Pyrimidine derivatives as alk-5 inhibitors

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrimidine derivatives of formula (I) in free form or in form of a pharmaceutically acceptable salt or solvate, which are useful in treating inflammatory or obstructive airways, pulmonary hypertension, pulmonary fibrosis, liver fibrosis, muscle diseases and systemic skeletal disorders and other diseases which are mediated by activity of the ALK-5 receptor or ALK-4 receptor. The invention also relates to a method of producing compounds of formula (I) and pharmaceutical compositions. In formula , T is a pyridin-2-yl which is optionally substituted in one position with R1; T1 is a pyridinyl which is optionally substituted in one or two positions with R1, R2, R5, C1-C4-alkoxy group, C1-C4-alkoxycarbonyl or cyano group; and Ra and Rb are independently hydrogen; C1-C8-alkyl, optionally substituted in one, two or three positions with R4; C3-C10-cycloalkyl, which is optionally substituted in one or two positions with a hydroxy group, amino group, C1-C8-alkyl, C1-C8-alkoxy group, halogen, cyano group, oxo group, carboxy group or nitro group; or C6-C15-aryl, optionally substituted in one, two or three positions with a halogen, hydroxy group, amino group, cyano group, oxo group, carboxy group, nitro group or R5; R1 is C1-C8-alkyl; R2 is C6-C15-aryl, optionally substituted in one, two or three positions with a halogen, hydroxy group, R1, R5, C1-C8-alkylthio group, amino group, C1-C8-alkylamino group, etc. The rest of the values of the radicals are given in the claim.

EFFECT: high efficiency of using said compounds.

20 cl, 2 tbl

 

The text descriptions are given in facsimile form.

1. The compound of formula I:

in free form or pharmaceutically acceptable salt or MES, where
T1is the feast of the DIN-2-yl, optionally substituted in one position for R1;
T2represents pyridinyl, optionally substituted at one or two positions R1, R2, R5With1-C4-alkoxygroup,1-C4-alkoxycarbonyl or cyano;
and Raand Rbindependently represent hydrogen; C1-C8-alkyl, optionally substituted in one, two or three positions R4;3-C10-cycloalkyl, optionally substituted at one or two positions by hydroxy-group, amino group, C1-C8-alkyl, C1-C8-alkoxygroup, halogen, cyano, exography, carboxypropyl or nitro-group; or (C6-C15aryl, optionally substituted in one, two or three positions by halogen, hydroxy-group, amino group, cyano, exography, carboxypropyl, nitrogroup, or R5;
provided that Raand Rbboth simultaneously represent hydrogen;
R1represents a C1-C8-alkyl;
R2represents a C6-C15aryl, optionally substituted in one, two or three positions by halogen, hydroxy-group, R1, R5With1-C8-alkylthiophene, an amino group, a C1-C8-alkylaminocarbonyl, di(C1-C8-alkyl)aminogroup is, by cyano, carboxypropyl, a nitro-group, -O-C6-C15-aryl, halogen-C1-C8-alkyl, -NR6R7, -C1-C8-alkyl-NR6R7, -O-C1-C8-alkyl-NR6R7- 1-C8-alkyl-R5, -O-R1, -O-R5, -C(=O)-R5, -C(=O)-NH2, -C(=O)NR6R7, -C(=O)-O-R1, -O-C(=O)-R1, -SO2-NH2, -SO2-R1, -NH-SO2-C1-C8-alkyl, -C(=O)-NH-R5, -SO2-C6-C15-aryl, -SO2-R5, -SO2NR6R7or1-C8-alkoxygroup, optionally substituted in one position di(C1-C8-alkyl)amino group;
R4represents a hydroxy-group, amino group, With1-C8-alkoxygroup, C1-C8-allylthiourea, halogen, halogen-C1-C8-alkyl, C1-C8-alkylamino, di(C1-C8-alkyl)amino, cyano, carboxypropyl, a nitrogroup, N(H)-C(=NH)-NH2, -N(H)-SO2-R2, -R2, -C(=O)-R2, -C(=O)-R5, -O-R2, -O-R5, -N(H)-R5, -N(H)-R2, -NR6R7, -C(=O)-R1, -C(=O)-NH2, -SO2-R5,-C(=O)-O-R1, -C(=O)-O-R2, -C(=O)-O-R5, -SO2-R2or-C(=O)-N(H)-C1-C8-alkyl-C(=O)-N(H)-R2;
or R4represents 4-14-membered heterocyclic group which is optionally substituted in one, two or three positions by hydroxy-group, halogen, exography, cyano, amino, C1-C8-alkylaminocarbonyl, di(C1-C8-alkyl) - amino group, carboxypropyl, nitrogroup, -N(H)R1, -N(H)-SO2-C1-C6-alkyl,
-N(H)-C(=O)-C1-C4-alkyl-R2, -C(=O)-NH2, -C(=O)-NR6R7-C(=O)-N(H)-C1-C8-alkyl-R6, -C(=O)-R2, -C(=O)-R5With1-C8-alkoxygroup, C1-C8-alkylthiophene,3-C10-cycloalkyl, -C(=O)-R1, halogen-C1-C8-alkyl, R2- 1-C8-alkyl-R2, -R5, -SO2-C1-C8-alkyl, -SO2-R2, -SO2-R5or-SO2NR6R or C1-C8-alkyl, optionally substituted at one position by hydroxy-group;
or R4represents a C6-C15aryl, optionally substituted in one, two or three positions by hydroxy-group, With1-C8-alkoxygroup, -O-C6-C15-aryl or C1-C8-alkyl, optionally substituted at one position by hydroxy-group;
or R4represents a C3-C10-cycloalkyl substituted in one, two or three positions by hydroxy-group, amino group, halogen, cyano, carboxypropyl, nitrogroup or1-C8R5represents 4-14-membered heterocyclic group, optionally substituted at one or two positions by exography, amino, halogen, C1-C8-alkylaminocarbonyl, di(C1-C8-alkyl)amino, cyano, hydroxy-group, carboxypropyl, nitrogroup, -R1With1-C8-alkoxygroup,1-C8-alkylthiol, halogen-C1-C8-alkyl, -C(=O)-NH2or-SO2-NH2;
R6and R7independently represent hydrogen, -R1With1-C8-alkylamino, di(C3-C8-alkyl)amino, C6-C15-aryl, -C1-C8-alkyl-C6-C15-aryl, R5or-C1-C8-alkyl-R5;
where C3-C10-cycloalkyl means a fully saturated monocyclic or bicyclic carbocyclic ring containing 3 to 10 ring carbon atoms;
provided that, if T1represents pyridin-2-yl, T2represents pyridin-3-yl and Rarepresents hydrogen, then Rbdoes not represent 2-(1H-indol-3-yl)ethyl.

2. The compound according to claim 1 or its salt,
where T1represents pyridin-2-yl, optionally substituted in one position for R1;
T2represents pyridinyl group, not necessarily for sennou in one or two positions R 1, R2, R5With1-C4-alkoxygroup, C1-C4-alkoxycarbonyl or cyano;
Raand Rbindependently represent hydrogen; C1-C8-alkyl, optionally substituted at one or two positions R4;3-C10-cycloalkyl; or (C6-C15aryl, optionally substituted at one or two positions R5;
provided that Raand Rbboth simultaneously represent hydrogen;
R1represents a C1-C8-alkyl;
R2represents a C6-C10aryl, optionally substituted at one or two positions by halogen, R5With1-C3-alkyl-R5, -C(=O)-R5, -SO2-NH2, -SO2-R1, -NH-SO2-C1-C6-alkyl, -C(=O)-NH-R5or C1-C8-alkoxygroup, optionally substituted in one position di(C1-C8-alkyl)amino group;
R4represents a hydroxy-group, -C(=O)-R5or-SO2-R2;
or R4represents 4-14-membered heterocyclic group which is optionally substituted in one or two positions by hydroxy-group, halogen, cyano, amino, carboxypropyl, -N(H)-SO2-C1-C8-alkyl, C1-C8-alkoxygroup,3-C10-cyclea the kilometres, -C(=O)-R1, R2, -SO2-C1-C8-alkyl, R5or C1-C8-alkyl, optionally substituted at one position by hydroxy-group;
or R4represents a C6-C15aryl, optionally substituted at one or two positions by hydroxy-group, With1-C8-alkoxygroup, -O-C6-C15-aryl or C1-C8-alkyl, optionally substituted at one position by hydroxy-group; and
R5is a 4-10 membered heterocyclic group, optionally substituted at one or two positions With1-C4-alkyl.

3. The compound according to claim 2, or its salt,
where T1represents pyridin-2-yl, optionally substituted in one position for R1;
T2represents pyridinyl group, optionally substituted at one or two positions R1, R2, R5With1-C4-alkoxygroup,1-C4-alkoxycarbonyl or cyano;
Rarepresents hydrogen;
Rbrepresents a C1-C4-alkyl, optionally substituted at one or two positions-R4;3-C6-cycloalkyl; or (C6-C10aryl, optionally substituted in one position-R5;
R1represents a C1-C4-alkyl;
R2not only is em a phenyl, optionally substituted in one position with halogen, R5With1-C4-alkyl-R5, -C(=O)-R5, -SO2-NH2, -SO2-R1, NH-SO2-C1-C4-alkyl, -C(=O)-NH-R5or1-C4-alkoxygroup, optionally substituted in one position di(C1-C4-alkyl)amino group;
R4represents a hydroxy-group, -C(=O)-R5or-SO2-R2;
or R4represents 4-14-membered heterocyclic group which is optionally substituted in one or two positions by hydroxy-group, halogen, cyano, amino, carboxypropyl, -N(H)-SO2-C1-C4-alkyl, C1-C4-alkoxygroup,3-C6-cycloalkyl, -C(=O)-R1, phenyl, -SO2-C1-C4-alkyl, R5or1-C4-alkyl, optionally substituted at one position by hydroxy-group;
or R4represents a C6-C10aryl, optionally substituted at one or two positions by hydroxy-group, With1-C4-alkoxygroup, -O-C6-C10-aryl or C1-C4-alkyl, optionally substituted at one position by hydroxy-group; and
R5is a 4-10 membered heterocyclic group, optionally substituted in one or two positions of the C1-C -alkyl.

4. The compound according to claim 1 or its salt, selected from the following compounds:
(1H-indol-4-ylmethyl)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(1H-indol-4-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(1H-indol-3-yl)ethyl]-[2-(6-methylpyridin-2-yl)-6-pyridin-3-Yeremey-4-yl]amine,
4-{2-[2-(6-methylpyridin-2-yl)-6-pyridin-3-Yeremey-4-ylamino]ethyl}phenol,
4-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]phenol,
[2-(1H-indol-4-yl)ethyl]-[2-(6-methylpyridin-2-yl)-6-pyridin-3-Yeremey-4-yl]amine,
(1H-indazol-4-ylmethyl)-[2-(6-methylpyridin-2-yl)-6-pyridin-3-Yeremey-4-yl]amine,
(1H-indol-4-ylmethyl)-[2-(6-methylpyridin-2-yl)-6-pyridin-3-Yeremey-4-yl]amine,
3-{2-[2-(6-methylpyridin-2-yl)-6-pyridin-3-Yeremey-4-ylamino]ethyl}-1H-indol-5-ol,
[2-(2-methyl-1H-indol-3-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(7-methyl-1H-indol-3-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(2,3-dihydrobenzofuran-7-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(5-methyl-1H-indol-3-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(6-methyl-1H-indol-3-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(5-fluoro-1H-indol-3-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(6-fluoro-1H-indol-3-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(2-pyridine-2-retil)-(6-pyridin-3-yl-2-pyridin-2-Lai is rimidine-4-yl)amine,
[2-(1H-indol-3-yl)ethyl]-(2-pyridin-3-yl-6-pyridin-2-Yeremey-4-yl)amine,
[2-(1-methyl-1H-indol-3-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(5-chloro-1H-indol-3-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(2-pyridin-3-retil)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(2-methyl-1-phenyl-1H-indol-3-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(1H-indol-3-ylmethyl)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(3-phenoxybenzyl)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)-1-o-trilateral,
2-methyl-3-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]-1H-indol-5-carbonitril,
1-piperazine-1-yl-3-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)propane-1-he,
(1H-indol-2-ylmethyl)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
3-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]-1H-indol-5-ol,
[2-(6-chloro-1H-indol-3-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(6-methoxy-1H-indol-3-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(2,3-dimethyl-1H-indol-5-ylmethyl)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(1H-indol-6-ylmethyl)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(1H-indol-4-ylmethyl)-[2-(3-methylpyridin-2-yl)-6-pyridin-3-Yeremey-4-yl]amine,
(2-indol-1-retil)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(5-methyln-[1,2,4]triazole-3-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(2-pyrazin-2-retil)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(2-benzosulfimide)-(2-pyridin-2-yl-6-pyridin-3-Yeremey-4-yl)amine,
(S)-1-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]-pyrrolidin-3-ol,
(R)-1-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]-pyrrolidin-3-ol,
1-{5-methoxy-3-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)-ethyl]indol-1-yl}Etalon,
[2-(7-fluoro-1H-indol-3-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(2-morpholine-4-espiridion-4-ylmethyl)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(5-cyclopropyl-1H-pyrazole-4-ylmethyl)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(4-chlorobenzenesulfonyl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
1-pyridin-2-yl-2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)-ethanol,
[2-(1H-indol-3-yl)ethyl]-[2-(3-methylpyridin-2-yl)-6-pyridin-3-Yeremey-4-yl]amine,
3-{2-[2-(6-methylpyridin-2-yl)-6-pyridin-3-Yeremey-4-ylamino]-ethyl}phenol,
2-methyl-3-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]-1H-indol-5-ol,
(2-benzoimidazol-1-retil)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(1H-indol-3-yl)propyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
3-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]-1H-indol-7-ol,
[2-(4-methyl-1H-indol-3-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
3-[2-(6-pyridin-3-yl-2-pyridin-2-illerimi the Jn-4 ylamino)ethyl]-1H-indol-4-ol,
{3-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]-1H-indol-5-yl}methanol,
3-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]-1H-indole-5-carboxylic acid,
3-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]-1H-indol-5-ylamine,
3-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]-1H-indol-6-ol,
4-[1-hydroxy-2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]phenol,
2-propyl-4-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]phenol,
4-[(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)methyl]phenol,
2-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]phenol,
{3-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)propyl]phenyl}methanol,
[3-(1H-pyrazole-3-yl)phenyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(2-morpholine-2-retil)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(5-methylisoxazol-3-ylmethyl)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
N-{3-[2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]-1H-indol-5-yl}methanesulfonamide,
3-[1-methyl-2-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)ethyl]-1H-indol-5-ol,
[2-(1-methanesulfonyl-1 H-indol-3-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(2-methyl-1H-indol-5-ylmethyl)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(4-methoxyphenyl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
3-[(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-ylamino)is ethyl]phenol,
(1H-indol-5-ylmethyl)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(1-methyl-1H-indol-4-ylmethyl)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
benzyl-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(4-methoxybenzyl)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(2-benzofuran-3-retil)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
(1H-indazol-4-ylmethyl)-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(1H-indol-6-yl)ethyl]-(6-pyridin-3-yl-2-pyridin-2-Yeremey-4-yl)amine,
[2-(4-methoxyphenyl)ethyl]-[2-(6-methylpyridin-2-yl)-6-pyridin-3-Yeremey-4-yl]amine,
[2-(1H-indol-6-yl)ethyl]-[2-(6-methylpyridin-2-yl)-6-pyridin-3-Yeremey-4-yl]amine,
[2-(6-methyl-1H-indol-3-yl)ethyl]-[2-(6-methylpyridin-2-yl)-6-pyridin-3-Yeremey-4-yl]amine,
triptorelin[2-(1H-indol-3-yl)ethyl]-(2-pyridin-2-yl-[4,5']bipyridinyl-6-yl)amine,
(1H-indol-4-ylmethyl)-[6-(5-methoxypyridine-3-yl)-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]amine,
[2-(1H-indol-3-yl)ethyl]-[6-(5-methoxypyridine-3-yl)-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]amine,
[2-(1H-indol-4-yl)ethyl]-[6-(5-methoxypyridine-3-yl)-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]amine,
[6-(3,5-dimethylisoxazol-4-yl)-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]-[2-(1H-indol-3-yl)ethyl]amine,
[2-(1H-indol-3-yl)ethyl]-[6-(5-methoxypyridine-3-yl)-2-pyridin-2-Yeremey-4-yl]amine,
[2-(1H-indol-3-yl)ethyl]-[6-(5-vinylpyridin-3-yl)-2-pyridin-2-Yeremey-4-yl]amine,
5-{6-[2-(1H-indol-3-yl)ethyl) - Rev. Mino]-2-pyridine-2-Yeremey-4-yl}nicotinamide,
5-{6-[(1H-indol-4-ylmethyl)amino]-2-pyridine-2-Yeremey-4-yl}nicotinamide,
(1H-indol-4-ylmethyl)-{2-pyridin-2-yl-6-[5-(1H-tetrazol-5-yl)pyridine-3-yl]pyrimidine-4-yl}amine,
ethyl ester 5-{6-[2-(1H-indol-3-yl)ethylamino]-2-pyridine-2-Yeremey-4-yl}nicotinic acid,
[6-(3,5-dimethylisoxazol-4-yl)-2-pyridin-2-Yeremey-4-yl]-[2-(1H-indol-3-yl)ethyl]amine,
{4-[5-(6-methylamino-2-pyridine-2-Yeremey-4-yl)pyridine-3-yl]phenyl}-(4-methylpiperazin-1-yl)methanon,
{6-[5-(4-forfinal)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}-[2-(1H-indol-3-yl)ethyl]amine,
{6-[5-(3-methoxyphenyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}methylamine,
N-{3-[5-(6-methylamino-2-pyridine-2-Yeremey-4-yl)pyridine-3-yl]phenyl} methanesulfonamide,
3-({6-[5-(3-methoxyphenyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-ylamino}methyl)phenol,
(1H-indol-4-ylmethyl)-{6-[5-(3-methoxyphenyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}amine,
benzyl-{6-[5-(3-methoxyphenyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}amine,
cyclopropyl-{6-[5-(3-methoxyphenyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}amine,
ethyl-{6-[5-(3-methoxyphenyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}amine,
methyl-{6-[5-(4-(morpholine-4-ylmethylene)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}amine,
methyl-{6-[5-(3-morpholine-4-ylphenyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}amine,
{4-[5-(6-methylamino-2-pyridine-2-Yeremey-4-yl)pyridine-3-yl]phenyl}morpholine-4-ylmethanone,
methyl-{2-Piri is in-2-yl-6-[5-(3-pyrrolidin-1-ylphenyl)pyridine-3-yl]pyrimidine-4-yl}amine,
{6-[5-(1H-indol-4-yl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}methylamine,
{6-[5-(3-ethoxyphenyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}methylamine,
{6-[5-(3-methanesulfonyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}methylamine,
3-[5-(6-methylamino-2-pyridine-2-Yeremey-4-yl)pyridine-3-yl]benzosulfimide,
{6-[5-(4-forfinal)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}methylamine,
[2-(1H-indol-3-yl)ethyl]-[6-(5-methylpyridin-3-yl)-2-pyridin-2-Yeremey-4-yl]amine,
{6-[5-(4-methoxyphenyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}methylamine,
{6-[5-(2-methoxyphenyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}methylamine,
methyl-{2-pyridin-2-yl-6-[5-(4-pyrrolidin-1-ylmethylene)pyridine-3-yl]pyrimidine-4-yl}amine,
{4-[5-(6-methylamino-2-pyridine-2-Yeremey-4-yl)pyridine-3-yl]phenyl}pyrrolidin-1-ylmethanone,
methyl-{2-pyridin-2-yl-6-[5-(3-pyrrolidin-1-ylmethylene)pyridine-3-yl]pyrimidine-4-yl}amine,
{3-[5-(6-methylamino-2-pyridine-2-Yeremey-4-yl)pyridine-3-yl]phenyl}pyrrolidin-1-ylmethanone,
{3-[5-(6-methylamino-2-pyridine-2-Yeremey-4-yl)pyridine-3-yl]phenyl}morpholine-4-ylmethanone,
methyl-{6-[5-(3-morpholine-4-ylmethylene)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}amine,
methyl-{6-[5-(4-(morpholine-4-ylphenyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}amine,
methyl-{2-pyridin-2-yl-6-[5-(4-pyrrolidin-1-ylphenyl)pyridine-3-yl]pyrimidine-4-yl}amine,
(6-{5-[4-(2-dimethylaminoethoxy)phenyl]pyridine-3-yl}-2-pyridine-2-Lai is rimidine-4-yl)methylamine,
(6-{5-[3-(2-dimethylaminoethoxy)phenyl]pyridine-3-yl}-2-pyridine-2-Yeremey-4-yl)methylamine,
3-[5-(6-methylamino-2-pyridine-2-Yeremey-4-yl)pyridine-3-yl]-N-(tetrahydropyran-4-yl)benzamid,
4-[5-(6-methylamino-2-pyridine-2-Yeremey-4-yl)pyridine-3-yl]-N-(tetrahydropyran-4-yl)benzamid,
3-({6-[5-(3-morpholine-4-ylmethylene)pyridine-3-yl]-2-pyridine-2-Yeremey-4-ylamino}methyl)phenol,
3-({2-pyridin-2-yl-6-[5-(3-pyrrolidin-1-ylphenyl)pyridine-3-yl]pyrimidine-4-ylamino}methyl)phenol,
3-({6-[5-(3-morpholine-4-ylphenyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-ylamino}methyl)phenol,
3-({2-pyridin-2-yl-6-[5-(3-pyrrolidin-1-ylmethylene)pyridine-3-yl]pyrimidine-4-ylamino}methyl)phenol,
(4-{5-[6-(3-hydroxybenzylidene)-2-pyridin-2-Yeremey-4-yl]pyridine-3-yl}phenyl)morpholine-4-ylmethanone,
3-({6-[5-(4-(morpholine-4-ylphenyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-ylamino}methyl)phenol,
3-[(6-{5-[4-(4-methylpiperazin-1-yl)phenyl]pyridine-3-yl}-2-pyridine-2-Yeremey-4-ylamino)methyl]phenol,
(3-{5-[6-(3-hydroxybenzylidene)-2-pyridin-2-Yeremey-4-yl]pyridine-3-yl}phenyl)-(4-methylpiperazin-1-yl)methanon,
3-[(6-{5-[3-(2-dimethylaminoethoxy)phenyl]pyridine-3-yl}-2-pyridine-2-Yeremey-4-ylamino)methyl]phenol,
3-[(6-{5-[4-(2-dimethylaminoethoxy)phenyl]pyridine-3-yl}-2-pyridine-2-Yeremey-4-ylamino)methyl]phenol,
{3-[5-(6-benzylamino-2-pyridine-2-Yeremey-4-yl)pyridine-3-yl]phenyl}morpholine-4-ylmethanone,
benzyl-(6-{5-[4-(2-dimethylaminoethoxy the si)phenyl]pyridine-3-yl}-2-pyridine-2-Yeremey-4-yl)amine,
{4-[5-(6-benzylamino-2-pyridine-2-Yeremey-4-yl)pyridine-3-yl]phenyl}-(4-methylpiperazin-1-yl)methanon,
benzyl-(6-{5-[3-(2-dimethylaminoethoxy)phenyl]pyridine-3-yl}-2-pyridine-2-Yeremey-4-yl)amine,
benzyl-{6-[5-(3-morpholine-4-ylphenyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-yl}amine,
benzyl-{2-pyridin-2-yl-6-[5-(3-pyrrolidin-1-ylphenyl)pyridine-3-yl]pyrimidine-4-yl}amine,
benzyl-(6-{5-[4-(4-methylpiperazin-1-yl)phenyl]pyridine-3-yl}-2-pyridine-2-Yeremey-4-yl)amine,
benzyl-(6-{5-[4-(4-methylpiperazin-1-ylmethyl)phenyl]pyridine-3-yl}-2-pyridine-2-Yeremey-4-yl)amine,
methyl-(6-{5-[4-(4-methylpiperazin-1-yl)phenyl]pyridine-3-yl}-2-pyridine-2-Yeremey-4-yl)amine,
methyl-(6-{5-[4-(4-methylpiperazin-1-ylmethyl)phenyl]pyridine-3-yl}-2-pyridine-2-Yeremey-4-yl)amine,
3-[(6-{5-[4-(4-methylpiperazin-1-ylmethyl)phenyl]pyridine-3-yl}-2-pyridine-2-Yeremey-4-ylamino)methyl]phenol,
3-({6-[5-(4-piperidine-1-ylphenyl)pyridine-3-yl]-2-pyridine-2-Yeremey-4-ylamino}methyl)phenol,
[6-[5-(4-forfinal)pyridine-3-yl]-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]methylamine,
[6-[5-(3-methoxyphenyl)pyridine-3-yl]-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]methylamine,
3-{[6-[5-(3-methoxyphenyl)pyridine-3-yl]-2-(6-methylpyridin-2-yl)pyrimidine-4-ylamino]methyl}phenol,
3-{[6-[5-(4-forfinal)pyridine-3-yl]-2-(6-methylpyridin-2-yl)pyrimidine-4-ylamino]methyl}phenol,
[6-[5-(4-methoxyphenyl)pyridine-3-yl]-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]methylamine,
[6-[5-(2-methoxyphenyl)p is ridin-3-yl]-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]methylamine,
methyl-{2-(6-methylpyridin-2-yl)-6-[5-(4-pyrrolidin-1-ylmethylene)pyridine-3-yl]pyrimidine-4-yl}amine,
(4-{5-[6-methylamino-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]pyridine-3-yl}phenyl)pyrrolidin-1-ylmethanone,
methyl-{2-(6-methylpyridin-2-yl)-6-[5-(3-pyrrolidin-1-ylmethylene)pyridine-3-yl]pyrimidine-4-yl}amine,
(3-{5-[6-methylamino-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]pyridine-3-yl}phenyl)pyrrolidin-1-ylmethanone,
methyl-{2-(6-methylpyridin-2-yl)-6-[5-(3-morpholine-4-ylmethylene)pyridine-3-yl]pyrimidine-4-yl}amine,
(3-{5-[6-methylamino-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]pyridine-3-yl}phenyl)morpholine-4-ylmethanone,
[6-{5-[4-(2-dimethylaminoethoxy)phenyl]pyridine-3-yl}-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]methylamine,
[6-{5-[3-(2-dimethylaminoethoxy)phenyl]pyridine-3-yl}-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]methylamine,
3-{5-[6-methylamino-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]pyridine-3-yl}-N-(tetrahydropyran-4-yl)benzamid,
4-{5-[6-methylamino-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]pyridine-3-yl}-N-(tetrahydropyran-4-yl)benzamid,
3-{5-[6-methylamino-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]pyridine-3-yl}benzosulfimide,
[6-[5-(3-methanesulfonyl)pyridine-3-yl]-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]methylamine,
benzyl-{2-(6-methylpyridin-2-yl)-6-[5-(3-pyrrolidin-1-ylphenyl)pyridine-3-yl]pyrimidine-4-yl}amine,
3-({2-(6-methylpyridin-2-yl)-6-[5-(3-pyrrolidin-1-ylphenyl)pyridine-3-yl]pyrimidine-4-ylamino}methyl)phenol,
benzyl-[6-{5-[3-(4-IU reparacin-1-yl)phenyl]pyridine-3-yl}-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]amine,
methyl-{2-(6-methylpyridin-2-yl)-6-[5-(3-pyrrolidin-1-ylphenyl)pyridine-3-yl]pyrimidine-4-yl}amine,
methyl-{2-(6-methylpyridin-2-yl)-6-[5-(3-morpholine-4-ylphenyl)pyridine-3-yl]pyrimidine-4-yl}amine,
methyl-[6-{5-[4-(4-methylpiperazin-1-yl)phenyl]pyridine-3-yl}-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]amine,
(4-{5-[6-methylamino-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]pyridine-3-yl}phenyl)-(4-methylpiperazin-1-yl)methanon,
methyl-[6-{5-[4-(4-methylpiperazin-1-ylmethyl)phenyl]pyridine-3-yl}-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]amine,
methyl-[6-{5-[3-(4-methylpiperazin-1-ylmethyl)phenyl]pyridine-3-yl}-2-(6-methylpyridin-2-yl)pyrimidine-4-yl]amine, and
its pharmaceutically acceptable salt.

5. The compound according to any one of claims 1 to 4 for use as a pharmaceutical agent intended for the treatment of condition mediated by receptor ALK-5 or receptor ALK-4.

6. The pharmaceutical composition intended for the treatment of condition mediated by receptor ALK-5 or receptor ALK-4, comprising the compound according to any one of claims 1 to 4 in an effective amount and a suitable pharmaceutically acceptable excipient.

7. The use of compounds according to any one of claims 1 to 4 for the manufacture of a medicinal product for the treatment of condition mediated by receptor ALK-5 or receptor ALK-4.

8. The use of compounds according to claim 7 for the treatment of pulmonary hypertension, chronic renal disease, the OS is cerned renal disease, wound healing, arthritis, osteoporosis, kidney disease, congestive heart failure, ulcers, eye disorders, damage to the cornea, diabetic nephropathy, reduced neurological function, Alzheimer's disease, atherosclerosis, peritoneal and subcutaneous adhesion, kidney fibrosis, lung fibrosis and liver fibrosis, hepatitis b, hepatitis C, alcohol-induced hepatitis, haemochromatosis, primary biliary cirrhosis, restenosis, retroperitoneal fibrosis, mesenteric fibrosis, endometriosis, keloids, cancer, abnormal bone function, inflammatory disorders, scarring and photoaging of the gauge.

9. The method of obtaining the compounds of formula I according to claim 1, which includes
(i) reaction of compounds of formula II:

where T1and T2are as defined in claim 1, and X represents a halogen, with a compound of formula III:

where Raand Rbare as defined in claim 1; and
(ii) removing the product in free form or salt form or MES.

10. The method of obtaining the compounds of formula I according to claim 1, which includes (i) the reaction of compounds of formula IV:

where T1, Raand Rbare as defined in claim 1, and X represents a halogen, with a compound form is s V:

where T2is such as defined in claim 1; and
(ii) removing the product in free form or in salt form or MES.

11. The compound according to claim 1, where T1represents unsubstituted pyridinyl-2-yl or pyridinyl-2-yl, substituted C1-C4-alkyl.

12. The compound according to claim 1, where T2represents pyridinyl, substituted by a methoxy group or a phenyl substituted in one position With1-C4-alkoxygroup, or R5.

13. The connection section 12, where Rarepresents N and Rbrepresents a C1-C4-alkyl, optionally substituted in one position for R4.

14. The connection indicated in paragraph 13, where R4represents indolyl, optionally substituted in one position with halogen, hydroxy-group, C1-C8-alkyl, C1-C8-alkoxygroup or cyano; or R4represents phenyl, optionally substituted at one position by hydroxy-group, C1-C8-alkyl or C1-C8-alkoxygroup.

15. The compound according to claim 1, where Rarepresents N and Rbrepresents a C3-C10-cycloalkyl.

16. The compound according to claim 1, where R1represents a C1-C4-alkyl.

17. The compound according to claim 1, where R4represents phenyl, optional for ewenny in one or two positions by hydroxy-group, With1-C4-alkyl or C1-C4-alkoxygroup.

18. The compound according to claim 1, where R5represents 5 - or 6-membered heterocyclic group, optionally substituted at one or two positions by oxopropoxy or1-C4-alkyl.

19. Connection p, where R3is a piperazine-2-it, morpholinyl, pyrazolyl, pyrrolidinyl, piperazinil or tetrahydropyranyl.

20. The pharmaceutical composition intended for the treatment of condition mediated by receptor ALK-5 or receptor ALK-4, including the connection 13 in an effective amount and a suitable pharmaceutically acceptable excipient.



 

Same patents:

Cytokine inhibitors // 2485113

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to imidazole compounds of formula wherein the radical values A, X, R1, R2, R3 are presented in clause 1 of the patent claim.

EFFECT: there are disclosed pharmaceutical compositions of sail compounds for cytokine (eg TNFα or IL-1β) reduction.

16 cl, 107 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing substituted pyrimidin-5-yl carboxylic acids of formula I and can be used in organic chemistry. The method is realised by reacting N-substituted guanidines and hetarylamidines with ethoxymethylene derivatives of 1,3-ketoesters according to a scheme given below (where the substitutes are as defined in the claim).

EFFECT: improved method of producing substituted pyrimidin-5-yl carboxylic acids of formula I.

2 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to isoxazole-pyridine derivatives of formula , where X; R1; R2, R3, R4, R5 and R6 are as described in claim 1 of the invention and a pharmaceutically acceptable salt thereof. The invention also relates to a medicinal agent for treating diseases associated with the binding site of the GABA A α5 receptor based on compounds of formula I and use of said compounds in preparing a medicinal agent.

EFFECT: novel compounds are active towards the binding site of said receptor and are useful in treating cognitive disorders such as Alzheimer's disease.

22 cl, 372 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to substituted oxazolidinones of formula (I), wherein R1 means methyl, ethyl, n-propyl, methoxy, methoxymethyl or ethoxymethyl, R2 means hydrogen or methyl, and R3 means a group of formulas or , wherein * means an attachment point to an oxopyridine ring, n means number 1, 2, 3 or 4, m means number 1 or 2, R4 means hydrogen, methyl, ethyl, cyclopropyl, cyclobutyl, 2-hydroxyet-1-yl, 3-hydroxyprop-1-yl or 4-hydroxycyclohex-1-yl, R5 means hydrogen, methyl or ethyl, or R4 and R5 together with a nitrogen atom whereto attached, form a ring of morpholin-4-yl, a ring of 4-methyl-piperazin-1-yl or 4-hydroxy-piperidine-1-yl, R6 means hydrogen, cyclopropyl, cyclobutyl, 2-hydroxyet-1-yl, 3-hydroxyprop-1-yl, 2-methoxyet-1-yl, 3-methoyprop-1-yl, 4-hydroxycyclohex-1-yl, tetrahydrofuran-2-ylmethyl or 1,4-dioxan-2-ylmethyl, R7 means hydrogen, methyl or ethyl, or R6 and R7 together with a nitrogen atom whereto attached, form a ring of pyrrolidin-1-yl, a ring of 2-methoxymethyl-pyrrolidin-1-yl, a ring of 1,1-dioxo-morpholin-4-yl, a ring of 1,4-oxazepan-4-yl, a ring of 4-methyl-piperazin-1-yl or 4-hydroxy-piperidine-1-yl, or to physiologically acceptable salts thereof. The invention also concerns a method for preparing said compounds.

EFFECT: there are prepared new compounds which can find application in medicine for treating and/or preventing the diseases caused by thrombembolia.

8 cl, 2 tbl, 40 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (1), wherein n means 0, 1, 2 or 3, R1 means chlorine, methyl, ethyl, n-propyl, methoxy, methoxymethyl or ethoxymethyl, R2 means hydrogen. The invention also refers to pharmaceutically acceptable salts of the compounds of formula (I) and to a method for preparing the compounds of formula (I).

EFFECT: preparing the compounds of formula (I) for treating and/or preventing thromboembolic diseases.

6 cl, 68 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (1), in which Ar is a group of formula (Ar-1) or (Ar-2), in which R1 is a halogen, R2 is hydrogen, R3 is hydrogen, R4 is hydrogen, alkyl or alkenyl, X is a nitrogen atom or CH, R5 and R6 are each hydrogen and h equals 1; 1 equals 1 or 2; m equals 1 or 2; n equals 0, 1 or 2; o equals an integer from 0 to 3, under the condition that n and o are equal to 0 at the same time. Values of group A are as given in claim 1 of the invention. Described also is a pharmaceutical composition having agonistic activity with respect to 7 serotonin (5-HT4-receptors), which contains a compound of formula (1) and an agent which stimulates enterokinesis or improves functioning of the alimentary canal, which contains a compound of formula (1) as an active ingredient.

EFFECT: novel compounds are obtained and described, which have strong affinity towards 4 serotonin receptors, which are useful as an agent which stimulates enterokinesis or an agent which improves functioning of the alimentary canal.

28 cl, 233 ex, 29 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (I), wherein A represents a pyrrole group or a pyrazole group, and X represents a carbon atom or a nitrogen atom; R1 represents a carboxy group; R2 independently represents a group specified in a substitute group α; R3 independently represents phenyl(C1-C6alkyl)group substituted by, phenyl(C1-C6alkyl)group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α); m is equal to 0, 1, 2 or 3, n is equal to 0 or 1; each of R4, R5, R6 and R7 independently represents a hydrogen atom, C1-C6alkyl group or a halogen atom; B represents a substituted naphthyl group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α), or the group represented by formula (II), wherein B1, B2 and α are those as specified in the patent claim. Also, the invention refers to a pharmaceutical composition possessing lipolysis inhibiting activity, to the use of the compounds of formula (I) in preparing a drug preparation for treating hyperlipidemia, dislipidemia, abnormal lipid metabolism, arteriosclerosis or type II diabetes mellitus and to a method of treating or preventing the mentioned diseases.

EFFECT: preparing the compounds of formula (I) possessing lipolysis inhibiting activity.

36 cl, 1 dwg, 1 tbl, 69 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula

, wherein X represents a halogen atom or C1-6-alkyl; and has the value of 0, 1, 2 or 3; R1 represents H; R2 represents or ; R3 represents C1-6-alkyl, C3-10-cycloalkyl, phenyl, 6-member heterocycloalkyl representing tetrahydropyranyl, or 5-10-member heteroaryl specified in pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, benzo[1,3]dioxolyl and 2,3-dihydrobenzo[1,4]dioxynyl; which be substituted and contains one to five substitutes specified in the patent claim. The invention also refers to pharmaceutical compositions possessing high affinity to dopamine D3 receptor and serotonin 5-HT2A receptor containing said compounds, and the use thereof in preparing drugs.

EFFECT: preparing the compounds of formula (I) possessing high affinity to dopamine D3 receptor and serotonine 5-HT2A receptor.

15 cl, 4 dwg, 5 tbl, 78 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a phenylpyrazol derivative presented by formula (1) or to its pharmaceutically acceptable salt: wherein R1 and R2, which may be identical or different, each represents C1-C6 alkyl, or R1 and R2 are coupled together with an adjacent nitrogen atom to form a 5-6-merous saturated heterocylic ring (wherein the mentioned saturated heterocylic ring may be substituted by halogen or C1-C6 alkyl), n represents an integer 0 to 2, T represents a hydrogen atom, halogen or C1-C6 alkyl, and R has one of formulas (I)-(V), (VII) or (VIII):

(wherein Z1 and Z2, which may be identical or different, each represents -CH2-, -O- or -NR11-, p represents an integer 0 to 3, q represents an integer 0 to 1, r and s which may be identical or different, which represents an integer 0 to 2, R3 represents halogen, C1-C6 alkyl, or hydroxy, R4 and R5 which may be identical or different, each represents a hydrogen atom, C1-C6 alkyl (wherein said C1-C6 alkyl may be substituted by hydroxy, hydroxy- C1-C6 alkoxy, C2-C7 alkoxycarbonyl or carboxy), or formula -(CH2)m-Ar1 (wherein Ar1 represents wherein (wherein said phenyl is substituted by halogen or C1-C6 alkyl), and m represents an integer 0 to 1), R6 represents oxo, R7 represents a hydrogen atom or C1-C6 alkyl, R8 represents C1-C6 alkyl (wherein said C1-C6 alkyl may be substituted by halogen), C1-C6 alkoxy (wherein said C1-C6 alkoxy is substituted by halogen) or formula -(CH2)1-Ar2 (wherein Ar2 represents phenyl (wherein said phenyl is substituted by C1-C6 alkoxy, hydroxyl or cyano) or pyridinyl, and 1 represents an integer O to 1), G represents -CO- or -SO2-, R9 represents C1-C6 alkyl, C1-C6 alkoxy, phenyl (wherein said phenyl may be substituted by halogen or pyridinyl, and R11 represents C1-C6 alkyl)}.

EFFECT: there are produced new compounds and a preventive or therapeutic agent on the basis of said compounds which can find application in medicine for treating dementia, Alzheimer's disease, attention deficit/hyperactivity disorder, schizophrenia, epilepsy, convulsions of central genesis, eating behaviour disorders, obesity, diabetes, hyperlipidemia, sleep disturbances, narcolepsy, sleeping apnoea syndrome, circadian rhythm disorder, depression or allergic rhinitis.

12 cl, 3 tbl, 72 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted N-phenyl-bipyrrolidine ureas of formula (I) ,

where values of R, R1, R2, R3, R4 and R5 are given in claim 1.

EFFECT: compounds are capable of binding with the H3 receptor, which enables use thereof to prepare a pharmaceutical composition and for diseases associated with the central nervous system.

10 cl, 36 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of general formula III which possess the properties of JAK pathway inhibitors and JAK-kinase inhibitors. In formula III: X is specified in a group consisting of C1-C10alkyl, amino, halogen, carboxyl, carboxylic acid ester, C2alkynyl, substituted tri-C1-C6alkylsilyl; R represents hydrogen; the cycle A is specified in a group consisting of C6aryl, bicycloheptene, five-and sis-member mono- or 10-member bicyclic heteroaryl including 1 to 3 heteroatoms specified in a group of heteroatoms, including N, O or S, and five- or six-member mono- or 10-member bicyclic heterocycle, including 1 to 2 heteroatoms specified in a group of heteroatoms, including N or O; p means 0, 1, 2 or 3; each of R2 is independently specified in a group consisting of C1-C6alkyl, C1-C4alkyl substituted by 1 to 3 substitutes. The other substitute and radical values are specified in the patent claim.

EFFECT: compounds may be used in preparing a therapeutic agent for T-cell mediated autoimmune disease, for treating or preventing allograft rejection in a recipient, for treating or preventing a type IV hypersensitivity reactions, which includes administering the above agent containing the compound according to cl 1-11, in an amount effective to treat the autoimmune disease or the allograft rejection or the type IV hypersensitivity.

23 cl, 7 dwg, 12 tbl, 43 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds for treating cell-proliferative disorders having formula (II): wherein the values R1,R2, X, A, B, R6, R7, R9 are specified in cl. 1 of the patent claim with the exception of the compound of formula: .

EFFECT: there are presented compounds possessing anticancer activity.

95 cl, 27 dwg, 11 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula I , as well as to enantiomers and salts thereof, wherein R1 and R1a are independently specified in H, Me, Et, CH=CH2, CH2OH, CF3, CHF2 or CH2F; R2 and R2a are independently specified in H or F; R5 represents H, Me, Et or CF3; A is presented by formula: ; wherein G, R6, R7, Ra, Rb ,Rc, Rd, R8, m, n and p are presented in cl. 1 of the patent claim.

EFFECT: compounds according to the invention may be used as the protein kinase Akt inhibitors and for treating hyperproliferative diseases, such as cancer.

15 cl, 1 tbl, 43 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to novel tetrahydroisoquinolin-1-one derivatives of general formula or pharmaceutically acceptable salts thereof, where R1 is: lower alkylene-OH, lower alkylene-N(R0)(R6), lower alkylene-CO2R0, C5-6cycloalkyl, C6-10cycloalkenyl, aryl, heterocyclic group, -(lower alkylen, substituted OR0)-aryl or lower alkylene-heterocyclic group, where the lower alkylene in R1 can be substituted with 1-2 groups G1; cycloalkyl, cycloalkenyl and heterocyclic group in R1 can be substituted with 1-2 groups G2; aryl can be substituted with 1-2 groups G3; R0: identical or different from each other, each denotes H or a lower alkyl; R6: R0, or -S(O)2-lower alkyl, R2 is: lower alkyl, lower alkylene-OR0, lower alkylene-aryl, lower alkylene-O-lower alkylene-aryl, -CO2R0, -C(O)N(R0)2, -C(O)N(R0)-aryl, -C(O)N(R0)-lower alkylene-aryl, aryl or heterocyclic group, where the aryl in R2 can be substituted with 1-3 groups G4; R3 is: H or lower alkyl, or R2 and R3 can be combined to form C5-alkylene; R4 is: -N(R7)(R8), -N(R10)-OR7, -N(R0)-N(R0)(R7), -N(R0)-S(O)2-aryl or -N(R0)-S(O)2-R7, R7 is: lower alkyl, halogen-lower alkyl, lower alkylene-CN, lower alkylene-OR0, lower alkylene-CO2R0, lower alkylene-C(O)N(R0)2, lower alkylene-C(O)N(R0)N(R0)2, lower alkylene-C(=NOH)NH2, heteroaryl, lower alkylene-X-aryl or lower alkylene-X-heterocyclic group, where the lower alkylene in R7 can be substituted with 1-2 groups G1; aryl, heteroaryl and heterocyclic group in R7 can be substituted with 1-2 groups G6; X is: a single bond, -O-, -C(O)-, -N(R0)-, -S(O)p- or *-C(O)N(R0)-, where * in X has a value ranging from a bond to a lower alkylene, m is: an integer from 0 to 1, p is: is 2, R8 is: H, or R7 and R6 can be combined to form a lower alkylene-N(R9)-lower alkylene group, R9 is: aryl, R10 is: H, R5 is: lower alkyl, halogen, nitro, -OR0, -N(R0)2, or -O-lower alkylene-aryl, where the group G1 is: -OR0, N(R0)(R6) and aryl; group G2 is: lower alkyl, lower alkylene-OR0, -OR0, -N(R0)2, -N(R0)-lower alkylene-OR0, -N(R0)C(O)OR0, -N(R0)C(O)-lower alkylene-OR0, -N(R0)C(O)N(R0)2, -N(R0)C(=NR0)-lower alkyl, -N(R0)S(O)2-lower alkyl, -N(lower alkylene-CO2R0)-S(O)2-lower alkyl, -N(R0)S(O)2-aryl, -N(R0)S(O)2N(R0)2, -S(O)2-lower alkyl, -CO2R0, -CO2-lower alkylene-Si(lower alkyl)3, -C(O)N(R0)2, -C(O)N(R0)-lower alkylene-OR0, -C(O)N(R0)-lower alkylene-N(R0)2, -C(O)N(R0)-lower alkylene-CO2R0, -C(O)N(R0)-O-lower alkylene-heterocyclic group, -C(O)R0, -C(O)-lower alkylene-OR0, C(O)-heterocyclic group and oxo; under the condition that "aryl" in group G2 can be substituted with one lower alkyl; group G3 is: -OR0; group G4 is: halogen, CN, nitro, lower alkyl, -OR0, -N(R0)2) -CO2R0; group G5 is: halogen, -OR0, -N(R0)2 and aryl; group G6 is: halogen, lower alkyl which can be substituted with -OR0, halogen-lower alkyl which is substituted with -OR0, -OR0, -CN, -N(R0)2, -CO2R0, -C(O)N(R0)2, lower alkylene-OC(O)R0, lower alkylene-OC(O)-aryl, lower alkylene-CO2R0, halogen-lower alkylene-CO2R0, lower alkylene-C(O)]N(R0)2, halogen-lower alkylene-C(O)N(R0)2, -O-lower alkylene-CO2R0, -O-lower alkylene-CO2-lower alkylene-aryl, -C(O)N(R0)S(O)2-lower alkyl, lower alkylene-C(O)N(R0)S(O)2-lower alkyl, -S(O)2-lower alkyl, -S(O)2N(R0)2, heterocyclic group, -C(-NH)=NO-C(O)O-C1-10-alkyl, -C(=NOH)NH2, C(O)N=C(N(R0)2)2, -N(R0)C(O)R0, -N(R0)C(O)-lower alkylene-OR0, -N(R0)C(O)OR0, -C(aryl)3 and oxo; under the condition that the "heterocyclic group" in group G6 is substituted with 1 group selected from a group consisting of -OR0, oxo and thioxo (=S); where the "cycloalkenyl" relates to C5-10 cycloalkenyl, including a cyclic group which is condensed with a benzene ring at the site of the double bond; the "aryl" relates to an aromatic monocyclic C6-hydrocarbon group; the "heterocyclic group" denotes a cyclic group consisting of i) a monocyclic 5-6-member heterocycle having 1-4 heteroatoms selected from O, S and N, or ii) a bicyclic 8-9-member heterocycle having 1-3 heteroatoms selected from O, S and N, obtained via condensation of the monocyclic heterocycle and one ring selected from a group consisting of a monocyclic heterocycle, a benzene ring, wherein the N ring atom can be oxidised to form an oxide; the "heteroaryl" denotes pyridyl or benzimidazolyl; provided that existing compounds given in claim 1 of the invention are excluded. The invention also relates to a pharmaceutical composition based on the compound of formula (I), use of the compound of formula (I) and a method of treatment using the compound of formula (I).

EFFECT: obtaining novel tetrahydroisoquinolin-1-one derivatives which are useful as a BB2 receptor antagonist.

11 cl, 302 tbl, 59 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new compound of 2-[3-(2,2-difluorobenzo[1,3]dioxol-5-ylamino)-5-(2,6-dimethylpyridin-4-yl)-[1,2,4]triazol4-yl]-N-ethylacetamide and/or pharmaceutically acceptable salts, or hydrate, or solvates, as well as to a method for preparing it; a pharmaceutical composition based on this compound and using its in therapy for prevention and treatment of mental disorders, intellectual disorders or diseases, inflammatory diseases or conditions wherein α7 nicotinic receptor modulation is considered to be favourable. The invention also refers to a product containing such compound and α7-nicotinic receptor agonist.

EFFECT: preparing the compounds applicable in therapy for prevention or treatment of mental disorders, intellectual disorders or diseases, inflammatory diseases or conditions wherein α7 nicotinic receptor modulation is considered to be favourable.

6 cl, 1 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to compounds of formula I or pharmaceutically acceptable salts thereof, where W is where each R4 independently denotes H or CN; R2 denotes a cycloalkyl which can be independently substituted with two of the following substitutes: C(1-3)alkyl; Z denotes H; J denotes CH or N; X denotes or ; where R1 denotes -ORa, -CN, -NA1A2, -SO2CH3, -COORa, -CO2CH3, -CH2-NA1A2, -CONA1A2, -CH2ORa, -NHCH2CH2ORa, -OC(1-4)alkylNA1A2, OCH2CO2Ra and tetrazolyl; Rz and Ry independently denotes H or -C(1-4)alkyl, where both Rz may have syn or anti stereochemistry; alternatively both Rz in syn interaction may be taken together to form -(CH2)n-, where n equals 2; R3 denotes C(1-3)alkyl-CF3 or -COCH3; A1 denotes H or -C(1-4)alkyl; A2 denotes H or -C(1-4)alkyl; alternatively, A1 and A may be taken together with a nitrogen atom with which they are bonded to form a heterocyclic ring selected from: , where Ra denotes H or C(1-4)alkyl; Rbb denotes H, -C(1-4)alkyl, and -CH2CO2H, where cycloalkyl relates to a partially unsaturated ring with 6 carbon atoms. The invention also relates to specific compounds of formula I, a pharmaceutical composition based on the compound of formula I and methods of treating inflammation and autoimmune diseases.

EFFECT: novel compounds of formula I which are useful as c-fms inhibitors are obtained.

10 cl, 2 tbl, 44 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrimidine derivatives and their pharmaceutically acceptable salts possessing the properties of a mTOR kinase inhibitor. In formula (I): A represents a 6-8-member mono- or bicyclic heterocyclic ring containing 1 to 2 heteroatoms optionally specified in N and O as apexes of the ring and having 0-2 double bonds; and wherein the ring A is additionally substituted by 0 to 2 substitutes RA specified in a group consisting of -ORa, -Rc and -(CH2)1-4-ORa wherein Ra is optionally specified in hydrogen and C1-6alkyl; Rc represents C1-6alkyl; G is specified in a group consisting of -C(O)-, -OC(O)-, -NHC(O)- and -S(O)0-2-; B is specified in a group consisting of phenylene and 5-6-member heteroarylene consisting 1-2 nitrogen heteroatom as apexes of the ring, and substituted by 0 to 1 substitutes RB specified in F, Cl, Br, I and Rp; wherein Rp represents C1-6 alkyl; D is specified in a group consisting of -NR3C(O)NR4R5, -NR4R5, C(O)NR4R5, -NR3C(=N-CN)NR4R5, -NR3C(O)R4, -NR3C(O)OR4 and -NR3S(O)2R4, and wherein the group D and a substitute placed on an adjoining atom in the ring B, optionally combined to form a 5-6-member heterocyclic or heteroaryl ring containing 1 to 3 heteroatoms specified in N, O and S, as apexes of the ring and substituted by the substitute 0-1 RD. The R1-R5 radical values are presented in the patent claim.

EFFECT: invention also refers to a pharmaceutical composition containing said compounds, and to the use of the compounds for preparing a drug for treating a malignant tumour mediated by mTOR kinase activity.

33 cl, 13 dwg, 4 tbl, 498 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel imidazole derivatives of formula where A is pyridinyl; and B is a condensed ring system consisting of: a. a phenyl ring bonded to a molecular residue, b. a second heterocyclic 5- or 6-member ring which is condensed with the phenyl ring, and has one nitrogen or oxygen atom, and to tautomeric forms thereof.

EFFECT: obtaining novel imidazole derivatives which are antagonists of adrenergic receptors.

6 cl, 1 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to novel heterocyclyl-pyrimidinyl-amino derivatives of formula (I), and agrochemically acceptable salts thereof, intermediate compounds of formula (II) for production thereof, fungicide compositions and a method of controlling phytopathogens and fungi, primarily of plants. In the compound of general formulae and , Het denotes a heterocycle selected from a group consisting of: , Y independently denotes a halogen atom, C1-C8-alkyl, C1-C8-haloalkyl with 1-5 halogen atoms, C1-C8-alkylamino, di-C1-C8-alkylamino, C1-C8-alkoxy, C1-C8-haloalkoxy with 1-5 halogen atoms, C2-C8-haloalkenyloxy with 1-5 halogen atoms, substituted with C1-C8-alkyl or unsubstituted C1-C8-alkoxyalkyl, substituted with C1-C8-alkyl or unsubstituted C1-C8-haloalkoxyalkyl with 1-5 halogen atoms; p equals 0, 1 or 2; Ra denotes a hydrogen atom, C1-C4-alkyl, C3-C6-cycloalkyl, C1-C4-haloalkyl with 1-5 halogen atoms; Rb and Rc independently denote a hydrogen atom, a halogen atom, C1-C4-alkyl, C1-C4-haloalkyl with 1-5 halogen atoms; X independently denotes C1-C4-alkyl, C1-C4-haloalkyl or a halogen atom; n equals 0, 1 or 2; L1 and L2 independently denote a hydrogen atom, C1-C8-alkyl, unsubstituted or substituted with C1-C8-alkoxy, di-C1-C8-alkylamino, hydroxy or C3-C6-cycloalkyl; C3-C6-cycloalkyl; C1-C4-haloalkyl with 1-5 halogen atoms; C3-C6-halocycloalkyl with 1-5 halogen atoms; C2-C6-alkenyl; C2-C6-alkynyl; C1-C4-alkoxy; C1-C4-haloalkoxy with 1-5 halogen atoms; C2-C6-alkenyloxy; C2-C6-alkynyloxy; C2-C6-haloalkenyloxy with 1-5 halogen atoms; C2-C6-haloalkynyloxy with 1-5 halogen atoms; (2-oxopyrrolidin-1-yl)- C1-C8-alkyl; (2-oxopyrrolidin-1-yl)-C1-C8-haloalkyl with 1-5 halogen atoms, W denotes a leaving group such as a halogen atom.

EFFECT: efficiency of the compound.

14 cl, 4 dwg, 128 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrimidine derivatives of general formula (I-a), having the capacity to simulate axonal growth coupled with the capacity to stimulate angiogenesis and can be used in treating spinal chord damage, damage to the central nervous system as a result of head injuries, ischaemic stroke, ischemic heart disease, peripheral arterial occlusive disease, vascular dementia, cerebrovascular dementia or senile dementia. In the compound of formula (I-a): R0 is a group where R3 and R4 denote a hydrogen atom; R1 is a methyl group; R2 is a methyl group; R5 is a hydrogen atom; R6 is a hydrogen atom; R7 is a methyl group; E is an oxygen atom; is a benzyl group, a cyclohexyl methyl group, an isobutyl group, a cyclohexane carbonyl group, an acetyl group, a phenylsulphonyl group, a cyclohexyl group, a piperidine-1-carbonyl group, a methylbenzyl group, a phenyl group, a fluorobenzyl group, a methoxybenzyl group or a trifluorobenzyl group; or a pharmaceutically acceptable salt thereof.

EFFECT: high efficiency of using the compounds.

4 cl, 16 dwg, 27 tbl, 148 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new carboxamide compounds of formula I-A' or I-A" , as well as to tautomers thereof and pharmaceutically acceptable salts thereof, wherein R1 means hydrogen, C1-C10-alkyl, C3-C7-cycloalkyl-C1-C4alkyl, aryl-C1-C6-alkyl or hetaryl-C1-C4-alkyl, wherein aryl and hetaryl in the two last mentioned radicals may be substituted or have 1 radical R1c; wherein R1a represents C1-C6-alkoxy, R1c is independently specified in halogen, CN, CF3, O-CF3, O-CHF2, C1-C6-alkyl, C1-C6-alkoxy, hetaryl, O-CH2-aryl, - (CH2)p-NRc6Rc7 with p = 0 or 1; wherein Rc6 represents C1-C6-alkyl or SO2-C1-C6-alkyl, and Rc7 represents C1-C6-alkyl, or the two radicals Rc6 and Rc7 together with an N atom form 5- or 6-member, optionally substituted C1-C4-alkyl nitrogen-containing heterocyclyl which can optionally have 1 heteroatom from the group O and N as ring members, R2 means C1-C10-alkyl, C3-C7-cycloalkyl, aryl, hetaryl, wherein aryl and hetaryl in the two last mentioned radicals may be unsubstituted or carry 1, 2 or 3 identical or different R2c radicals; wherein R2c have one of the values specified for R1c; R3a and R3b together with a carbon atom whereto attached, are C=O; X means hydrogen or a radical of formulas C(=O)-O-Rx1 or C(=O)-NRx2Rx3, wherein Rx1 means C1-C6-alkyl, Rx2 means H or C1-C6-alkyl, and Rx2 means H, one of the variables Y1, Y2, Y3 and Y4 forms a nitrogen atom, and the rest variables Y1, Y2, Y3 and Y4 mean CH, n is equal to 0 or 1, Ry is independently specified in halogen, CN, aryl, -NH-SO2-Ry4, -(CH2)p-NRy6Ry7 with p = 0; wherein Ry4 means C1-C6-alkyl, Ry6 has one of the values specified for Rc6, and Ry7 has one of the values specified for Rc7; m means 0 or 1 for formulas I-A', and Rw is specified in halogen, C1-C6-alkyl, C1-C6-alkoxy, wherein C1-C6-alkyl can have 1 substitute Rwa, aryl, -(CH2)p-NRw6Rw7 with p = 0 or 1, Rwa has one of the values specified for R1a, or represents NRa2SO2Ra4, Ra2 represents H, Ra4 represents C1-C6-alkyl, Rw6 has one of the values specified for Rc6, Rw7 has one of the values specified for Rc7, m is equal to 0, 1 or 2 for formula I-A", and Rw6* has one of the values specified for Rw, E has one of the values specified for: -CHRE2-CHRE3-, -CH2-O-, -O-CH2-, -S-CH2-, -CH2-S-, -CH2-SO2-, -SO2-CH2-, wherein Re2, Re3 represent hydrogen; wherein aryls defined above, represent mono- or bicyclic aromatic hydrocarbon radicals such as phenyl or naphthyl, and hetaryls defined above, represent 5 - or 6-member aromatic heterocyclic radicals containing 1 or 2 heteroatoms specified in nitrogen, oxygen and sulphur and can additionally contain a condensed benzene ring. Also, the invention refers to specific compounds, pharmaceutical compositions containing them and use thereof.

EFFECT: there are prepared new derivatives of carboxamide compounds effective in the treating the disorders caused by higher activity of calpain.

15 cl, 1 tbl, 195 ex

Up!