Amide derivatives

FIELD: chemistry.

SUBSTANCE: claimed invention relates to compound of formula I where m equals 0 or 1; R1 represents halogeno, (C1-6)alkyl, (C1-6)alkoxy, amino-(C2-6)alkoxy, (C2-6)alkylamino-(C2-6)alkoxy, di-[(C1-6)alkyl]amino-(C2-6)alkoxy, (C1-6)alkoxy-(C2-6)alkoxy, carbamoyl-(C1-6)alkoxy, N-(C1-6)alkylcarbamoyl-(C1-6)alkoxy, amino-(C1-6)alkyl, (C1-6)alkylamino-(C1-6)alkyl, di(C1-6)alkyl]amino-(C1-6)alkyl, carbamoyl-(C1-6)alkyl, N-(C1-6)alkylcarbamoyl-(C1-6)alkyl, (C1-6)alkoxy-(C2-6)alkylamino, heteroaryloxy, heterocyclyl-(C1-6)alkyl, heterocyclyloxy or heterocyclyl-(C1-6)alkoxy, and where any heteroaryl or heterocyclyl group in substituent R1 probably can have 1 or 2 substituents, selected from hydroxy, halogeno, (C1-6)alkyl, (C1-6)alkoxy, (C2-6)alkanoyl, hydroxy-(C1-6)alkyl, (C1-6)alkoxy-(C1-6)alkyl, and where any of determined above R1 substituents, which contains CH2 group bound with 2 carbon atoms, or group CH3, bound with an atom of carbon or nitrogen, probably can have on each said CH2 or CH3 group one or more substituents, selected from halogeno, hydroxy, amino, oxo, (C1-6)alkyl, (C2-6)alkenyl, (C2-6)alkinyl,. (C3-6)cycloalkyl, (C3-6)cycloalkoxy, (C1-6)alkoxy, (C1-6)alkoxy-(C1-6)alkyl, (C1-6)alkylsulphamoyl, heteroaryl, heteroaryl-(C1-6)alkyl and heterocyclyl, and where any heterocyclyl group in substituent R1 probably can have 1 or 2 oxo or tioxo substituents; R2 represents (C1-6)alkyl; R3 represents hydrogen; R4 represents (C3-6)cycloalkyl, (C1-6)alkyl or heteroaryl, and R4 probably can be substituted with one or more substituents, selected from halogeno, (C1-6)alkyl, (C1-6)alkoxy; and R5 represents hydrogen, halogeno or (C1-6)alkyl; or its pharmaceutically acceptable salt, to method of obtaining said compounds, to pharmaceutical composition for application in treatment of diseases mediated by based on them cytokines. Invention also relates to methods of inhibiting p38α-kinase enzymes, TNFα production and production of cytokines.

EFFECT: obtained and described are novel compounds, which can be applied in treatment of medical conditions mediated by cytokines.

14 cl, 31 ex, 9 tbl

 

The text descriptions are given in facsimile form.

1. The compound of formula I,

where m is 0 or 1;
R1represents halogeno, (C1-6)alkyl, (C1-6)alkoxy, amino-(C2-6)alkoxy, (C1-6)alkylamino-(C2-6)alkoxy, di-[(C1-6)alkyl]amino-(C2-6)alkoxy, (C1-6)alkoxy-(C2-6)alkoxy, carbarnoyl-(C1-6)alkoxy, N-(C1-6)allylcarbamate-(C1-6)alkoxy, amino-(C1-6)alkyl, (C1-6)alkylamino-(C1-6)alkyl, di[(C1-6)alkyl]amino-(C1-6)alkyl, carbarnoyl-(C1-6)alkyl, N-(C1-6)allylcarbamate-(C1-6)alkyl, (C1-6)alkoxy-(C2-6)alkylamino, heteroaromatic, heterocyclic-(C1-6)alkyl, heterocyclic or heterocyclic-(C1-6)alkoxy,
ihde any heteroaryl or heterocyclyl group in the substituent R 1may possibly have 1 or 2 substituent selected from hydroxy, halogeno, (C1-6)alkyl, (C1-6)alkoxy, (C2-6)alkanoyl, hydroxy-(C1-6)alkyl, (C1-6)alkoxy-(C1-6)alkyl, and where any of the above defined substituents R1that contains a group of CH2connected to 2 carbon atoms, or a group CH3connected to the carbon atom or nitrogen, may possibly have on each specified group of CH2or CH3one or more substituents selected from halogeno, hydroxy, amino, oxo, (C1-6)alkyl, (C2-6)alkenyl, (C2-6)quinil, (C3-6)cycloalkyl, (C3-6)cycloalkane, (C1-6)alkoxy, (C1-6)alkoxy-(C1-6)alkyl, (C1-6)alkylsulfonyl, heteroaryl, heteroaryl-(C1-6)alkyl and heterocyclyl,
and where any heterocyclyl group in the substituent R1may possibly have 1 or 2 substituent oxo or thioxo;
R2is a (C1-6)alkyl;
R3represents hydrogen;
R4is a (C3-6)cycloalkyl, (C1-6)alkyl or heteroaryl, and
R4may possibly be substituted by one or more substituents selected from halogeno, (C1-6)alkyl, (C1-6)alkoxy; and R5represents hydrogen, halogeno or (C1-6)alkyl;
or its pharmaceutical is Eski acceptable salt.

2. The compound of formula I according to claim 1, where
R1represents halogeno, (C1-6)alkoxy, amino-(C2-6)alkoxy, (C1-6)alkylamino-(C2-6)alkoxy, di-[(C1-6)alkyl] amino-(C2-6)alkoxy, di[(C1-6)alkyl]amino-(C1-6)alkyl, carbarnoyl-(C1-6)alkyl, heterocyclic and heterocyclic-(C1-6)alkoxy,
and where any heteroaryl or heterocyclyl group in the substituent R1may possibly have 1 or 2 substituent selected from hydroxy, halogeno, (C1-6)alkyl, (C1-6)alkoxy, hydroxy-(C1-6)alkyl, (C1-6)alkoxy-(C1-6)alkyl,
and where any of the above defined substituents R1that contains a group of CH2connected to 2 carbon atoms, or a group CH3connected to the carbon atom or nitrogen, may possibly have on each specified group of CH2or CH3one or more substituents selected from halogeno, hydroxy, (C1-6)alkyl, (C3-6)cycloalkyl, (C1-6)alkoxy, (C1-6)alkoxy-(C1-6)alkyl, heteroaryl-(C1-6)alkyl and heterocyclyl;
or its pharmaceutically acceptable salt.

3. The compound of formula I according to claim 1, where m is equal to 1; or its pharmaceutically acceptable salt.

4. The compound of formula I according to claim 1, where R4is cyclopropyl, cyclobutyl, cyclopentyl, methyl, ethyl, PR is drank, isoxazolyl, oxazolyl, furanyl, thiazolyl, pyrazolyl or pyridyl; or its pharmaceutically acceptable salt.

5. The compound of formula I according to claim 1, where m is 0 or 1;
R1represents heterocyclyl-(C1-6)alkyl, heterocyclic or heterocyclic-(C1-6)alkoxy,
and where any heterocyclyl group in the substituent R1may possibly have 1 or 2 substituent selected from hydroxy, halogeno, (C1-6)alkyl, (C1-6)alkoxy, hydroxy-(C1-6)alkyl and (C1-6)alkoxy-(C1-6)alkyl,
and where any of the above defined substituents R1that contains a group of CH2connected to 2 carbon atoms, or a group CH3connected to the carbon atom, may possibly have on each specified group CH2or CH3one or more substituents selected from hydroxy, amino, (C1-6)alkyl, (C2-6)alkenyl, (C2-6)quinil and (C1-6)alkoxy;
R2represents methyl;
R3represents hydrogen;
R4is cyclopropyl, cyclobutyl, cyclopentyl, methyl, ethyl, propyl, isoxazolyl, oxazolyl, furanyl, thiazolyl, pyrazolyl or pyridyl, and R4may possibly be substituted by one or more substituents selected from halogeno and (C1-6)alkyl; and
R5represents hydrogen;
or its farmaci is almost acceptable salt.

6. The compound of formula I according to claim 1, chosen from:
N-cyclopropyl-4-methyl-3-(1-oxoethyl-2(1H)-yl)benzamide;
N-cyclopropyl-3-(7-methoxy-1-oxoethyl-2(1H)-yl)-4-methylbenzamide;
N-cyclopropyl-3-[7-[2-(dimethylamino)ethoxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
3-(7-bromo-1-oxoethyl-2(1H)-yl)-N-cyclopropyl-4-methylbenzamide;
N-cyclopropyl-4-methyl-3-[1-oxo-7-(2-piperidine-1-ylethoxy)isoquinoline-2(1H)-yl]benzamide;
N-cyclopropyl-3-(7-hydroxy-1-oxoethyl-2(1H)-yl)-4-methylbenzamide;
N-picoprobe-3-[7-{2-[(3R)-3-ftorpirimidinu-1-yl]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-4-methyl-3-[7-[2-(1,4-oxazepan-4-yl)ethoxy]-1-oxoethyl-2(1H)-yl]benzamide;
N-cyclopropyl-3-[7-{2-[(2-methoxyethyl)(methyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
3-[7-{2-[(cyclobutylmethyl)(methyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-N-cyclopropyl-4-methylbenzamide;
N-cyclopropyl-4-methyl-3-[7-(2-morpholine-4-ylethoxy)-1-oxoethyl-2(1H)-yl]benzamide;
N-cyclopropyl-4-methyl-3-[1-oxo-7-(2-pyrrolidin-1 ylethoxy)isoquinoline-2(1H)-yl]benzamide;
N-cyclopropyl-3-[7-{2-[(3R)-3-hydroxypyrrolidine-1-yl]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-{2-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-{2-[isopropyl(2-methoxyethyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-4-IU ilasamaja;
N-cyclopropyl-3-[7-{2-[isopropyl(methyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-[3-(dimethylamino)propoxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
3-[7-[2-(dimethylamino)ethoxy]-1-oxoethyl-2(1H)-yl]-N-isoxazol-3-yl-4-methylbenzamide;
3-[7-[2-(dimethylamino)ethoxy]-1-oxoethyl-2(1H)-yl]-N-ethyl-4-methylbenzamide;
N-cyclopropyl-3-[7-[(1-ethylpiperazin-4-yl)oxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-isoxazol-3-yl-4-methyl-3-[7-(4-methylpiperazin-1-yl)-1-oxoethyl-2(1H)-yl]benzamide;
N-cyclopropyl-4-methyl-3-[7-(4-methylpiperazin-1-yl)-1-oxoethyl-2(1H)-yl]benzamide;
N-cyclopropyl-4-methyl-3-[7-{2-[methyl(tetrahydro-2H-Piran-4-yl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]benzamide;
N-cyclopropyl-4-methyl-3-[7-{2-[methyl(tetrahydrofuran-2-ylmethyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]benzamide;
N-cyclopropyl-4-methyl-3-[7-{2-[methyl(prop-2-in-1-yl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]benzamide;
N-cyclopropyl-3-[7-{2-[(3S)-3-ftorpirimidinu-1-yl]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-[2-(4,4-deformability-1-yl)ethoxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-[2-(3,3-debtorprovidian-1-yl)ethoxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-[2-(4-foreperiod-1-yl)ethoxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-[2-(3-foreveri the Jn-1-yl)ethoxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-{2-[(2S,6S)-2,6-dimethylmorpholine-4-yl]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-{2-[(2R,6S)-2,6-dimethylmorpholine-4-yl]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-4-methyl-3-[1-oxo-7-[3-(4-propenylbenzene-1-yl)propoxy]isoquinoline-2(1H)-yl]benzamide;
N-ethyl-4-methyl-3-[7-(2-morpholine-4-ylethoxy)-1-oxoethyl-2(1H)-yl]benzamide;
N-cyclopropyl-3-[7-[3-(4,4-deformability-1-yl)propoxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-{3-[isopropyl(methyl)amino]propoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-4-methyl-3-[1-oxo-7-(3-piperidine-1-ylpropionic)isoquinoline-2(1H)-yl]benzamide;
N-cyclopropyl-4-methyl-3-[7-{3-[methyl(tetrahydrofuran-2-ylmethyl)amino]propoxy}-1-oxoethyl-2(1H)-yl]benzamide;
N-cyclopropyl-3-[7-{3-[(2R,6S)-2,6-dimethylmorpholine-4-yl]propoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-4-methyl-3-[1-oxo-7-(3-pyrrolidin-1 ipropose)isoquinoline-2(1H)-yl]benzamide;
N-cyclopropyl-4-methyl-3-[7-(3-morpholine-4-ylpropionic)-1-oxoethyl-2(1H)-yl]benzamide;
N-cyclopropyl-4-methyl-3-[7-{3-[methyl(prop-2-in-1-yl)amino]propoxy}-1-oxoethyl-2(1H)-yl]benzamide;
N-cyclopropyl-3-[7-[3-(3,3-debtorprovidian-1-yl)propoxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-[3-(3-foreperiod-1-yl)propoxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzene is a;
N-cyclopropyl-4-methyl-3-[7-{2-[4-(methylsulphonyl)piperazine-1-yl]ethoxy}-1-oxoethyl-2(1H)-yl]benzamide;
N-ethyl-3-[7-{2-[isopropyl(methyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-ethyl-3-[7-{2-[(3R)-3-ftorpirimidinu-1-yl]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-4-methyl-3-[7-{3-[methyl(tetrahydro-2H-Piran-4-yl)amino]propoxy}-1-oxoethyl-2(1H)-yl]benzamide;
3-[7-[3-(dimethylamino)propyl]-1-oxoethyl-2(1H)-yl]-N-isoxazol-3-yl-4-methylbenzamide;
N-cyclopropyl-3-[7-[3-(4-foreperiod-1-yl)propoxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-{3-[(3R)-3-ftorpirimidinu-1-yl]propoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-{3-[(3S)-3-ftorpirimidinu-1-yl]propoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-ethyl-4-methyl-3-[1-oxo-7-(2-piperidine-1-ylethoxy)isoquinoline-2(1H)-yl]benzamide;
N-[-ethyl-3-(7-hydroxy-1-oxoethyl-2(1H)-yl)-4-methylbenzamide;
N-cyclopropyl-3-[7-{2-[isobutyl(methyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-{2-[ethyl(methyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-[2-(diisopropylamino)ethoxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-4-methyl-3-[7-{2-[(2S)-2-methylpiperidin-1-yl]ethoxy}-1-oxoethyl-2(1H)-yl] benzamide;
N-cyclopropyl-3-[7-{2-[ethyl(isopropyl)amino]ethoxy}-1-oxo chinolin-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-[2-(diethylamino)ethoxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
3-[7-{2-[tert-butyl(methyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-N-cyclopropyl-4-methylbenzamide;
3-[7-{2-[cyclohexyl(isopropyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-N-cyclopropyl-4-methylbenzamide;
3-[7-{2-[cyclohexyl(ethyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-N-cyclopropyl-4-methylbenzamide;
3-[7-{2-[cyclohexyl(methyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-N-cyclopropyl-4-methylbenzamide;
N-cyclopropyl-3-[7-{2-[2-(hydroxymethyl)morpholine-4-yl]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[7-{2-[(2S)-2-(hydroxymethyl)piperidine-1-yl]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
3-[7-(2-azetidin-1 ylethoxy)-1-oxoethyl-2(1H)-yl]-N-ethyl-4-methylbenzamide;
N-cyclopropyl-3-[7-[2-(isopropylamino)ethoxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
3-[7-{2-[allyl(methyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-N-ethyl-4-methylbenzamide;
N-ethyl-3-[7-{2-[ethyl(methyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
3-[7-[2-(diethylamino)ethoxy]-1-oxoethyl-2(1H)-yl]-N-ethyl-4-methylbenzamide;
N-ethyl-3-[7-{2-[ethyl(isopropyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclobutyl-3-(7-hydroxy-1-oxoethyl-2(1H)-yl)-4-methylbenzamide;
N-cyclopropyl-4-methyl-3-[7-[2-(methylamino)ethoxy]-1-oxoethyl-2(1H)-yl]benzamide;
N-ethyl-3-7-{2-[(3R)-3-hydroxypyrrolidine-1-yl]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-ethyl-4-methyl-3-[1-oxo-7-(2-pyrrolidin-1 ylethoxy)isoquinoline-2(1H)-yl]benzamide;
N-ethyl-3-[7-[2-(4-hydroxypiperidine-1-yl)ethoxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-ethyl-4-methyl-3-[7-(2-{methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}ethoxy)-1-oxoethyl-2(1H)-yl]benzamide;
N-ethyl-3-[7-[2-(4-foreperiod-1-yl)ethoxy]-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-ethyl-4-methyl-3-[1-oxo-7-{2-[(3aR,6aS)-tetrahydro-5H-[1,3]dioxolo[4,5-C]pyrrol-5-yl]ethoxy}isoquinoline-2(1H)-yl]benzamide;
3-(7-hydroxy-1-oxoethyl-2(1H)-yl)-4-methyl-N-(1-methylcyclopropyl)benzamide;
N-isoxazol-3-yl-4-methyl-3-[7-(3-morpholine-4-ylpropyl)-1-oxoethyl-2(1H)-yl]benzamide;
N-isoxazol-3-yl-4-methyl-3-[7-(2-morpholine-4-ylethoxy)-1-oxoethyl-2(1H)-yl]benzamide;
3-[7-(2-aminoethoxy)-1-oxoethyl-2(1H)-yl]-N-cyclopropyl-4-methylbenzamide;
N-isoxazol-3-yl-4-methyl-3-[1-oxo-7-(2-piperidine-1-ylethoxy)isoquinoline-2(1H)-yl]benzamide;
3-[7-{2-[tert-butyl(methyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-N-ethyl-4-methylbenzamide;
3-[7-{2-[isopropyl(methyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methyl-N-(1-methyl-1H-pyrazole-3-yl)benzamide;
3-[7-{2-[isopropyl(methyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-4-methyl-N-(1-methyl-1H-pyrazole-5-yl)benzamide;
3-[7-{2-[isopropyl(methyl)amino]ethoxy}-1-oxoethyl-2(1H)-yl]-N-methoxy-4-methylbenzamide;
N-cyclobutyl-3-[7-{2-[isopropyl(methyl)amino]ethoxy}-1-oxoethyl-(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-(7-methoxy-4-methyl-1-oxoethyl-2(1H)-yl)-4-methylbenzamide;
N-cyclopropyl-3-[7-{2-[isopropyl(methyl)amino]ethoxy}-4-methyl-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-ethyl-3-[7-{2-[isopropyl(methyl)amino]ethoxy}-4-methyl-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclopropyl-3-[4-(hydroxymethyl)-7-methoxy-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-ethyl-3-[7-{2-[ethyl(methyl)amino]ethoxy}-4-methyl-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
3-[7-[2-(dimethylamino)ethoxy]-4-methyl-1-oxoethyl-2(1H)-yl]-N-ethyl-4-methylbenzamide;
N-cyclobutyl-3-[7-{2-[isopropyl(methyl)amino]ethoxy}-4-methyl-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
N-cyclobutyl-3-[7-{2-[ethyl(methyl)amino]ethoxy}-4-methyl-1-oxoethyl-2(1H)-yl]-4-methylbenzamide; and
N-cyclobutyl-3-[7-[2-(dimethylamino)ethoxy]-4-methyl-1-oxoethyl-2(1H)-yl]-4-methylbenzamide;
or its pharmaceutically acceptable salt.

7. The method of obtaining the compounds of formula I according to claim 1 or its pharmaceutically acceptable salts, including: dehydration of compounds of formula II,

where R1, m, R2, R4and R5are as defined in claim 1, and where any functional group is optionally protected, and:
(1) removing any protective groups; and
(2) may form pharmaceutically acceptable salts.

8. Pharmaceutical composition for the use in the treatment of diseases, mediated by cytokines, containing the compound of the formula I according to any one of claims 1 to 6, or its pharmaceutically acceptable salt in combination with a pharmaceutically acceptable diluent or carrier.

9. The compound of formula I according to any one of claims 1 to 6, or its pharmaceutically acceptable salt having the ability to inhibit the enzyme 38α-kinase.

10. The method of inhibition of the enzyme 38α-kinase, comprising introducing an effective amount of the compounds of formula I according to any one of claims 1 to 6, or its pharmaceutically acceptable salt.

11. Method of inhibiting TNFα production, including the introduction of inhibitory cytokines amount of the compounds of formula I according to any one of claims 1 to 6, or its pharmaceutically acceptable salt.

12. Method of inhibiting the production of cytokines, including the introduction of inhibitory cytokines amount of the compounds of formula I according to any one of claims 1 to 6, or its pharmaceutically acceptable salt.

13. The compound of formula I according to any one of claims 1 to 6, or its pharmaceutically acceptable salt for use in the manufacture of drugs having the ability to inhibit the enzyme 38α-kinase.

14. The compound of formula I according to any one of claims 1 to 6, or its pharmaceutically acceptable salt in the manufacture of a medicinal product for use in the treatment of medical conditions mediated by cytokines.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I)

, pharmaceutical compositions based on the said compounds, as well as methods of using said compounds in preparing medicinal agents.

EFFECT: obtaining compounds and a composition which can inhibit phosphatase cdc25, particularly phosphatase cdc25-C and can be particularly used for treating cancer.

12 cl, 56 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to compounds of formula I or to pharmaceutically acceptable salts thereof, where Ar is imidazole or pyrazole, where the said Ar can be substituted with substitute(s) selected from a group consisting of a C1-C6 alkyl group, a phenyl group and a halogen atom, each of Y1, Y2 and Y3 is a carbon ot nitrogen atom, A is an oxygen atom, a sulphur atom or a group of formula -SO2-, R1 is a hydrogen atom, a C1-C6 alkyl group which can be substituted with one phenyl group (where the said phenyl group can be substituted with one substitute selected from a group consisting of a halogen atom and a C1-C6 alkyl group), or a phenyl group, R2 is a C1-C6 alkyl group, R3 is (i) a C1-C18 alkyl group, (ii) C2-C8 alkenyl group, (iii) C2-C8 alkynyl group, (iv) C3-C8 cycloalkyl group, (v) C1-C6 alkyl group substituted with 1-3 substitutes selected from a group given in paragraph 1 of the formula of invention, or (vi) a phenyl group, a naphthyl group, a pyrazolyl group, a pyridyl group, an indolyl group, a quinolinyl group or an isoquinolinyl group, where each of the said groups can be substituted with 1-3 substitutes selected from a group given in paragraph 1, R4 is a hydrogen atom or a C1-C6 alkyl group, and R5 is (i) C1-C10 alkyl group, (ii) C1-C10 alkyl group which is substituted with one or two substitutes selected from a group given in paragraph 1, (iii) C2-C8 alkenyl group which can be substituted with a phenyl group, or (iv) phenyl group, naphthyl group, thienyl group, pyrrolyl group, pyrazolyl group, pyridyl group, furanyl group, benzothienyl group, isoquinolinyl group, isoxazolyl group, thiazolyl group, benzothiadiazolyl group, benzoxadiazolyl group, phenyl group, condensed with a 5-7-member saturated hydrocarbon ring which can contain one or two oxygen atoms as ring members, uracyl group or tetrahydroisoquinolinyl group, where each of the said groups can be substituted with 1-5 substitutes selected from a group given in paragraph 1, provided that when Ar is a group of formula 5, which can be substituted with a C1-C6 alkyl group, R5 is not a C1-C10 alkyl group, and the formula (I) compound is not 5-(3,5-dichlorophenylthio)-4-isopropyl-2-methane-sulfonylaminomethyl-1-methyl-1H-imidazole or 5-(3,5-dichlorophenylthio)-4-isopropyl-1-methyl-2-p-toluene-sulfonylaminomethyl-1H-imidazole. The invention also relates to a pharmaceutical composition based on the formula I compound and to formula II compounds, radicals of which are defined in the formula of invention.

EFFECT: obtaining novel compounds with inhibitory effect on the bond between S1P and its Edg-1 (SIP1) receptor.

32 cl, 43 tbl, 18 ex

FIELD: medicine.

SUBSTANCE: invention refers to new compounds of formula I in the form of salt where J means a C1-C2 alkylene; R1 means cyclopentane, cyclohexyl, phenyl or thiophenes; R2 means hydroxy; R3 means a cyclopentane, cyclohexyl, phenyl or thiophenes; with R1 and R3 are not identical, or -CR1R2R3 together form a group of the formula , where Ra means a chemical bond, and Rb means hydroxy; R4 means methyl; R5 means C1 alkyl substituted with -CO-NH-R6; R6 means 5- or 6-membered heterocyclic group that contains in a cycle at least one heteroatom selected from nitrogen, oxygen and sulfur; or J means C1-C2 alkylene; R1 and R3 both mean phenyl; R2 means hydroxy; R4 means methyl, R5 means C1 alkyl substituted with -CO-NH-R9; and R9 means 5- or 6-membered heterocyclic group that contains in a cycle at least one heteroatom selected from nitrogen, oxygen and sulfur. The invention also refers to pharmaceutical composition, to application of compound according to any of clauses 1-3, as well as to method for obtaining a compound of formula I according to clause 1.

EFFECT: obtaining new biologically active compounds having antagonistic activity against muscarinic receptor M3.

7 cl, 21 ex

FIELD: chemistry.

SUBSTANCE: in the formula (I) , R1 is metoxymethyl; R2 is selected out of -C(O)NR4R5, -SO2NR4R5, -S(O)PR4 and HET-2; R3 is selected out of halogeno, fluoromethyl, metoxy and cyano; HET-1 is 5- or 6-member heteroaryl ring linked by C atom and containing nitrogen atom in 2 position and possibly 1 or 2 additional ring heteroatoms selected independently out of O, N and S, which is possible substituted at available carbon atom or at ring nitrogen atom by 1 substitute selected independently out of R6, provided that it would not cause ring quaternisation. The other radicals are indicated in the invention claim. Also invention refers to pharmaceutical composition containing claimed compound as active component, and methods of obtaining compound of the formula (I).

EFFECT: compounds with glucokinase inhibition effect.

19 cl, 2 tbl, 61 ex

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of the formula (I) and pharmaceutically acceptable salts, where R1-R7 mean the same as provided in the invention description and claim. Compounds of the formula (I) are specific inhibitors of 11b-HSD1. They can be applied in treatment and/or prevention of diseases caused by dysfunctions related to 11b-HSD1 enzyme, particularly in treatment and/or prevention of metabolic diseases, obesity, dyslipidemia, hypertension and/or diabetes, especially diabetes type "П". Additionally subject matter includes pharmaceutical composition for treatment and/or prevention of the said diseases.

EFFECT: improved efficiency of derivatives.

21 cl, 1 tbl, 146 ex

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of the formula (I): , where R1 is C1-C8alkyl optionally substituted with one to three substitutes selected out of substitute group A; R2 is C1-C6alkyl or C1-C6alkoxyC1-C6alkyl; R3 is C1-C6alkyl or C1-C6alkoxy; or R2 and R3 together with adjoining carbon atoms form optionally substituted non-aromatic 5-10-member carbon ring; R4 is hydrogen; G is group represented by the formula: or the rest as provided in the invention claim; and to pharmaceutical composition, application of claimed compounds, and method of atopic dermatitis prevention or treatment.

EFFECT: novel compounds useful as atopic dermatitis treatment medication and antipruritic medicines.

24 cl, 75 ex, 290 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to cyclic derivatives of aminobenzoic acid and to their pharmaceutically acceptable salts of general formula , in which ring Ar is a phenyl group, a 5-member aromatic heterocyclic group containing 1-2 heteroatoms selected from nitrogen, sulphur and oxygen, or a benzothiazolyl group; where the said groups can have 1-2 substitutes selected from a group comprising lower alkyl; a phenyl group; a phenyl group substituted with 1-2 halogens; a phenyl group substituted with a lower alkoxy group; a phenyl group substituted with a halogen-substituted lower alkyl group; a phenoxy group substituted with a halogen; a halogen; Z is an oxygen atom or -(CH2)-n (where n equals 0, 1 or 2); Y is C1-C4 alkylene, C2-C4 alkenylene or general formula (2) -T-A-U- (2) in which T is a single bond, C1-C4 alkylene or C2-C4 alkenylene; U is single bond, C1-C4 alkylene; values of the rest of radicals are given in the formula of invention.

EFFECT: obtaining a PPARα, agonist which contains an active ingredient in form of at least one cyclic derivative of aminobenzoic acid, and an agent which reduces the level of lipids which contains an active ingredient in form of at least one cyclic derivative of aminobenzoic acid.

12 cl, 16 tbl, 184 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to phenylalanine derivatives and their pharmaceutically acceptable salts. In formula (1) R11 is a hydroxyl group, an alkoxyl group having 1-6 carbon atoms, which can be substituted with a methoxy group, cycloalkoxyl group having 3-6 carbon atoms, or a benzyloxy group; R12 and R13 each independently represents a hydrogen atom, alkyl group having 1-6 carbon atoms, cycloalkyl group having 3-6 carbon atoms, acetyl group or methyloxycarbonyl group, or N(R12)R13 is a 1-pyrrolidinyl group, 1-piperidinyl group, 4-morpholinyl group; R14 is a methyl group; R1' is a hydrogen atom, fluorine atom; X1 is -CH(R1a)-, -CH(R1a)CH(R1b)-, -CH(R1a)CH(R1b)CH(R1c)-, -N(R1a)CH(R1b)CH(R1c)-, -OCH(R1a)CH(R1b)-, -OCH(R1a)CH(R1b)CH(R1c)- or 1,3-pyrrolidinylene, where R1a, R1b, each independently represents a hydrogen atom or a methyl group, and R1c is a hydrogen atom; Y11 and Y12 represent any of the combinations (CI, Cl), (CI, Me), (CI, F). Invention also relates to phenylalanine derivatives of formulae (2)-(14), given in the formula of invention.

EFFECT: obtaining a pharmaceutical composition having antagonistic effect on α4-integrin, containing a phenylalanine derivative as an active ingredient, a α4-integrin antagonist and a therapeutic agent.

65 cl, 51 tbl, 244 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new imidazole derivatives of general formula I , where R1 is C1-C10alkyl or C3-C10cycloalkyl, each possibly and independently substituted with 1 substitute selected from C3-C10cycloalkyl or aryl or a heteroaryl group, possibly substituted with one or two halogens; aryl or heteroaryl; R2 is C1-C10alkoxy or C1-C10thioalkyl; R3 is C1-C10alkoxy, possibly substituted with one C1-C10alkoxy or nitrile, where the said alkoxy group can be cyclic or can contain one O heteroatom; R4 is C1-C10alkyl; C2-C10alkenyl; C1-C10alkoxy or C3-C10cycloalkyl, each possibly and independently substituted with 1 or 2 substitutes selected from C1-C10alkoxy, C3-C10cycloalkyl, carboxylic ester, or with one or two aryl or heteroaryl groups, possibly substituted with one substitute selected from C1-C10alkyl, C3-C10cycloalkyl, nitro or halogen; aryl or heteroaryl, each possibly and independently substituted with 1-3 substitutes selected from C1-C10alkyl, C3-C10cycloalkyl, C1-C10alkoxy, phenoxy, thiophenyl, halogen, nitro, nitrile or aryl group, possibly substituted with one halogen; where up to three hydrogen atoms of the alkyl group can be substituted with fluorine atoms; where the said cycloalkyl can independently have one or two carbon atoms substituted with O or N; where the said aryl denotes an aromatic ring having 6 to 10 carbon atoms, including mono- and bicyclic compounds; and where the said heteroaryl denotes an aromatic ring having 3 to 10 carbon atoms, including mono- and bicyclic compounds in which one to three ring atoms are oxygen, nitrogen or sulphur atoms; except compounds given in paragraph 1. The invention also pertains to use of the said compounds for making a medicinal agent, a treatment and prevention method, a compound of formula II (values of radicals are given in the formula of invention).

EFFECT: new imidazole derivatives having positive allosteric modulator effect on GABAB receptor are obtained.

30 cl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of a 5-hydroxy-4-thiomethylpyrazole compound, where a pyrazole compound of general formula is reacted with a sulphur compound of general formula X-S(O)n-R (2) in the presence of a base and formaldehyde to form a 5-hydroxy-4-thiomethyl compound of general formula , where radicals and symbols in the said formulae are defined in the formula of invention.

EFFECT: easier synthesis of the desired 5-hydroxy-4-thiomethylpyrazole compound with high output in mild conditions in a single step without using special equipment, expensive catalyst or a transition metal etc, where the process can be carried out virtually without formation of hazardous wastes from a catalyst etc; owing to this, the method is environmentally safe and can be used in industry.

6 cl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I') which have inhibitory effect on ALK kinase: , where n' is selected from 1 and 2; R'2 is selected from halogen; R'3 is selected from -S(O)2NR'5R'6, -S(O)2R'6 and -C(O)NR'5R'6, where R'5 is selected from hydrogen and C1-6alkyl, and R'1 is selected from C1-6alkyl; and R'1 is selected from phenyl which is substituted with 3 radicals independently selected from C2-6alkoxy group, C1-6alkyl, -X'R'4 and -OXR'4, where X' denotes a bond, and R'4 is selected from piperazinyl, piperidinyl, pyrrolidinyl, morpholino, where R'4 can be optionally substituted with 1-3 radicals independently selected from C1-6 alkyl, provided that the following compound is excluded .

EFFECT: design of a method of inhibiting and using compounds for making a medicinal agent for treating diseases which respond to ALK kinase inhibition.

7 cl, 61 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to compounds of formula I or to pharmaceutically acceptable salts thereof, where Ar is imidazole or pyrazole, where the said Ar can be substituted with substitute(s) selected from a group consisting of a C1-C6 alkyl group, a phenyl group and a halogen atom, each of Y1, Y2 and Y3 is a carbon ot nitrogen atom, A is an oxygen atom, a sulphur atom or a group of formula -SO2-, R1 is a hydrogen atom, a C1-C6 alkyl group which can be substituted with one phenyl group (where the said phenyl group can be substituted with one substitute selected from a group consisting of a halogen atom and a C1-C6 alkyl group), or a phenyl group, R2 is a C1-C6 alkyl group, R3 is (i) a C1-C18 alkyl group, (ii) C2-C8 alkenyl group, (iii) C2-C8 alkynyl group, (iv) C3-C8 cycloalkyl group, (v) C1-C6 alkyl group substituted with 1-3 substitutes selected from a group given in paragraph 1 of the formula of invention, or (vi) a phenyl group, a naphthyl group, a pyrazolyl group, a pyridyl group, an indolyl group, a quinolinyl group or an isoquinolinyl group, where each of the said groups can be substituted with 1-3 substitutes selected from a group given in paragraph 1, R4 is a hydrogen atom or a C1-C6 alkyl group, and R5 is (i) C1-C10 alkyl group, (ii) C1-C10 alkyl group which is substituted with one or two substitutes selected from a group given in paragraph 1, (iii) C2-C8 alkenyl group which can be substituted with a phenyl group, or (iv) phenyl group, naphthyl group, thienyl group, pyrrolyl group, pyrazolyl group, pyridyl group, furanyl group, benzothienyl group, isoquinolinyl group, isoxazolyl group, thiazolyl group, benzothiadiazolyl group, benzoxadiazolyl group, phenyl group, condensed with a 5-7-member saturated hydrocarbon ring which can contain one or two oxygen atoms as ring members, uracyl group or tetrahydroisoquinolinyl group, where each of the said groups can be substituted with 1-5 substitutes selected from a group given in paragraph 1, provided that when Ar is a group of formula 5, which can be substituted with a C1-C6 alkyl group, R5 is not a C1-C10 alkyl group, and the formula (I) compound is not 5-(3,5-dichlorophenylthio)-4-isopropyl-2-methane-sulfonylaminomethyl-1-methyl-1H-imidazole or 5-(3,5-dichlorophenylthio)-4-isopropyl-1-methyl-2-p-toluene-sulfonylaminomethyl-1H-imidazole. The invention also relates to a pharmaceutical composition based on the formula I compound and to formula II compounds, radicals of which are defined in the formula of invention.

EFFECT: obtaining novel compounds with inhibitory effect on the bond between S1P and its Edg-1 (SIP1) receptor.

32 cl, 43 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel triazole-substituted aminobenzophenone compounds of formula (Ia) or (Ib), (values of radicals are given in the formula of invention) and a pharmaceutical composition containing the said compounds.

EFFECT: obtaining novel compounds which can be used in treating inflammatory, ophthalmological diseases or cancerous growths.

20 cl, 67 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of the formula (I) and pharmaceutically acceptable salts, where R1-R7 mean the same as provided in the invention description and claim. Compounds of the formula (I) are specific inhibitors of 11b-HSD1. They can be applied in treatment and/or prevention of diseases caused by dysfunctions related to 11b-HSD1 enzyme, particularly in treatment and/or prevention of metabolic diseases, obesity, dyslipidemia, hypertension and/or diabetes, especially diabetes type "П". Additionally subject matter includes pharmaceutical composition for treatment and/or prevention of the said diseases.

EFFECT: improved efficiency of derivatives.

21 cl, 1 tbl, 146 ex

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of the formula (I): , where R1 is C1-C8alkyl optionally substituted with one to three substitutes selected out of substitute group A; R2 is C1-C6alkyl or C1-C6alkoxyC1-C6alkyl; R3 is C1-C6alkyl or C1-C6alkoxy; or R2 and R3 together with adjoining carbon atoms form optionally substituted non-aromatic 5-10-member carbon ring; R4 is hydrogen; G is group represented by the formula: or the rest as provided in the invention claim; and to pharmaceutical composition, application of claimed compounds, and method of atopic dermatitis prevention or treatment.

EFFECT: novel compounds useful as atopic dermatitis treatment medication and antipruritic medicines.

24 cl, 75 ex, 290 tbl

FIELD: chemistry.

SUBSTANCE: in novel compounds of the formula (I) R is radical selected out of i) , ii) , iii) , iv) , where R7 is halogen, cyano, C1-4alkyl, C1-4alkoxy; p is integer within 0 to 3; R1 is hydrogen, C2-4alkenyl or C1-4alkyl; R2 is hydrogen or C1-4alkyl; R3 and R4 are independently hydrogen or C1-4alkyl; R5 is: phenyl substituted with 1-3 groups selected independently out of trifluoromethyl, C1-4alkyl, cyano or halogen; naphthyl substituted with 1-3 groups selected independently out of trifluoromethyl, C1-4alkyl, cyano or halogen; benzofurane substituted with 1-3 groups selected independently out of C1-4alkyl or halogen; R6 is hydrogen or (CH2)qR8; R8 is hydrogen; m is zero or 1; n is 1; q is an integer within 1 to 4; r is 1 or 2; provided that if R5 is phenyl substituted with 1-3 groups selected independently out of trifluoromethyl, C1-4alkyl, cyano or halogen, then R is not radical i) ; and pharmaceutically acceptable salts or solvates thereof. The invention also refers to method (A) of compound obtainment, to compound application, to pharmaceutical composition, as well as to mammal treatment method.

EFFECT: obtainment of novel bioactive compounds with tachykinin receptor antagonist activity.

16 cl, 116 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I

where A, B and D each denotes N or CR5, where one of A, B and D denotes N, R1 denotes OR6, R2 denotes halogen, C1-C4alkyl, halogen(C1-C4)alkyl or OR7, R3 denotes a heteroarylalkyl group in which the heteroaryl fragment contains 5-6 atoms in the ring, at least one of which is an N atom, and the alkyl fragment with a branched or straight chain contains 1-5 carbon atoms, R4 denotes C3-C10cyclalkyl, C6-C14aryl, unsubstituted or substituted with one or more substitutes selected from a group comprising halogen, alkoxy, terazol-5-yl, 2-(heterocyclyl)tetrazol-5-yl or a carboxy group; heteroaryl containing 5-6 atoms in the ring; heterocyclic group saturated or partially saturated, containing 5-6 atoms in the ring, at least one of which is an N atom, unsubstituted or substituted with one or more substitutes selected from a group comprising alkoxy, alkoxyalkoxy, oxo, alkoxycarbonyl, alkylsulfanyl, alkylsufonyl or phenylsulfonyl; R5 denotes H; R6 denotes H or C1-C4alkyl with a branched or straight chain, unsubstituted or substituted with one or more halogens, R7 denotes H or C1-C12alkyl with a branched or straight chain, unsubstituted or substituted with one or more substitutes selected from a group which includes halogen; C3-C10cyclalkyl; saturated heterocyclic group containing 5-6 atoms in the ring, at least one of which is an O atom, or a heterocylcylalkyl group in which the heterocyclic fragment is saturated, partially saturated or unsaturated and contains 5-10 atoms in the ring, at least one of which is an O atom; or to a pharmaceutically acceptable salt thereof, as well as to a pharmaceutical composition for inhibiting PDE4 enzyme activity and to use of the said compound to prepare a medicinal agent.

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

65 cl, 17 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted cycloalkene derivatives of formula (I) in which X and Y are a group, in which X and Y together with a carbon atom on ring B to which they are bonded form a ring A, X and Y together represent a ring B substitute, or each of X and Y is a hydrogen atom.

EFFECT: invention relates to a medicinal agent based on the said compounds, which has inhibitory effect on intracellular signal transduction or cell activation induced by an endotoxin.

21 cl, 3 tbl, 191 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound or its salt of formula 1: , where A, E, D, R0, R1-R4 and a assume values given in the formula of invention. The invention also relates to an antioxidant medicinal agent.

EFFECT: effectiveness during treatment of ischemic diseases of organs, during treatment of diseases caused by oxidation cell disorders and when inhibiting disorders of the retina.

4 cl, 1 tbl, 6 ex

Triazole derivative // 2383536

FIELD: chemistry.

SUBSTANCE: described are novel triazole derivatives with general formula where values of radicals are given in the formula of invention, a pharmaceutical composition containing said derivatives, and a method of treating autoimmune diseases. Compounds with general formula (1) and their pharmaceutically acceptable salts have inhibition effect on S1P and its Edg-1 receptor (S1P1).

EFFECT: possibility of use as a pharmaceutical product.

43 cl, 10 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (1), their tautomers and pharmaceutically acceptable salts. The disclosed compounds have thromobopoietin receptor agonist properties. In formula (1) , A is a nitrogen atom or CH, when A is a nitrogen atom, B is NR9 (where R9 is a C1-10 alkyl group), and when A is CH, B is a sulphur atom, R1 is a phenyl group (the phenyl group is substituted with one or more substitutes selected from a group consisting of halogen atoms, C1-10 alkyl groups and C1-10 alkoxy groups (C1-10 alkyl groups and C1-10 alkoxy groups are unsubstituted or substituted with one or more halogen atoms)), L1 is bond, X is OH, R2 is a C1-10 alkyl group, L2 is a bond, L3 is NH, L4 is a bond or NH, Y is a sulphur atom, and when L4 is a bond, R3 is a piperidinyl group, a piperazinyl group (the piperidinyl group and the piperazinyl group are substituted with substitutes selected from a group containing C1-10 alkoxycarbonyl groups, carboxyl group, hydroxyl groups, di-C1-10 alkylaminocarbonyl groups, C1-10 alkylaminocarbonyl groups and C1-10 alkyl groups (C1-10 alkylaminocarbonyl groups and C1-10 alkyl groups are substituted with a substitute selected from a group containing pyridyl groups, hydroxyl groups and carboxyl groups)), or when L4 is NH, R3 is a C1-10 alkyl group (C1-10 alkyl group is substituted with a substitute selected from a group containing C1-10 alkoxy groups, C1-10 alkoxycarbonyl groups or carboxyl groups).

EFFECT: obtaining a thrombopoietin receptor activator which is a formula (1) compound and a medicinal agent which contains the disclosed compound as an active ingredient.

10 cl, 3 tbl, 47 ex

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