Phosphodiestarase 4 inhibitors, containing n-substituted aniline and diphenylamine analogues

FIELD: chemistry.

SUBSTANCE: invention relates to N-substituted aniline and diphenylamine analogues, chosen from 3,4-bisdifluoromethoxy-(3-carboxyphenyl)-N-(5-(2-chloropyridinylmethyl))-aniline, 3,4-bisdifluoromethoxy - N-(3-carboxyphenyl) - N-(3-(2-chloropyridylmethyl))-aniline, 3,4 - bisdifluoromethoxy - N-(3-carboxyphenyl) - N-(4-(3,5-dimethylisoxazolylmethyl)) aniline, 3 - cyclopentyloxy - 4-methoxy - N-(3-aminocarbonylphenyl) - N-(3-pyridylmethyl) aniline and other compounds given in paragraph 1 of the formula of invention and to their pharmaceutically acceptable salts as inhibitors of PDE4 enzyme.

EFFECT: compounds can be used for treating and preventing diseases caused by activity of the PDE4 enzyme.

15 cl, 8 dwg, 58 ex

 

The text descriptions are presented in facsimile form.

1. A compound selected from the following:
3,4-Mediformatica-N-(3-carboxyphenyl)-N-(5-(2-chloropyridinyl))-aniline,
3,4-Mediformatica-N-(3-carboxyphenyl)-N-(3-(2-chloropyridinyl))-aniline,
3,4-Mediformatica-N-(3-carboxyphenyl)-N-(4-(3,5-dimethylisoxazole))aniline,
3 Cyclopentyloxy-4-methoxy-N-(3-aminocarbonylmethyl)-N-(3-pyridylmethyl)aniline,
3,4-Mediformatica-N-(3-carboxyphenyl)-N-(5-(4-chloropyridinyl))-aniline,
3,4-Mediformatica-N-(3-carboxy-4-chlorophenyl)-N-(3-pyridylmethyl)-aniline,
3,4-Mediformatica-N-(4-(1-pyrrol-1-yl)phenyl)-N-(3-pyridylmethyl)-aniline,
3,4-Mediformatica-N-(3-carboxyphenyl)-N-(5-(4-methoxypyridine))aniline,
3 Cyclopentyloxy-4-methoxy-N-phenyl-N-(3-(2-ethoxypyridine))-aniline,
3 Cyclopentyloxy-4-methoxy-N-(3-methylaminoethanol)-N-(3-pyridylmethyl)aniline,
3-Cyclopent is loxi-4-methoxy-N-(3-(2-hydroxyethyl)-aminocarbonylmethyl)-N-(3-pyridylmethyl)aniline,
3 Cyclopentyloxy-4-methoxy-N-(4-carboxyphenyl)-N-(5-(4-chloropyridinyl))aniline,
3,4-Mediformatica-N-(3-carboxyphenyl)-N-(4-(3,5-dichloropyridine))aniline,
3 Cyclopentyloxy-4-methoxy-N-cyclohexylaniline,
3 Cyclopentyloxy-4-hydroxy-N-(3-tert-butyloxycarbonyl)-N-(3-pyridylmethyl)aniline,
3 Cyclopentyloxy-4-hydroxy-N-(3-carboxyphenyl)-N-(3-pyridylmethyl)-aniline,
3 Cyclopentyloxy-4-methoxy-N-(3-tert-butyloxycarbonyl)-N-(3-pyridylmethyl)aniline,
4-Methoxy-3-(R)-tetrahydropyranyloxy-N-(3-carboxy-4-chlorophenyl)-N-(3-pyridylmethyl)aniline,
3 Cyclopentyloxy-4-methoxy-N-(3-carboxyphenyl)-N-(4-(3-chloropyridine))aniline,
3 Cyclopentyloxy-4-methoxy-N-phenyl-N-(4-(3-chloropyridine))-aniline,
4-Methoxy-3-(R)-tetrahydropyranyloxy-N-(3-carboxyphenyl)-N-(4-pyridylmethyl)aniline,
4-Methoxy-3-(R)-tetrahydropyranyloxy-N-(3-pyridyl)-N-(4-pyridylmethyl)aniline,
3 Cyclopentyloxy-4-methoxy-N-(4-carboxyphenyl)-N-(4-pyridylmethyl)-aniline,
3 Cyclopentyloxy-4-methoxy-N-(4-carboxy-3-chlorophenyl)-N-(3-pyridylmethyl)aniline,
3 Cyclopentyloxy-4-methoxy-N-(4-carboxy-3-were)-N-(3-pyridylmethyl)aniline,
3 Cyclopentyloxy-4-methoxy-N-(4-carboxy-3-forfinal)-N-(3-pyridylmethyl)aniline,
3 Cyclopentyloxy-4-methoxy-N-(3-carboxy-4-chlorophenyl)-N-(3-pyridylmethyl))aniline,
3 Cyclopentyloxy-4-methoxy-N-(3-carboxy-4-forfinal)-N-(3-pyridylmethyl)aniline,
3 Cyclopen is yloxy-4-methoxy-N-(3-carboxyphenyl)-N-(4-(3,5-dichloropyridine))aniline,
3 Cyclopentyloxy-4-methoxy-N-(4-carboxyphenyl)-N-(4-(3,5-dichloropyridine))aniline,
3 Cyclopentyloxy-4-methoxy-N-(4-carboxyphenyl)-N-(4-(3-chloropyridine))aniline,
4-Methoxy-3-(R)-tetrahydropyranyloxy-N-(4-carboxyphenyl)-N-(4-(3,5-dichloropyridine))aniline,
4-Methoxy-3-(R)-tetrahydropyranyloxy-N-(3-carboxyphenyl)-N-(4-(3,5-dichloropyridine))aniline,
3 Cyclopentyloxy-4-methoxy-N-(3-carboxy-4-methoxyphenyl)-N-(3-pyridylmethyl)aniline,
3 Cyclopentyloxy-4-methoxy-N-(3-carboxy-4-were)-N-(3-pyridylmethyl)aniline,
3 Cyclopentyloxy-4-methoxy-N-(4-amino-3-carboxyphenyl)-N-(3-pyridylmethyl)aniline,
3 Cyclopentyloxy-4-methoxy-N-(3-carboxy-4-triptoreline)-N-(3-pyridylmethyl)aniline,
3 Cyclopentyloxy-4-methoxy-N-(4-acetamido-3-carboxyphenyl)-N-(3-pyridylmethyl)aniline,
3 Cyclopentyloxy-4-methoxy-N-(4-(N,N-bis-(2,4-dimethoxy)benzyl)-aminosulphonylphenyl)-N-(3-pyridylmethyl)aniline,
Methyl-N-(3-cyclopentyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-aminobenzoate,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-bromaniline,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(N-piperidinyl)aniline,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(N-morpholinomethyl)aniline,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(N,N-diethylamino)methyl)aniline,
N-(4-Methoxy-3-(3R)-tetrahydrofur nisoxetine)-N-(3-pyridylmethyl)-5-methylthioinosine,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-methylthioinosine,
N-(3-(2-(Hydroxy)cyclopentyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-2-aminoisoquinoline acid,
N-(3-Hydroxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(3-(3-(Hydroxy)cyclopentyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-amino-2-chlorbenzene acid,
N-(3,4-Bis-deformational)-N-(3-pyridylmethyl)-4-aminobenzoic acid,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-3-amino-6-methylbenzoic acid,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-aminobenzoic acid,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(5-fluoro-3-pyridylmethyl)-4-aminobenzoic acid,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(5-(1,3-dimethylpyrazole)-3-aminobenzoic acid,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-5-trifluoromethyl-3-aminobenzoic acid,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-6-trifluoromethyl-3-aminobenzoic acid,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-aminobenzoic acid,
N-(3-Cyclopentyloxy-4-methoxide who yl)-N-(5-fluoro-3-pyridylmethyl)-3-aminobenzoic acid,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(5-fluoro-3-pyridylmethyl)-4-aminobenzoic acid,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(3-CYCLOBUTANE-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(3-Cyclohexyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(3-Cyclohexyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(4-Methoxy-3-(4-pyranyloxy)phenyl)-N-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(3-[2,2,2-Bicycloalkyl]hydroxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(2,6-diferensial)-3-aminobenzoic acid,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(4-(3,5-dimethylisoxazole))-3-aminobenzoic acid,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-amino-5-Formentera acid,
N-(3-Cyclopentyloxy-4-deformational)-N-(3-pyridylmethyl)-3-amino-5-Formentera acid,
N-(3,4-Bis-deformational)-N-(3-pyridylmethyl)-3-amino-5-Formentera acid,
N-(3-CYCLOBUTANE-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-aminobenzoic acid,
N-(3-Cyclohexyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-aminobenzoic acid,
N-(4-Methoxy-3-(2-(2-pyridylacetic))phenyl)-N-(3-pyridylmethyl)-4-aminobenzoic acid,
N-(3,4-Acid)-N-(3-pyridylmethyl)-4-aminobenzoic Ki the lot,
N-(3-Ethoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-aminobenzoic acid,
N-(3-Isopropoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-aminobenzoic acid,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(2-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-3-chloro-4-(5-(2H)-tetrazolyl)aniline,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-chloro-4-(5-tetrazolyl)aniline,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(4-(3,5-dichloropyridine)methyl)-4-(5-(2H)-tetrazolyl)aniline,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(4-(2H)-morpholinyl)aniline,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(4-N-methyl-1-piperazinil)aniline,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(1-piperazinil)aniline,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(N,N-diethylamino)aniline,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-methanesulfonanilide,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-3-methanesulfonanilide,
N-(3-Cyclopropylmethoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-aminobenzoic acid,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(5-chloro-3-pyridylmethyl)-3-aminobenzoic acid,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-terbisil)-4-aminobenzoic acid,
N-(3-Qi is opentrace-4-deformational)-N-(3-pyridylmethyl)-4-aminobenzoic acid,
N-(3,4-Acid)-N-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(3-Ethoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(4-Methoxy-3-(1-propyl)oxyphenyl)-N-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(4-Methoxy-3-(2-propyl)oxyphenyl)-N-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(3-Cyclopropylmethoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(3-Cyclobutylmethyl-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-aminobenzoic acid,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-3-hydroxymethylbilane,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-hydroxymethylbilane,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(4-piperidinyl)sulfanilamide,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-methylsulfonylmethane,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-(2-were)sulfonylacetonitrile,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-vinylsulfonylacetamido,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-vinylsulfonylacetamido,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-methylsulfonylbenzoyl,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(4-forfinal)sulfonylacetonitrile,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(4-(3,5-dichloro-pyridylmethyl)-4-methylsulfonylbenzoyl,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-metilsulfonilmetane,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(2-forfinal)sulfonylacetonitrile,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(4-methoxyphenyl)sulfonylacetonitrile,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(3-chlorophenyl)sulfonylacetonitrile,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-methylsulfonylbenzoyl,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-vinylsulfonylacetamido,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-vinylsulfonylacetamido,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(5-fluoro-3-pyridylmethyl)-3-(4-forfinal)sulfonylacetonitrile,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-3-methylsulfonylmethane,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-3-vinylsulfonylacetamido,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(3-chlorophenyl)sulfonylacetonitrile,
N-(4-Deform the toxi-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(2-forfinal)sulfonylacetonitrile,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(2,4-differenl)sulfonylacetonitrile,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(3,4-differenl)sulfonylacetonitrile,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(1,1-dimethylethyl)sulfonylacetonitrile,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(5-chloro-2-thienyl)sulfonylacetonitrile,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(3-thienyl)sulfonylacetonitrile,
N-(3,4-Mediformatica-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(4-forfinal)sulfonylacetonitrile,
N-(3,4-Mediformatica-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(3-forfinal)sulfonylacetonitrile,
N-(3,4-Mediformatica-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(3-chlorophenyl)sulfonylacetonitrile,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(3-cyanophenyl)sulfonylacetonitrile,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(4-forfinal)sulfonylacetonitrile,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(2-thienyl)-sulfonylacetonitrile,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(3-forfinal)sulfonylacetonitrile,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(3-cyanophenyl)sulfonylacetonitrile,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(2,6-diferensial)-4-(4-forfinal)sulfonylacetonitrile,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(3-forfinal)sulfonylacetonitrile,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(2,4-differenl)sulfonylacetonitrile,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(3,4-differenl)sulfonylacetonitrile,
N-(3-Cyclopropylmethoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(3-chlorophenyl)sulfonylacetonitrile,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-terbisil)-4-(4-forfinal)sulfonylacetonitrile,
N-(3-Cyclopropylmethoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-(4-forfinal)sulfonylacetonitrile,
N-(3-Cyclopropylmethoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-(3-forfinal)sulfonylacetonitrile,
N-(4-Deformedarse-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-metilsulfonilmetane,
N-(3-Cyclopentyloxy-4-deformational)-N-(3-pyridylmethyl)-4-(3-cyanophenyl)sulfonylacetonitrile,
N-(3-Cyclopentyloxy-4-deformational)-N-(3-pyridylmethyl)-4-(4-forfinal)sulfonylacetonitrile,
N-(3-Qi is opentrace-4-deformational)-N-(3-pyridylmethyl)-4-(3-forfinal)sulfonylacetonitrile,
N-(3-Cyclopentyloxy-4-deformational)-N-(3-pyridylmethyl)-4-(3-chlorophenyl)sulfonylacetonitrile,
N-(3-Ethoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-(2,4-differenl)sulfonylacetonitrile,
N-(3,4-Mediformatica-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-methylsulfonylbenzoyl,
N-(3-Cyclopropylmethoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-metilsulfonilmetane,
N-(3-Ethoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-(4-forfinal)sulfonylacetonitrile,
N-(3-Ethoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-(3-chlorophenyl)sulfonylacetonitrile,
N-(3-Ethoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-(3,4-differenl)sulfonylacetonitrile,
N-(3-Ethoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-(2-thienyl)-sulfonylacetonitrile,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-cyclopentanecarbonitrile,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(4-forfinal)carboalumination,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(1-ethyl-5-methylpyrazole-4-yl)carboalumination,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-(4-methylpiperazin-1-yl)sulfanilamide,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-3-(4-morpholinyl)sulfanilamide,
N-(3-Cyclopentyloxy-methoxyphenyl)-N-(3-pyridylmethyl)-4-(4-methylpiperazin-1-yl)sulfanilamide,
N-(3-Cyclopentyloxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-(4-morpholinyl)sulfanilamide,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-3-(4-methylpiperazin-1-yl)sulfanilamide,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(4-methylpiperazin-1-yl)sulfanilamide,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(4-morpholinyl)sulfanilamide,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-3-(4-morpholinyl)sulfanilamide,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(4-ethylpiperazin-1-yl)sulfanilamide,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(4-cyclohexylpiperazine-1-yl)sulfanilamide,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(3,5-dimethylpiperazine-1-yl)sulfanilamide,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(4-(2-pyridyl)piperazine-1-yl)sulfanilamide,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(4-(4-forfinal)piperazine-1-yl)sulfanilamide,
N-(4-Methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-(2,5-dimethylpyrrole-1-yl)sulfanilamide
and their pharmaceutically acceptable salts,
where compounds that are not necessarily optically active, can be in the form of their separated enantiomers or mixtures thereof, including racemeetings.

2. The compound according to claim 1, which is a 3 cyclopentyloxy-4-methoxy-N-(3-tert-butyloxycarbonyl)-N-(3-pyridylmethyl)aniline or its pharmaceutically acceptable salt.

3. The compound according to claim 1, which is N-(3,4-bis-deformational)-N-(3-pyridylmethyl)-4-aminobenzoic acid or its pharmaceutically acceptable salt.

4. The compound according to claim 1, which is N-(4-methoxy-3-(3R)-tetrahydropyranyloxy)-N-(3-pyridylmethyl)-4-aminobenzoic acid or its pharmaceutically acceptable salt.

5. The compound according to claim 1, which is N-(4-methoxy-3-(3R)-tetrahydropyranyloxy)-N-(5-fluoro-3-pyridylmethyl)-4-aminobenzoic acid or its pharmaceutically acceptable salt.

6. The compound according to claim 1, which is N-(3-CYCLOBUTANE-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-aminobenzoic acid or its pharmaceutically acceptable salt.

7. The compound according to claim 1, which is N-(3,4-acid)-N-(3-pyridylmethyl)-4-aminobenzoic acid or its pharmaceutically acceptable salt.

8. The compound according to claim 1, which is N-(3-ethoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-aminobenzoic acid or its pharmaceutically acceptable salt.

9. The compound according to claim 1, which is N-(3-isopropoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-aminobenzoic acid or its farmacevtichesky acceptable salt.

10. The compound according to claim 1, which is N-(3-cyclopropylmethoxy-4-methoxyphenyl)-N-(3-pyridylmethyl)-4-aminobenzoic acid or its pharmaceutically acceptable salt.

11. The compound according to claim 1, which is N-(4-methoxy-3-(3R)-tetrahydropyranyloxy)-N-(5-chloro-3-pyridylmethyl)-3-aminobenzoic acid or its pharmaceutically acceptable salt.

12. The compound according to claim 1, which is N-(3,4-acid)-N-(3-pyridylmethyl)-3-aminobenzoic acid or its pharmaceutically acceptable salt.

13. A method of inhibiting the activity of PDE4 enzyme, comprising introducing an effective amount of a compound according to any one of claims 1 to 12.

14. Pharmaceutical composition having inhibitory activity against PDE4 enzyme, comprising the compound according to any one of claims 1 to 12 and a pharmaceutically acceptable carrier.

15. The composition according to 14, characterized in that it contains from 0.1 to 50 mg of the compounds.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention refers to the new compounds of general formula (II) , whereat values R1, R2, X, R11, R12, R18, R19, m, n are displayed in claim 1 of the formula.

EFFECT: compounds display agonistic and antagonistic activity which allows to propose their usage in pharmaceutical compositions for treatment of diseases and distresses connected with histamine H3 receptor.

38 cl, 80 ex

Cynnamide compound // 2361872

FIELD: chemistry.

SUBSTANCE: invention relates to a compound with formula (I) , where Ar1 is an imidazolyl group, which can be substituted with 1-3 substitutes; Ar2 is a pyridinyl group, pyrimidinyl group or phenyl group, which can be substituted with 1-2 substitutes; X1 is (1) -C≡C- or (2) double bond etc., which can be substituted, R1 and R2 are, for example, C1-6-alkyl group or C3-8-cycloalkyl group, which can be substituted; or to a pharmacologically acceptable salt of the said compound and pharmaceutical drugs for lowering production of Aβ42, containing formula (I) compound as an active ingredient.

EFFECT: wider field of use of the compounds.

26 cl, 1119 ex, 31 tbl

FIELD: chemistry, medicine.

SUBSTANCE: invention refers to the triheterocylic compounds of formula (Ia) and their pharmaceutically acceptable salts used as growth inhibitors of the cancer or tumor cells, to the preparation method and pharmaceutical compositions thereof, to the treatment method used aforesaid compounds as well as to the intermediates of formula (II) the to the method of its preparation. In general formulas (Ia) and

, Q1 is -N(R1)-; Q2 is -C(R3)-; Q3 is -C(R5)-; Q4 is -C(R9)-; R1 is -Ym(Ra), where -Ra is -H, -OH, -C(O)R14, -O-C(O)R14, -C(O)N(R14)2, -C(O)OR14, -OS(O)2ONa-; R2 is -H; R3, R4 and R5 independently are -Ym(Rb), where Rb is -H, halogen, -C1-C8 alkyl, -O-(C1-C8 alkyl) or -OR14, -at condition that if value m of radical Ym(Rb) is equal 0, then R5 is not H; R6 is -H; R7 is -Ym-(RC), where -RC is -O-(C1-C8 alkyl) or -NH(phenyl), R8 is -Ym(Rd), where - Rd is -H, -OH, R9, R10, R11, R12 and R13 independently are -Ym(Re), where Re is -H, halogen, 5-6-membered heterocycle containing 2 heteroatoms selected from N or O, -OR14, or -O-C(O)OR14; every R14 independently is -H, -C1-C8 alkyl, -phenyl, 5-6-membered heterocycle containing one heteroatom being S; every Y independently is -C1-C8 alkylene-; every m independently is equal 0 or 1.

EFFECT: claimed compounds can find application for treatment of different cancer species.

41 cl, 4 tbl, 4 dwg, 8 ex

FIELD: chemistry, medicine.

SUBSTANCE: invention refers to the new substituted dihydroquinazolines of formula (I) and to their pharmaceutically acceptable salts having antiviral properties. In general formula (I) , Ar is phenyl group which can be mono-, di- or trisubstituted. The substituting group are independently selected from the group including C1-6 alkyl-, C1-6 alkoxy-, trifluoromethyl groups and halogen atoms or two substituting groups together with linked carbon atoms form 1,3-dioxolane; R1 is hydrogen atom, amine group, C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkylthiol group, cyanic group, halogen atoms, nitro group or trifluoromethyl group; R2 is hydrogen atom, C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkylthiol group, cyanic group, halogen atoms, nitro group or trifluoromethyl group; R3 is C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkylthiol group, cyanic group, halogen atoms, nitro group or trifluoromethyl group; or one of the radicals R1, R2 and R3 is hydrogen atom and two others together with linked carbon atoms form cyclopentane or cyclohexane ring, R4 is hydrogen atom or C1-6 alkyl group, R5 is hydrogen atom or alkyl group, R6 is carboxyl, aminocarbonyl, alkoxycarbonyl groups, halogen atoms, cyanic or hydroxyl groups, R7 is hydrogen atom or halogen atoms and R8 is hydrogen atom or halogen atoms, its pharmaceutically acceptable salts.

EFFECT: claimed compounds can find application for treatment and prevention of diseases and as antiviral agents.

21 cl, 3 tbl, 201 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new nitroxide compounds with formula I: where one of A, B and D represents N-O and others represent CR6; R1 represents alkyl, containing 1 to 4 carbon atoms, which is branched or straight and which is unsubstituted or substituted once or several times with a halogen; R2 represents alkyl, containing 1 to 12 carbon atoms, which is branched or straight and which is unsubstituted or substituted once or several times with a halogen; cycloalkylalkylk, containing 3 to 10 carbon atoms, which is unsubstituted or substituted once or several times with oxo, aryl, containing 6 to 14 carbon atoms, which is unsubstituted or substituted once or several times with OCF3; or a heterocyclic group, which is saturated, partially saturated or unsaturated, with 5 to 10 atoms in the ring, where at least 1 atom in the ring is an atom of N, O, or S; R3 represents cycloalkyl, containing 3 to 10 carbon atoms, which is unsubstituted once or several times with oxo, aryl, containing from 6 to 14 carbon atoms or which is unsubstituted or substituted once or several times with OCF3; or heteroaryl, with 5 to 10 atoms in the ring, in which at least 1 atom in the ring is a heteroatom; R represents H or alkyl, containing 1 to 4 carbon atoms. The invention also relates to pharmaceutically used salts of these compounds, pharmaceutical compositions containing these compounds, method of inhibiting PDE4 enzyme and to methods treatment using these compounds.

EFFECT: new compounds with useful biological properties.

62 cl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of formula 1: where R1 stands for cycloalkyl containing 3 to 10 carbon atoms, R2 stands for alkyl containing 1 to 4 carbon atoms, R3 stands for pyridylmethyl, R4 stands for phenyl unsubstituted or substituted with carboxy-, cyanogroup or alkoxycarbonyl; or to its pharmaceutically acceptable salts provided the specified compounds is not 4-(2-chlor-4-methoxyphenyl)-5-methyl-2-[N-(1-propylindazole-6-yl)-N-propylamino]thiazole where optically active compound can be in the form of one of its separated enantiomers or their mixtures, including racemic mixtures, or to compounds of formula II: where R3 stands for hydrogen or pyridylmethyl, R4 stands for hydrogen or phenyl unsubstituted or substituted with carboxy-, cyanogroup, alkoxycarbonyl, tetrazole-5-yl or phenylsulphonyl aminocarbonyl; R7 stands for alkoxygroup containing 1 to 4 carbon atoms being branched or nonbranched; R8 stands for -CO-C1-4- alkyl or dioxanyl, and at least one of R3 and R4 is different from hydrogen, or to its pharmaceutically acceptable salts where optically active compound can be in the form of one of its separated enantiomers or their mixtures, including racemic mixtures. Additionally, the invention refers to pharmaceutical enzyme PDE4, based on compounds of formula I and II and to their application for producing medical products for enzyme PDE4 inhibition in treatment of various diseases.

EFFECT: compound improvement.

35 cl, 11 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: new compounds of formula (I) and its pharmaceutically acceptable salts. Offered compounds possess properties of bacterial gyrase and Topo-IV activity inhibitor. In general formula (I) , W is chosen from CH or CF; X represents CH; Z represents O or NH; R1 represents phenyl or 5-6-merous heteroaryl ring containing 1-3 nitrogen atoms where R1 is substituted with 0-3 groups independently chosen from -(T)y-Ar, R', oxo, C(O)R', OR', N(R')2, SR', CN or C(O)N(R')2; R2 is chosen from C1-3alkyl and C3-7-cycloalkyl; and ring A represents 5-6-merous heteroaryl ring containing 1-3 heteroatoms, independently chosen of nitrogen, oxygen or sulphur provided the specified ring has hydrogen bond acceptor in position adjacent to that of joining to B ring where ring A is substituted with 0-3 groups independently chosen from R', oxo, CO2R', OR', N(R')2, halogen, CN, C(O)N(R')2, NR'C(O)R', or NR'SO2R', and where two substitutes in adjacent positions of ring A, together can form 6-merous saturated heterocyclic or heteroaryl ring containing 1-2 nitrogen atoms.

EFFECT: pharmaceutical compositions with properties of bacterial gyrase and Topo-IV activity inhibitor containing disclosed compound as active component, method of gyrase and/or Toro IV-activity inhibition, method of bacteria number reduction.

25 cl, 3 tbl, 4 dwg, 29 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of formula I or its pharmaceutically acceptable salts: , where R1 is phenyl group optionally substituted by substitutes selected out of halogen atom, -O-C1-6-alkyl; or R1 is phenyl condensed with aromatic or non-aromatic 5-7-member ring where the ring can optionally include up to three heteroatoms selected independently out of N, O and S; R2 is hydrogen, -O-C1-6-alkyl, -C1-6-alkyl or halogen atom; R3 is C1-6-alkyl, -(CH2)P-NO2, -(CH2)p-NR4R5, -(CH2)P-CONHOH, -(CH2)p-CN, -(CH2)P-CO2H, -(CH2)p-CO2R4, -(CH2)P-CONR4R5, -(CH2)p-OR4, -(CH2)p-NHCOR4 or -(CH2)p-NHSO2R4; R4 and R5 are independently hydrogen or C1-6-alkyl; p is 0, 1, 2, 3 or 4; X is C1-10-alkylene group; one of A1 and A2 is nitrogen atom, while the other is NR7; and R7 is hydrogen atom or OH-group. Also invention concerns pharmaceutical composition, method of TGF-β and/or activine signal transit route inhibition, method of reduction of excessive exocellular matrix accumulation for mammals, method of tumour cell metastasis inhibition for mammals, method of treatment of cancer neoplasm caused by TGF-β superexpression by TGF-β signal transit route inhibition for mammals, method of disease treatment, and method of thrombosis inhibition for mammals.

EFFECT: new compounds with useful biological properties.

16 cl, 19 ex, 2 tbl, 8 dwg

FIELD: chemistry.

SUBSTANCE: present invention pertains to new macrocyclic compounds with formula (I): (where R3, R6, R7 and R21 can be identical or different from each other, and each of them assume values given in the description), their salts used in pharmacology and their hydrate. Compounds with formula (I) are capable of inhibiting angiogenesis, particularly VEGF production in hypoxic conditions, and can be used as therapeutic means of treating solid malignant tumours. The invention also relates to medicinal agents based on these compounds, prevention and treatment method and use of these compounds in making preparations for preventing and treating cancerous diseases.

EFFECT: obtaining compounds, capable of inhibiting angiogenesis, particularly VEGF production in hypoxic conditions, which can be used as therapeutic means of treating solid malignant tumours.

35 cl, 3 tbl, 147 ex

FIELD: chemistry.

SUBSTANCE: description is given of a piperidine derivative with general formula (I) , where L represents CH or N; M represents CH or N; under the condition that, L and M both do not represent CH; R1 represents phenyl (possibly substituted with a halogen or C1-4alkyl), S(O)2(C1-4alkyl), S(O)2(C1-4fluroalkyl), S(O)2phenyl (possibly substituted with CF3 or OCF3), benzyl, benzoyl (possibly substituted with a halogen) or C(O)NHphenyl (possibly substituted with a halogen); R2 represents phenyl, possibly substituted with a halogen; R3 represents hydrogen or C1-4alkyl; R4 represents methyl or ethyl; R5 represents phenyl-NH, phenyl (C1-2alkyl), phenyl(C1-C2)alkyl-NH or pyridyl(C1-2alkyl). The phenyl can be substituted with a halogen, cyano, C1-4alkyl, C1-4alkoxy, S(O)k(C1-4alkyl) or S(O)2NR8R9; k is equal to 2; R8 and R9 represent hydrogen or its pharmaceutical salts. The compound is a modulator of the activity of the CCR5 receptor. Description is given of the method of obtaining the compound, where L represents N, and the pharmaceutical composition based on a compound with formula (I).

EFFECT: design of a method of obtaining a compound, where L represents N, and a pharmaceutical composition based a compound with formula (I).

7 cl, 7 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: in formula (1) compound, cysteinprotease is cathepsin K, cathepsin S, cathepsin L or cathepsin B. In formula (I) R is , AA1 is a bond, AA2 is a bond, R7 and R8 each independently represents hydrogen, C1-8 alkyl, CycA or C1-8 alkyl, substituted CycA, R9 is hydrogen, values of the rest of the radicals are given in the formula of invention. The invention also relates to a pharmaceutical composition, containing a formula (I) compound as an active ingredient, to a cysteinprotease inhibitor, method of inhibiting cysteinprotease, use of formula (I) compound in obtaining cysteinprotease inhibitor.

EFFECT: compound has inhibitory activity towards cysteinprotease.

10 cl, 16 tbl, 8 dwg, 224 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to the new compounds of formula (I): whereat R1 is -SO2NR102R103, -NR101SO2R104 or -COOR105 whereat R101 is hydrogen atom, R102 and R103 each independently represents hydrogen atom or C1-4 alkyl, R104 is C1-4 alkyl and R105 is hydrogen atom or C1-4 alkyl ; X is bond, -CH2- or -O-; Y is -CH2-; ring A and ring B, which are same or different, each independently is benzene, pyridine, pyrazol or piperidine which can have the following substituents: C1-4 alkyl or halogen; ring D is piperidine; R2 is whereat the arrow shows the position of the bond with the ring D; R51 is (1) hydrogen atom a, (2) C1-6alkyl, which can have the following substituents: (a) hydroxy, (b) methoxy, (c) cyano, (d) carboxy, (e) halogen, (f) methyl sulphonylamino, (g) C3-8cycloalkyl or phenyl, which can have the following substituents: methyl, halogen, hydroxy or methoxy, (h) thienyl, pyrazolyl, tetrahydropyranyl, thiazolyl, isooxalyl, imidazolyl, tetraazolyl, pyridyl, pyrimidinyl which can have the following substituents: methyl, trifluoromethyl or hydroxy, (3) C2-10alkenyl, (4) C2-10alkynyl, (5) phenyl which can have the following substituents: C1-4alkyl or halogen, or (6) pyridine or tetrahydropyran; R52 is (1) hydrogen atom a, (2) C1-6alkyl which can have the following substituents: (a) hydroxy, (b) methoxy, (c) carboxy, (d) C3-8cycloalkyl, (e) phenyl or (f) oxo, (3) C3-8cycloalkyl or phenyl which can have the following substituents: C1-4alkyl, hydroxy, cyano, oxo, carbamoyl, N-methyl aminocarbonyl, carboxy, halogen, methoxy, trifluoromethoxy, methythio, methylsulphonyl, acetylamino, dimethylamino, acetyl, tetraazolyl, trifluoromethyl or methylsulphonylamino (4) C3-10cycloalkenyl, (5) adamantyl, (6) thienyl, pyrazolyl, tetrahydropyranyl, isoxaazolyl, isothiazolyl, thiadiazolyl, piperidinyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, indolyl, benzothiazolyl, benzoisothiazolyl, benzotriazolyl, dioxaindanyl, benzodioxaindanyl which can have the following substituents: C1-4alkyl, hydroxy, oxo, halogen, azido or trifluoromethyl or (7) benzyloxy groups; and R53 is hydrogen atom or C1-6alkyl; to its salts or its solvates. The invention refers also to the regulator CCR5, to the agent of prevention and/or treatment of HIV infection, immunological or inflammatory diseases, to the pharmaceutical composition, to the medicinal preparation, to the method of disease treatment or prevention as well as to the application of compound as in claim 1.

EFFECT: obtaining of new bioactive compounds possessing anti CCR5 receptor activity.

23 cl, 41 ex

FIELD: chemistry.

SUBSTANCE: invention refers to the new compounds of general formula (II) , whereat values R1, R2, X, R11, R12, R18, R19, m, n are displayed in claim 1 of the formula.

EFFECT: compounds display agonistic and antagonistic activity which allows to propose their usage in pharmaceutical compositions for treatment of diseases and distresses connected with histamine H3 receptor.

38 cl, 80 ex

Cynnamide compound // 2361872

FIELD: chemistry.

SUBSTANCE: invention relates to a compound with formula (I) , where Ar1 is an imidazolyl group, which can be substituted with 1-3 substitutes; Ar2 is a pyridinyl group, pyrimidinyl group or phenyl group, which can be substituted with 1-2 substitutes; X1 is (1) -C≡C- or (2) double bond etc., which can be substituted, R1 and R2 are, for example, C1-6-alkyl group or C3-8-cycloalkyl group, which can be substituted; or to a pharmacologically acceptable salt of the said compound and pharmaceutical drugs for lowering production of Aβ42, containing formula (I) compound as an active ingredient.

EFFECT: wider field of use of the compounds.

26 cl, 1119 ex, 31 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to new coumarin derivatives and their carboxamides, with general formula (I) , where R3 is chosen from a group consisting of H, carboxyl, alkyloxycarbonyl, 5'-(phenyloxadiazol-2')-yl, 5'-(pyridyl-4"-oxadiazol-2')-yl, , CONHR9, where R9 is chosen from a group consisting of fatty acids C2-C8, benzoxamido, isonicotinamido, unsubstituted, or mono-, or polysubstituted phenyl, in which the substitute can be hydroxy, C1-C8-alkoxy, CF3, carboxyl, alkyloxycarbonyl, OCH2CO2H, NO2, halogen, SO3H, SO2NHR11, where R11 is chosen from a group consisting of hydrogen, amidino, 2"-thizolyl, 3"-(511-methylisooxazolyl), 2"-pyrimidinyl, 2"-(4",6"-dimethylpyrimidinyl), 4"-(5",6"-dimethoxypyrimidinyl); R4 is chosen from a group consisting of hydrogen, CONHR10, where R10 is chosen from a group consisting of C2-C8 fatty acids, unsubstituted phenyl; R5 is chosen from a group consisting of H, C1-C4 alkyl; R6 is chosen from a group consisting of H, C1-C12-alkyl, halogen, NO2, CONHR13, where R13 is substituted phenyl; R7 is chosen from a group consisting of H, hydroxyl, C1-C4alkyl or alkoxyl, carboxyalkyleneoxyl, OCH2CONHR14, where R14 is chosen from a group consisting of unsubstituted, mono-, or polysubstituted phenyl, in which the substitute can be hydroxyl, OCH3, CF3, CO2H, CO2C2H5, NO2; R8 is chosen from a group consisting of H, C1-C4-alkyl or alkoxyl, NO2; under the condition that, when R3, R5 and R6 are H, and R7 is OH, R4 and R7 are not groups, chosen from H, C1-C6-alkyl or C1-C6-alkoxy. The invention also relates to pharmaceutical compositions based on formula I compounds and their use as medicinal preparations for protecting kidneys, for curing hypertonia, cardio-cerebrovascular diseases, non-achrestic diabetes, tumours, precancerous diseases and oedema.

EFFECT: enhanced effectiveness of the composition and treatment method.

17 cl, 6 tbl, 51 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new pyrimidine derivatives with general formula (I), their tautomeric or stereoisomeric form, in free form, in form of pharmaceutically acceptable salt or C1-6alkyl ester which are effective antagonists of CRTH2 (G-protein-associated chemoattractant receptor, ex prone on Th2 cells) and can be used for preventing and treating diseases related to CRTH2 activity, particularly in treatment of allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, diseases related to eosinophil. In formula (I) R1 is hydrogen, or in which n is an integer from 0 to 6; -Q1- is -NH-, -N(C1-6alkyl)- or -O; Y is hydrogen, C1-6alkyl, C3-6cycloalkyl, optionally substituted with C1-6alkyl, C3-6cycloalkyl, condensed with a benzene ring, phenyl, naphthyl or 5-6-member heteroaryl, possibly condensed with a benzene ring, and containing at least one heteroatom, chosen from a group consisting of oxygen and nitrogen, where the said phenyl, naphthyl or heteroaryl are optionally substituted on the displaceable position with one or several substitutes, chosen from a group consisting of cyano, halogen, nitro, guanidine, pyrroyl, sulfamoyl, phenyloxy, phenyl, di(C1-6)alkylamino, C1-6alkanoylamino, C1-6alkyl, optionally mono-, di- or tri-substituted with halogen, C1-6alkoxy, optionally mono-, di- or tri-substituted with halogen and C1-6alkylthio, optionally mono-, di- or tri-substituted with halogen; or phenyl, condensed with 1,3-dioxolane; R2 is hydrogen or C1-6alkyl; R3 is a halogen, C1-6alkoxy, optionally mono-, di- or tri-substituted with halogen, or , R3a and R3b are independently C3-8cycloalkyl or C1-6alkyl, this C1-6alkyl is optionally substituted with hydroxyl, carboxy, C3-6cycloalkylcarbamoyl, C5-6heterocyclocarbonyl containing a heteroatom in form of nitrogen, or C1-6alkoxy, q is an integer from 1 to 3; R3c is hydrogen, hydroxyl or carboxy; Xa is -O-; R4 is hydrogen, halogen, di(C1-6alkyl) amino or C1-6alkyl, optionally substituted C1-6alkoxy or mono- , di- or tri-substituted with halogen; R5 is hydrogen or C1-6alkyl; and R6 is carboxy, carboxamide, nitrile or tetrazolyl.

EFFECT: wider field of use of compounds.

32 cl, 9 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention is related to the compound of general formula 1 or its tautomer or pharmaceutically acceptable salt, where W selected from N and CR4; X is selected from CH(R8), O, S, N(R8), C(=O), C(=O)O, C(=O)N(R8), OC(=O), N(R8)C(=O), C(R8)-CH and C(=R8); G1 - bicyclic or tricyclic condensed derivative of azepin, selected from general formulas 2-9 , or derivative of aniline of common formula 10 , where A1, A4, A7 and A10 are independently selected from CH2, C=O, O and NR10; A2, A3, A9, A11, A13, A14, A15, A19 and A20 are independently selected from CH and N; or A5 stands for covalent connection, and A6 represents S; or A5 stands for N=CH, and A6 represents covalent connection; A8 , A12 , A18 and A21 are independently selected from CH=CH, NH, NCH3 and S; A16 and A17 both represent CH2, or one from A16 and A17 represents CH2, and the one another is selected from C=O, CH(OH), CF2, O, SOc and NR10; Y is selected from CH=CH or S; R1 and R2 are independently selected from H, F, Cl, Br, alkyl, CF3 and group O-alkyl; R3 is selected from H and alkyl; R4-R7 are independently selected from H, F, Cl, Br, alkyl, CF3, OH and group O-alkyl; R8 is selected from H, (CH2)bR9 and (C=O)(CH2)bR9; R9 is selected from H, alkyl, possibly substituted aryl, possibly substituted heteroaryl, OH, groups O-alkyl, OC(=O)alkyl, NH2, NHalkyl, N(alkyl)2, CHO, CO2H, CO2alkyl, CONH2, CONHalkyl, CON(alkyl)2 and CN; R10 is selected from H, alkyl, group COalkyl and (CH2)dOH; R11 is selected from alkyl, (CH2)dAr, (CH2)dOH, (CH2)dNH2, group (CH2)aCOOalkyl, (CH2)dCOOH and (CH2)dOAr; R12 and R13 are independently selected from H, alkyl, F, CI, Br, CH(OCH3)2, CHF2, CF3, groups COOalkyl, CONHalkyl, (CH2)dNHCH2Ar, CON(alkyl)2, CHO, COOH, (CH2)dOH, (CH2)dNH2, N(alkyl)2, CONH(CH2)dAr and Ar; Ar is selected from possibly substituted heterocycles or possibly substituted phenyl; a is selected from 1, 2 and 3; b is selected from 1, 2, 3 and 4; c is selected from 0, 1 and 2; and d is selected from 0, 1, 2 and 3. Besides, the invention is related to pharmaceutical compound and to method for activation of vasopressin receptors of type 2.

EFFECT: compounds according to invention represent agonists of receptor of vasopressin V2, which stipulates for their application (another object of invention) for preparation of medicine for treatment of condition selected from polyuria, including polyuria, which is due to central diabetes insipidus, nocturnal enuresis of nocturnal polyurea, for control of enuresis, to postpone bladder emptying and for treatment of disorders related to bleeds.

21 cl, 228 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new nitroxide compounds with formula I: where one of A, B and D represents N-O and others represent CR6; R1 represents alkyl, containing 1 to 4 carbon atoms, which is branched or straight and which is unsubstituted or substituted once or several times with a halogen; R2 represents alkyl, containing 1 to 12 carbon atoms, which is branched or straight and which is unsubstituted or substituted once or several times with a halogen; cycloalkylalkylk, containing 3 to 10 carbon atoms, which is unsubstituted or substituted once or several times with oxo, aryl, containing 6 to 14 carbon atoms, which is unsubstituted or substituted once or several times with OCF3; or a heterocyclic group, which is saturated, partially saturated or unsaturated, with 5 to 10 atoms in the ring, where at least 1 atom in the ring is an atom of N, O, or S; R3 represents cycloalkyl, containing 3 to 10 carbon atoms, which is unsubstituted once or several times with oxo, aryl, containing from 6 to 14 carbon atoms or which is unsubstituted or substituted once or several times with OCF3; or heteroaryl, with 5 to 10 atoms in the ring, in which at least 1 atom in the ring is a heteroatom; R represents H or alkyl, containing 1 to 4 carbon atoms. The invention also relates to pharmaceutically used salts of these compounds, pharmaceutical compositions containing these compounds, method of inhibiting PDE4 enzyme and to methods treatment using these compounds.

EFFECT: new compounds with useful biological properties.

62 cl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention concerns novel amidomethyl-substituted derivatives of 2-(4-sulfonylamino)-3-hydroxy3,4-dihydro-2N-chromen-6-yl of the general formula (I) where R1 is C1-C4alkyl, R2 is C1-C4alkyl, R3 is phenyl optionally once or twice substituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy group or trifluoromethyl, naphthyl or biphenyl, R4 is hydrogen, C1-C6alkyl or C3-C7cycloalkyl-C1-C4alkyl, R5 is hydrogen, and R6 is C1-C6 alkyl, phenyl-C1-C4alkyl, phenyl group optionally substituted by halogen, furyl-C1-C4alkyl or tetrahydronaphthyl, or R5 and R6 together with nitrogen atom linking them form piperazine ring optionally substituted by phenyl.

EFFECT: also invention claims method of obtaining claimed compounds, and intermediary products used in method implementation, as well as medicines containing compounds of the formula (I) with antiarrhythmic effect, and application of these medicines.

11 cl, 6 tbl, 6 ex

FIELD: chemistry.

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

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

16 cl, 433 ex, 6 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds with general formula I, in which R1 represents hydrogen or a group, which forms a biologically labile ester, R2 represents hydrogen, C1-C4-alkyl or C1-C4-hydroxyalkyl, and R3 represents C1-C4-alkyl; C1-C4-alkoxy-C1-C4-alkyl; C1-C4-hydroxyalkyl, which is optionally substituted with a second hydroxy group and all hydroxy groups of which are optionally esterified with C2-C4-alkanoyl or amino-acid residue; (C0-C4-alkyl)2amino-C1-C6-alkyl; C3-C7-cycloalkyl; C3-C7-cycloalkyl-C1-C4-alkyl; phenyl-C1-C4-alkyl, the phenyl group of which is optionally substituted 1-2 times with C1-C4-alkyl, C1-C4-alkoxy group and/or halogen; naphthyl-C1-C4-alkyl; C3-C6-oxoalkyl; phenylcarbonylmethyl, the phenyl group of which is optionally substituted 1-2 times with C1-C4-alkyl, C1-C4-alkoxy group and/or halogen, or 2-oxoazepanyl, or R2 and R3 together represent C4-C7-alkylene, methylene groups of which are optionally substituted 1-2 times with carbonyl, nitrogen, oxygen and/or sulphur and/or optionally substituted once with a hydroxy group, which is optionally esterified with C2-C4-alkanoyl or amino-acid residue; C1-C4-alkyl; C1-C4-hydroxyalkyl, the hydroxy group of which is optionally esterified with C2-C4-alkanoyl or amino-acid residue; phenyl or benzyl, and R4 represents hydrogen or a group, which forms a biologically labile ester, where R1 and R4 groups are independently chosen from C1-C4-alkyl; C1-C4-alkoxy-C1-C4-alkoxy-C1-C4-alkyl; C3-C7-cycloalkyl; C3-C7-cycloalkyl-C1-C4-alkyl; N,N-di-(C0-C4-alkyl)amino-C1-C6-alkyl; phenyl or phenyl-C1-C4-alkyl, optionally substituted 1 or 2 times in the phenyl ring with halogen, C1-C4-alkyl or C1-C4-alkoxy group or C1-C4-alkylene chain, bonded with two neighbouring carbon atoms; dioxolanylmethyl, optionally substituted in the dioxolane ring with C1-C4-alkyl; C1-C6-alkanoyloxy-C1-C4-alkyl, optionally substituted in the oxy-C1-C4-alkyl group with C1-C4-alkyl; 1-[[(C1-C4-alkyl)carbonyl]oxy]C1-C4-alkyl esters; 1-[[(C4-C7 cycloalkyloxy)carbonyl]oxy]C1-C4-alkyl esters, 2-oxo-1,3-dioxolan-4-yl-C1-C4-alkyl esters, which optionally contain a double bond in the dioxolane ring; 2-oxo-1,3-dioxolan-4-ylmethyl; and to physiologically compatible salts of acids with formula I and/or to physiologically compatible acid-additive salts of formula I compounds. The invention also relates to a pharmaceutical composition, to use of formula I compounds in paragraph 1, to a method of obtaining formula I compounds, as well as to compounds with general formula II.

EFFECT: obtaining new biologically active compounds, with inhibitory activity towards neutral endopeptidase, endothelin converting enzyme and soluble human endopeptidase.

20 cl, 80 ex, 9 tbl

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