Diketohydrazine derivatives, pharmaceutical composition containing such derivatives as active ingredient, and their use

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

 

The text descriptions are presented in facsimile form.

1. The compound of formula (I)

in which R represents a

where R16represents (1) C1-8 alkyl, (2) C2-8 alkenyl or (4) Sousa,
Sousse is a cyclopropane, CYCLOBUTANE, cyclopentane cyclohexane, Cycloheptane, benzene, piperidine or tetrahydropyran;
AA1represents (1) communications
AA2represents (1) communications
R7and R8each independently represents (1) hydrogen, (2) C1-8 alkyl, (3) Sousa or (4) C1-8 alkyl, substituted Sousa,
R9represents hydrogen,
group

represents a group selected from the group (1) or group (2):

[where RA1and RA2each independently represents (i) hydrogen, (ii) C1-8 alkyl, (iii) C2-8 alkenyl or (viii) of the CycP;
SSR represents a benzene, pyridine, furan or tetrahydropyran, and
R10denotes hydrogen, or
RA1and RA2together with the neighboring carbon atom to designate SSN

(where SSN means
,,,,,
and R10denotes hydrogen)],

[where RA3and RA4together with the neighboring carbon atoms and nitrogen to represent a group

(where Succ means
,,,,
and R10denotes hydrogen),
Sousa, SSN, Suck and SSR may be each independently substituted by 1-5 R27,
R27represents (1) C1-8 alkyl, (2) halogen, (4) -OR13, (6) CycG, (9) oxo, (10) -COR14, (11) -SO2R14or (15) C1-8 alkyl substituted by 1-5 groups selected from (i) halogen or (iii) OR13where R13represents hydrogen or C1-4 alkyl,
CycG is a benzene,
R14represents a C1-8 alkyl or-OR13],
or its pharmaceutically acceptable salt.

2. The compound according to claim 1, where
represents
(where all the symbols have the meanings indicated in claim 1 or its pharmaceutically acceptable salt.

3. The compound according to claim 1 where in the compound of formula (I)
represents
(where all the symbols have the meanings indicated in claim 1 or its pharmaceutically acceptable salt.

4. The pharmaceutical composition inhibiting cysteinate comprising the compound of formula (I) or its pharmaceutically acceptable salt described in claim 1, as active ingredient together with an inert diluent, where cysteinate represents cathepsin K, cathepsin S, cathepsin L or cathepsin Century

5. The inhibitor cysteinate comprising the compound of formula (I) or its pharmaceutical is Eski acceptable salt, described in claim 1, as active ingredient together with an inert diluent, where cysteinate represents cathepsin K, cathepsin S, cathepsin L or cathepsin Century

6. The inhibitor according to claim 5, where cysteinate represents cathepsin K.

7. Method of inhibiting cysteinate in a mammal, wherein the mammal is administered an effective amount of the compounds of formula (I) or its pharmaceutically acceptable salt according to claim 1, where cysteinate represents cathepsin K, cathepsin S, cathepsin L or cathepsin Century

8. The use of compound or its pharmaceutically acceptable salt according to claim 1 for obtaining inhibitor cysteinate where cysteinate represents cathepsin K, cathepsin S, cathepsin L or cathepsin Century

9. The compound according to claim 1, which represents the
hydrochloride N'-(3-tert-butyl-1,3-thiazolidin-2-ilidene)[3 cyclohexylcarbodiimide-2-oxo-3-(tetrahydropyran-4-yl)propionitrile],
N-((1S)-3-methyl-1-{oxo[(2Z)-2-(3-phenyl-1,3-thiazolidin-2-ilidene)hydrazino]acetyl}butyl)cyclohexanecarboxylic,
the hydrochloride of N-{1-[1-(2,2-dimethylpropanoyl)piperidine-4-yl]-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
the dihydrochloride of N'-(1,3-dimethylimidazolidin-2-ilidene)-3-cyclohexyl-3-cyclohexylcarbodiimide-2-oxopropylidene,
hydrochloride N'-(1-methylpyrrolidine-2-ilidene)(cyclohexylcarbodiimide-5-methyl-2-oxohexanoate),
N-{1-isopropyl-3-[(3-methyl-2-Oxymetazoline-1-yl)amino]-2,3-disopropyl}cyclohexanecarboxylic,
N-{1-isopropyl-2,3-dioxo-3-[(2-oxo-1,3-oxazolidin-3-yl)amino]propyl}cyclohexanecarboxylic,
N-{3,3-dimethyl-1-[[(3-methyl-2-Oxymetazoline-1-yl)amino](oxo)acetyl]butyl}cyclohexanecarboxylic,
N-{3-methyl-1-[[(3-methyl-2-Oxymetazoline-1-yl)amino](oxo)acetyl]butyl}cyclohexanecarboxylic,
N-(3,3-dimethyl-1-{oxo[(2-oxopyrrolidin-1-yl)acetyl]butyl}cyclohexenecarboxylic,
N-{2,3-dioxo-3-[(2-oxopyrrolidin-1-yl)amino]-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexanecarboxylic,
the hydrochloride of N-{1-cyclohexyl-3-[(2E)-2-(1-methylpyrrolidine-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
N-{1-cyclohexyl-3-[(3-methyl-2-Oxymetazoline-1-yl)amino]-2,3-disopropyl}cyclohexenecarboxylic,
N-{3-[(3-methyl-2-Oxymetazoline-1-yl)amino]-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexanecarboxylic,
N-{3-[(3-benzyl-2-Oxymetazoline-1-yl)amino]-1-cyclohexyl-2,3-disopropyl}cyclohexenecarboxylic,
N-{3-[(3-benzyl-2-Oxymetazoline-1-yl)amino]-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexanecarboxylic,
N'-benzylidene[(3S)-3-cyclohexylcarbodiimide-5-methyl-2-oxohexanoate],
N-{(1S)-3-methyl-1-[[2-(1-methylethylidene)hydrazino](oxo)acetyl]butyl}cyclohexanecarboxylic,
N-((1S)-3-methyl-1-{oxo[(2E)-2-(1-fenretinide)hydrazino]acetyl}is util)cyclohexanecarboxylic,
the hydrochloride of N-(3-methyl-1-{oxo[(2E)-2-(pyridine-2-ylmethylene)hydrazine]acetyl}butyl)cyclohexanecarboxylic,
N-{(1S)-1-[[(2E)-2-(3-furylmethyl)hydrazino](oxo)acetyl]-3-methylbutyl}cyclohexanecarboxylic,
N-{(1S)-3-methyl-1-[[(2E)-2-(3-methylbutyrate)hydrazino](oxo)acetyl]butyl}cyclohexanecarboxylic,
N-((1S)-3-methyl-1-{oxo[(2E)-2-(tortugero-2H-Piran-4-ylmethylene)hydrazine]acetyl}butyl)cyclohexanecarboxylic,
N-((1S)-3-methyl-1-[oxo(2-(tortugero-2H-Piran-4-eldererotica)acetyl]butyl)cyclohexanecarboxylic,
the hydrochloride of N-(3,3-dimethyl-1-{oxo[(2E)-2-(1-pyridin-2-iletiler)hydrazino]acetyl)butyl)cyclohexanecarboxylic,
the hydrochloride of N-(3,3-dimethyl-1-{oxo[(2E)-2-(1-pyridine-4-iletiler)hydrazino]acetyl}butyl)cyclohexanecarboxylic,
N-{3,3-dimethyl-1-[oxo((2E)-2-{1-[3-(trifluoromethyl)phenyl]ethylidene}hydrazino)acetyl]butyl}cyclohexanecarboxylic,
N-{3,3-dimethyl-1-[oxo((2E)-2-{1-[4-(trifluoromethyl)phenyl]ethylidene}hydrazino)acetyl]butyl}cyclohexanecarboxylic,
1-(3-cyclohexylcarbodiimide-5,5-dimethyl-2-oxohexanoate)-2,5-dioxopiperidin,
N-{3-[(2,5-dioxopiperidin-1-yl)amino]-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexanecarboxylic,
N-{1-cyclohexyl-3-[(2,5-dioxopiperidin-1-yl)amino]-2,3-disopropyl}cyclohexanecarboxylic,
N-{3-[(2,5-dioxopiperidin-1-yl)amino]-2,3-dioxo-1-phenylpropyl}cyclohexanecarboxylic,
N-{3-{(4,4-dimethyl-2,6-voxopop ridin-1-yl)amino]-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexanecarboxylic,
N-{3-[(3,3-dimethyl-2,6-dioxopiperidin-1-yl)amino]-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexanecarboxylic,
N-{1-cyclohexyl-3-[(3,5-dioxaborolan-4-yl)amino]-2,3-disopropyl}cyclohexanecarboxylic,
N-{(1S)-3-[(2,5-dioxopiperidin-1-yl)amino]-1-isopropyl-2,3-disopropyl}cyclohexanecarboxylic,
N-{1-cyclohexyl-3-[(3,3-dimethyl-2,5-dioxopiperidin-1-yl)amino]-2,3-disopropyl}cyclohexanecarboxylic,
N-{1-[[(3,3-dimethyl-2,5-dioxopiperidin-1-yl)amino](oxo)acetyl]-3,3-dimethylbutyl}cyclohexanecarboxylic,
(2E)-N-{1-cyclohexyl-3-[(2,5-dioxopiperidin-1-yl)amino]-2,3-disopropyl}-4,4-dimethylpent-2-UNAMID,
N-{3-[(2,5-dioxopiperidin-1-yl)amino]-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexenecarboxylic,
N-{1-cyclohexyl-3-[(2,5-dioxopiperidin-1-yl)amino]-2,3-disopropyl}cyclohexenecarboxylic,
N-{(1S)-1-cyclohexyl-3-[(2,5-dioxopiperidin-1-yl)amino]-2,3-disopropyl}cyclohexenecarboxylic,
N-{(1R)-1-cyclohexyl-3-[(2,5-dioxopiperidin-1-yl)amino]-2,3-disopropyl}cyclohexenecarboxylic,
N'-(3-methyl-4-oxo-1,3-thiazolidin-2-ilidene)[3 cyclohexylcarbodiimide-3-(tetrahydropyran-4-yl)-2-oxopropylidene],
N-{1-cyclohexyl-3-[(2Z)-2-(3-methyl-4-oxo-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylic,
N-{3-[(2Z)-(3-benzyl-4-oxo-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexanol is the oksamid,
hydrochloride N'-(3-propyl-1,3-thiazolidin-2-ilidene)(3 cyclohexylcarbodiimide-3-(tetrahydropyran-4-yl)-2-oxopropylidene),
the hydrochloride of N-{(1S)-3-methyl-1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]butyl}cyclohexanecarboxylate,
the hydrochloride of 4-bromo-N-{(1S)-3-methyl-1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]butyl}benzamide,
the hydrochloride of N-{(1S)-1-isopropyl-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]2,3-disopropyl}cyclohexanecarboxylate,
the hydrochloride of N-{(1S)-3,3-dimethyl-1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]butyl}cyclohexenecarboxylic,
the hydrochloride of N-{(1S)-2-methyl-1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]butyl}cyclohexanecarboxylate,
the hydrochloride of N-{(1S)-1-benzyl-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
the hydrochloride of N-{(1S)-1-tert-butyl-3-[(2Z]-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
the hydrochloride of N-{(1S)-1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]pentyl}cyclohexanecarboxylate,
the hydrochloride of N-{3,3-dimethyl-1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]butyl}cyclohexanecarboxylate,
the hydrochloride of N-{(1S)-3-methyl-1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]butyl}acetamide,
the hydrochloride of N-{(1S)-3-methyl-1-[[(2Z)-2-(3-methyl-,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]butyl}tetrahydro-2H-Piran-4-carboxamide,
hydrochloride of 2,2-dimethyl-N-{(1S)-3-methyl-1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]butyl}propanamide,
the hydrochloride of N-{(1S)-3-methyl-1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]butyl}benzamide,
the hydrochloride of N-{(1S)-3-methyl-1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]butyl}cyclohexenecarboxylic,
the hydrochloride of N-{(1S)-1-[[(2Z)-2-(3-ethyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]-3-methylbutyl}cyclohexanecarboxylate,
the hydrochloride of N-((1S)-3-methyl-1-{oxo[(2Z)-2-(3-propyl-1,3-thiazolidin-2-ilidene)hydrazino]acetyl}butyl)cyclohexanecarboxylic,
the hydrochloride of N-{3,3-dimethyl-1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]butyl}cyclohexenecarboxylic,
the hydrochloride of N-{(1S)-1-[[(2Z)-2-(3-benzyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]-3-methylbutyl}cyclohexanecarboxylate,
the hydrochloride of N-{(1S)-1-[[(2Z)-2-(3-isopropyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]-3-methylbutyl}cyclohexanecarboxylate,
the hydrochloride of N-{3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexanecarboxylate,
the hydrochloride of N-{1-cyclohexyl-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
hydrochloride (2E)-4,4-dimethyl-N-{(1S)-3-methyl-1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]butyl}Penta-2-enamide,
the hydrochloride of N-{(1S)-1-[{(2Z)--[3-(2-hydroxyethyl)-1,3-thiazolidin-2-ilidene)hydrazino}(oxo)acetyl]-3-methylbutyl}cyclohexanecarboxylate,
the hydrochloride of N-{1-cyclopropyl-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
the hydrochloride of N-{1-cyclopentyl-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
the hydrochloride of N-{1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]-2-propylpentyl}cyclohexanecarboxylate,
the hydrochloride of N-{3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-dioxo-1-phenylpropyl}cyclohexanecarboxylate,
the hydrochloride of N-{3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-dioxo-1-piperidine-4-ylpropyl}cyclohexanecarboxylate,
the hydrochloride of N-{3-[(2Z)-2-(3-benzyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexanecarboxylate,
the hydrochloride of N-{1-(acetylpiperidine-4-yl)-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
the hydrochloride of N-{2-ethyl-1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]butyl}cyclohexanecarboxylate,
hydrochloride tert-butyl ester 4-{1-[(cyclohexylcarbonyl)amino]-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}piperidine-1-carboxylic acid,
N-{3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-dioxo-1-[4-(trifluoromethyl)phenyl]propyl}cyclohexanecarboxylate,
the hydrochloride of N-{1-(4-methoxyphenyl)-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)Hijazi what about]-2,3-disopropyl}cyclohexanecarboxylate,
the hydrochloride of N-{1-[1-(methylsulphonyl)piperidine-4-yl]-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
the hydrochloride of N-{1-(2-were)-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
the hydrochloride of N-{1-(2-chlorophenyl)-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
the hydrochloride of N-{1-(2-methoxyphenyl)-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
the hydrochloride of N-((1S)-3-methyl-1-{oxo[(2Z)-2-(3,5,5-trimethyl-1,3-thiazolidin-2-ilidene)hydrazino]acetyl}butyl)cyclohexanecarboxylic,
the hydrochloride of N-{2,3-dioxo-1-tetrahydro-2H-Piran-4-yl-3-[(2Z)-2-(3,5,5-trimethyl-1,3-thiazolidin-2-ilidene)hydrazino]propyl}cyclohexanecarboxylate,
the hydrochloride of N-{3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexenecarboxylic,
the hydrochloride of N-{(1S)-1-isopropyl-2,3-dioxo-3-[(2Z)-2-(3-propyl-1,3-thiazolidin-2-ilidene)hydrazino]propyl}cyclohexanecarboxylate,
the hydrochloride of N-{(1S)-3-[(2Z)-2-(3-benzyl-1,3-thiazolidin-2-ilidene)hydrazino]-1-isopropyl-2,3-disopropyl}cyclohexanecarboxylate,
the hydrochloride of N-{(1S)-1-cyclohexyl-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
the hydrochloride of N-{3-[(2Z)-2-(3-benzyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-is ioxo-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexenecarboxylic,
hydrochloride (2E)-N-{3-[(2Z)-2-(3-benzyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl}-4,4-dimethylpent-2-enamide,
hydrochloride (2E)-4,4-dimethyl-N-{3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl}Penta-2-enamide,
hydrochloride (2E)-N-{1-cyclohexyl-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}-4,4-dimethylpent-2-enamide,
hydrochloride (2E)-N-(1-cyclohexyl-3-{(2Z)-2-[3-(2-hydroxyethyl)-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-disopropyl)-4,4-dimethylpent-2-enamide,
the hydrochloride of N-(1-cyclohexyl-3-{(2Z)-2-[3-(2-hydroxyethyl)-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-disopropyl)cyclohexanecarboxylate,
the hydrochloride of N-{(1R)-1-cyclohexyl-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
the hydrochloride of N-{1-cyclohexyl-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexenecarboxylic,
the hydrochloride of N-{(1S)-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexenecarboxylic,
the hydrochloride of N-{(1R)-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexenecarboxylic,
the hydrochloride of N-{(1R)-1-isopropyl-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
the hydrochloride of N-{(1R)-1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)g is kasino](oxo)acetyl]pentyl}cyclohexanecarboxylate,
the hydrochloride of N-{(1R)-3,3-dimethyl-1-[[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino](oxo)acetyl]butyl}cyclohexanecarboxylate,
the hydrochloride of N-{(1R)-1-cyclopropyl-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexanecarboxylate,
hydrochloride N'-(3-methyl-1,3-targetrotation-2-ilidene)[3 cyclohexylcarbodiimide-2-oxo-3-(tetrahydropyran-4-yl)exonerated],
hydrochloride N'-(3-methyl-1,3-thiazolidin-2-ilidene)[3 cyclohexylcarbodiimide-3-methyl-2-oxobutanoate],
N'-(3-methyl-1,3-targetrotation-2-ilidene)(3 cyclohexylcarbodiimide-2-oxo-5-methylhexanoate),
hydrochloride N-(3,4,4-trimethyl-1,3-thiazolidin-2-ilidene)[3 cyclohexylcarbodiimide-3-(tetrahydropyran-4-yl)-2-oxopropylidene],
hydrochloride N'-(3-methyl-1-{oxo[(2Z)-2-(3,4,4-trimethyl-1,3-thiazolidin-2-ilidene)hydrazino]acetyl}butyl)cyclohexanecarboxylic,
the hydrochloride of N-(3,3-dimethyl-1-{oxo[(2Z)-2-(3,4,4-trimethyl-1,3-thiazolidin-2-ilidene)hydrazino]acetyl}butyl)cyclohexanecarboxylic,
hydrochloride (2E)-N-{2,3 dioxo-1-tetrahydro-2H-Piran-4-yl-3-[(2Z)-2-(3,4,4-trimethyl-1,3-thiazolidin-2-ilidene)hydrazino]propyl}-4,4-dimethylpent-2-enamide,
the hydrochloride of N-{2,3 dioxo-1-tetrahydro-2H-Piran-4-yl-3-[(2Z)-2-(3,4,4-trimethyl-1,3-thiazolidin-2-ilidene)hydrazino]propyl}cyclohexenecarboxylic,
the hydrochloride of N-{1-cyclohexyl-2,3-dioxo-3-[(2Z)-2-(3,4,4-trimethyl-1,3-thiazolidin-2-ilidene)hydrazino]propyl}cycle is hexanecarboxylic,
the hydrochloride of N-{1-cyclohexyl-2,3-dioxo-3-[(2Z)-2-(3,4,4-trimethyl-1,3-thiazolidin-2-ilidene)hydrazino]propyl}cyclohexenecarboxylic,
the hydrochloride of N-{(1S)-1-isopropyl-2,3-dioxo-3-[(2Z)-2-(3,4,4-trimethyl-1,3-thiazolidin-2-ilidene)hydrazino]propyl}cyclohexanecarboxylate,
hydrochloride N'-(4,4-dimethyl-3-ethyl-1,3-thiazolidin-2-ilidene)[3 cyclohexylcarbodiimide-3-(tetrahydropyran-4-yl)-2-oxopropylidene],
N'-(3-ethyl-4-methyl-1,3-thiazolidin-2-ilidene)[3 cyclohexylcarbodiimide-3-[(3S)-(tetrahydropyran-4-yl)]-2-oxopropylidene],
N-(3-{(2Z)-2-[(4S)-3,4-dimethyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-{(1S)-1-cyclohexyl-3-[(2Z)-2-(3-methyl-1,3-thiazolidin-2-ilidene)hydrazino]-2,3-disopropyl}cyclohexenecarboxylic,
N-{(1R)-3-{(2Z)-2-[(4S)-3,4-dimethyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-ylpropyl}cyclohexenecarboxylic,
N-(3-{(2Z)-2-[(4R)-3,4-dimethyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-[(1S)-3-{(2Z)-2-[(4R)-3,4-dimethyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-(tetrahydro-2H-Piran-4-yl)propyl]cyclohexenecarboxylic,
N-(3-{(2Z)-2-[(4R)-3,4-dimethyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-(3-{(2Z)-2-[(4R)-4-isopropyl-3-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-PYRAN-ylpropyl)cyclohexenecarboxylic,
N-(3-{(2Z)-2-[(4R)-4-isobutyl-3-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-(3-{(2Z)-2-[(4R)-4-isopropyl-3-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-(3-{(2Z)-2-[(4R)-4-isobutyl-3-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-(1-cyclohexyl-3-{(2Z)-2-[(4R)-4-isopropyl-3-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-disopropyl)cyclohexenecarboxylic,
N-(1-cyclohexyl-3-{(2Z)-2-[(4R)-4-isobutyl-3-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-disopropyl)cyclohexenecarboxylic,
N-(3-{(2Z)-2-[(5R) - for 3,5-dimethyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-(3-{(2Z)-2-[(5R) - for 3,5-dimethyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-(1-cyclohexyl-3-{(2Z)-2-[(5R) - for 3,5-dimethyl-l,3-thiazolidin-2-ilidene]hydrazino}-2,3-disopropyl)cyclohexenecarboxylic,
N-(3-{(2Z)-2-[(4R)-3,4-diethyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-(1-cyclohexyl-3-{(2Z)-2-[(4R)-3,4-diethyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-disopropyl)cyclohexenecarboxylic,
N-((1R)-3-{(2Z)-2-[(4R)-3,4-diethyl-l,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarbonyl the amide,
N-((1R)-3-{(2Z)-2-[(4R)-3-ethyl-4-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-(3-{(2Z)-2-[(4R)-4-ethyl-3-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-(3-{(2Z)-2-[(4R)-4-ethyl-3-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-(1-cyclohexyl-3-{(2Z)-2-[(4R)-4-ethyl-3-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-disopropyl)cyclohexenecarboxylic,
N-[2,3-dioxo-3-((2Z)-2-{3-[(1R)-1-phenylethyl]-1,3-thiazolidin-2-ilidene}hydrazino)-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexenecarboxylic,
N-[2,3-dioxo-3-((2Z)-2-{3-[(1R)-1-phenylethyl]-1,3-thiazolidin-2-ilidene}hydrazino)-1-tetrahydro-2H-Piran-4-ylpropyl}cyclohexanecarboxylic,
N-((1R)-3-{(2Z)-2-[(4R)-3-ethyl-4-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-((1S)-3-{(2Z)-2-[(4S)-3-ethyl-4-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-(3-{(2Z)-2-[(4R)-4-benzyl-3-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-(3-{(2Z)-2-[(4R)-4-benzyl-3-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-(1-cyclohexyl-3-{(2Z)-2-[(4R)-3-ethyl-4-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dio is isopropyl)cyclohexenecarboxylic,
N-((1R)-3-{(2Z)-2-[(4R)-3-benzyl-4-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-((1R)-3-{(2Z)-2-[(4R)-3-benzyl-4-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-(3-{(2Z)-2-[(4R)-4-benzyl-3-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-1-cyclohexyl-2,3-disopropyl)cyclohexenecarboxylic,
N-((1R)-3-{(2Z)-2-[(4R)-3-benzyl-4-ethyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-((1R)-3-{(2Z)-2-[(4R)-3-benzyl-4-ethyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-[1-cyclohexyl-2,3-dioxo-3-((2Z)-2-{3-[(1R)-1-phenylethyl]-1,3-thiazolidin-2-ilidene}hydrazino)propyl]cyclohexenecarboxylic,
N-[2,3-dioxo-3-((2Z)-2-{3-[(1S)-1-phenylethyl]-1,3-thiazolidin-2-ilidene}hydrazino)-1-tetrahydro-2H-Piran-4-ylpropyl]cyclohexanecarboxylic,
N-(3-{(2Z)-2-[(4R)-3-methyl-4-phenyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-(3-{(2Z)-2-[(4R)-3-methyl-4-phenyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-((1R)-3-{(2Z)-2-[(4R)-3-(2-methoxyethyl)-4-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-((1R)-3-{(2Z)-2-[(4R)-3-(2-methoxyethyl)-4-methyl-1,3-thiazolidin-2-Liden]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-((1R)-3-{(2Z)-2-[(4R)-4-ethyl-3-(2-methoxyethyl)-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-((1R)-3-{(2Z)-2-[(4R)-4-ethyl-3-(2-methoxyethyl)-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-((1R)-3-{(2Z)-2-[(5R)-3-benzyl-5-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-((1R)-3-{(2Z)-2-[(5R)-3-benzyl-5-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-((1S)-3-{(2Z)-2-[(4S)-3-(2-methoxyethyl)-4-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-((1S)-3-{(2Z)-2-[(4S)-3-(2-methoxyethyl)-4-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-((1S)-3-{(2Z)-2-[(4S)-3-benzyl-4-methyl-l,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-((1S)-3-{(2Z)-2-[(4S)-3-benzyl-4-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-(3-{(2Z)-2-[(5R)-3-ethyl-5-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-(3-{(2Z)-2-[(5R)-3-ethyl-5-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexanecarboxylic,
N-(3-{(2Z)-2-[(4)-3-ethyl-4-methyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
N-((1R)-3-{(2Z)-2-[(4R)-3,4-dimethyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-tetrahydro-2H-Piran-4-ylpropyl)cyclohexenecarboxylic,
or its pharmaceutically acceptable salt.

10. The connection according to claim 9 which is N-[(1S)-3-{(2Z)-2-[(4R)-3,4-dimethyl-1,3-thiazolidin-2-ilidene]hydrazino}-2,3-dioxo-1-(tetrahydro-2H-Piran-4-yl)propyl]cyclohexenecarboxylic.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: described are derivatives of 1,3,4-oxadiazol-2-on of formula (I) , where ARYL represents phenyl; Z represents -O(CH2)n- and n represents independent integer number from 1 to 5; X represents S; R1 represents C1-6alkyl; R2 represents phenyl, substituted with C1-6perfluoralkyl; or its pharmaceutically acceptable salt; based on it pharmaceutical composition; and method of disease treatment, where disease can be modulated by activity of PPAR-delta binding.

EFFECT: obtaining compounds which possess agonistic or antagonistic activity.

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

EFFECT: new compounds have useful biological properties.

18 cl, 195 ex

FIELD: chemistry, medicine.

SUBSTANCE: in the general formula (I): X is oxygen atom; R1 is C1-10-alkyl , substituted if necessary by phenyl or thienyl group; or R1 is C3-7-cycloalkyl, thienyl, pyridinyl; the thienyl groups can be substituted if necessary by 1-2 C1-3-alkyl groups; phenyl can be substituted if necessary by 1-2 halogen atoms; R2 is C1-6-alkyl; or R2 is C3-7-cycloalkyl, phenyl or pyridinyl; phenyl if necessary can be substituted by one or more halogen atoms or by the CN, C1-3-alkyl, C1-3-alkoxyl, C1-3-fluoroalkyl groups; R3 is C1-6-alkyl; R4 is hydrogen atom or C1-6-alkyl; R5 and R5' are independently of each other the hydrogen atom, hydroxyl; or R5 and R5' form together the oxo-group; n is integer value in the range from 0 to 3; R6 is independently of each other hydrogen atom, halogen atom, C1-3-alkyl, C1-3-alkoxyl.

EFFECT: compounds of present invention can find application as pharmaceutical for pathology treatment where the inhibitor of β-amiloyd peptide β-A4 is useful.

8 cl, 1 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention is related to compounds of formula (II) as inhibitor of leukotriene A4-hydrolase (LTA4H) and their enantiomers, racemic compounds and pharmaceutically acceptable salts, and also to treatment methods, method inhibition and pharmaceutical composition on their basis. In general formula (II) , X is selected from group that consists of O and S; Y is selected from group that consists of CH2 and O; R4 represents H; R6 represents H or F; and R2' is determined as R2, and R3' is determined as R3, as follows: R2 and R3, each, is independently selected from group that consists of A) H, C1-7alkyl, C3-7cycloalkyl, where each of substitutes of A) is independently substituted with 0 or 1 RQ, and each of mentioned RQ is substitute at carbon, which is distanced from nitrogen at least by one carbon atom; alternatively, R2 and R3, taken together with nitrogen, to which they are connected, create heterocyclic ring, which contains at least one heteroatom, which is specified nitrogen of connection, and specified heterocyclic ring is selected from group that consists of i) (4-7)-member heterocyclic ring HetRb, where specified (4-7)-member heterocyclic ring HetRb has single heteroatom, which is specified nitrogen of connection, and 0, 1 or 2 are substituted by substitutes at the same or different substituted atoms, at that specified substitutes are selected from group that consists of -RY, -C(O)RY, -C0-4alkylCO2RY, -C0-4alkylC(O)NRYRZ, -C0-4alkylNRYC(O)Rz, -C0-4alkylNRYC(O)CH2ORY, -C0-4alkylNRYCO2RY, -C0-4alkylNRYC(O)NRYRz, -C0-4alkylNRyC(S)NRyRz, -NRyC(O)CO2Ry, -C0-4alkylNRwSO2RY, tetrazol-5-yl, -C0-4alkylN(RY)(SO2)NRYRY, -C0-4alkylN(RY)(SO2)NRYCO2RY, ii) (5-7)-member heterocyclic ring HetRc, where specified (5-7)-member heterocyclic ring has single additional heteroatom distanced from specified nitrogen of connection at least by one carbon atom, thereat the specified additional heteroatom is selected from group that consists of O, S(=O)0-2 and >NRM, and where mentioned (5-7)-member heterocyclic ring HetRc has 0 or 1 carbonyl group; iv) one of 2,8-diazaspyro[4.5]decan-1-on-8-yl, 4-{[(2-tret- butoxycarbonylaminocyclobutancarbonyl)amino]methyl}-piperidine-1-yl, 4-{[(2-aminocyclobutancarbonyl)amino]methyl}piperidine-1-yl, tret-butyl ether of 3,9-diazaspyro [5.5]undecan-3-carbonic acid-9-yl; where RK is selected from group that consists of H, -C1-4alkyl, each not necessarily substituted by 1 substitute RN; RM is selected from group that consists of -SO2RY, -C(O)RY, -C(O)C1-4alkylORY, each not necessarily substituted by 1 substitute RN; RN is selected from group that consists of OH, NH2, CF3; RQ is selected from group that consists of -C0-4alkylRAr', -C0-4alkylCO2RY, -C0-4alkylNRYRz, -C0-4alkylNRYCORY, -C0-4alkylNRyCONRyRz; Rw is selected from group that consists of RY and -C3-7cycloalkyl; RY is selected from group that consists of H, -C1-4alkyl, -C0-4alkylRAr and -C0-4alkylRAr', each not necessarily substituted by 1 substitute RN; Rz is selected from group that consists of RY, -C1-2alkylCO2RY; RAr represents fragment connected via carbon atom, and specified fragment is selected from phenyl, pyridyl; RAr' represents (5-6)-member cyclic ring, having 1 or 2 heteroatoms selected from group that consists of O, N and >NRY, having 0 unsaturated connections, having 0 or 1 carbonyl group, where each atom, when allows for valency, in every of mentioned cyclic rings is independently substituted by 0 or 1 RK; provided that (a) specified R2' and R3', moreover, satisfy the following requirements: (e1): specified R2' and R3', both, are not H, when Y represents O and X represents S; (e3): specified R2' and R3', taken together with nitrogen, with which they are connected, do not create piperazine group, when X represents O and Y is one of O and CH2; (e4): specified R2' and R3', taken together with nitrogen, with which they are connected, do not create piperidine group, which is mono-substituted by 6-member cyclic group, when X represents O and Y is one of O and CH2; and (e5): specified R2' and R3', taken together with nitrogen, with which they are connected, create neither substituted piperidine group or substituted piperazine group, where specified substituted piperidine group or specified substituted piperazine group is substituted in position 4 by substitute XG, at that specified XG has structure , where n=0, 1, and when ne=1, then XL represents C1-6alkyl, OSG represents O or S, and XR1 and XR2, taken together with nitrogen, with which they are connected, create one of piperidine group, piperazine group, morpholine group, thiomorpholine group and pyrrolidine group, or each of XR1 and XR2, taken independently, represent one of H, C1-6alkyl, aryl, aralkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-6alkyl, heteroalkyl, heteroaryl-C1-6alkyl, heterocycloalkyl and heterocycloalkyl-C1-6alkyl; where aryl, aralkyl, cycloalkyl, heteroaryl or heterocycloalkyl may be not necessarily substituted by one or several substitutes, independently selected from halogen, hydroxy, C1-6alkyl, C1-6alkoxy, halogenated C1-6alkyl, halogenated C1-6alkoxy, nitro, cyano, amino, C1-4alkylamino, di(C1-4alkyl)amino, heteroaryl or heterocycloalkyl; and (b) further provided that when X represents S and Y represents O, then one of R2' and R3' is not XCG, while the other represents C1-6alkyl, where XCG represents group , where HC16 represents one of H, C1-6alkyl, halogenC1-6alkyl, allyl and C1-6alcoxymethyl, and GO represents group connected to carbon atom, which has substitute =0, creating amido group with nitrogen, with which all mentioned GO group is connected.

EFFECT: compounds may find application for treatment and prevention of diseases mediated by LTA4H, for instance, asthma, chronic obstructive lung disease, atherosclerosis, rheumatoid arthritis, disseminated sclerosis, inflammatory disease of bowels and psoriasis.

39 cl, 8 tbl, 12 dwg, 484 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: invention refers to new compounds of general formula (I) where R1 stands for hydrogen or linear, branched, saturated or unsaturated hydrocarbon radical; D stands for nitrogen atom or C-R2; E stands for nitrogen atom or C-R3; F stands for nitrogen atom or C-R4; G stands for nitrogen atom or C-R5; R2, R3, R4 and R5 are identical or different and individually represent hydrogen, halogen, alkoxy, linear or branched, saturated or unsaturated hydrocarbon radical; W stands for oxygen atom; X stands for radical of formula radical -(CH2)k-C(O)-(CH2)m-, -(CH2)n- or -(CH2)r-O-(CH2)s-, where k, m, r and s are equal to integers 0 to 6, and n is equal to an integer 1 to 6. Said radicals are optionally substituted with one or more substitutes independently chosen from the group consisting of R7; Y stands for radical of formula radical -(CH2)i-NH-C(O)-(CH2)j-, -(CH2)n-, -(CH2)r-O-(CH2)s-, -(CH2)t-NH-(CH2)u-, where i, j, n, r, s, t and u are equal to integers 0 to 6. Said radicals are optionally substituted C1-3alkyl, or C1-3alkyl-C1-3alkylsulphonylamino; radicals R7, B, R8, A, R9 are as it is presented in the patent claim. The invention also describes the pharmaceutical composition possessing inhibitory activity of receptor tyrosine kinase to KDR receptor including described compounds.

EFFECT: compounds possess inhibitory activity of receptor tyrosine kinase to KDR receptor and can be effective in therapy of the diseases associated uncontrolled angiogenesis.

29 cl, 746 ex, 6 tbl

FIELD: pharmacology.

SUBSTANCE: claimed invention relates to novel 2,4-pyridindiamine compounds of formula (1). In structural formula (I) L1 is direct bond; L2 is direct bond; R2 is phenyl group, three times substituted with three groups R8; R4 is X represents N; Y is selected from group consisting of O, NH, S, SO and SO2; Z is selected from group consisting of O, NH; on condition that if Y is selected from group consisting of NH, S, SO and SO2, Z is not the same as Y; R5 is selected from group consisting from R6, halogen; each R6 is independently selected from group consisting of hydrogen, halogen; R8 is selected from group consisting from Ra, Rb, Ra substituted with one or several similar or different groups Ra or Rb, -ORa, -O-CHRaRb; each R35 independently on others is selected from group consisting of hydrogen and R35, or in alternative case, two groups R35, bound to one and the same carbon atom are taken together with formation of oxogroup (=O), and the remaining two groups R35 each independently on each other are selected from group consisting from hydrogen and R8; each Ra is independently selected from group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl; each Rb is suitable group which is independently selected from group consisting of -ORd, halogen, -CF3, -C(O)NRcRc, and -OC(O)ORd; each Rc is independently protective group or Ra; each Rd is independently protective group or Ra; each index m is independently integer number from 1 to 3.

EFFECT: novel compounds can be used for treatment or prevention of autoimmune diseases, for instance such as rheumatoid arthritis and/or related to it symptoms, systemic lupus erythematosus and/or related to it symptoms, as well as and/or related to it symptoms.

41 cl, 14 dwg, 1 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: compounds of formula (I) as inhibitors of phosphotyrosine phosphotase 1B and their pharmaceutically acceptable salts, their application, based pharmaceutical composition and method of production. In general formula (I) , R1 indicates phenyl, naphthyl, thionaphthyl, pyridyl. Phenyl, naphthyl, thionaphthyl and pyridyl can be single- or multiple-substituted with F, Cl, Br, (CH2)0-2OH, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkinyl, CF3, OCF3, N(R9)(R10), piperidinone, piperazine, piperazinone, N-(C1-C6-alkylene)-piperazine, N-(C1-C6-alkylene)-piperazinone, morpholine, thiomorpholine, NO2, CN, O-(C1-C6)-alkyl, S(O)0-2-(C1-C6)-alkyl, SO2-N(R9)(R10), CO-(C1-C6)-alkyl, -COOH, (C1-C6)-alkylene-COOH, COO(C1-C6)-alkyl, (C1-C6)-alkyleny-COO(C1-C6)-alkyl, (C3-C10)-cycloalkyl, phenyl. These piperidinone, piperazine, piperazinone, N-(C1-C6-alkylene)-piperazine, N-(C1-C6-alkylene)-piperazinone, morpholine, thiomorpholine, and phenyl rings can be single- or multiple-substituted with F, Cl, Br, (CH2)0-2OH, COOH, CN, NO2, O-(C1-C6)-alkyl, -NH-O-(C1-C6)-alkyl, -(CO)-NH-O-(C1-C6)-alkylene-N(R9)(R10), -(CO)-(C1-C6)-alkyl, -(C1-C6)-alkyl, CF3, OCF3, N(R9)(R10); R2 indicates H, (C1-C6)-alkyl, COOH, (C1-C6)-alkylene-COOH, COO(C1-C6)-alkyl, (C1-C6)-alkylene-COO(C1-C6)-alkyl; R3 indicates H, (C1-C6)-alkyl, (C1-C6)-alkylenphenyl, -C(O)-phenyl, (C1-C6)-alkylenheterocycle, where heterocycle represents 5-6-merous heterocyclic ring containing 1-2 heteroatoms, chosen of nitrogen and oxygen, CO-(C1-C6)alkyl; R4, R5 indicate H; R6 indicates H, R9 indicates H, (C1-C4)-alkyl; R10 indicates H, (C1-C4)-alkyl.

EFFECT: applications for treating diseases mediated with phosphotyrosine phosphotase 1B activity, such as diabetes type II, lipidosis and carbohydrate metabolic imbalance, insulin resistivity, reduced sugar content in blood.

9 cl, 2 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: there is disclosed compounds of formula II , where each R2 independently stands for H, halogen, cyano, NO2, OR5, NR6R7, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo, arylalkyl, substituted arylalkyl, heterocycloalkyl or substituted heterocycloalkyl; B represents O, S, SO or SO2; each W and X independently represents C or N; n is within 0 to 4 if both W and X represent C, 0 to 3, if either X or W represent N, and 0 to 2 if both X and W represent N; R3, R5, R6, R7 are independently chosen from H, alkyl, substituted alkyl, alkenyl, alkinyl, substituted alkinyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo; R4 represents optionally substituted 5-6-merous heteroaryl containing nitrogen atom provided (a) if R4 stands for pyridyl, R4 is not substituted with both hydroxy and methoxy groups; and (b) R4 stands for pyrimidinyl, it is n-substituted =O; A is chosen from following compounds of formula: , where D stands for S or O; m is within 0 to 6; R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26 and R27 are independently chosen from H, halogen, NR30R31, OR32, CO2R33, SO2R36, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkinyl, substituted alkinyl, -CN, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl or substituted heterocycloalkyl; R28 and R29 are independently chosen from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl or together they form carbocyclic or heterocyclic ring consisting of 3 to 8 atoms; and R30, R31, R32, R33 and R36 are independently chosen from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkinyl, substituted alkinyl, cycloalkyl, substituted cycloalkyl, alkoxycarbonyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo, heterocycloalkyl or substituted heterocycloalkyl as pharmaceutical composition for cancer treatment containing compound of formula II.

EFFECT: production of new compounds and based pharmaceutical composition applied for cancer treatment.

18 cl, 147 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 concerns new 2-pyridone derivatives of formula (I): where R1, R2, R4, R5, G1, G2, L, Y and n are as specified in the invention formula, and their pharmaceutically acceptable salts, pharmaceutical compositions containing these compounds, and their application in therapy. These compounds have neutrophil elastase inhibition effect.

EFFECT: new compounds with useful biological properties.

7 cl, 1 tbl, 150 ex

FIELD: chemistry.

SUBSTANCE: invention concerns method of obtaining heterocycles of formula I , where X, A, R10-R17 are as defined in point 1 of the claim, while a) isothiocyanate of formula II is transformed into thiourea of formula IV by interaction with primary amine of formula III, and b) thiourea of formula IV is transformed into compound of formula I by interaction with sulfochloride R6SO2Cl in the presence of a base, where A, X, n, m and R10 to R17 in compounds of formulae II, III and IV are as defined in formula I, and R6 is (C1-C4)-alkyl, trifluoromethyl or phenyl non-sustituted or substituted by methyl, trifluoromethyl, F, CI, Br or polymer carreir. The transportation is shown by combination formulae

EFFECT: new multipurpose synthesis technique for heterocyclic compounds of the general formula I.

8 cl, 31 ex

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