[[2-(4-chlorophenyl)-4-methylthiazole-5-yl]methoxy-methyl]piperidine-1-yl]benzoic acid
(R)-2-[3-[[2-(4-chlorophenyl)-4-methyl shall eazol-5-yl]methoxy-methyl]piperidine-1-yl]benzoic acid
(R)-3-[3-[[2-(4-chlorophenyl)-4-methylthiazole-5-yl]methoxy]piperidine-1-yl]benzoic acid
(S)-2-[3-[[2-(4-chlorophenyl)-4-methylthiazole-5-yl]carbonylmethyl]piperidine-1-yl]benzoic acid
(R)-2-[3-[[2-(4-chlorophenyl)-4-methylthiazole-5-yl]carbonylmethyl]piperidine-1-yl]benzoic acid
(S)-3-[3-[[2-(4-chlorophenyl)-4-methylthiazole-5-yl]carbylamine]piperidine-1-yl]benzoic acid, or
(R)-3-[3-[[2-(4-chlorophenyl)-4-methylthiazole-5-yl]carbylamine]piperidine-1-yl]benzoic acid, or its pharmaceutically acceptable salt.

11. The PPARα agonist, containing as active ingredient at least one cyclic derivative of aminobenzoic acid according to any one of claims 1 to 10, or its pharmaceutically acceptable salt.

12. Means for reducing the level of lipid containing as active ingredient at least one cyclic derivative of aminobenzoic acid according to any one of claims 1 to 10, or its pharmaceutically acceptable salt.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula 1 , where R1, R2, R3, R4, R5, R6, R7 and R8 are independently selected from hydrogen, halogen, alkylcarboxylate, alkyl, alkenyl, cycloalkyl, nitro, sulfonyl chloride, sufonyl hydrazide, alkyl sulfonyl, heterocycylsulfonyl, heteroarylsufonyl, sulfonamide, alkyl-NH-SO2-, cycloalkyl-NH-SO2-, heterocyclyl-NH-SO2-, heteroalkyl-NH-SO2-, heteroarylalkyl-NH-SO2-, heterocyclyl, heteroaryl, guanidinocarbonyl, guanidine, -NR'R" and N=R'"; R' and R" are independently selected from hydrogen, alkyl, cycloalkyl, aryl, aralkyl, halogenalkyl, hydroxyalkyl, alkoxyalkyl, carboxyalkyl, aminoalkyl, mono- or dialkyl substituted aminoalkyl, cycloalkylaminoalkyl, aralkylaminoalkyl, alkoxyaralkylaminoalkyl, heterocyclylalkyl, heterocyclylaminoalkyl, heterocyclylalkylaminoalkyl, heterocyclylalkyl-N(alkyl) alkyl, heteroarylalkyl, heteroaralkylaminoalkyl, alkoxyaralkyl-N(alkyl)alkyl, aralkyl-N(alkyl)alkyl, alkoxycarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl alkylcarbonyl; R'" is selected from heterocyclyl, cycloalkyl and alkyl; where the alkyl is unsubstituted or substituted with 1, 2 or 3 identical or different substitutes selected from halogen, halogen alkyl, hydroxy, alkoxy, alkylamino, carbonyl, cycloalkylamino, nitro, cycloalkyl, aryl, heteroaryl and heterocyclyl; aryl is (C6-C10)aryl which is unsubstituted or substituted with 1-2 identical or different substitutes selected from nitro, alkyl, alkoxy, halogen, halogenalkyl, amino and mono or dialkylamino-; heteroaryl is a 5- or 6-member ring system containing 1, 2 or 3 atoms in the ring selected from N, O and S, which is unsubstituted or substituted with 1-2 identical or different groups selected from halogen, nitro, amino, alkylamino, alkyl, alkoxy and cycloalkyl; heterocyclyl is a 5- or 6-member ring system containing 1, 2 or 3 atoms in the ring selected from N, O and S, which is unsubstituted or substituted with 1-2 identical or different groups selected from alkyl, cycloalkyl, hydroxyalkyl, alkylaminoalkyl, cycloalkylalkyl, cycloalkylcarbonyl, heterocyclylalkyl, heteroarylalkyl, heteroarylcarbonyl, arylalkyl and oxo; and guanidino and guanidinocarbonyl are unsubstituted or substituted with 1, 2 or 3 identical or different groups selected from alkyl and alkylcarbonyl; provided that at least one of R1, R2, R3, R4, R5, R6, R7 or R8 is guanidine or guanidine carbonyl; U is C(O), CRaRb, O or NRa; V is CRaRb or NRa; and W is S(O)m; where Ra is H, alkyl, cycloalkyl or alkenyl; Rb is H, alkyl, OH or ORa, and m equals 1 or 2; or to pharmaceutically acceptable salts thereof. The invention also relates to a method of obtaining formula 1 compounds, to a pharmaceutical composition, as well as to use of the said compounds.

EFFECT: obtaining new biologically active compounds which are sodium/proton exchange (Na+/H+) (NHE) inhibitors.

19 cl, 203 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to benzazepin derivatives of formula (I), where R1 is unsubstituted cyclobutyl, R2 is 3-pyrazinyl, substituted CON(H)(Me) or 2-pyridinyl-M-pyrrolidinyl, where the said pyrrolidinyl group is substituted with a =O group; which is: methylamide 5-(3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy) pyrazine-2-carboxylic acid

or 1-{6-[(3-cyclbutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-3-pyridinyl}-2-pyrrolidinone

EFFECT: obtaining compounds which have affinity to histamine H3 receptor and pharmaceutical compositons containing said compounds.

11 cl, 288 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) and to their pharmaceutically acceptable salts, optical isomers or their mixture as glucokinase activators. In general formula (I) where R1 is C3-8-cycloalkyl, C3-8-cycloalkenyl, a 6-member heterocyclyl with 1 nitrogen atom, condensed phenyl-C3-8-cycloalkyl, each of which is possibly substituted with one or two substitutes R3, R4, R5 and R6; R2 is C3-8-cycloalkyl, a 5-6-member heterocyclyl with 1-2 heteroatoms selected from N, O, or S, each of which can be substituted with one or two substitutes R30, R31, R32 and R33, and R3, R4, R5, R6, R30, R31, R32 and R33 are independently selected from a group consisting of halogen, hydroxy, oxo, -CF3; or -NR10R12; or C1-6-alkyl, phenyl, C1-6-alkoxy, C1-6-alkyl-C(O)-O-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; or -C(O)-R27, -S(O)2-R27; or two substitutes selected from R3, R4, R5 and R6 or R30, R31, R32 and R33, bonded to the same atom or to neighbouring atoms, together form a -O-(CH2)2-O- radical; R10 and R11 independently represent hydrogen, C1-6-alkyl, -C(O)-C1-6-alkyl, -C(O)-O- C1-6-alkyl, -S(O)2- C1-6-alkyl; R27 is C1-6-alkyl, C1-6-alkoxy, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, phenyl, phenyl-C1-6-alkyl, a 5-6-member heteroaryl with 1-2 heteroatoms selected from N or S, a 6-member heteroaryl-C1-6-alkyl with 1 nitrogen atom, a 6-member heterocyclyl-C1-6-alkyl with 1-2 heteroatoms selected from N or O, R10R11-N- C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; R12 is a halogen, CF3, C1-6-alkoxy, -NR10R11; A is a 5-9-member heteroaryl with 1-3 heteroatoms selected from N, O or S, which is possibly substituted with one or two substitutes independently selected from R7, R8 and R9; R7, R8 and R9 are independently selected from halogen, cyano, -CF3; or C1-6-alkyl, C2-6-alkenyl, C1-6-alkoxy, C1-6-alkylthio, -C(O)-O-C1-6-alkyl, formyl, - C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-O-C(O)-C1-6-alkyl or hydroxy-C1-6-alkyl, each of which is possibly substituted with a substitute independently selected from R16; or phenyl, 5-member heteroaryl-C1-6-alkylthio with 2-4 nitrogen atoms, phenylthio, 5-6-member heteroarylthio with 1-2 nitrogen atoms, each of which is possibly substituted on the aryl or heteroaryl part with one or two substitutes independently selected from R17; or C3-8-cycloalkyl; or a 6-member heterocyclyl with 2 nitrogen atoms, 5-7-member heterocyclyl-C1-6-alkylthio with 1-2 heteroatoms selected from N or O, each of which is possibly substituted with one substitute independently selected from R16; or C1-6-alkyl-NR19R20, -S(O)2-R21 or -S(O)2-NR19R20; or -C(O)NR22R23; R16, R17 and R18 independently represent C1-6-alkyl, carboxy, -C(O)-O-C1-6-alkyl, -NR19R20, -C(O)NR19R20; R19 and R20 independently represent hydrogen, C1-6-alkyl, phenyl, 5-member heteroaryl with 2 heteroatoms selected from N or S, 6-member heterocyclyl with 1 nitrogen atom, -C(O)-O-C1-6-alkyl or -S(O)2-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R24; or R19 and R20 together with a nitrogen atom to which they are bonded form a 5-7-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring possibly contains one additional heteroatom selected from nitrogen, oxygen and sulphur, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R21 is selected from C2-6-alkenyl; or R22 and R23 are independently selected from hydrogen, -C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-S(O)2-C1-6-alkyl, C3-8-cycloalkyl; or R22 and R23 together with a nitrogen atom to which they are bonded form a 6-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R24 is oxo, C1-6-alkyl, carboxy- C1-6-alkyl, a 6-member heterocyclyl with 1 nitrogen atom, -NH-S(O)2R28 or -S(O)2R28, where each cyclic group is possibly substituted with one substitute independently selected from R29; R28 is C1-6-alkyl, -C1-6-alkyl-C(O)-O- C1-6-alkyl or -N(CH3)2; R29 is C1-6-alkyl.

EFFECT: obtaining compounds which can be used for treating and preventing diseases mediated by low glucokinase activity.

21 cl, 1 dwg, 608 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: described are compounds of formula (I)

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

EFFECT: compounds are highly efficient.

16 cl, 27 ex

FIELD: chemistry.

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

EFFECT: more effective treatment.

30 cl, 1 tbl, 142 ex

Organic compounds // 2382783

FIELD: chemistry.

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

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

6 cl, 9 tbl, 154 ex

FIELD: chemistry.

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

EFFECT: more effective treatment.

12 cl, 36 ex

FIELD: chemistry.

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

EFFECT: novel compounds have useful biological properties.

44 cl, 5 tbl, 66 ex

FIELD: chemistry.

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

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

2 cl, 485 ex, 3 tbl

FIELD: chemistry.

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

EFFECT: more effective treatment.

13 cl, 3 tbl, 46 ex

FIELD: chemistry.

SUBSTANCE: agent is a 6-bromo-5-methoxy-indole-3-carboxylic acid derivative of general formula (I) , where B is a N(R)2 group, where both R groups together with the nitrogen atom to which they are bonded form a 5-6-member heterocyclic ring containing 1-2 heteroatoms selected from nitrogen, such as pyrrolidine, piperidine, piperazine or morpholine, where each of the said heterocyclic rings can be substituted with C1-4alkyl, phenyl, benzyl, phenethyl, carbonylamino, -COOC1-4alkyl group or -COOC1-4alkyl group and phenyl, which can also be substituted or have substitutes selected from halogen, C1-4alkyl, C1-4alkoxy, and alkyl in the said groups can be linear or branched; R1 is C1-4alkyl, phenyl, possibly substituted with C1-4alkyl or C1-4alkoxy, halogen atoms; R2 is -S-phenyl, -S-benzyl, -O-phenyl, where in each of the said groups, the phenyl ring is possibly substituted with C1-4alkyl, C1-4alkoxy, halogen atoms, or R2 denotes a -N(R)2 group, or pharmaceutically acceptable salts thereof.

EFFECT: agent has antiviral activity towards influenza A virus.

3 dwg, 2 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) and to their pharmaceutically acceptable salts, optical isomers or their mixture as glucokinase activators. In general formula (I) where R1 is C3-8-cycloalkyl, C3-8-cycloalkenyl, a 6-member heterocyclyl with 1 nitrogen atom, condensed phenyl-C3-8-cycloalkyl, each of which is possibly substituted with one or two substitutes R3, R4, R5 and R6; R2 is C3-8-cycloalkyl, a 5-6-member heterocyclyl with 1-2 heteroatoms selected from N, O, or S, each of which can be substituted with one or two substitutes R30, R31, R32 and R33, and R3, R4, R5, R6, R30, R31, R32 and R33 are independently selected from a group consisting of halogen, hydroxy, oxo, -CF3; or -NR10R12; or C1-6-alkyl, phenyl, C1-6-alkoxy, C1-6-alkyl-C(O)-O-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; or -C(O)-R27, -S(O)2-R27; or two substitutes selected from R3, R4, R5 and R6 or R30, R31, R32 and R33, bonded to the same atom or to neighbouring atoms, together form a -O-(CH2)2-O- radical; R10 and R11 independently represent hydrogen, C1-6-alkyl, -C(O)-C1-6-alkyl, -C(O)-O- C1-6-alkyl, -S(O)2- C1-6-alkyl; R27 is C1-6-alkyl, C1-6-alkoxy, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, phenyl, phenyl-C1-6-alkyl, a 5-6-member heteroaryl with 1-2 heteroatoms selected from N or S, a 6-member heteroaryl-C1-6-alkyl with 1 nitrogen atom, a 6-member heterocyclyl-C1-6-alkyl with 1-2 heteroatoms selected from N or O, R10R11-N- C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; R12 is a halogen, CF3, C1-6-alkoxy, -NR10R11; A is a 5-9-member heteroaryl with 1-3 heteroatoms selected from N, O or S, which is possibly substituted with one or two substitutes independently selected from R7, R8 and R9; R7, R8 and R9 are independently selected from halogen, cyano, -CF3; or C1-6-alkyl, C2-6-alkenyl, C1-6-alkoxy, C1-6-alkylthio, -C(O)-O-C1-6-alkyl, formyl, - C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-O-C(O)-C1-6-alkyl or hydroxy-C1-6-alkyl, each of which is possibly substituted with a substitute independently selected from R16; or phenyl, 5-member heteroaryl-C1-6-alkylthio with 2-4 nitrogen atoms, phenylthio, 5-6-member heteroarylthio with 1-2 nitrogen atoms, each of which is possibly substituted on the aryl or heteroaryl part with one or two substitutes independently selected from R17; or C3-8-cycloalkyl; or a 6-member heterocyclyl with 2 nitrogen atoms, 5-7-member heterocyclyl-C1-6-alkylthio with 1-2 heteroatoms selected from N or O, each of which is possibly substituted with one substitute independently selected from R16; or C1-6-alkyl-NR19R20, -S(O)2-R21 or -S(O)2-NR19R20; or -C(O)NR22R23; R16, R17 and R18 independently represent C1-6-alkyl, carboxy, -C(O)-O-C1-6-alkyl, -NR19R20, -C(O)NR19R20; R19 and R20 independently represent hydrogen, C1-6-alkyl, phenyl, 5-member heteroaryl with 2 heteroatoms selected from N or S, 6-member heterocyclyl with 1 nitrogen atom, -C(O)-O-C1-6-alkyl or -S(O)2-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R24; or R19 and R20 together with a nitrogen atom to which they are bonded form a 5-7-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring possibly contains one additional heteroatom selected from nitrogen, oxygen and sulphur, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R21 is selected from C2-6-alkenyl; or R22 and R23 are independently selected from hydrogen, -C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-S(O)2-C1-6-alkyl, C3-8-cycloalkyl; or R22 and R23 together with a nitrogen atom to which they are bonded form a 6-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R24 is oxo, C1-6-alkyl, carboxy- C1-6-alkyl, a 6-member heterocyclyl with 1 nitrogen atom, -NH-S(O)2R28 or -S(O)2R28, where each cyclic group is possibly substituted with one substitute independently selected from R29; R28 is C1-6-alkyl, -C1-6-alkyl-C(O)-O- C1-6-alkyl or -N(CH3)2; R29 is C1-6-alkyl.

EFFECT: obtaining compounds which can be used for treating and preventing diseases mediated by low glucokinase activity.

21 cl, 1 dwg, 608 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound N-(1-{(3R)-3-(3,5-difluorophenyl)-3-[1-(methylsulfonyl) piperidin-4-yl]propyl}piperidin-4-yl)-N-ethyl-2-[4- (methylsufonyl)phenyl]acetamide or its pharmaceutically acceptable salts. The invention also relates to a method for synthesis of the compound in paragraph 1, as well as to a pharmaceutical composition.

EFFECT: obtaining a novel biologically active compound with activity towards CCR5 (chemokine receptor 5).

6 cl, 6 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention concerns derivatives of thiazolidine-4-one of general formula (I) and general formula (II), to their isomers and pharmaceutically acceptable salts which can be used as a medical product with immunosuppressive activity. In formulae (I) and (II), R1 and R14 independently represent lower alkyl, lower alkenyl; cycloalkyl; 5,6,7,8-tetrahydronaphth-1-yl; phenyl group or phenyl group independently mono- or disubstituted with lower alkyl, halogen, lower alkoxy or group -CF3; R2 and R15 independently represent lower alkyl; allyl; cyclopropyl; or di- lower alkylamino; R3 represents -NR5R6 or -O-CR7R8-CR9R10-(CR11R12)n-O-R13; R23 represents hydrogen; hydroxycarbonyl-lower alkyl or 1-glyceryl. Values of the other radicals are specified in the patent claim. The invention also concerns application of one or more compounds of general formula (I) or (II) for preparation of a medical product with immunosuppressive activity.

EFFECT: agent exhibits improved efficiency.

24 cl, 1 tbl, 157 ex

FIELD: medicine.

SUBSTANCE: in formula (1), R1 is di-C1-6alkoxyphenyl group; A is one of the following groups (i)-(vi); (i) -CO-B-, where B is C1-6alkylene group; (ii) -CO-Ba-, where Ba is C2-6alkenylene group; (iii) -CH(OH)-B-; (iv) -COCH((C)OOR3)-Bb-, where R3 is C1-6alkyl group and Bb is C1-6alkylene group. Values of the other radicals are specified in the patent claim. Invention also concerns the pharmaceutical composition exhibiting properties of a phosphodiesterase PDE4 inhibitor containing the compound under the invention; the phosphodiesterase 4 inhibitor containing as an active component the compound of the invention; preventive or therapeutic preparation for atopic dermatitis containing as an active component the compound of the invention.

EFFECT: higher effectiveness of application of the compound.

8 cl, 24 tbl, 262 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: 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: 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

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