New 1,2-dihydroquinoline derivatives possessing glucocorticoid receptor binding activity

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to organic chemistry, namely to new 1,2-dihydroquinoline derivatives of general formula , or to a pharmaceutically acceptable salt thereof, wherein R1 represents a lower alkyl group; R2 represents a hydrogen atom; each of R3 and R4 represents a lower alkyl group; R5 represents a lower alkyl group; R6 represents a halogen atom, a lower alkyl group, a lower alkoxy group, a nitro group; X represents -CO-, -C(O)NR8 - or -S(O)2-; each of R7 and/or R8 may be identical or different, and represents a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower cycloalkyl group, a phenyl or naphthyl group, a saturated or unsaturated monocyclic 5- or 6-member heterocyclyl with one or two heteroatoms specified in nitrogen, oxygen and sulphur atoms, and 3-5 carbon atoms in a cycle, a lower alkoxy group, a phenoxy group; provided R7 and/or R8 represent a lower alkyl group, a lower alkoxy group, the mentioned lower alkyl group and lower alkoxy group may contain one or three groups specified in a halogen atom, a phenyl group, an unsubstituted monocyclic 6-member heterocyclyl with one heteroatom specified in a nitrogen atom, and 5 carbon atoms in a cycle, a lower alkoxy group, and -NRaRb as a substitute (substitutes); provided R7 and/or R8 represent a phenyl group, a saturated or unsaturated monocyclic 5- or 6-member heterocyclyl with one or two heteroatoms specified in nitrogen, oxygen and sulphur atoms, and 3-5 carbon atoms in a cycle, a phenoxy group, the mentioned phenyl group, saturated or unsaturated monocyclic 5- or 6-member heterocyclyl with one or two heteroatoms specified in nitrogen, oxygen and sulphur atoms, and 3-5 carbon atoms in a cycle, phenoxy group may contain one or two groups specified in a halogen atom, a lower alkyl group, a halogen-substituted lower alkyl group, a phenyl group, a hydroxyl group, a lower alkoxy group, a halogen-substituted lower alkoxy group, a lower alkylthio group, a lower alkylcarbonyl group, a lower alkoxycarbonyl group, a lower alkylcarbonyloxy group, -NRaRb, a nitro group and a cyano group as a substitute (substitutes); Ra and Rb may be identical or different, and each of them represents a hydrogen atom, a lower alkyl group, a lower alkoxycarbonyl group; Y represents a lower alkylene group; Z represents an oxygen atom; p is equal to 2, provided p is equal to 2, R6 may be identical or different. The invention also relates to a pharmaceutical composition and a glucocorticoid receptor modulator of the compound of formula (1).

EFFECT: there are produced new 1,2-dihydroquinoline derivatives possessing glucocorticoid receptor binding activity.

7 cl, 1 tbl, 4 ex

 

The text descriptions are given in facsimile form.

1. The compound of General formula (1), or its pharmaceutically acceptable salt

where in the General formula (1)
R1represents a lower alkyl group;
R2represents a hydrogen atom;
R3and R4represent each a lower alkyl group;
R5represents a lower alkyl group;
R6represents a halogen atom, a lower alkyl group, lower alkoxygroup, the nitro-group;
X represents-CO-, -C(O)NR8- or-S(O)2-;
R7and/or R8may be the same or different and represent each a hydrogen atom, a lower alkyl group, lower alkenylphenol group, lower cycloalkyl group, phenyl or naftalina group, saturated or Nene is sydeny single 5 - or 6-membered heterocyclyl with one or two heteroatoms, selected from nitrogen atoms, oxygen and sulfur, and 3-5 carbon atoms in the cycle, the lower alkoxygroup, fenoxaprop;
in the case when R7and/or R8represents a lower alkyl group, lower alkoxygroup, a lower alkyl group, lower alkoxygroup can contain one or three groups selected from a halogen atom, phenyl group, unsaturated single 6-membered heterocycle with one heteroatom selected from a nitrogen atom, and 5 carbon atoms in the cycle, the lower alkoxygroup, and-NRaRbas the substituent(s);
in the case when R7and/or R8represents a phenyl group, a saturated or unsaturated mononuclear 5 - or 6-membered heterocyclyl with one or two heteroatoms selected from nitrogen atoms, oxygen and sulfur, and 3-5 carbon atoms in the cycle, fenoxaprop, phenyl group, saturated or unsaturated mononuclear 5 - or 6-membered heterocyclyl with one or two heteroatoms selected from nitrogen atoms, oxygen and sulfur, and 3-5 carbon atoms in the cycle, fenoxaprop can contain one or two groups selected from a halogen atom, a lower alkyl group, halogen-substituted lower alkyl groups, phenyl groups, hydroxy-group, the lower alkoxygroup, halogen-substituted lower alkoxygroup, low allylthiourea, lower alkylcarboxylic the Oh group, lower alkoxycarbonyl group, lower alkylcarboxylic, -NRaRb, nitro and ceanography, as substituent(s);
Raand Rbmay be the same or different and represent each a hydrogen atom, a lower alkyl group, lower alkoxycarbonyl group;
Y represents a lower alkylenes group;
Z represents an oxygen atom;
p is equal to 2, when p is 2, R6may be the same or different.

2. The compound or its pharmaceutically acceptable salt according to claim 1, where in the General formula (1)
R1represents a lower alkyl group;
R2represents a hydrogen atom;
R3and R4represent a lower alkyl group;
R5represents a lower alkyl group;
R6represents a halogen atom, a lower alkyl group, lower alkoxygroup or nitro-group;
X represents-CO-, -C(O)NR8- or-S(O)2-;
R7represents a lower alkyl group, lower alkenylphenol group, lower cycloalkyl group, phenyl or naftalina group, saturated or unsaturated mononuclear 5 - or 6-membered heterocyclyl with one or two heteroatoms selected from nitrogen atoms, oxygen and sulfur, and 3-5 carbon atoms in the cycle, the lower alkoxygroup or is exigrep;
in the case when R7represents a lower alkyl group or lower alkoxygroup, a lower alkyl group or lower alkoxygroup may contain one or three groups selected from a halogen atom, phenyl group, lower alkoxygroup and-NRaRbas the substituent(s);
in the case when R7represents a phenyl group, a saturated or unsaturated mononuclear 5 - or 6-membered heterocyclyl with one or two heteroatoms selected from nitrogen atoms, oxygen and sulfur, and 3-5 carbon atoms in the cycle, or fenoxaprop, phenyl group, saturated or unsaturated mononuclear 5 - or 6-membered heterocyclyl with one or two heteroatoms selected from nitrogen atoms, oxygen and sulfur, and 3-5 carbon atoms in the cycle or fenoxaprop can contain one or two groups selected from a halogen atom, a lower alkyl group, halogen-substituted lower alkyl group, phenyl group, a hydroxy-group, the lower alkoxygroup, halogen-substituted lower alkoxygroup, low allylthiourea, lower alkylcarboxylic group, lower alkoxycarbonyl group, lower alkylcarboxylic, -NRaRb, nitro and ceanography, as substituent(s);
Raand Rbmay be the same or different and represents each atom bodoro is a, lower alkyl group or lower alkoxycarbonyl group;
R8represents a hydrogen atom or a lower alkyl group;
in the case when R8represents a lower alkyl group, a lower alkyl group can contain one or three groups selected from a phenyl group or unsaturated single 6-membered heterocycle with one heteroatom selected from a nitrogen atom, and 5 carbon atoms in the cycle, as substituent(s);
Y represents a lower alkylenes group;
Z represents an oxygen atom;
p is equal to 2, when p is 2, R6may be the same or different.

3. The compound or its pharmaceutically acceptable salt according to claim 1, where in the General formula (1)
R1represents a lower alkyl group;
R2represents a hydrogen atom;
R3and R4represent a lower alkyl group;
R5represents a lower alkyl group;
R6represents a halogen atom, a lower alkyl group, lower alkoxygroup or nitro-group;
X represents-CO-, -C(O)NR8- or-S(O)2-;
R7represents a lower alkyl group, lower alkenylphenol group, lower cycloalkyl group, phenyl or naftalina group, saturated or unsaturated mononuclear 5 - or 6-h is i.i.d. heterocyclyl with one or two heteroatoms, selected from nitrogen atoms, oxygen and sulfur, and 3-5 carbon atoms in the cycle, the lower alkoxygroup or fenoxaprop;
in the case when R7represents a lower alkyl group, a lower alkyl group can contain one or three groups selected from a halogen atom, phenyl group, unsaturated single 6-membered heterocycle with one heteroatom selected from a nitrogen atom, and 5 carbon atoms in the cycle, the lower alkoxygroup and-NRaRbas the substituent(s);
in the case when R7represents a phenyl group, the phenyl group may contain one or two groups selected from a halogen atom, a lower alkyl group, halogen-substituted lower alkyl groups, lower alkoxygroup, halogen-substituted lower alkoxygroup, low allylthiourea, lower alkylcarboxylic group, lower alkoxycarbonyl group, lower alkylcarboxylic, -NRaRb, nitro and ceanography, as substituent(s);
in the case when R7represents a saturated or unsaturated mononuclear 5 - or 6-membered heterocyclyl with one or two heteroatoms selected from nitrogen atoms, oxygen and sulfur, and 3-5 carbon atoms in the cycle, heterocyclyl may contain one or two groups selected from a halogen atom, a lower alkyl group, vanilin the th group, hydroxy-group, the lower alkoxygroup, low allylthiourea, lower alkylcarboxylic group, lower alkoxycarbonyl group or nitro group as substituent(s);
in the case when R7represents a lower alkoxygroup lowest alkoxygroup may contain one or three groups selected from a halogen atom and phenyl groups as a substituent(s);
in the case when R7is fenoxaprop, fenoxaprop may contain one or two groups selected from a halogen atom and lower alkoxygroup, as substituent(s);
Raand Rbmay be the same or different, and each represents a hydrogen atom, a lower alkyl group or lower alkoxycarbonyl group; and/or
R8represents a hydrogen atom or a lower alkyl group;
in the case when R8represents a lower alkyl group, a lower alkyl group can contain one or three groups selected from a phenyl group or unsaturated single 6-membered heterocycle with one heteroatom selected from a nitrogen atom, and 5 carbon atoms in the cycle, as substituent(s);
Y represents a lower alkylenes group;
Z represents an oxygen atom;
p is equal to 2, when p is 2, R6may be the same or the difference is significant.

4. The compound or its pharmaceutically acceptable salt according to any one of claims 1 to 3,
where in the General formula (1) R1, R3, R4and R5represent a methyl group, R2represents a hydrogen atom, Y represents a methylene group.

5. The compound or its pharmaceutically acceptable salt according to claim 1, selected from the group which includes
6-(4-benzoyloxy-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-tert-butoxycarbonylamino-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(4-methoxybenzyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(3-methoxybenzyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(2-methoxybenzyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-(2-chlorobenzoyloxy)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-cyclohexylcarbonyl-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(pyridine-3-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-butyryloxy-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxy the l)-6-(2-methoxy-4-propionyloxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-acryloyloxy-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(thiophene-3-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[4-(furan-2-ylcarbonyl)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-(4-isobutyryloxy-2-methoxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-(2-methoxy-4-phenylacetonitrile)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-(2-methoxy-5-propionyloxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(thiophene-2-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(3-phenylpropionylamino)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[4-(furan-3-ylcarbonyl)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(pyridine-2-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(4-nitrobenzyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(pyridine-4-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-5-(pyridine-2-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydr the quinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-5-(pyridine-4-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-(2-acetoxybenzoic)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-(1-tert-butoxycarbonylamino-4-ylcarbonyl)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(2-methylthiazole)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-(1-tert-butoxycarbonylamino-4-ylcarbonyl)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(thiazol-4-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(thiazol-5-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(oxazol-4-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-(3-acetylbenzoate)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-(2-perbenzoate)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-(3-perbenzoate)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(5-methylfuran-2-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-FPO is-2-methylphenoxyacetic)-6-[2-methoxy-4-(2-methylpyridin-3-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(pyridine-3-RECETOX)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-(4-acetylbenzoate)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(3-ethoxycarbonylmethoxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(6-methylpyridin-3-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(4-methylpyridin-3-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(3-methylfuran-2-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-tert-butoxycarbonylamino-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(pyrimidine-5-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(5-nitrofuran-2-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-(2-chloropyridin-4-ylcarbonyl)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[4-(3-herperidin-4-ylcarbonyl)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[2-methoxy-4-(2-methoxybenzyloxy)phenyl]-5-(2-methyl-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[2-m is toxi-4-(pyridine-3-ylcarbonyl)phenyl]-5-(2-methyl-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-(furan-2-ylcarbonyl)-2-methoxyphenyl]-5-(2-methyl-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-(2-chlorobenzoyloxy)-2-methoxyphenyl]-5-(2-methoxy-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[2-methoxy-4-(2-methylpyridin-3-ylcarbonyl)phenyl]-5-(2-methoxy-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[2-methoxy-4-(2-methoxybenzyloxy)phenyl]-5-(2-methoxy-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(2-methoxy-5-nitrophenoxy)-6-[2-methoxy-4-(thiophene-3-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-(furan-3-ylcarbonyl)-2-methoxyphenyl]-5-(2-methyl-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[2-methoxy-4-(2-methylpyridin-3-ylcarbonyl)phenyl]-5-(2-methyl-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(2-methoxypyridine-3-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-aminoethoxy-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-(2-methoxy-4-propylsulfonyl)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-ethylsulfonyl-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-(4-isopropylphenoxy-2-methoxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-butylsulfonyl-2-methoxide the l)-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(2-methoxy-5-nitrophenoxy)-6-(2-methoxy-4-propylsulfonyl)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-cyclopropylmethoxy-2-methoxyphenyl)-5-(2-methoxy-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-isopropylphenoxy-2-methoxyphenyl)-5-(2-methoxy-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-ethylsulfonyl-2-methoxyphenyl)-5-(2-methyl-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(2-methoxy-4-propylsulfonyl)-5-(2-methyl-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-isopropylphenoxy-2-methoxyphenyl)-5-(2-methyl-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-cyclopropylmethoxy-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-(4-isobutylacetophenone-2-methoxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-cyclopentyloxy-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(3,3,3-triftormetilfullerenov)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(2-methoxybenzeneboronic)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-(2-chlorpheniramineydrocodone)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxy the Teal)-6-[2-methoxy-4-(3-methoxyphenylacetylene)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(4-methoxyphenylacetylene)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(4-methoxycarbonylaminophenyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-dimethylaminomethylene-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-(4-cyanobenzeneboronic)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
5-(5-fluoro-2-methylphenoxyacetic)-6-[2-methoxy-4-(morpholine-4-ylcarbonyl)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-isopropylaminocarbonyl-2-methoxyphenyl)-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[2-methoxy-4-(Marilyn-4-ylcarbonyl)phenyl]-5-(2-methoxy-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[2-methoxy-4-(Marilyn-4-ylcarbonyl)phenyl]-5-(2-methyl-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-(4-dimethylaminomethylene-2-methoxyphenyl)-5-(2-methyl-5-nitrophenoxy)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-[N-benzyl-N-(2-dimethylaminoethyl)aminocarbonyl]-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline,
6-[4-[N-(2-dimethylaminoethyl)-N-(pyridine-3-ylmethyl)aminocarbonyl]-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline and
6-[4-[N-(2-dimethylaminoethyl)-N-ethylamino is bonelace]-2-methoxyphenyl]-5-(5-fluoro-2-methylphenoxyacetic)-2,2,4-trimethyl-1,2-dihydroquinoline.

6. Pharmaceutical composition having activity of binding of the glucocorticoid receptor, comprising the compound or its pharmaceutically acceptable salt according to any one of claims 1 to 5.

7. The modulator of the glucocorticoid receptor, comprising as active ingredient the compound or its pharmaceutically acceptable salt according to any one of claims 1 to 5.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pyrrol derivatives of formula (1): or a pharmaceutically acceptable salt thereof wherein the values A, R1-R3, n are specified in clause 1 of the patent claim.

EFFECT: compounds (1) inhibit activity against the interleukin IL-6 production that allows using them both in pharmaceutical compositions, and in a prophylactic drug for ocular inflammatory disease.

23 cl, 2 tbl, 22 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing substituted pyrimidin-5-yl carboxylic acids of formula I and can be used in organic chemistry. The method is realised by reacting N-substituted guanidines and hetarylamidines with ethoxymethylene derivatives of 1,3-ketoesters according to a scheme given below (where the substitutes are as defined in the claim).

EFFECT: improved method of producing substituted pyrimidin-5-yl carboxylic acids of formula I.

2 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to a method of producing M-(1,5,3-dithiazepan-3-yl)amides of general formula (1) where R = p-C5H4N (a), (CH3)3CO (b), o-CH3OC6H4 (c), which involves reaction of N1,N1,N6,N6-tetramethyl-2,5-dithiahexane-1,6-diamine with a hydrazide of general formula RC(O)NHNH2 [R is as described above] in the presence of a samarium nitrate crystalline hydrate Sm(NO3)3·6H2O catalyst with molar ratio N1,N1,N6,N6-tetramethyl-2,5-dithiahexane-1,6-diamine:RC(O)NHNH2:Sm(NO3)3·6H2O=10:10:(0.3-0.7) at temperature of 65-75°C and atmospheric pressure in the mixture of solvents - ethyl alcohol and chloroform for 20-28 hours.

EFFECT: method of producing N-(1,5,3-dithiazepan-3-yl)amides with high selectivity and output, which can be used as biologically active compounds, selective sorbents and extractants of noble and precious metals.

1 cl, 1 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds for treating cell-proliferative disorders having formula (II): wherein the values R1,R2, X, A, B, R6, R7, R9 are specified in cl. 1 of the patent claim with the exception of the compound of formula: .

EFFECT: there are presented compounds possessing anticancer activity.

95 cl, 27 dwg, 11 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to a method of producing N-(1,5,3-dithiazepinan-3-yl)amides of general formula (1): where R = p-C5H4N (a), (CH3)3CO (b), o-CH3OC6H4 (c) which involves reaction of t-butyl-1,5,3-dithiazepinane with a hydrazide of general formula RC(O)NHNH2 [R is as described above] in the presence of an iron chloride crystalline hydrate catalyst FeCl3-6H2O in molar ratio t-butyl-1,5,3-dithiazepinane:RC(O)NHNH2:FeCl3-6H2O=10:10:(0.3-0.7) at temperature of 65-75°C and atmospheric pressure of a mixture of solvents - ethyl alcohol-chloroform for 40-48 hours.

EFFECT: novel method of producing N-(1,5,3-dithiazepinan-3-yl)amides with high selectivity and output, which can be used as biologically active compounds, selective sorbents and extractants of noble and precious metals.

1 cl, 1 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (I), wherein A represents a pyrrole group or a pyrazole group, and X represents a carbon atom or a nitrogen atom; R1 represents a carboxy group; R2 independently represents a group specified in a substitute group α; R3 independently represents phenyl(C1-C6alkyl)group substituted by, phenyl(C1-C6alkyl)group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α); m is equal to 0, 1, 2 or 3, n is equal to 0 or 1; each of R4, R5, R6 and R7 independently represents a hydrogen atom, C1-C6alkyl group or a halogen atom; B represents a substituted naphthyl group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α), or the group represented by formula (II), wherein B1, B2 and α are those as specified in the patent claim. Also, the invention refers to a pharmaceutical composition possessing lipolysis inhibiting activity, to the use of the compounds of formula (I) in preparing a drug preparation for treating hyperlipidemia, dislipidemia, abnormal lipid metabolism, arteriosclerosis or type II diabetes mellitus and to a method of treating or preventing the mentioned diseases.

EFFECT: preparing the compounds of formula (I) possessing lipolysis inhibiting activity.

36 cl, 1 dwg, 1 tbl, 69 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound selected from a group consisting of: 4-[(2-{[(2S)-2-fluoropropyl](pyridin-2-ylsulfonyl)amino}-4,5-dimethylphenoxy)methyl]benzoic acid, 4-[(2-{[(2R)-2-fluoropropyl](pyridin-2-ylsulfonyl)amino}-4,5-dimethylphenoxy)methyl]benzoic acid, 4-{[(6-{[(2R)-2-fluoropropyl](pyridin-2-ylsulfonyl)amino}-2,3-dihydro-1H-inden-5-yl)oxy)methyl} benzoic acid, 4-[(5-chlor-2-{[(2S)-2-fluoropropyl](pyridin-2-ylsulfonyl)amino}-4-methylphenoxy)methyl]benzoic acid, 4-[(5-chlor-2-{[(2R)-2-fluoropropyl](pyridin-2-ylsulfonyl)amino}-4-methylphenoxy)methyl]benzoic acid, 4-[(2-{[(2R)-3-fluor-2- methylpropyl](pyridin-2-ylsulfonyl)amino}-4,5-dimethylphenoxy)methyl]benzoic acid, 4-[(2-{[(2S)-3-fluor-2- methylpropyl](pyridin-2-ylsulfonyl)amino}-4,5-dimethylphenoxy)methyl]benzoic acid, 4-{[(6-{[(2R)-2-fluorobutyl](pyridin-2-ylsulfonyl)amino}-2,3-dihydro-1H-inden-5-yl)oxy)methyl} benzoic acid, 4-{[(6-{[(2S)-2-fluorobutyl](pyridin-2-ylsulfonyl)amino}-2,3-dihydro-1H-inden-5-yl)oxy)methyl}benzoic acid, 4-[(5-chlor-2-{[(2R)-2-fluoropropyl] (pyridin-3-ylsulfonyl)amino}-4-methylphenoxy)methyl]benzoic acid, 4-[(5-chlor- 2-{[(2S)-2-fluoropropyl](pyridin-3-ylsulfonyl)amino}-4-methylphenoxy)methyl] benzoic acid, 4-[(2-{[(2S)-2-fluoropropyl](pyridin-3-ylsulfonyl)amino}-4,5-dimethylphenoxy)methyl]benzoic acid, 4-[(2-{[(2R)-2-fluoropropyl](pyridin-3-ylsulfonyl)amino}-4,5-dimethylphenoxy)methyl] benzoic acid, 4-{[(6-{[(2S)-2-fluoropropyl](pyridin-3-ylsulfonyl)amino}-2,3-dihydro-1H-inden-5-yl)oxy)methyl} benzoic acid and 4-{[(6-{[(2R)-2-fluoropropyl](pyridin-3-ylsulfonyl)amino}-2,3-dihydro-1H-inden-5-yl)oxy)methyl}benzoic acid, or a pharmaceutically acceptable salt thereof. These compounds have an EP1 receptor antagonist effect and may be used for treating the dysfunction pollakiuria.

EFFECT: preparing the sulfonamide compounds with a strong EP1 receptor antagonist effect.

23 cl, 24 tbl, 31 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrimidine derivatives and their pharmaceutically acceptable salts possessing the properties of a HIV replication inhibitor. In formula (I'): , R1 means a hydrogen atom; R7 means a hydrogen atom; C1-6alkyl; R8 means a hydrogen atom; C1-6alkyl; R4 means cyano; R9 means -CH=CH-CN; R5 means C3-7cycloalkyl; C1-6alkyloxy; aryl; Het; C1-6alkyl substituted by a radical specified in hydroxy, C1-6alkyloxy, cyano, amino, mono- and di-C1-6alkylamino, C1-6alkylcarbonylamino, aryl, Het, dioxoalanine optionally substituted by one or two C1-6alkyl radicals, tetrahydrofuranyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl optionally substituted by C1-6alkyl or C1-6alkylcarbonyl, C1-6alkyloxycarbonyl, aryl C1-6alkyloxycarbonyl and C3-7cycloalkyl; or R5 means C1-6alkyl substituted by two C1-6alkyloxy radicals; R6 means a hydrogen atom or C1-6alkyl; X means -NR1- or -O; the values of Het are presented in the patent claim. The invention also refers to a pharmaceutical composition containing said compounds.

EFFECT: preparing the pharmaceutically acceptable salts possessing the properties of a HIV replication inhibitor.

9 cl, 2 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 2,2'-dibenzthiazolyl-disulphide via electrochemical oxidation of an alkaline solution of 2-mercaptobenzthiazole at temperature of 70°C and current density of 1 A/cm2, wherein the process is carried out on alternating current with frequency of 55…575 Hz, preferably 100…120 Hz and more preferably 105…115 Hz. The highest current output is achieved using alternating current with frequency of 110 Hz.

EFFECT: high efficiency of the electrolysis cell, reduced electric power consumption, avoiding use of toxic and expensive reagents.

2 cl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (1) and pharmaceutically acceptable salts thereof, which exhibit inhibitory activity on phospholipase A2 enzyme and therefore have prostaglandin and/or leucotriene production suppressing action. In formula X is a halogen atom, cyano group, C1-C3 alkyl group, which can be substituted with halogen atoms, C1-C3 alkoxy group or hydroxy group, C2-C4 alkenyl group, C1-C3 alkoxy group or hydroxy group; Y is a hydrogen atom or C1-C3 alkyl group; Z is C1-C3 alkyl group; G is selected from formulae and , where in formulae (G2) and (G5) R4 is a hydrogen atom or C1-C6 alkyl group which can be substituted with halogen atoms; D is -NR10C(O)-, -C(O)NR10-, -S(O)2NR10- or -N(R11)-; R10 is a hydrogen atom; R11 is a hydrogen atom or C1-C3 alkyl group; A is a single bond, C1-C6 alkylene, which can be substituted with a phenyl group, or C2-C4 alkenylene; Q is a phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, S, optionally substituted with a benzene ring; R5, R6 and R7 all or independently denote a hydrogen atom, a halogen atom, C1-C6 alkyl group which can be substituted with halogen atoms, C1-C6 alkoxy group which can be substituted with halogen atoms, phenyloxy group, phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, where said phenyl group and 5-6-member aromatic heterocyclic group can be substituted with a C1-C3 alkyl group which can be substituted with halogen atoms or a C1-C3 alkoxy group. The invention also relates to specific compounds, a medicinal agent, a pharmaceutical composition, a phospholipase A2 enzyme activity inhibitor and a treatment method.

EFFECT: improved method.

21 cl, 56 tbl, 561 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pyrrol derivatives of formula (1): or a pharmaceutically acceptable salt thereof wherein the values A, R1-R3, n are specified in clause 1 of the patent claim.

EFFECT: compounds (1) inhibit activity against the interleukin IL-6 production that allows using them both in pharmaceutical compositions, and in a prophylactic drug for ocular inflammatory disease.

23 cl, 2 tbl, 22 ex

FIELD: chemistry.

SUBSTANCE: invention relates to N-hydroxylsulphonamide derivatives of formula or , where R1 is H; R2 is H; n is 0; b is an integer in the range of 1-4; R3, R4, R5, R6 and R7 are independently selected from H, halogen, carboxyl, carboxyl ester selected from a group including -C(O)O-morpholino, -C(O)O-C1-C8alkyl and -C(O)O-substituted C1-C8alkyl, where the substitute is morpholino; acylamino, which is a -C(O)NRaRb group, where Ra and Rb are independently C1-C8alkyl, or Ra and Rb together with a nitrogen atom to which they are bonded form morpholino; and sulphonylamino, which is a SO2NR2 group, where two groups R, together with a nitrogen atom to which they are bonded, form morpholino; R8 is selected from halogen and carbonylamino, selected from a -CONH-substituted C1-C8alkyl, where the substitute is morpholino; and -CONR2, where two groups R, together with a nitrogen atom to which they are bonded, form morpholino; C is a heteroaromatic ring which contains cyclic fragments Q9, Q10, Q11, Q12, Q13 and Q14, which are independently selected from C, CH and S, under the condition that at least one of the fragments Q9, Q10, Q11, Q12, Q13 and Q14 is S. The invention also relates to a method of modulating nitroxyl levels, a method of treating diseases which respond to treatment with nitroxyl, a treatment set and a pharmaceutical composition containing compounds of formula (I) or (III).

EFFECT: compounds of formula (I) or (III) for treating diseases which respond to treatment with nitroxyl.

20 cl, 5 ex, 4 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing substituted pyrimidin-5-yl carboxylic acids of formula I and can be used in organic chemistry. The method is realised by reacting N-substituted guanidines and hetarylamidines with ethoxymethylene derivatives of 1,3-ketoesters according to a scheme given below (where the substitutes are as defined in the claim).

EFFECT: improved method of producing substituted pyrimidin-5-yl carboxylic acids of formula I.

2 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to isoxazole-pyridine derivatives of formula , where X; R1; R2, R3, R4, R5 and R6 are as described in claim 1 of the invention and a pharmaceutically acceptable salt thereof. The invention also relates to a medicinal agent for treating diseases associated with the binding site of the GABA A α5 receptor based on compounds of formula I and use of said compounds in preparing a medicinal agent.

EFFECT: novel compounds are active towards the binding site of said receptor and are useful in treating cognitive disorders such as Alzheimer's disease.

22 cl, 372 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (I), wherein A represents a pyrrole group or a pyrazole group, and X represents a carbon atom or a nitrogen atom; R1 represents a carboxy group; R2 independently represents a group specified in a substitute group α; R3 independently represents phenyl(C1-C6alkyl)group substituted by, phenyl(C1-C6alkyl)group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α); m is equal to 0, 1, 2 or 3, n is equal to 0 or 1; each of R4, R5, R6 and R7 independently represents a hydrogen atom, C1-C6alkyl group or a halogen atom; B represents a substituted naphthyl group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α), or the group represented by formula (II), wherein B1, B2 and α are those as specified in the patent claim. Also, the invention refers to a pharmaceutical composition possessing lipolysis inhibiting activity, to the use of the compounds of formula (I) in preparing a drug preparation for treating hyperlipidemia, dislipidemia, abnormal lipid metabolism, arteriosclerosis or type II diabetes mellitus and to a method of treating or preventing the mentioned diseases.

EFFECT: preparing the compounds of formula (I) possessing lipolysis inhibiting activity.

36 cl, 1 dwg, 1 tbl, 69 ex

FIELD: chemistry.

SUBSTANCE: invention relates to pyrazinone derivatives of formula (I):

, where R1, R2, R3, R4, R5, R and R7 are as defined in claim 1 of the invention. The invention also describes a crystalline form, compounds of formula I, use of the compound of formula I in producing a medicinal agent for treating chronic obstructive pulmonary disease. A pharmaceutical composition and a pharmaceutical product are also described. Methods of obtaining compounds of formula I are also described.

EFFECT: novel compounds which can be used in therapy are obtained and described.

20 cl, 334 ex, 15 tbl, 12 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (1) and pharmaceutically acceptable salts thereof, which exhibit inhibitory activity on phospholipase A2 enzyme and therefore have prostaglandin and/or leucotriene production suppressing action. In formula X is a halogen atom, cyano group, C1-C3 alkyl group, which can be substituted with halogen atoms, C1-C3 alkoxy group or hydroxy group, C2-C4 alkenyl group, C1-C3 alkoxy group or hydroxy group; Y is a hydrogen atom or C1-C3 alkyl group; Z is C1-C3 alkyl group; G is selected from formulae and , where in formulae (G2) and (G5) R4 is a hydrogen atom or C1-C6 alkyl group which can be substituted with halogen atoms; D is -NR10C(O)-, -C(O)NR10-, -S(O)2NR10- or -N(R11)-; R10 is a hydrogen atom; R11 is a hydrogen atom or C1-C3 alkyl group; A is a single bond, C1-C6 alkylene, which can be substituted with a phenyl group, or C2-C4 alkenylene; Q is a phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, S, optionally substituted with a benzene ring; R5, R6 and R7 all or independently denote a hydrogen atom, a halogen atom, C1-C6 alkyl group which can be substituted with halogen atoms, C1-C6 alkoxy group which can be substituted with halogen atoms, phenyloxy group, phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, where said phenyl group and 5-6-member aromatic heterocyclic group can be substituted with a C1-C3 alkyl group which can be substituted with halogen atoms or a C1-C3 alkoxy group. The invention also relates to specific compounds, a medicinal agent, a pharmaceutical composition, a phospholipase A2 enzyme activity inhibitor and a treatment method.

EFFECT: improved method.

21 cl, 56 tbl, 561 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to novel tetrahydroisoquinolin-1-one derivatives of general formula or pharmaceutically acceptable salts thereof, where R1 is: lower alkylene-OH, lower alkylene-N(R0)(R6), lower alkylene-CO2R0, C5-6cycloalkyl, C6-10cycloalkenyl, aryl, heterocyclic group, -(lower alkylen, substituted OR0)-aryl or lower alkylene-heterocyclic group, where the lower alkylene in R1 can be substituted with 1-2 groups G1; cycloalkyl, cycloalkenyl and heterocyclic group in R1 can be substituted with 1-2 groups G2; aryl can be substituted with 1-2 groups G3; R0: identical or different from each other, each denotes H or a lower alkyl; R6: R0, or -S(O)2-lower alkyl, R2 is: lower alkyl, lower alkylene-OR0, lower alkylene-aryl, lower alkylene-O-lower alkylene-aryl, -CO2R0, -C(O)N(R0)2, -C(O)N(R0)-aryl, -C(O)N(R0)-lower alkylene-aryl, aryl or heterocyclic group, where the aryl in R2 can be substituted with 1-3 groups G4; R3 is: H or lower alkyl, or R2 and R3 can be combined to form C5-alkylene; R4 is: -N(R7)(R8), -N(R10)-OR7, -N(R0)-N(R0)(R7), -N(R0)-S(O)2-aryl or -N(R0)-S(O)2-R7, R7 is: lower alkyl, halogen-lower alkyl, lower alkylene-CN, lower alkylene-OR0, lower alkylene-CO2R0, lower alkylene-C(O)N(R0)2, lower alkylene-C(O)N(R0)N(R0)2, lower alkylene-C(=NOH)NH2, heteroaryl, lower alkylene-X-aryl or lower alkylene-X-heterocyclic group, where the lower alkylene in R7 can be substituted with 1-2 groups G1; aryl, heteroaryl and heterocyclic group in R7 can be substituted with 1-2 groups G6; X is: a single bond, -O-, -C(O)-, -N(R0)-, -S(O)p- or *-C(O)N(R0)-, where * in X has a value ranging from a bond to a lower alkylene, m is: an integer from 0 to 1, p is: is 2, R8 is: H, or R7 and R6 can be combined to form a lower alkylene-N(R9)-lower alkylene group, R9 is: aryl, R10 is: H, R5 is: lower alkyl, halogen, nitro, -OR0, -N(R0)2, or -O-lower alkylene-aryl, where the group G1 is: -OR0, N(R0)(R6) and aryl; group G2 is: lower alkyl, lower alkylene-OR0, -OR0, -N(R0)2, -N(R0)-lower alkylene-OR0, -N(R0)C(O)OR0, -N(R0)C(O)-lower alkylene-OR0, -N(R0)C(O)N(R0)2, -N(R0)C(=NR0)-lower alkyl, -N(R0)S(O)2-lower alkyl, -N(lower alkylene-CO2R0)-S(O)2-lower alkyl, -N(R0)S(O)2-aryl, -N(R0)S(O)2N(R0)2, -S(O)2-lower alkyl, -CO2R0, -CO2-lower alkylene-Si(lower alkyl)3, -C(O)N(R0)2, -C(O)N(R0)-lower alkylene-OR0, -C(O)N(R0)-lower alkylene-N(R0)2, -C(O)N(R0)-lower alkylene-CO2R0, -C(O)N(R0)-O-lower alkylene-heterocyclic group, -C(O)R0, -C(O)-lower alkylene-OR0, C(O)-heterocyclic group and oxo; under the condition that "aryl" in group G2 can be substituted with one lower alkyl; group G3 is: -OR0; group G4 is: halogen, CN, nitro, lower alkyl, -OR0, -N(R0)2) -CO2R0; group G5 is: halogen, -OR0, -N(R0)2 and aryl; group G6 is: halogen, lower alkyl which can be substituted with -OR0, halogen-lower alkyl which is substituted with -OR0, -OR0, -CN, -N(R0)2, -CO2R0, -C(O)N(R0)2, lower alkylene-OC(O)R0, lower alkylene-OC(O)-aryl, lower alkylene-CO2R0, halogen-lower alkylene-CO2R0, lower alkylene-C(O)]N(R0)2, halogen-lower alkylene-C(O)N(R0)2, -O-lower alkylene-CO2R0, -O-lower alkylene-CO2-lower alkylene-aryl, -C(O)N(R0)S(O)2-lower alkyl, lower alkylene-C(O)N(R0)S(O)2-lower alkyl, -S(O)2-lower alkyl, -S(O)2N(R0)2, heterocyclic group, -C(-NH)=NO-C(O)O-C1-10-alkyl, -C(=NOH)NH2, C(O)N=C(N(R0)2)2, -N(R0)C(O)R0, -N(R0)C(O)-lower alkylene-OR0, -N(R0)C(O)OR0, -C(aryl)3 and oxo; under the condition that the "heterocyclic group" in group G6 is substituted with 1 group selected from a group consisting of -OR0, oxo and thioxo (=S); where the "cycloalkenyl" relates to C5-10 cycloalkenyl, including a cyclic group which is condensed with a benzene ring at the site of the double bond; the "aryl" relates to an aromatic monocyclic C6-hydrocarbon group; the "heterocyclic group" denotes a cyclic group consisting of i) a monocyclic 5-6-member heterocycle having 1-4 heteroatoms selected from O, S and N, or ii) a bicyclic 8-9-member heterocycle having 1-3 heteroatoms selected from O, S and N, obtained via condensation of the monocyclic heterocycle and one ring selected from a group consisting of a monocyclic heterocycle, a benzene ring, wherein the N ring atom can be oxidised to form an oxide; the "heteroaryl" denotes pyridyl or benzimidazolyl; provided that existing compounds given in claim 1 of the invention are excluded. The invention also relates to a pharmaceutical composition based on the compound of formula (I), use of the compound of formula (I) and a method of treatment using the compound of formula (I).

EFFECT: obtaining novel tetrahydroisoquinolin-1-one derivatives which are useful as a BB2 receptor antagonist.

11 cl, 302 tbl, 59 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted N-phenylpyrrolidinyl methylpyrrolidine amides of formula , where R, R1, R2 and R3 are identical or different and independently denote H, (C1-C4)alkyl, CF3; R4 denotes phenyl, cyclohexyl, pyridinyl, furanyl, isoxazolyl, quinolinyl, naphthyridinyl, indolyl, benzoimidazolyl, benzofuranyl, chromanyl, 4-oxo-4H-chromenyl, 2,3-dihydrobenzofuranyl, benzo[1,3]dioxolyl and 2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[e]][1,4]diazepinyl; where said R4 is optionally substituted one to more times with a substitute selected from halogen, hydroxy, (C1-C4) alkyl, (C1-C4) alkoxy, CF3, hydroxymethyl, 2-hydroxyethylamino, methoxyethylamide, benzyloxymethyl, piperidinyl, N-acetylpiperidinyl, pyrrolyl, imidazolyl, 5-oxo-4,5-dihydropyrazolyl; or pharmaceutically acceptable salt thereof or enantiomer or diastereomer thereof.

EFFECT: compounds have modulating activity on histamine H3 receptor, which enables use thereof to prepare a pharmaceutical composition.

10 cl, 3 dwg, 29 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted N-phenylbipyrrolidine carboxamides of formula , where R denotes (C1-C4)-alkyl; R1 and R2 are identical or different and independently denote H, (C1-C4)-alkyl, CF3; R3 denotes H; R4 denotes cyclopropyl, cyclopentyl, cyclohexyl, bicyclo[2,2,1]heptyl, cyclopentylmethyl, tetrahydropyranyl, furanyl, oxazolyl, isoxazolyl and pyrazolyl; where R4 is optionally substituted one or more times by a substitute selected from methyl, ethyl, pyridinyl, 2-oxo-2H-pyridin-1-yl; or a pharmaceutically acceptable salt thereof, an enantiomer or a diastereomer thereof.

EFFECT: compounds have activity which binds to the H3 ligand, which allows use thereof to prepare a pharmaceutical composition for treating central nervous system diseases.

10 cl, 46 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula: , wherein Y represents -CO2H; A represents -(CH2)n-Ar-(CH2)o-, wherein Ar represents thiophenyl; total m and o is equal to 3, and wherein 1 group -CH2- may be substituted by O; G and G' represents -H; and B represents phenyl containing 1 to 2 substitutes independently specified in -F, -Cl and -Br. The invention also refers to a composition on the basis of the mentioned compounds.

EFFECT: there are produced new compounds and pharmaceutical composition on their basis which can find application in medicine for treating glaucoma or ocular hypertension.

10 cl, 1 tbl, 2 ex

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