Compounds and compositions - hedgehog signalling pathway modulators

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a compound of formula I ; or to its pharmaceutically acceptable salts where n represents 0, 1 or 2; Y1 represents a bond or a group C(O); Y2, represents a bond, the groups C(O) or S(O)2; R1 represents hydrogen, halogen, cyano, C1-2alkyl; R2 represents hydrogen, halogen, cyano, C1-4alkyl, C1-3alkoxy, halogen-substituted-C1-3alkyl, halogen-substituted-C1-3alkoxyl, C6aryl-C0alkyl, tetrazolyl, C3-6cycloalkyl-C0alkyl, C6-7heterocycloalkyl-C0-4alkyl where 1 or 2 carbon atoms in the ring are substituted by the groups selected from -O-, -NH-, -S(O) and -SO2-; and phenoxy groups; where said aryl and heterocycloalkyl groups R2 can be substituted by 1 or 2 radicals independently selected from C1-6alkyl; R3 represents hydrogen, halogen, cyano, C1-3alkoxy or halogen-substituted-C1-2alkyl group and a group -NR6aR6b where R6a and R6b are independently selected from hydrogen and C1-4alkyl; R4 represents hydrogen, halogen, cyano, C1-3alkoxy or halogen-substituted-C1-2alkyl group; R5 represents hydrogen or C1-3alkyl group; L represents a bivalent radical selected from ; ; ; ; ; ; ; ; ; ; ; ; and ; where asterisks the junctions of Y2 and R2; where any bivalent radical L can be substituted by 1 or 2 radicals independently selected from halogen, hydroxy, cyano, C1-4alkyl, C1-4alkyl carbonylamino, C1-4alkoxy, C1-4alkoxycarbonyl, halogen-substituted - C1-4alkyl, C1-3alkylsulfonyl, C1-3alkylsulfonyl-amino, cyano-substituted - C1-4alkyl and halogen-substituted -C1-4alkoxy radicals. Also, the invention refers to a method of Hedgehog path inhibition in a cell and to a method of undesired cell proliferation inhibition which involves the interaction of the compound of formula I and the cell.

EFFECT: new substituted imidazole derivatives which can be effective in treatment of some types of cancer are prepared.

13 cl, 1 tbl, 3 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

in which n represents 0, 1 or 2;
Y1represents a bond or a group S(O);
Y2represents a bond, C(O) or S(O)2group;
R1represents hydrogen, halogen, cyano, C1-2alkyl;
R2represents hydrogen, halogen, cyano, C1-4alkyl, C1-3CNS, halogensubstituted-C1-3alkyl, halogen-substituted-C1-3CNS, With6aryl-C0alkyl, tetrazole is inuu, With3-6cycloalkyl-C0alkyl, C6-7heteroseksualci-C0-4alkyl, where 1 or 2 carbon atoms in ring substituted by groups selected from-O-, -NH-, -S(O) - and-SO2and phenoxy group;
where these aryl and heterocytolysine group R2may be substituted by 1 or 2 radicals independently selected from C1-6alkyl;
R3represents hydrogen, halogen, cyano, C1-3CNS or halogensubstituted-C1-2alkyl groups and the group-NR6aR6bwhere R6aand R6bindependently selected from hydrogen and C1-4of alkyl;
R4represents hydrogen, halogen, cyano, C1-3CNS or halogensubstituted-C1-2alkyl group;
R5represents hydrogen or C1-3alkyl group;
L represents a divalent radical chosen from:
;;;;;;;;;;;;;
where the asterisk indicates the point of attachment between Y2and R2; where any is vocalistas radical L can be substituted by 1 or 2 radicals, independently selected from halogen, hydroxy, cyano, C1-4alkyl, C1-4alkylcarboxylic,1-4alkoxy, C1-4alkoxycarbonyl, halogensubstituted-C1-4alkyl, C1-3alkylsulfonyl, C1-3alkylsulfonyl-amino, cyanobalamin-C1-4alkyl and halogen-substituted-C1-4alkoxy radicals,
and its pharmaceutically acceptable salts.

2. The compound according to claim 1, in which:
n represents 0 and 1;
Y1represents a bond or a group S(O);
Y2represents a bond, C(O) or S(O)2group;
R1represents hydrogen, halogen, or C1-2alkyl group;
R2represents hydrogen, halogen, cyano, C1-3alkyl, C1-3CNS, halogensubstituted-C1-3alkyl, halogen-substituted-C1-3CNS, With6aryl-C0alkyl, tetrazolyl,3-6cycloalkyl-C0alkyl, C6-7heteroseksualci-C0alkyl, phenoxy group;
where these aryl and heterocytolysine group R2may be substituted by 1 or 2 radicals independently selected from C1-6alkyl;
R3represents hydrogen, halogen, cyano, C1-3CNS, halogensubstituted-C1-2alkyl, and-NR6aR6bgroup; R6aand R6bindependently selected from hydrogen and C1-4 of alkyl;
R4represents hydrogen, halogen, cyano or halogen-substituted-C1-2alkyl group;
R5represents hydrogen or C1-3alkyl group;
L represents a divalent radical chosen from:
;;;;;;;;;;;;;
where the asterisk indicates the point of attachment between Y2and R2; where any divalent radical L can be substituted by 1 or 2 radicals independently selected from halogen, hydroxy, cyano, C1-4alkyl, C1-3alkylsulfonyl, C1-3alkylsulfonyl, C1-3alkylcarboxylic, C1-3alkoxy, C1-3alkoxycarbonyl, cyanobalamin-C1-3alkyl and halogen-substituted-C1-3alkoxy groups.

3. The compound according to claim 2, in which: n represents 0 and 1; Y1represents a bond or a group S(O); Y2represents a bond, C(O) or S(O)2group; R1represents a hydrogen, chlorine or methyl.

4. The compound according to claim 3 in which R1is the Wallpaper hydrogen, halogen, methyl, ethyl, cyano, methoxy, ethoxy, trifluoromethyl, triptoreline, phenoxy, morpholino, cyclohexyl, thiomorpholine, 1H-tetrazol-1-yl, piperidinyl and azepin-1-yl radicals; where these phenoxy, morpholino, cyclohexyl, thiomorpholine radicals of R2may be substituted by 1 or 2 metal radicals; where the specified sulfur atom thiomorpholine can be associated with 1 or 2 oxygen atoms.

5. The compound according to claim 4, in which R3represents hydrogen, chlorine, fluorine, cyano, trifluoromethyl, methoxy, diethylamino group; R4represents hydrogen and chlorine; R5represents hydrogen and methyl; and L represents a divalent radical chosen from:
;;;;;;;;;;;;;
where the asterisk indicates the point of attachment between Y2and R2; where any divalent radical L can be substituted by 1 or 2 radicals independently selected from hydroxy, bromine, chlorine, fluorine, methyl, ethyl, cyano, methylcobalamine, butyl, methoxy trifluoromethyl, triptoreline, 2-cyanoprop-2-yl, triptoreline, methoxycarbonyl, propoxy, methylsulphonyl, methylsulfonylamino, ethylsulfonyl, propylsulfonyl, isopropylphenyl, isopropoxy, ethoxy radicals.

6. The compound according to claim 1, selected from [4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-[6-(2-methyl-morpholine-4-yl)-isoquinoline-1-yl]-amine, [4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-[2-(2-methyl-morpholine-4-yl)-quinoline-5-yl]-amine, [4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-[2-(2-methyl-morpholine-4-yl)-[1,6]naphthiridine-5-yl]-amine, [4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-[6-(2,6-dimethyl-morpholine-4-yl)-isoquinoline-1-yl]-amine, [4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-(6-morpholine-4-yl-isoquinoline-1-yl)-amine, N-[4-chloro-3-(4-phenyl-1H-imidazol-2-yl)-phenyl]-4-morpholine-4-yl-benzamide, N-[4-chloro-3-(4-phenyl-1H-imidazol-2-yl)-phenyl]-4-cyclohexyl-benzamide, [4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-(2-morpholine-4-yl-quinoline-5-yl)-amine, [4-methyl-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-(6-piperidine-1-yl-isoquinoline-1-yl)-amine, (6-azepin-1-yl-isoquinoline-1-yl)-[4-methyl-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-amine, N-[4-methyl-3-(4-phenyl-1H-imidazol-2-yl)-phenyl]-4-morpholine-4-yl-benzamide, 4-cyclohexyl-N-[4-methyl-3-(4-phenyl-1H-imidazol-2-yl)-phenyl]-benzamide, N-(3-[5-(4-chloro-phenyl)-1H-imidazol-2-yl]-4-methyl-phenyl)-4-morpholine-4-yl-benzamide, [4-methyl-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-(2-morpholine-4-yl-[1,6]naphthiridine-5-yl)-amine, (6-azepin-1-yl-isoquinoline-1-yl)-[4-chloro-3-(-phenyl-1H-imidazol-2-yl)-phenyl]-amine, [4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-(6-piperidine-1-yl-isoquinoline-1-yl)-amine, 3,5-dimethoxy-N-[4-methyl-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-benzamide, N-(3-[4-(4-diethylamino-phenyl)-1H-imidazol-2-yl]-4-methyl-phenyl)-4-morpholine-4-yl-benzamide, N-(4-chloro-3-[4-(4-chloro-phenyl)-1H-imidazol-2-yl]-phenyl)-4-morpholine-4-yl-benzamide, (6-morpholine-4-yl-isoquinoline-1-yl)-[3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-amine, N-(3-[5-(4-fluoro-phenyl)-1H-imidazol-2-yl]-4-methyl-phenyl)-4-morpholine-4-yl-benzamide, (6-morpholine-4-yl-isoquinoline-1-yl)-[3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-amine, (2-morpholine-4-yl-quinoline-5-yl)-[3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-amine, 6-morpholine-4-yl-N-[3-(4-phenyl-1H-imidazol-2-yl)-phenyl]-nicotinamide, N-(3-[5-(3-chloro-phenyl)-1H-imidazol-2-yl]-4-methyl-phenyl)-4-morpholine-4-yl-benzamide, 4-cyclohexyl-N-[3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-benzamide, 4-morpholine-4-yl-N-[3-(4-phenyl-1H-imidazol-2-yl)-phenyl]-benzamide, N-(3-[5-(2-chloro-phenyl)-1H-imidazol-2-yl]-4-methyl-phenyl)-4-morpholine-4-yl-benzamide, 4-cyclohexyl-N-(3-[4-(4-fluoro-phenyl)-1H-imidazol-2-yl]-phenyl)-benzamide, N-(3-[5-(4-cyano-phenyl)-1H-imidazol-2-yl]-4-methyl-phenyl) - for 3,5-dimethoxy-benzamide, 6-azepin-1-yl-N-[3-(4-phenyl-1H-imidazol-2-yl)-phenyl]-nicotinamide, 4-morpholine-4-yl-N-[3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-benzamide, N-(4-methyl-3-[5-(4-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-phenyl)-4-morpholine-4-yl-benzamide, [4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-isoquinoline-1-yl-amine, 4-cyclohexyl-N-(3-[4-(4-methoxy-phenyl)-1H-shall midazol-2-yl]-phenyl)-benzamide, 3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carboxylic acid [3-(4-phenyl-1H-imidazol-2-yl)-phenyl]-amide, 6-azepin-1-yl-N-[2-methyl-3-(4-phenyl-1H-imidazol-2-yl)-phenyl]-nicotinamide, N-(3-[4-(4-cyano-phenyl)-1H-imidazol-2-yl]-phenyl)-4-cyclohexyl-benzamide, 4-morpholine-4-yl-N-[3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-benzosulfimide, [2-methyl-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-(6-morpholine-4-yl-isoquinoline-1-yl)-amine, N-[4-chloro-3-(5-methyl-4-phenyl-1H-imidazol-2-yl)-phenyl]-4-morpholine-4-yl-benzamide, N-[4-methyl-3-(5-methyl-4-phenyl-1H-imidazol-2-yl)-phenyl]-4-morpholine-4-yl-benzamide, N-(6-morpholine-4-yl-pyridine-3-yl)-3-(4-phenyl-1H-imidazol-2-yl)-benzamide, N-[2-methyl-3-(4-phenyl-1H-imidazol-2-yl)-phenyl]-6-morpholine-4-yl-nicotinamide, 3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carboxylic acid [2-methyl-3-(4-phenyl-1H-imidazol-2-yl)-phenyl]-amide, 4-cyclohexyl-N-[2-methyl-3-(4-phenyl-1H-imidazol-2-yl)-phenyl]-benzamide, [4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-[2-(2,6-dimethyl-morpholine-4-yl)-quinoline-5-yl]-amine, [4-chloro-3-(4-phenyl-1H-imidazol-2-yl)-phenyl]-[2-(2,6-dimethyl-morpholine-4-yl)-[1,6]the naphthiridine-5-yl]-amine, N-[4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-2-methoxy-isonicotinamide, 2-chloro-N-[4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-6-methyl-isonicotinamide, 2,6-dichloro-N-[4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-isonicotinamide, N-[4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-2-methoxy-isonicotinamide, 6-chloro-N-[4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-nicotinamide, N-[4-chloro-3-(5-f the Nile-1H-imidazol-2-yl)-phenyl]-6-trifluoromethyl-nicotinamide, 2-chloro-N-[4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-6-methoxy-isonicotinamide, N-[4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-nicotinamide, N-[4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-5-methoxy-2-(2,2,2-triptoreline)-benzamide, N-[4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-3,4-diethoxy-benzamide, N-[4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-3-methoxy-4-methyl-benzamide, 4-chloro-N-[4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-3-methoxy-benzamide, 2,2-debtor-benzo[1,3]dioxol-4-carboxylic acid [4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-amide, N-[4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-3-methoxy-2-methyl-benzamide, N-[4-chloro-3-(5-phenyl-1H-imidazole-2-yl)-phenyl]-2,5-dimethoxy-benzamide, N-[4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl] - for 3,5-dimethoxy-4-methyl-benzamide, [4-chloro-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-[8-methyl-2-(2-methyl-morpholine-4-yl)-quinoline-5-yl]-amine, [2-(2,6-dimethyl-morpholine-4-yl)-benzothiazol-7-yl]-[4-methyl-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-amine, [2-(2,6-dimethyl-morpholine-4-yl)-1H-benzoimidazol-4-yl]-[4-methyl-3-(5-phenyl-1H-imidazol-2-yl)-phenyl]-amine, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-3-methoxybenzamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-methylbenzamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-(trifluoromethyl)benzamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2,3-dimethoxybenzamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)benzo[d]thiazole-6-carboxamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)picolylamine, N-(4-the PRS-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-3-(triptoreline)benzamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-4-methoxy-2-methylbenzamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-hydroxynicotinate, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-hydroxy-6-nicotine amide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-3-methylphthalimide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-3-ethoxy-2-methylbenzamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-(2,2,2-triptoreline)nicotinamide, 2-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-(trifluoromethyl)nicotinamide, 6-bromo-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)nicotinamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-canonicalname, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-nicotine amide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-hydroxynicotinate,N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-methoxynicotinate, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-5-the nicotine amide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-5-fioricetonline, 5-bromo-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)nicotinamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-ethoxilated, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-ethyl-3-methoxybenzamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-methoxynicotinate, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-fioricetonline, 2-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)nicotinamide, 2-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-nicotine amide, 5,6-dichloro-N-4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)nicotinamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-nicotine amide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-ehtoksiatsyetanilida, 2-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)isonicotinamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)isonicotinamide, methyl-6-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenylcarbamoyl)nicotinate, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-(2-cyanoprop-2-yl)isonicotinamide, 2-tert-butyl-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)isonicotinamide, 2-bromo-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)isonicotinamide, 3-bromo-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-fermentated, 2-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-3,4-dimethoxybenzamide, 3-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)isonicotinamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-methylethanolamine, 4-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)nicotinamide, 2,5-dichloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)isonicotinamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-(1H-tetrazol-1-yl)isonicotinamide, 4-bromo-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)picolinate, 2,6-dichloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)isonicotinamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-4-nicotine amide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-hydroxy-6-(trifluoromethyl)nicotinamide, 2-acetamido-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)isonicotinamide, 3-bromo-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-is)phenyl)-2-methylbenzamide, 2-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-methylbenzamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-3-(trifluoromethyl)benzamide, N-(4-chloro-3-(4-phenyl-1H-imidazol-2-yl)phenyl)-3-(morpholinomethyl)pyridin-2-amine N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-hydroxyphthalimide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-3-hydroxyphthalimide, 6-bromo-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)picolylamine, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-methylphthalimide, 5-butyl-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)picolinate, 4-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)picolylamine, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2,6-dimethoxybenzamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-phenoxyimine, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2,6-dimethoxyisoquinoline, 6-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)picolylamine, N-(4-hdor-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-horizontalidad, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-ethoxilated, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-(2,2,2-triptoreline)isonicotinamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-isopropylacrylamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-propoxyimino, 2,3-dichloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)isonicotinamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-hydroxy-6-methylethanolamine, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-propox is isonicotinamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-methyl-6-(trifluoromethyl)nicotinamide, 5-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-methoxyethylamine, 3-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-methoxyethylamine, 3,5-dichloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)isonicotinamide, 2,6-dichloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)nicotinamide, 2-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-4-(methylsulphonyl)benzamide, 2,3-dichloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)benzamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-4-isopropoxy-2-methylbenzamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-3-isopropoxy-2-methylbenzamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-2-isopropoxyaniline, 2-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-methoxynicotinate, 2-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-4-ethoxybenzene, 2-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-4-isopropoxybenzoic, 2-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-isopropylacrylamide, N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-6-methoxy-2-nicotine amide, 2,3-dichloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-4-(ethylsulfonyl)benzamide, 2-((2S,6R)-2,6-dimethylmorpholine)-N-(4-methyl-3-(4-phenyl-1H-imidazol-2-yl)phenyl)thiazole-5-carboxamide, 2-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-4-(ethylsulfonyl)benzamide, 2-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-4-(isopropylthio who yl)benzamide, 2-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-4-(propylsulfonyl)benzamide and 2-chloro-N-(4-chloro-3-(5-phenyl-1H-imidazol-2-yl)phenyl)-4-(methylsulfanyl)benzamide.

7. A method of inhibiting the Hedgehog pathway in a cell, including the interaction of the compounds according to claim 1 with a cell.

8. The method according to claim 7, in which the cell has a phenotype of loss of Ptc function, the enhanced activity of the Hedgehog, increased activity of smoothened, the enhanced activity of the Gli or overexpression of this gene Hedgehog ligands.

9. The method according to claim 8, in which the cell interacts with a Hedgehog antagonist in vivo or in vitro.

10. The method according to claim 9, in which the compound is injected animals as part of therapy.

11. The method according to claim 10, in which the treatment is carried out for non-melanoma skin cancer, myeloma, lymphoma, psoriasis, pancreatic cancer, prostate cancer, Protocol, basal cell carcinoma and small cell lung cancer.

12. Method of inhibiting unwanted cell proliferation, including the interaction of a cell with a compound according to claim 1.

13. The method according to item 12, in which the cell belongs to non-melanoma skin cancer, myeloma, lymphoma, psoriasis, pancreas cancer, prostate cancer, medulloblastoma, basal cell carcinoma and small-cell lung cancer.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a condensed cyclic aromatic compound having the formula [2] given below: , where each R1 R2, R3, R5-R8, R10-R13, R15-R18, R20 denotes a hydrogen atom, R4, R9, R14, R19 denote phenyl, optionally substituted with two substitutes selected from tertbutyl. The invention also relates to use of said compound as an organic light-emitting layer in an organic light-emitting device.

EFFECT: obtaining a substance which can be used to make a light-emitting device which is durable and has high radiation efficiency.

2 cl, 6 ex, 2 tbl, 6 dwg

FIELD: medicine.

SUBSTANCE: invention refers to new amino acid derivatives of formula (I), , in which R-groups have the following value: -R1 is -H;-R2 is -C(O)R15 or -SO2R15; -R3 is -H;-R4 is -H or -(1-4C)alkyl; -R6 is -H; -R7 is -H; -R8 is -H, cyanogroup, halogen, nitrogroup; -(1-6C)alkyl optionally substituted by amino group, hydroxyl or halogen; -heteroaryl representing a 5 or 6-members aromatic ring containing one or more heteroatoms N optionally substituted by -(1-4C) alkyl; -C(R16)NOR16, -C(O)N(R17)2, -C(O)R18 or -C(O)OR19; -R9 is -H; -R10 is -H or -(1-4C)alkyl; -R11 is -H; -R12 is -H; -R13 is -H; -R14 is -H; -R15 is -H; -(1-6C)alkyl, -(2-6C)alkynyl, -O(2-6C)alkyl) all optionally substituted by one or more, halogen, cyanogroup or 5-members heteroaryl where 5-members heteroaryl represents an aromatic ring containing one or more heteroatoms selected from a group including N, O or S; -(hetero)aryl representing 5 or 6-members aromatic ring system containing one or more heteroatoms selected from group including N, O or S, optionally substituted by -(1-4C)alkyl, halogen or NH2; -NH2, -(di)(1-4C)alkylamihogroup, -(1-4C)alkylamihogroup or -NR16OR16; R16 is -H or -(1-4C)alkyl; -R17 is -H or -(1-6C)alkyl optionally substituted by halogen, or 5 or 6-members heteroaryl or aryl optionally substituted by halogen, -(1-4C)alkyl or -(1-4C)alkoxygroup where heteroaryl represents an aromatic ring containing one or more heteroatoms selected from the group including N, O or S; -R18 is -H or -(1-4C)alkyl; -R19 is -H or -(1-6C)alkyl.

EFFECT: compounds of this invention are high-specific to glucocorticoid receptor and can be used for treating inflammatory diseases.

6 cl, 58 ex

FIELD: medicine.

SUBSTANCE: invention refers to aryl-izoxazole-4-yl-imidazo[1,5-a]pyridine derivatives of formula I and to their pharmaceutically acceptable acid addition salts. In formula I , R1 represents hydrogen atom; R2 represents hydrogen atom; R3 represents hydrogen atom, cyano or -(CO)-Ra; Ra represents lower alkoxy or NR'R" where each of R' and R" independently represents hydrogen atom, 6-members heterocycloalkyl with the 1st heteroatom selected from O, or lower alkyl substituted by C3-C7-cycloalkyl. The invention also refers to a drug exhibiting affinity and selectivity to GABA(A) α5-receptor binding sites, containing one or more compounds of formula I and to an application of the compound of the invention in producing the drug exhibiting affinity and selectivity to GABA(A) α5-receptor binding sites.

EFFECT: improved efficacy of the drug.

7 cl, 2 dwg, 8 ex

FIELD: medicine.

SUBSTANCE: invention refers to a compound of formula (I): in which the radicals R1, R2, R3 and R4 independently represent hydrogen atom, halogen atom, hydroxy group, amino group, nitro group, an alkyl, alkenyl, cycloalkyl or aralkyl radical. And all these radicals can to be optionally substituted by haloalkyl or hydroxyalkyl, or radicals R2 and R3 in combination can represent a part of an aryl rings; R5 represents hydrogen atom, halogen atom, hydroxy group or thiol group, an alkyl, alkenyl, alkinyl, aryl, cycloalkyl, aralkyl radical or a 5-merous heteroaromatic ring containing 1, 2 heteroatoms selected from nitrogen and oxygen; the radicals R6 and R7 independently represent hydrogen atom, an alkyl or aryl radical; and X represents a group of formula where represents a bond or CH2, V represents O, W represents NH, a Y represents OH, or to its pharmaceutically acceptable salts, and besides to pharmaceutical composition based on said compound showing an inhibitory action on peptide deformylase (PDF).

EFFECT: new compounds which attract a great interest as new antibiotics are produced and described.

11 cl, 1 tbl

FIELD: medicine.

SUBSTANCE: compounds can be used for treating neurological conditions, more specifically for treating neurodegenerative conditions, such as Alzheimer's disease. In a compound of formula I R2 represents H or CH2NR1R4 where R1 and R4 are independently selected from H, unsubstituted C1-6alkyl, substituted or unsubstituted C3-6 cycloalkyl, R3 represents H; substituted or unsubstituted C1-4alkyl; substituted or unsubstituted C2-4alkenyl; substituted or unsubstituted 6-members aryl condensed or uncondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl, containing 1-2 nitrogen atoms in a cycle; substituted or unsubstituted saturated or unsaturated 5 or 6-members N-containing heterocycle which can additionally contain nitrogen, oxygen or the sulphur atom condensed or ucondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl containing nitrogen in a cycle; (CH2)nR6 where n is an integer from 1 to 6, and the values of R6 and the values of other radicals are specified in the patent claim.

EFFECT: increased antiamyloidogenic action.

20 cl, 20 tbl, 6 dwg, 7 ex

FIELD: chemistry.

SUBSTANCE: invention describes a compound of structural formula IIIm: or pharmaceutically acceptable salt thereof, where: R81 is selected from a group comprising hydrogen, halogen, possibly substituted C1-6alkyl, possibly substituted C2-6alkenyl, possibly substituted C2-6alkynyl, possibly substituted cycloalkyl, possibly substituted heterocycloalkyl, possibly substituted aryl, possibly substituted heteroaryl, -OH, -NH2, -CN, -NO2, -C(O)OH, -S(O)2NH2, -C(O)NH2, -C(S)NH2, -NHC(O)NH2, -NHC(S)NH2, -NHS(O)2NH2, -OR68, -SR68, -NR69R68, -C(O)R68, -C(S)R68, -C(O)OR68, -C(O)NR69R68, -C(S)NR69R68, -S(O)2NR69R68; -NR69C(O)R68, -NR69C(S)R68, -NR69S(O)2R68, -NR69C(O)NH2, -NR69C(O)NR69R68, -NR69C(S)NH2, -NR69C(S)NR69R68, -NR69S(O)2NH2, -NR69S(O)2NR69R68, -S(O)R68 and -S(O)2R68, R83 is selected from a group comprising hydrogen, fluro and chloro; R112 is selected from a group comprising possibly substituted C2-6alkyl, possibly substituted aryl, possibly substituted heteroaryl and -NR79 R80; R68 is selected from a group comprising possibly substituted C1-6alkyl, possibly substituted C2-6alkenyl, but provided that when R68 is possibly substituted C2-6alkenyl, then one of its alkene carbons is not bonded with N, S, O, S(O), S(O)2, C(O) or C(S) from -OR68, -SR68, -NR69R68, -C(O)R68, -C(S)R68, -C(O)OR68, -C(O)NR69R68, -C(S)NR69R68, -S(O)2NR69R68, -NR69C(O)R68, -NR69C(S)R68, -NR69S(O)2R68, -NR69C(O)NH2, -NR69C(O)NR69R68, -NR69C(S)NH2, -NR69C(S)NR69R68, -NR69S(O)2NH2, -NR69S(O)2NR69R68, -S(O)R68 or -S(O)2R68, possibly substituted C2-6alkynyl, but provided that when R68 is possibly substituted C2-6alkynyl, then one of its alkyne carbons is not bonded with N, S, O, S(O), S(O)2, C(O) or C(S) from -OR68, -SR68, -NR69R68, -C(O)R68, -C(S)R68, -C(O)OR68, -C(O)NR69R68, -C(S)NR69R68, -S(O)2NR69R68, -NR69C(O)R68, -NR69C(S)R68, -NR69S(O)2R68, -NR69C(O)NH2, -NR69C(O)NR69R68, -NR69C(S)NH2, -NR69C(S)NR69R68, -NR69S(O)2NH2, -NR69S(O)2NR69R68, -S(O)R68 or -S(O)2R68, possibly substituted cycloalkyl, possibly substituted heterocycloalkyl, possibly substituted aryl and possibly substituted heteroaryl; R69 is selected from a group comprising hydrogen and possibly substituted C1-6alkyl; and R79 and R80 independently denote hydrogen or possibly substituted C1-6alkyl or R79 and R80 together with the nitrogen atom to which they are bonded form a possibly substituted 5-7-member heterocycloalkyl. Described also is a composition and a set for modulating protein kinase based on said compounds and use of said compounds in preparing a medicinal agent.

EFFECT: novel compounds which are active towards protein kinase are obtained and described.

71 cl, 59 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to heterocyclic derivatives of general formula (I) where R1 denotes hydrogen, halogen, cyano, lower alkoxy or lower alkyl; R2 denotes aryl or a 5- or 6-member heteroaryl; R3 denotes hydrogen, aryl, a 5- or 6-member heteroaryl, where aryl, cycloalkyl, heterocycloalkyl or 5- or 6-member heteroaryl groups for R2 and R3 may be unsubstituted or substituted with halogen, cyano, lower alkyl, possibly substituted with one or more halogens, lower alkoxy, S(O)2-alkyl, -C(O)R', where R' is a lower alkyl, lower alkoxy; as well as pharmaceutically acceptable salts thereof. The invention also relates to a medicine based on said compounds for treating and preventing diseases mediated by the mGIuR5 receptor and use of compounds of formula (I) in preparing medicines.

EFFECT: novel compounds which are metabotropic glutamate receptor antagonists are obtained and described.

17 cl, 81 ex

FIELD: chemistry.

SUBSTANCE: invention relates to use of compounds, characterised by formulae (I) and (IB), or pharmaceutically acceptable salts thereof, isomers or hydrates to prepare a medicinal agent for treating or preventing diseases or conditions mediated by the sigma-receptor, selected from psychosis, neuropathic pain or inflammatory pain and movement disorder, such as dystonia or tardive dyskinesia, motor defects, including allodynia/or hyperalgesia. Radicals and symbols in compounds of formulae (I) and (IB) are described in claims 1 and 2. The invention also relates to novel compounds of formulae (I') and (IB'), in which radicals and symbols are described in claims 4 and 5, having pharmacological activity on the sigma-receptor, methods of producing such compounds, a pharmaceutical composition containing said compounds and use of said compounds in preparing a medicinal agent for treating and/or preventing diseases or conditions whose development involves the sigma-receptor. (I), (IB) (I') and (IB').

EFFECT: high effectiveness of the inhibitors.

22 cl, 1 tbl, 3 dwg, 64 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I) where R1 is chosen from a group consisting of phenyl, unsubstituted or substituted by one or two groups independently chosen from (lower) alkyl, (lower) phenylalkyl wherein a phenyl ring can be unsubstituted or substituted by one or two groups independently chosen from halogen; R2 represents hydrogen; or R1 and R2 together with nitrogen atom whereto attached, form a saturated 5- or 6-members heterocyclic ring optionally containing an additional oxygen heteroatom, said saturated heterocyclic ring is unsubstituted or substituted by one, two or three groups independently chosen from (lower) alkyl, halogen; R3 is chosen from a group consisting of hydrogen, (lower) alkyl, (lower) hydroxyalkyl, (lower) alkoxyalkyl, (lower) haloalkyl, (lower) cycloalkylalkyl, (lower) cyanoalkyl, (lower) alkylsulfonyl, phenyl unsubstituted or substituted by one or two groups independently chosen from halogen; R4 represents hydrogen or halogen; R5 represents a group chosen from where m represents 0 or 1; n represents 0,1 or 2; X represents CR13R13'; R6, R6', R7, R7', R8,R8', R13, R13' are independently chosen from a group consisting of hydrogen, (lower) alkyl, halogen; p represents 0 or 1; R9 is chosen from (lower) alkyl, cycloalkyl, (lower) cycloalkylalkyl; q represents 0 or 1; R10 represents (lower) alkyl; and to their pharmaceutically acceptable salts, as well as to a pharmaceutical composition exhibiting histamine 3 receptor antagonistic and/or antagonistic activity and based on the compounds of formula I.

EFFECT: there are prepared and described new compounds which can be effective in treatment and/or prevention of the diseases associated with H3 receptor modulation.

24 cl, 34 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to oxazolidinone derivatives covered by general graphic formula (I) and to their pharmaceutically acceptable salts. In formula (I) R1, R2, R3 and R4 are independently chosen from a group including -H and halogen; A is chosen from a group including R5 and R6 are independently chosen from a group including -H, -F, -CI, -Br, -OH, alkyl(C1-C6), haloalkyl(C1-C6), alkoxygroup(C1-C6); R7 is chosen from a group including -H, alkyl(C1-C6); either R7 and R5 or R6 taken together form a cycle of 2 carbon atoms and include 1 group chosen from O which in turn can be substituted by one substitute chosen from alkyl(C1-C6); R12 is chosen from a group including -H, -COR14, -CSR14, -COOR14; R14 is chosen from a group including alkyl (C1-C6), cycloalkyl(C3-C6), alkenyl(C2-C6), R16, R17 and R18 represent -H; R21 is chosen from a group including -H, alkyl(C1-C6); X is chosen from a group including O, S, and Y is chosen from a group including O, S, SO, SO2, and NR12; and optional substitutes of alkyl(C1-C6) groups can represent one or two groups chosen from the following: -OR21, -CN.

EFFECT: invention refers to methods for preparing the compounds of the invention, to application of oxazolidinone derivatives for preparing a drug for treating bacterial infections and to a pharmaceutical composition for treating bacterial infections, including a therapeutically effective amount of the compound of the invention.

36 cl, 10 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel oxadiazole compounds of formula (1) and pharmaceutically acceptable salts thereof, where R1 and R2 assume values given in the description, Y is a single bond. The invention also relates to use of said compounds as DGAT1 inhibitors, for example for treating obesity and diabetes, and a method of inhibiting.

EFFECT: high treatment efficiency.

13 cl, 65 tbl, 712 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound having structure

, radicals are as described in the formula of invention, as well as pharmaceutically-acceptable salt, prodrug, tautomer and stereoisomer thereof. The invention also relates to a composition, a set for modulating PPAR based on said compound, a method of treating a patient suffering from a disease or condition or at risk of a disease or condition, for which PPAR modulation is therapeutically useful.

EFFECT: novel compounds which are active towards PPAR are obtained and described.

41 cl, 622 ex, 8 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 3-(1,3-oxazol-4-yl)pyridin-2(1H)-one derivatives of general formula 1, , where 1a R=Br, R'=CH2OCH3, R"=CH3; 1b R=H, R'=CH2, R"=CH3; 1c R=H, R1=CH2OCH3, R"=Ph; 1d R=H, R'=CH3, R"=Ph; 1e R=Br, R=CH3, R" - fur-2-yl, which can be used as potential biologically active substances and intermediate products for synthesis of novel heterocyclic systems. The method of producing 3 -(2-substituted-1,3 -oxazol-4-yl)pyridin-2( 1 H)-ones of general formula I involves formation of a heterocyclic system of 3-(1,3-oxazol-4-yl)pyridin-2(1H)-one as a result of base-catalysed regrouping of 3-acylamino-2-furfurylfuro[2,3-b]pyridines while boiling said compounds in ethanol for 4-20 hours with addition of 6-7 mmol of potassium hydroxide per 1 mol of the initial 3-acylamino-2-furfurylfuro[2,3-b]pyridine.

EFFECT: high yield.

1 cl, 2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 2-quinolyloxazoles of formula (I) or pharmaceutically acceptable salts thereof, having PDE4 inhibiting properties, a pharmaceutical composition based on said compounds and use thereof to prepare a medicinal agent which inhibits inflammatory cell recruitment in respiratory tracts. , where is , X is O, R1 is alkyl, R3 and R4 are independently selected from H, R5 and R6 are independently selected from a group comprising H, alkyl, hydroxyalkyl, t equals 1 or 2. Values of substitutes R7-R11, R13 are given in the formula of invention.

EFFECT: high efficiency of using the composition.

24 cl, 1 dwg, 64 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to oxazolidinone derivatives covered by general graphic formula (I) and to their pharmaceutically acceptable salts. In formula (I) R1, R2, R3 and R4 are independently chosen from a group including -H and halogen; A is chosen from a group including R5 and R6 are independently chosen from a group including -H, -F, -CI, -Br, -OH, alkyl(C1-C6), haloalkyl(C1-C6), alkoxygroup(C1-C6); R7 is chosen from a group including -H, alkyl(C1-C6); either R7 and R5 or R6 taken together form a cycle of 2 carbon atoms and include 1 group chosen from O which in turn can be substituted by one substitute chosen from alkyl(C1-C6); R12 is chosen from a group including -H, -COR14, -CSR14, -COOR14; R14 is chosen from a group including alkyl (C1-C6), cycloalkyl(C3-C6), alkenyl(C2-C6), R16, R17 and R18 represent -H; R21 is chosen from a group including -H, alkyl(C1-C6); X is chosen from a group including O, S, and Y is chosen from a group including O, S, SO, SO2, and NR12; and optional substitutes of alkyl(C1-C6) groups can represent one or two groups chosen from the following: -OR21, -CN.

EFFECT: invention refers to methods for preparing the compounds of the invention, to application of oxazolidinone derivatives for preparing a drug for treating bacterial infections and to a pharmaceutical composition for treating bacterial infections, including a therapeutically effective amount of the compound of the invention.

36 cl, 10 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates or tautomers thereof, where substitute M is selected from groups D1 and D2, having structural formulae given below, and R1, E, A and X are as described in the formula of invention. Disclosed also are pharmaceutical compositions which contain these compounds, methods for synthesis of these compounds, intermediate compounds and synthesis methods thereof, as well as use of compounds of formula (I) in preventing or treating diseases mediated by CDK kinases, GSK-3 kinases or Aurora kinases.

EFFECT: high effectiveness of the compounds.

40 cl, 8 dwg, 18 tbl, 84 ex

Aromatic compound // 2416608

FIELD: chemistry.

SUBSTANCE: invention describes a novel compound of general formula (1), where radicals R1, R2, X1, Y and A are as described in claim 1 of the invention. The invention also describes a method of obtaining compounds of formula (1), as well as a pharmaceutical composition based on said compounds, for treating fibrosis.

EFFECT: novel compounds with excellent collagen formation suppression, cause fewer side-effects and which are safer are obtained.

62 cl, 2717 ex, 432 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula 1, compounds of formula 5 and pharmaceutically acceptable salts thereof. In formulae 1 5 Y denotes -C(O)-, X denotes -N(R11)-, R1 denotes a residue of formula 1a or 1b - for formula 1 or residue of formulae 5a or 5b - for formula 5 1a 1b 5a 5b, R2 and R7 independently denote H, hydroxyl or (C1-C6)alkyl; R3 and R6 each independently denotes H, hydroxyl or (C1-C6)alkyl; R4 and R5 each independently denotes H or (C1-C6)alkyl; the rest of the radicals are described in the formula of invention. The invention also relates to separate compounds given in the formula of invention, a pharmaceutical composition having Bcl bound protein inhibiting properties, which contains a therapeutically effective amount of the disclosed compound, a method of treating a bc1 mediated disorder, involving introduction of a therapeutically effective amount of the disclosed compound and a method of treating a bc1 mediated disorder involving administration to a patient in need of treatment of an effective amount of camptothecin and therapeutically effective amount of the disclosed compound.

EFFECT: high efficiency of the composition.

84 cl, 12 tbl, 1 dwg, 217 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds described by formula in which radical and symbol values are specified in the patent claim, and their pharmaceutically acceptable salts. These compounds inhibit tompomyosine-related kinases (Trk), and can find application in treating a malignant growth, such as breast cancer, rectal cancer and prostate cancer. Also, the invention relates to a method for producing these compounds, a based pharmaceutical composition and to methods of application thereof.

EFFECT: preparation of the pharmaceutical composition which can find application in treating a malignant growth.

18 cl, 134 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: compound of formula pharmaceutically acceptable salt or solvate of a compound or salt (I), ring Q represents optionally substituted monocyclic or condensed (C6-C12)aryl or optionally substituted monocyclic or condensed heteroaryl where said substitutes are chosen from: halogen; (C1-C6)alkyl optionally substituted by 1-3 halogen atoms; (C1-C6)alkylsulphonyl; phenyl optionally substituted by 1 or 2 substitutes chosen from halogen, (C1-C6)alkyl which can be substituted by 1-3 halogen atoms, groups (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and (C1-C6)alkylthio; monocyclic or condensed heteroaryl optionally substituted by halogen; or oxo; Y1 represents a bond or -NR6-CO-, where R6 represents hydrogen, ring A represents optionally substituted a nonaromatic heterocyclyldiyl where said substitutes are chosen from (C1-C6)alkyl optionally substituted by groups hydroxy, (C1-C6)alkylamino, di(C1-C6)alkylamino, morpholino, (C1-C6)alkylaminocarbonyl, di(C1-C6)alkylaminocarbonyl; cyano; (C3-C6)cycloalkyl; (C1-C6)alkoxy; (C1-C6)alkoxy(C1-C6)alkyl; phenyl; benzyl; benzyloxymethyl; thienyl; 4-8-members monocyclic nonaromatic heterocycle having 1 or 2 heteroatoms chosen from N or O, and optionally substituted by 1 or 2 substitutes chosen from (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and oxo; (C1-C6)alkylamino; di(C1-C6)alkylamino; a group of formula: -Y2Z'- represents a group of formula: [Formula 2] each R7 independently represents hydrogen, (C1-C6)alkyl or (C3-C6)cycloalkyl, each of R8 and R9 independently represents hydrogen or (C1-C6)alkyl, n is equal to an integer 0 to 3, Z1 represents a bond, -O-, -S- or-NR9 - where R9 represents hydrogen, (C1-C6)alkyl, acyl or (C1-C6)alkylsulphonyl, ring B represents optionally substituted aromatic carbocyclediyl or optionally substituted aromatic heterocyclediyl where said substitutes are chosen from (C1-C6)alkyl, halogen, (C1-C6)alkoxy and oxo; Y3 represents a bond optionally substituted (C1-C6)alkylene or (C3-C6)cycloalylene, optionally interrupted -O- or optionally substituted (C2-C6)alkenylene where said substitutes are chosen from (C1-C6)alkyl, (C3-C6)cycloalkyl, halogen and (C1-C6)alkoxycarbonyl; Z2 represents COOR3; R3 represents hydrogen or (C1-C6)alkyl.

EFFECT: preparation of new compounds.

30 cl, 9 tbl, 944 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a compound which represents 6-(3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy)-N-methylnicotine amide , or to its pharmaceutically acceptable salt. This compound and its pharmaceutically acceptable salts exhibits affinity to a histamine H3 receptor and are antagonists and/or inverse agonists of said receptor.

EFFECT: development of an effective method of producing the benzazepin derivative, the pharmaceutical compositions containing it, and application of the benzazepin derivative for treating neurological and psychiatric disturbances.

18 cl, 6 ex, 1 tbl

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