Pyridazin-3(2h)-one derivatives and use thereof as pde4 inhibitors

FIELD: chemistry.

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

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

11 cl, 1 tbl, 182 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

in which R1denotes a lower alkyl group;
R2refers to a 5-10 membered monocyclic or polycyclic heteroaryl group containing at least one heteroatom selected from N and S, which optionally may be substituted by one or more Deputy chosen from:
atoms of halogen;
lower alkyl group;
R3denotes a group of the formula:
G-L1-(CRR')n-
in which n is a whole number equal to from 0 to 6;
R and R' are independently selected from the group comprising a hydrogen atom and lower alkyl group;
L1 represents a connecting group selected from the group comprising a direct bond, a group-CO-, -NR"-, -NR-CO-, -O(CO)NR"-,
-NR"(CO)O-, -O(CO)-, -O(CO)O-, -(CO)O - and-O(R"O)(PO)O-, where R" is selected from the group comprising a hydrogen atom and lower alkyl group;
G is selected from the group comprising a hydrogen atom and lower alkyl, cycloalkyl, phenyl, feniello, pyridyloxy and heterocyclyl group, where heterocyclyl group represents a non-aromatic C3-C10carbocyclic ring in which 1 or 2 carbon atoms substituted on a heteroatom, selected from N and O, where these groups may be optionally substituted by one or more Deputy chosen from:
atoms of halogen;
lower alkyl groups, which optionally may be substituted by one or more Deputy selected from halogen atoms; and
alkoxygroup, hydroxycarbonyl and alkoxycarbonyl group;
provided that R3does not denote a hydrogen atom,
R4denotes phenyl or thienyl group, which optionally can be substituted by one or more Deputy chosen from:
atoms of halogen;
lower alkyl group;
and its pharmaceutically acceptable salts.

2. The compound according to claim 1, in which R3means:
G-L1-(CRR')n-
where n is a whole number equal to from 0 to 3;
R and R' are independently selected from the group comprising a hydrogen atom and lower alkyl group;
L1 represents a connecting group selected from the group comprising a direct bond, -CO-, -O(CO)-, -O(CO)O -, and -(CO)O-; and G is selected from the group comprising a hydrogen atom and lower alkyl, cycloalkyl, phenyl, penalcol the Yu, pyridinol and heterocyclyl group, where heterocyclyl group represents a non-aromatic C3-C10carbocyclic ring in which 1 or 2 carbon atoms substituted on a heteroatom, selected from N and O, where these groups may be optionally substituted by one or more Deputy, selected from
atoms of halogen;
lower alkyl groups, which optionally may be substituted by one or more Deputy selected from halogen atoms; and
alkoxygroup, hydroxycarbonyl and alkoxycarbonyl group.

3. The compound according to claim 2, in which R3means:
G-L1-(CRR')n-
where n is a whole number equal to from 0 to 3;
R and R' are independently selected from the group comprising a hydrogen atom and a methyl group;
L1 represents a connecting group selected from the group comprising a direct bond, -CO-, -O(CO)-, -O(CO)O -, and -(CO)O-; and G is selected from the group comprising a hydrogen atom and lower alkyl, cycloalkyl, phenyl, feniello, pyridyloxy and heterocyclyl group, where heterocyclyl group represents a non-aromatic C3-C10carbocyclic ring in which 1 or 2 carbon atoms substituted on a heteroatom, selected from N and O, where these groups may be optionally substituted by one or more halogen atom.

4. The compound according to claim 2 and and 3, in which R stands for;
G-L1-(CRR')n-
where n is 0 or 1;
R denotes a hydrogen atom;
R' denotes a hydrogen atom or a metal group;
L1 represents a connecting group selected from the group comprising a direct bond, -O(CO)O -, and -(CO)O-; and
G is selected from the group comprising lower alkyl and cycloalkyl group, where these groups may be optionally substituted by one halogen atom.

5. The compound according to claim 1, in which R4denotes phenyl group.

6. The compound according to claim 1, which is one of the following:
4-(methoxycarbonyl)benzyl-1-ethyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)-1,6-dihydropyridin-4-carboxylate
benzyl-1-ethyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)-1,6-dihydropyridin-4-carboxylate
2-(benzyloxy)-2-oxoethyl-1-ethyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)-1,6-dihydropyridin-4-carboxylate
2 ethoxy-2-oxoethyl-1-ethyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)-1,6-dihydropyridin-4-carboxylate
2-oxo-2-pyrrolidin-1-ileti-1-ethyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)-1,6-dihydropyridin-4-carboxylate
3-amino-3-oxopropyl-1-ethyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)-1,6-dihydropyridin-4-carboxylate
2-(dimethylamino)ethyl-1-ethyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)-1,6-dihydropyridin-4-carboxylate
2-[(tert-butoxycarbonyl)amino]ethyl-1-ethyl-6-oxo-3-phenyl-5-
(quinoline-5-ylamino)-1,6-dihydropyridin-4-carboxylat
2-(atomic charges)ethyl-1-ethyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)-1,6-dihydropyridin-4-carboxylate
3-terbisil-1-ethyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)-1,6-dihydropyridin-4-carboxylate
[(2,2-dimethylpropanoyl)oxy]methyl-1-ethyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)-1,6-dihydropyridin-4-carboxylate
2-oxo-2-pyridin-4-ileti-1-ethyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)-1,6-dihydropyridin-4-carboxylate
2-(dimethylamino)-2-oxoethyl-1-ethyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)-1,6-dihydropyridin-4-carboxylate
2-amino-ethyl-1-ethyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)-1,6-dihydropyridin-4-carboxylate
ethyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
2-(benzyloxy)-2-oxoethyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
(butyryloxy)methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
3-oxo-1,3-dihydro-2-benzofuran-1-yl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
(atomic charges)methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
1-(atomic charges)ethyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
2-(dimethylamino)-2-oxoethyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
benzyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin is n-4-carboxylate
[(2,2-dimethylpropanoyl)oxy]methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-
1,6-dihydropyridin-4-carboxylate
1-(atomic charges)-1-methylethyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
ethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
[(2,2-dimethylpropanoyl)oxy]methyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
1-[(etoxycarbonyl)oxy]ethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
2-(benzyloxy)-2-oxoethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
1-[(etoxycarbonyl)oxy]ethyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
ethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
[(2,2-dimethylpropanoyl)oxy]methyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
1-(atomic charges)ethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
({[1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-yl]carbonyl}oxy)acetic acid
ethyl-1-ethyl-3-(3-were)-6-oxo-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
[(2,2-dimethylpropanoyl)oxy]methyl-1-ethyl-3-(3-were)-6-oxo-5-(pyridine-3-ylamino)-1,6-dihydropyridin is n-4-carboxylate
ethyl-1-ethyl-3-(3-forfinal)-6-oxo-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
(butyryloxy)methyl-1-ethyl-3-(3-forfinal)-6-oxo-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
ethyl-1-ethyl-3-(4-forfinal)-6-oxo-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
(butyryloxy)methyl-1-ethyl-3-(4-forfinal)-6-oxo-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
ethyl-5-[(2-chloropyridin-3-yl)amino]-1-ethyl-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
methyl-1-ethyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)-1,6-dihydropyridin-4-carboxylate
ethyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
2-(atomic charges)ethyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
2-[(tert-butoxycarbonyl)amino]ethyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate 2-ethoxy-2-oxoethyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
2-(benzyloxy)-2-oxoethyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
benzyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
ethyl-1-ethyl-5-(4-methylpyridin-3-ylamino)-6-oxo-3-Tien-2-yl-1,6-dihydropyridin-4-carboxylate
2-(atomic charges)ethyl-etil-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
2-[(tert-butoxycarbonyl)amino]ethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
ethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
2-(atomic charges)ethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
2-[(tert-butoxycarbonyl)amino]ethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
2 ethoxy-2-oxoethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
2-(benzyloxy)-2-oxoethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
benzyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
ethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
2-(atomic charges)ethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
2-[(tert-butoxycarbonyl)amino]ethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
2 ethoxy-2-oxoethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
2-(benzyloxy)-2-oxoethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
4-terbisil-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylat
4-(methoxycarbonyl)benzyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
ethyl-1-ethyl-3-(4-were)-6-oxo-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
ethyl-1-ethyl-5-(isoquinoline-4-ylamino)-3-(4-were)-6-oxo-1,6-dihydropyridin-4-carboxylate
ethyl-1-ethyl-3-(4-were)-5-[(4-methylpyridin-3-yl)amino]-6-oxo-1,6-dihydropyridin-4-carboxylate
[(2,2-dimethylpropanoyl)oxy]methyl-1-ethyl-3-(4-were)-6-oxo-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
[(2,2-dimethylpropanoyl)oxy]methyl-1-ethyl-5-(isoquinoline-4-ylamino)-3-(4-were)-6-oxo-1,6-dihydropyridin-4-carboxylate
[(2,2-dimethylpropanoyl)oxy]methyl-1-ethyl-3-(4-were)-5-[(4-methylpyridin-3-yl)amino]-6-oxo-1,6-dihydropyridin-4-carboxylate
1-[(isopropoxycarbonyl)oxy]ethyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
1-[(isopropoxycarbonyl)oxy]ethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
1-[(isopropoxycarbonyl)oxy]ethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
1-{[(cyclohexyloxy)carbonyl]oxy} ethyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
1-{[(cyclohexyloxy)carbonyl]oxy} ethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
1-{(cyclohexyloxy)carbonyl]oxy} ethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
ethyl-1-ethyl-6-oxo-3-phenyl-5-(thieno[2,3-C]pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
ethyl-1-ethyl-6-oxo-3-phenyl-5-(thieno[2,3-b]pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
[(2,2-dimethylpropanoyl)oxy]methyl-1-ethyl-6-oxo-3-phenyl-5-(thieno[2,3-b]pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate 7-ethoxy-7-oxoethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
6 ethoxy-6-oxohexyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
3-amino-3-oxopropyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
2 ethoxy-2-oxoethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
2-(benzyloxy)-2-oxoethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
1-{[(1-ethylpropoxy)carbonyl]oxy}ethyl-1-ethyl-6-oxo-3-phenyl-
5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
1-{[(1-ethylpropoxy)carbonyl]oxy}ethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
1-{[(1-ethylpropoxy)carbonyl]oxy}ethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate (butyryloxy)methyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
(atomic charges)methyl-1-ethyl-5-[(4-methylpyridin-3-yl)amine is]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
benzyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
4-(methoxycarbonyl)benzyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate (isobutyryloxy)methyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
(isobutyryloxy)methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
4-terbisil-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
4-(methoxycarbonyl)benzyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
[(isopropoxycarbonyl)oxy]methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
7 ethoxy-7-oxoethyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
6 ethoxy-6-oxohexyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
4-terbisil-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-
ylamino)-1,6-dihydropyridin-4-carboxylate ethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
chloromethyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
{[(cyclohexyloxy)to rbony]oxy}methyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
[(2,2-dimethylbutanol)oxy]methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
({N-[(benzyloxy)carbonyl]-L-felled}oxy)methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
ethyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
{[(cyclohexyloxy)carbonyl]oxy}methyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
{[(cyclohexyloxy)carbonyl] oxy} methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
2-(atomic charges)ethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
2-[(tert-butoxycarbonyl)amino]ethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
{[(1-ethylpropoxy)carbonyl] oxy} methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
(isobutyryloxy)methyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
2-(atomic charges)ethyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
2-[(is pet-butoxycarbonyl)amino]ethyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
2 ethoxy-2-oxoethyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
[(isopropoxycarbonyl)oxy]methyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
2-(benzyloxy)-2-oxoethyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
2 ethoxy-2-oxoethyl-1-ethyl-5- [(4-methylpyridin-3-yl)amino]-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
2-(benzyloxy)-2-oxoethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
{[(1-ethylpropoxy)carbonyl]oxy} methyl - 1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
benzyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
benzyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
[(isopropoxycarbonyl)oxy]methyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
6 ethoxy-6-oxohexyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
7 ethoxy-7-oxoethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
({[1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-yl]carbonyl} oxy)methyl-N-(tert-butoxycarbonyl)-L-Latinate
2-methoxy-2-oxoethyl-1-ethyl-5-(isoquinoline-4-yl) - Rev. Ino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
4-terbisil-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
4-(methoxycarbonyl)benzyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
(butyryloxy)methyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
6 ethoxy-6-oxohexyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
{[(1-ethylpropoxy)carbonyl]oxy}methyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
7 ethoxy-7-oxoethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
({[1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-yl]carbonyl} oxy)methyl-L-Latinate
benzyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
3-amino-3-oxopropyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
4-terbisil-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
4-(methoxycarbonyl)benzyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
[(2-methylbutanoyl)oxy]methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
4-(methoxycarbonyl)benzyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(3-thienyl)-16-dihydropyridin-4-carboxylate
7 ethoxy-7-oxoethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
7 ethoxy-7-oxoethyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
4-terbisil-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
6 ethoxy-6-oxohexyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
6 ethoxy-6-oxohexyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
1-{[(cyclohexyloxy)carbonyl]oxy} ethyl-1-ethyl-5-(1,7-naphthiridine-5-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
benzyl-1-ethyl-6-oxo-3-pyridin-4-yl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
({[1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-yl]carbonyl} oxy)methylmorpholin-4-carboxylate {[(methylamino)carbonyl]oxy}methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
{[(dimethylamino)carbonyl]oxy}methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-
ylamino)-1,6-dihydropyridin-4-carboxylate
(atomic charges)methyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
[(debutaniser)oxy]methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
(atomic charges)methyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(2-thienyl)-16-dihydropyridin-4-carboxylate
[(isopropoxycarbonyl)oxy]methyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
{[(cyclohexyloxy)carbonyl]oxy}methyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
(atomic charges)methyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
[(isopropoxycarbonyl)oxy]methyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
{[(cyclohexyloxy)carbonyl]oxy}methyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
(atomic charges)methyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
[(isopropoxycarbonyl)oxy]methyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
{[(cyclohexyloxy)carbonyl] oxy} methyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-(2-thienyl)-1,6-dihydropyridin-4-carboxylate
{[(cyclohexyloxy)carbonyl]oxy}methyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-3-(3-thienyl)-1,6-dihydropyridin-4-carboxylate
1-{[(cyclohexyloxy)carbonyl]oxy}ethyl-1-ethyl-5- [(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate-enantiomer
1-{[(cyclohexyloxy)carbonyl]oxy}ethyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate-enantiomer
hormati the-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
(propionyloxy)methyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
{[(1-ethylpropoxy)carbonyl]oxy}methyl-1-ethyl-3-(4-forfinal)-6-oxo-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
{[(cyclohexyloxy)carbonyl]oxy}methyl-1-ethyl-3-(4-forfinal)-6-oxo-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate chloromethyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
(propionyloxy)methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
(propionyloxy)methyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-oxo-3-phenyl-1,6-dihydropyridin-4-carboxylate
(pentanoate)methyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
2-oxo-1,3-dioxolane-4-yl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
vermeil-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-ylamino)-1,6-dihydropyridin-4-carboxylate
1-{[(cyclohexyloxy)carbonyl]oxy}ethyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-
ylamino)-1,6-dihydropyridin-4-carboxylate-enantiomer
1-{[(cyclohexyloxy)carbonyl]oxy}ethyl-1-ethyl-6-oxo-3-phenyl-5-(pyridine-3-
ylamino)-1,6-dihydropyridin-4-carboxylate-enantiomer 2, and their pharmaceutically acceptable salts.

7. The pharmaceutical composition intended for treating or preventing a pathological condition is s or disease, the course which is facilitated by inhibition of phosphodiesterase 4, comprising the compound according to any one of claims 1 to 6 in a mixture with a pharmaceutically acceptable diluent or carrier.

8. The use of compounds according to any one of claims 1 to 6 for the manufacture of a medicinal product intended for treating or preventing a pathological condition or disease, the occurrence of which is facilitated by inhibition of phosphodiesterase 4.

9. The use of claim 8, in which the drug is intended for use in the treatment or prevention of disorders, which is asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, atopic dermatitis, psoriasis or irritable bowel syndrome.

10. The method of treatment of a subject suffering from a pathological condition or disease, the occurrence of which is facilitated by inhibition of phosphodiesterase 4, including the introduction of a specified subject an effective amount of a compound according to any one of claims 1 to 6.

11. The method according to claim 10, in which the pathological condition or disease is asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, atopic dermatitis, psoriasis or irritable bowel syndrome.



 

Same patents:

FIELD: chemistry.

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

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

9 cl, 7 dwg, 2 tbl, 34 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of purifying thiopenes of formula (I) which are liquid at room temperature and can be used in organic synthesis to produce an electroconductive polymer or an organic semiconductor. The proposed method involves precipitation of thiophene of formula (I) , where R1 and R2 represent hydrogen, optionally broken by 1-5 O and/or S atoms C1-20alkyl, C1-20alkoxy, or R1 and R2 together represent optionally substituted C1-20dioxyalkylene or C6-20dioxyarylene group, where the thiophene is precipitated from a solution in isobutyl-methylketone, chloroform, methylene chloride, toluene, methanol, propanol, ethanol, acetone, isopropanol, n-butanol, fluorobutanol, dimethylformamide, methyl-tertbutyl ether, tetrahydrofuran, diethyl ether, hexane, pentane or mixtures thereof in ratio solvent : thiophene ranging from 0.01:1 to 10:1, cooled to temperature at least 10°C below melting point of the thiophene being purified in pure form, with subsequent separation of thiophene by filtration at low temperature.

EFFECT: design of a new efficient method of purifying low-melting thiophenes.

14 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel cyclic amine compounds of formula (1) or pharmaceutically acceptable salts thereof: . In formula (1), X is O, S, NR2 (where R2 is H, C1-C12 alkyl); when X is O, S, then R1 is H, CN, COOH, C2-C13 alkoxycarbonyl, carbamoyl group; and when X is NR2 (where R2 assumes values given above), R1 is CN; Ar1 and Ar2 are identical or different and each represents an aryl which can be substituted with 1-3 halogens; or Ar1 and Ar2 together with neighbouring carbon atoms to which they are bonded form a group with formula (b): (where ring S and ring T are identical and each is a benzene ring; Y is O); ring B is a benzene ring which can be substituted with 1-3 substitutes independently selected from a group comprising halogen, C1-C12 alkyl, C1-C8 halogenalkyl, C1-C12 alkoxy, C1-C8 halogenalkoxy group; n is an integer from 1 to 10; p, q are identical or different and each is an integer equal to 1 or 2. Formula (1) compounds are bonding inhibitors of the α2C-adrenoreceptor.

EFFECT: possibility of using compounds in pharmaceutical compositions.

7 cl, 1 tbl, 8 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: new compounds of thienopyrazole are described with formula (1) , where R1 means non-substituted C3-C8-cycloalkyl group or tetrahydropyranyl, R2 means non-substituted C1-C3alkyl group, R3 means atom of hydrogen, R4 means various groups mentioned in invention formula. Compounds inhibit PDE 7 and, accordingly, increase cell level of cyclic adenosine monophosphate. Pharmaceutical composition is also described, as well as method for inhibition of PDE, methods for production of compound with formula (1), where R4 means CO2R7, and intermediate compounds.

EFFECT: possibility to use for treatment of various types of such diseases as allergic diseases, inflammatory diseases or immunological diseases.

20 cl, 138 tbl, 440 ex

FIELD: medicine.

SUBSTANCE: invention is related to compound of formula (I), (values of radicals are described in formula of invention) or its pharmaceutically acceptable salts, to methods of its production, pharmaceutical composition, which contains it. Application of invention is described for manufacturing of medicinal agent intended for provision of inhibiting action in respect to HDAC in warm-blooded animal, in production of agent used for treatment of malignant tumor. Method is also described for provision of inhibiting action in warm-blooded animal.

EFFECT: compounds have inhibiting activity in respect to HDAC.

15 cl, 17 tbl, 24 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I)

, where R is selected from ethyl, n-propyl, iso-propyl, n-butyl and allyl; R' is selected from hydrogen, straight, branched or cyclic C1-C4alkyl; straight, branched or cyclic C1-C3alkoxy; fluorine, chlorine, bromine, trifluoromethyl and OCHxFy, where x=0, 1, 2, y=1, 2, 3 under the condition that, x+y=3; R" is selected from hydrogen, fluorine and chlorine, with the condition that, R" is selected from fluorine and chlorine only when R' is selected from fluorine and chlorine; R3 is selected from hydrogen and straight, branched or cyclic C1-C5alkyl; R4 is selected from hydrogen, CH2OCOC(CH3)3, pharmaceutically acceptable inorganic or organic cations, and COR4', where R' is straight, branched or cyclic C1-C5alkyl, phenyl, benzyl or phenethyl; R7 is selected from methyl and ethyl; one of A and B is sulphur, and the other is C-R2; when A is S, R2 is selected from hydrogen and methyl, with the condition that R2 is methyl only when R3 is not hydrogen; and when B is S, R2 is hydrogen; and to any tautomer thereof, as well as to a pharmaceutical composition which contains formula (I) compound, to a method of producing said compounds and to a method of treating diseases which are a result of autoimmune response or pathologic inflammation.

EFFECT: new compounds are disclosed, which can be used in treating diseases which are a result of autoimmune response or pathologic inflammation.

35 cl, 2 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: in formula compounds, each of R1, R2, R3, R4 is a substitute for a cyclic system, chosen from hydrogen, halogen, C1-C6-alkyl; C1-C6-alkoxy group; X is a heteroatom, chosen from oxygen or sulphur; R5 and R6 independently represent amino group substitutes, chosen from hydrogen, possibly substituted C1-C6-alkyl; possibly substituted C3-C6-cycloalkyl, which can be annealed with a benzene ring; possibly substituted phenyl, which can be annealed with dioxole, dioxine, -(CH2)n group, where n=4 to 6, or with a 5 or 6-member possibly substituted and possibly condensed azaheterocyclyl; possibly substituted saturated or unsaturated 5-6-member heterocyclyl, containing 1-2 heteroatoms, chosen form nitrogen, oxygen, sulphur and possibly condensed with a benzene ring, or R5 and R6 together with the nitrogen atom to which they are bonded, form an optionally substituted 5 or 6-member azahetero ring, possibly containing an additional heteroatom, chosen from nitrogen, and possibly annealed with a benzene ring or spiro-condensed with dioxole, where substitutes in the said alkyl, cycloalkyl, phenyl and heterocyclyl are chosen from halogen atoms, possibly substituted C1-C6-alkyl, CF3, possibly substituted C3-C6-cycloalkyl, possibly substituted phenyl, 5 or 6-member heterocyclyl, nitro group, substituted amino group, alkyloxycarbonyl, substituted carbonyl, aminocarbonyl, alkylsulphanyl.

EFFECT: design of an efficient method of producing new substituted furo[2,3-b]quinoline-2-carboxamides and substituted thieno[2,3-b]quinoline-2-carboxamides or their racemates, or their optical isomers, as well as their pharmaceutically acceptable salts and/or hydrates of general formula (I), which have antituberculous activity.

9 cl, 1 dwg, 7 tbl, 5 ex

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: medicine.

SUBSTANCE: invention relates to the method for production of the compound of the formula (1a), being an inhibitor of thrombocyte aggregation (1a), where X is halogen atom. The method includes interaction of compounds of the formula (II), (II), where X has above mentioned value and Y and Z independently from each other are leaving groups, with optically active alkamine with formation of diastereoisomers admixture.

EFFECT: development of the new advantageous method for production of the bioactive compound.

48 cl, 24 ex

FIELD: chemistry.

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

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

9 cl, 7 dwg, 2 tbl, 34 ex

FIELD: chemistry.

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

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

12 cl, 6 dwg, 1 tbl, 10 ex

FIELD: chemistry.

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

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

6 cl, 927 ex, 2 tbl

FIELD: chemistry.

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

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

31 cl, 331 ex, 7 tbl

FIELD: chemistry.

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

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

1 cl, 3 tbl, 2 dwg, 3 ex

FIELD: chemistry.

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

EFFECT: increased effectiveness of compounds.

11 cl, 13 ex, 11 tbl

FIELD: medicine.

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

EFFECT: increase of compound application efficiency.

38 cl, 5 dwg, 137 ex

FIELD: medicine.

SUBSTANCE: there are described new compounds of general formula

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

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

17 cl, 339 ex, 10 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (1) and their pharmaceutically acceptable salts as chemokine receptor CCR3 activity modulators, a pharmaceutical composition based on the said compounds, to synthesis method and use thereof. Said compounds can be used for treating and preventing diseases mediated by chemokine receptor CCR3 activity, such as inflammatory and allergic diseases etc. In general formula , R1 represents phenyl, [1,2,4]triazolo[4,3-a]pyridinyl, thiazolo [5,4-b]pyridinyl, benzothiazolyl, benzoxazolyl, pyridinyl, where each of the said phenyl or heterocycles can be substituted with one, two or three radicals R2; R2 each independently represents (C1-C6)halogenalkyl, halogen, COOR3; CONR3R4; R3 represents H or (C1-C6)alkyl; R4 represents H or (C1-C6)alkyl, R5 represents (C1-C6)alkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyl; R6 each independently represents (C1-C6)alkoxy, (C1-C6)halogenalkyl, halogen, OR3, CN, CONR3R4; A represents C(CH3)2-CH2-CH2-, CH2-CH2-CH2- or B represents phenyl; D-E represents CH-CH2- or C=CH-, X-W-V represents N-C=CR7 or C=C-NR7; R7 represents H or (C1-C6)alkyl; Y represents NR4, O, S(O)n; i, j, m each equals 1, n equals 0 or 2.

EFFECT: increased effectiveness of using said compounds.

13 cl, 37 ex

FIELD: 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: invention relates to a method for synthesis of 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidin-5-yl}-methyl)-2-thiophenecarboxamide by reacting 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-phenyl}-morpholin-3-one-hydrochloride with 5-chlorothiophene-2-carbonyl chloride, distinguished by that the reaction is carried out in a solvent selected from ether, alcohol, ketone and water or a mixture thereof using an inorganic base.

EFFECT: design of a simple method for synthesis of said thiophenecarboxamide without use of toxic solvents.

13 cl, 1 ex

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