Chiral cis-imidazolines

FIELD: chemistry.

SUBSTANCE: described are novel chiral cis-imidazolines selected from a group which includes 2-{4-[(4S,5R)-2-(2-tert-butyl-4-ethoxypyrimidin-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazin-1-yl}-acetamide, [(4S,5R)-2-(2-tert-butyl-4-ethoxypyrimidin-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazol-1-yl]-[4-(1,1-dioxohexahydrothiopyran-4-yl)-piperazin-1-yl]-methanone, [(4S,5R)-2-(2-tert-butyl-4-ethoxypyrimidin-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazol-1-yl]-[4-(3-methanesulphonylpropyl)-piperazin-1-yl]-methanone, 2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridin-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazin-1-yl}-N,N-bis-(2-methoxyethyl)-acetamide. 2-{1-[(48;5K)-2-(6-tert-butyl-4-ethoxypyridin-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidin-4-yl}-acetamide and others described by the general structural formula (I), and pharmaceutical composition containing said compounds.

EFFECT: compounds can be used as anti-cancer agents, particularly as agents for treating solid tumours.

8 cl, 217 ex

 

The text descriptions are given in facsimile form.

1. A compound selected from the group including
2-{4-[(4S,5R)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-acetamide", she
[(4S,5R)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihyd imidazol-1-yl]-[4-(1,1-dioxotetrahydrofuran-4-yl)-piperazine-1-yl]-methanon,
[(4S,5R)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3-methanesulfonyl)-piperazine-1-yl]-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3-methanesulfonyl)-piperazine-1-yl]-methanon,
rat-[(4S*,5R*)-2-(6-tert-butyl-2-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3-methanesulfonyl)-piperazine-1-yl]-methanon,
rat-[(4S*,5R*)-4,5-bis-(4-chlorophenyl)-2-(2,4-dimethoxypyrimidine-5-yl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3-methanesulfonyl)-piperazine-1-yl]-methanon,
rat-[(4S*,5R*)-4,5-bis-(4-chlorophenyl)-2-(2-dimethylamino-4-ethoxypyridine-5-yl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3-methanesulfonyl)-piperazine-1-yl]-methanon,
rat-[(4S*,5R*)-4,5-bis-(4-chlorophenyl)-2-(4-ethoxy-2-pyridine-3-Yeremey-5-yl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3-methanesulfonyl)-piperazine-1-yl]-methanon,
rat-[(4S*,5R*)-4,5-bis-(4-chlorophenyl)-2-(2,6-dimethoxypyridine-3-yl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3-methanesulfonyl)-piperazine-1-yl]-methanon,
4-[(4S,5R)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-2-it,
rat-[(4S*,5R*)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(2-hydroxyethyl)-piperazine-1-yl]-methanon,
2-(2-tert-butyl-4-ecoxib rimidine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-piperazine-1-ylmethanone,
[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-((R)-3,4-dihydroxybutyl)-piperazine-1-yl]-methanon,
dimethylamide 4-[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-carboxylic acid,
N-(2-{4-[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-ethyl)-acetamide", she
1-{4-[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-Etalon,
[(4S,5R)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-
4,5-dimethyl-4,5-dihydroimidazole-1-yl]-{4-[2-(2-hydroxyethoxy)-ethyl]-piperazine-1-yl}-methanon,
[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3-hydroxypropyl)-piperazine-1-yl]-methanon,
2-{4-[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N,N-dimethylacetamide,
[1,4']-bipiperidine-1'-yl-[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-methanon,
[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-hydroxy-[1,4']-bipiperidine-1'-yl)-methanon,
[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(3-Ki-the Roxy-[1,4']-bipiperidine-1'-yl)-methanon,
[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(3-hydroxymethyl-[1,4']-bipiperidine-1'-yl)-methanon,
[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-pyrrolidin-1-reparacin-1-yl)-methanon,
[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(3-hydroxypiperidine-1-yl)-methanon,
[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(3-hydroxyethylpiperazine-1-yl)-methanon,
1-{1-[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-[1,4]diazepan-5-he,
[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-hydroxypiperidine-1-yl)-methanon,
amide 1-[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-carboxylic acid,
amide 1-[2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-3-carboxylic acid,
[(4S,5R)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-((S)-2,3-dihydroxypropyl)-piperazine-1-yl]-methanon,
rat-[(4S*,5R*)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(2-methane is sulfonylated)-piperazine-1-yl]-methanon,
rat-[(4S*,5R*)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(2-methoxyethyl)-piperazine-1-yl]-methanon,
rat-N-tert-butyl-2-{4-[(4S*,5R*)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-acetamide", she
rat-2-{4-[(4S*,5R*)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-1-morpholine-4-ylatason,
rat-4-{4-[(4S*,5R*)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-butyronitrile,
rat-[(4S*,5R*)-4,5-bis-(4-chlorophenyl)-2-(4-ethoxy-2-methylsulfonylamino-5-yl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3-methanesulfonyl)-piperazine-1-yl]-methanon,
rat-4-[(4S*,5R*)-4,5-bis-(4-chlorophenyl)-2-(4-ethoxy-2-methylsulfonylamino-5-yl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-2-it,
rat-4-[(4S*,5R*)-4,5-bis-(4-chlorophenyl)-2-(4-ethoxy-2-morpholine-4-Yeremey-5-yl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-2-it,
rat-[(4S*,5R*)-4,5-bis-(4-chlorophenyl)-2-(2,4-detoxification-5-yl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3-methanesulfonyl)-piperazine-1-yl]-methanon,
rat-[(4S*,5R*)-4,5-bis-(4-chlorophenyl)-2-(4-methoxy-2-methylsulfonylamino-5-yl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3-methanesulfonyl)-piperazine-1-yl]-methanon,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-etox is pyridin-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-acetamide", she
rat-[(4S*,5R*)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-((S)-2,3-dihydroxypropyl)-piperazine-1-yl]-methanon,
1-[(4S,5R)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-[1,4]diazepan-5-he,
1-{1-[(4S,5R)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-[1,4]diazepan-5-he,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-methanesulfonylaminoethyl-1-yl)-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(2-methanesulfonyl)-piperidine-1-yl]-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(1,1-dioxohexane-1λ6-thiopyran-4-yl)-piperazine-1-yl]-methanon,
amide 3-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-propane-1-sulfonic acid,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(2-methanesulfonyl)-piperazine-1-yl]-methanon,
4-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-butyronitrile,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-the l)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3,3,3-cryptochromes)-piperazine-1-yl]-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3-acanaloniidae)-piperazine-1-yl]-methanon,
N-(2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-ethyl)-acetamide", she
1-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-2-(thiazol-2-ylamino)-Etalon,
1-{4-[(4S, 5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-2-methylpropan-1-he,
1-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-2,2-DIMETHYLPROPANE-1-he,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-(2-methoxyethyl)-ndimethylacetamide,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-cyclopropylacetic,
dimethylamide (4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carboxylic acid,
1-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-2-tetrazol-1-ylatason,
3-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dim the Teal-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-propionamide,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(1-methyl-1H-pyrrole-2-carbonyl)-piperazine-1-yl]-methanon,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-cyclopropylamine,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-(tetrahydrofuran-2-ylmethyl)-ndimethylacetamide,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3-methanesulfonyl)-piperidine-1-yl]-methanon,
1-{4-[(4S,5R)-2-(b-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-2-(4-methylthiazole-2-yl)-Etalon,
tert-butyl ester 9-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-3,9-diazaspiro[5.5]undecane-3-carboxylic acid,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(3,9-diazaspiro[5.5]undec-3-yl)-methanon,
2-{9-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-3,9-diazaspiro[5.5]undec-3-yl}-acetamide", she
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(1,1-dioxotetrahydrofuran-1λ6-thiophene-3-yl)-PI is erasin-1-yl]-methanon,
amide 3-{4-[(4S,5R)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-propane-1-sulfonic acid,
rat-[(4S*,5R*)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-piperidine-1-ylmethanone,
2-{1-[(4S,5R)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-acetamide", she
[(4S,5R)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(2-methanesulfonyl)-piperidine-1-yl]-methanon,
rat-[(4S*,5R*)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(1,2-dihydroxyethyl)-piperidine-1-yl]-methanon,
[(4S,5R)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-methanesulfonylaminoethyl-1-yl)-methanon,
[(4S,5R)-2-(2-tert-butyl-4-ethoxypyridine-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3-methanesulfonyl)-piperidine-1-yl]-methanon,
rat-[(4S*,5R*)-4,5-bis-(4-chlorophenyl)-2-(3,6-dimethoxypyridine-4-yl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3-methanesulfonyl)-piperazine-1-yl]-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-acanaloniidae-1-yl)-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-CHL is henyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(2-hydroxyethyl)-piperidine-1-yl]-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(2-methoxyethyl)-piperazine-1-yl]-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-pyrrolidin-1-reparacin-1-yl)-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-isopropylpiperazine-1-yl)-methanon,
[1,4']-bipiperidine-1'-yl-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-methanon,
1-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-Etalon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-dimethylaminopyridine-1-yl)-methanon,
hydrochloride {4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-acetic acid,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(tetrahydrofuran-2-carbonyl)-piperazine-1-yl]-methanon,
dimethylamide 4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-carboxylic acid,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-is]-[4-(3-methoxypropyl)-piperazine-1-yl]-methanon,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-1-(1,1-dioxo-λ6-thiomorpholine-4-yl)-Etalon,
4-(2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-acetyl)-piperazine-2-it,
1-(2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-acetyl)-[1,4]diazepan-5-he,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-hydroxypiperidine-1-yl)-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(3-hydroxypiperidine-1-yl)-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-hydroxyethylpiperazine-1-yl)-methanon,
2-{4-[(4S,5R-)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-1-pyrrolidin-1-ylatason,
1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-[1,4]diazepan-5-he,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-((R)-3-methylpiperazin-1-yl)-methanon,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazo the ol-1-carbonyl]-piperazine-1-yl}-N-(2,3-dihydroxypropyl)-ndimethylacetamide,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-isopropyl-N-methylacetamide,
N-tert-butyl-2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-acetamide", she
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-methanesulfonylaminoethyl-1-yl)-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-{4-[2-(2-hydroxyethoxy)-ethyl]-piperazine-1-yl}-methanon,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-1-(4-methylpiperazin-1-yl)-Etalon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-cyclopropanecarbonyl-1-yl)-methanon,
4-[4-(2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-acetyl)-piperazine-1-yl]-benzonitrile,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-(2-hydroxy-1,1-dimethylethyl)-ndimethylacetamide,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-(2-hydroxy-1-hydroxymethyl-1-m is teletel)-ndimethylacetamide,
4-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-piperazine-2-it,
4-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-1-methylpiperazin-2-it,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(3,4-dihydroxybutyl)-piperazine-1-yl]-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(1,1-dioxo-1-thiomorpholine-4-yl)-methanon,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-1-piperidine-1-ylatason,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-(2-hydroxyethyl)-acetamide", she
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-[1,4]dioxane-2-ylmethylene,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(3-hydroxypyrrolidine-1-yl)-methanon,
tert-butyl ester {(S)-1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-pyrrolidin-3-yl}-carbamino acid,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-thiazol-5-ylacetamide,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-pyridin-3-ylacetamide,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-phenylacetamide,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-pyridin-4-ylacetamide,
(3-aminopyrrolidine-1-yl)-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-methanon,
N-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-pyrrolidin-3-yl}-oxalate,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(2,3,4,5-tetrahydrobenzo[b][1,4]diazepin-1-yl)-methanon,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-1-(3-hydroxyazetidine-1-yl)-Etalon,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-(tetrahydropyran-4-yl)-acetamide", she
ethyl ester of (1S,5R)-3-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-3-azabicyclo[3.1.0]hexane-6-carboxylic acid,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ataxie the one-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N,N-bis-(2-methoxyethyl)-ndimethylacetamide,
1 azetidin-1-yl-2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-Etalon,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N,N-bis-(2-hydroxyethyl)-acetamide", she
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-[2-(4-methoxyphenyl)-ethyl]-acetamide", she
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-[2-(2-methoxyphenyl)-ethyl]-acetamide", she
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(7,8-dimethoxy-1,2,3,5-tetrahydrobenzo[e][1,4]diazepin-4-yl)-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(7,8-dimethoxy-2,3,4,5-tetrahydrobenzo[e][1,4]diazepin-1-yl)-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[(1S,5R)-6-(3-hydroxyazetidine-1-carbonyl)-3-azabicyclo[3.1.0]Gex-3-yl]-methanon,
(2-hydroxyethyl)-amide and (1S,5R)-3-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-3-azabicyclo[3.1.0] hexane-6-carboxylic acid,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-d is hydromedusa-1-yl]-[(1S,5R)-6-(3-hydroxypyrrolidine-1-carbonyl)-3-azabicyclo[3.1.0]Gex-3-yl]-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-methyl-[1,4]diazepan-1-yl)-methanon,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]diazepan-1-yl}-acetamide", she
4-(2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-[1,4]diazepan-1-yl}-acetyl)-piperazine-2-it,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-(6-methoxy-2-methylpyridin-3-yl)-acetamide", she
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-(2-methylpyridin-3-yl)-acetamide", she
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-(2-methoxypyridine-3-yl)-acetamide", she
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-[-ethyl-N-pyridin-3-ylacetamide,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-(2,6-dimethylpyridin-3-yl)-acetamide", she
tert-butylamide (S)-4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-2-carboxylic acid,
[(4S,5R)-2-(tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(4-methylpiperazin-1-yl)-piperidine-1-yl]-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-(morpholine-4-reparacin-1-yl)-methanon,
N-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-acetamide", she
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-methyl-[1,4']-bipiperidine-1'-yl)-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(4-ethylpiperazin-1-yl)-piperidine-1-yl]-methanon,
N-{1-[(4S,5R)-2-(b-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-N-methylmethanesulfonamide,
N-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-methanesulfonamide,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(2-methanesulfonamido)-piperidine-1-yl]-methanon,
methyl ester {1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-acetic acid,
2-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-1-pyrrolidin-1-ylatason,
2-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorphen is)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-N,N-dimethylacetamide,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(4-diethylaminophenyl-1-yl)-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-{4-[(2-methanesulfonyl)-methylamino]-piperidine-1-yl}-methanon,
2-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-N-(2-hydroxyethyl)-acetamide", she
1-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-3-metalmachine,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(pyrrolidin-1-carbonyl)-piperidine-1-yl]-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(piperazine-1-carbonyl)-piperidine-1-yl]-methanon,
1-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-3-methylsulfinylpropyl-1-he,
1-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-3-methanesulfonate-1-he,
(2-methanesulfonyl)-amide 1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-carboxylic acid,
(2-methanol phenylethyl)-methylamide 1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-carboxylic acid,
(2-hydroxyethyl)-amide 1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-carboxylic acid,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(1,1-dioxo-1 X-thiomorpholine-4-carbonyl)-piperidine-1-yl]-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(2-methansulfonate)-piperidine-1-yl]-methanon,
rat-4-[(4S*,5R*)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-2-it,
rat-[(4S*,5R*)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-[4-(morpholine-4-carbonyl)-piperazine-1-yl]-methanon,
4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-2-it,
2-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-acetamide", she
rat-1-{1-[(4S*,5R*)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-6HC-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-[1,4]diazepan-5-he,
1-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-[1,4]diazepan-5-he,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-di is hydromedusa-1-carbonyl]-piperazine-1-yl}-N-pyridin-2-ylacetamide,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-piperazine-1-ylmethanone,
((S)-3,4-dihydroxybutyl)-amide of (4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carboxylic acid,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(3,6-dihydro-2N-pyridine-1-yl)-methanon,
[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-(3,4-dihydroxypyridine-1-yl)-methanon,
methyl-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxy)-amide of (4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carboxylic acid,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-pyridin-2-ylmethylene,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-pyridin-3-ylmethylene,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-pyridin-4-ylmethylene,
2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N-furan-2-ylmethylene,
{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl}-45-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-acetic acid,
2-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-N-pyridin-2-ylmethylene,
2-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-N-pyridin-3-ylacetamide,
2-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-1-(4-methylpiperazin-1-yl)-Etalon,
2-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-N,N-bis-(2-methoxyethyl)-ndimethylacetamide,
dimethylamide 4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-sulfonic acid,
(2-hydroxyethyl)-amide of (4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carboxylic acid,
(2-hydroxyethyl)-methylamide (4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carboxylic acid,
bis-(2-methoxyethyl)-amide of (4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carboxylic acid,
tert-butyl ether ({1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-carbamino acid,
(4-aminopiperidin-1-the l)-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-yl]-methanon,
tert-butyl ether 4-{[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-amino}-piperidine-1-carboxylic acid,
(1-methanesulfonamido-4-yl)-amide (4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carboxylic acid,
ethylamide 4-{[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-amino}-piperidine-1-carboxylic acid,
(1-carbamoylmethyl-4-yl)-amide (4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carboxylic acid,
1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-one,
methyl ester 1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-carboxylic acid,
1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-carboxylic acid,
3-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yloxy}-propionamide,
3-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yloxy}-propionitrile,
1-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine the-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-3-isopropylamino,
1-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-3-pyridin-3-Ilocano and
2-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-ylamino}-ndimethylacetamide.

2. The Union, representing 2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazine-1-yl}-N,N-bis-(2-methoxyethyl)-ndimethylacetamide.

3. The Union, representing 2-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridine-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidine-4-yl}-ndimethylacetamide.

4. Pharmaceutical composition having anti-proliferative activity, comprising a compound according to any one of claims 1 to 3 together with a pharmaceutically acceptable inert filler.

5. The compound according to claims 1-3, intended for use as a medicine.

6. The compound according to claims 1-3, intended for use as a drug for cancer treatment.

7. The compound according to claims 1-3, intended for use as a drug for the treatment of solid tumors.

8. The compound according to claims 1-3, intended for use as a drug for the treatment of tumors of the breast, colon, lung and prostate is elez.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to an amide derivative of formula (I), where A is benzene or pyridine, where the benzene or pyridine optionally contain 1 or 2 or 3 identical or different substitutes selected from an alkyl containing 1-6 carbon atoms, a cycloalkyl containing 3-6 carbon atoms, an alkoxy containing 1-6 carbon atoms, a halogen atom, nitro, cyano, alkylsulphonyl containing1-6 carbon atoms, amino, cyclic amine selected from 1,1-di-oxoisothiazolidinyl, 2-oxooxazolidinyl, oxopyrrolidinyl, 1,1-dioxothiazinyl and 2-oxoimidazolidinyl optionally having a substitute selected from an alkyl containing 1-6 carbon atoms and an alkylcarbonyl containing a total of 2-7 carbon atoms, acylamino containing a total of 2-7 carbon atoms, and an alkylsulphonyl amino containing 1-6 carbon atoms, wherein the right-side bond is linked to the carbonyl and the left-side bond is linked to the nitrogen atom, R1 and R2 are identical or different and each is a hydrogen, an alkyl containing 1-6 carbon atoms and optionally containing 3 halogen atoms as substitutes, a cycloalkyl containing 3-6 carbon atoms, a phenyl, a halogen atom or a cyano group and R1 and R2 are not a hydrogen atom at the same time, R3 is a hydrogen atom, an alkyl containing 1-6 carbon atoms, an alkenyl containing 2-6 carbon atoms, a cycloalkyl containing 3-6 carbon atoms, or a halogen, R4a, R4b and R4c are each independently a hydrogen atom, an alkyl containing 1-6 carbon atoms, or an oxo, R5a, R5b and R5c are identical or different and each is a hydrogen atom, an alkyl containing 1-6 carbon atoms and optionally containing substitute(s) selected from phenyl, an alkoxy group containing 1-6 carbon atoms, optionally substituted with an alkoxy group containing 1-6 carbon atoms, a phyenylcarbonyloxy group and a hydroxy group, or a phenyl, X is a carbon atom (any of R4a, R4b and R4c can be bonded to a carbon atom, but the carbon atom is not substituted with oxo) or a nitrogen atom (if Y is a single bond, the nitrogen atom can be oxidised to form an N oxide), Y is a single bond, a carbonyl or an oxygen atom, Z1 and Z2 are each independently a carbon atom (substitute R3 is optionally bonded to a carbon atom) or a nitrogen atom, and m equals 1 or 2, a pharmacologically acceptable salt thereof. The amide derivative is used as a preventive/therapeutic drug for treating autoimmune diseases, inflammatory bowel diseases or osteoarthritis.

EFFECT: amide derivative which suppresses production of inductive type MMP-9.

14 cl, 4 tbl, 581 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: application describes prodrugs being 2-amino-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}thio)-4-[4-(2-hydroxyethoxy)-phenyl]pyridine-3,5-dicarbonitryl derivatives, and a method for preparing them.

EFFECT: invention can find application in treating and/or preventing cardiovascular diseases.

8 cl, 4 tbl, 18 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 compounds of formula I , wherein R2 means methyl, Y means carbon or nitrogen, and R1, R3 and R4 have the value specified in the patent claim. Also, the invention refers to a pharmaceutical composition for the use as a pharmaceutical drug having activity of a phosphatidylinositol-3-kinase inhibitor, to the use of the compounds of formula I for preparing the pharmaceutical drug for treating a disease mediated by phosphatidylinositol 3-kinase and to a method for preparing the compounds of formula I .

EFFECT: preparing the compounds of formula I possessing activity of the phosphatidylinositol-3-kinase inhibitor.

10 cl, 5 tbl, 51 ex

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: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (1) and pharmaceutically acceptable salts thereof, which exhibit inhibitory activity on phospholipase A2 enzyme and therefore have prostaglandin and/or leucotriene production suppressing action. In formula X is a halogen atom, cyano group, C1-C3 alkyl group, which can be substituted with halogen atoms, C1-C3 alkoxy group or hydroxy group, C2-C4 alkenyl group, C1-C3 alkoxy group or hydroxy group; Y is a hydrogen atom or C1-C3 alkyl group; Z is C1-C3 alkyl group; G is selected from formulae and , where in formulae (G2) and (G5) R4 is a hydrogen atom or C1-C6 alkyl group which can be substituted with halogen atoms; D is -NR10C(O)-, -C(O)NR10-, -S(O)2NR10- or -N(R11)-; R10 is a hydrogen atom; R11 is a hydrogen atom or C1-C3 alkyl group; A is a single bond, C1-C6 alkylene, which can be substituted with a phenyl group, or C2-C4 alkenylene; Q is a phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, S, optionally substituted with a benzene ring; R5, R6 and R7 all or independently denote a hydrogen atom, a halogen atom, C1-C6 alkyl group which can be substituted with halogen atoms, C1-C6 alkoxy group which can be substituted with halogen atoms, phenyloxy group, phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, where said phenyl group and 5-6-member aromatic heterocyclic group can be substituted with a C1-C3 alkyl group which can be substituted with halogen atoms or a C1-C3 alkoxy group. The invention also relates to specific compounds, a medicinal agent, a pharmaceutical composition, a phospholipase A2 enzyme activity inhibitor and a treatment method.

EFFECT: improved method.

21 cl, 56 tbl, 561 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I or use thereof to prepare a medicine for treating depression, anxiety or both: or pharmaceutically acceptable salts thereof, where m is 0-3; n is 0-2; Ar is: optionally substituted indolyl; optionally substituted indazolyl; azaindolyl; 2,3-dihydro-indolyl; 1,3-dihydro-indol-2-one-yl; optionally substituted benzothiophenyl; benzothiazolyl; benzisothiazolyl; optionally substituted quinolinyl; 1,2,3,4-tetrahydroquinolinyl; quinolin-2-one-yl; optionally substituted naphthalenyl; optionally substituted pyridinyl; optionally substituted thiophenyl or optionally substituted phenyl; R1 is: C1-6alkyl; hetero-C1-6alkyl; halo-C1-6alkyl; halo-C2-6alkenyl; C3-7cycloalkyl; C3-7cycloalkyl-C1-6alkyl; C1-6alkyl-C3-6cycloalkyl-C1-6alkyl; C1-6alkoxy; C1-6alkylsulphonyl; phenyl; tetrahydropyranyl-C1-6alkyl; phenyl-C1-3alkyl, where the phenyl part is optionally substituted; heteroaryl-C1-3alkyl; R2 is: hydrogen or C1-6alkyl; and each Ra and Rb is independently: hydrogen; C1-6alkyl; C1-6alkoxy; halo; hydroxy or oxo; or Ra and Rb together form C1-2alkylene; under the condition that, when m is 1, n is 2, and Ar is an optionally substituted phenyl, then R1 is not methyl or ethyl, and where optionally substituted denotes 1-3 substitutes selected from alkyl, cycloalkyl, alkoxy, halo, haloalkyl, haloalkoxy, cyano, amino, acylamino, monoalkylamino, dialkylamino, hydroxyalkyl, alkoxyalkyl, pyrazolyl, -(CH2)q-S(O)rRf; -(CH2)q-C(=O)-NRgRh; -(CH2)q-N(Rf)-C(=O)-Ri or -(CH2)q-C(=O)-Ri; where q is 0, r is 0 or 2, each Rf, Rg and Rh is independently hydrogen or alkyl, and each Ri is independently alkyl, and where "heteroaryl" denotes a monocyclic radical having 5-6 ring atoms, including 1-2 ring heteroatoms selected from N or S, wherein the rest of the ring atoms are C atoms, "heteroalkyl" denotes an alkyl radical, including a branched C4-C7-alkyl, where one hydrogen atom is substituted by substitutes selected from a group consisting of -ORa, -NRbH, based on the assumption that the bonding of heteroalkyl radical occurs through a carbon atom, where Ra is hydrogen or C1-6alkyl, Rb is C1-6alkyl. Pharmaceutical compositions based on said compound are also disclosed.

EFFECT: obtaining novel compounds which can be used in medicine to treat depression, anxiety or both.

14 cl, 1 tbl, 28 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a 2-aza-bicyclo[3.3.0]octane derivative of formula , with stereogenic centres in a (1S,3S,5S)-configuration, where A is a thiazolyl which is unsubstituted or monosubstituted, where the substitute is independently selected from a group comprising C1-4alkyl, C3-6cycloalkyl and NH2; B is phenyl which is unsubstituted or mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, trifluoromethyl, NHC(O)CH3 and halogen; and R1 is an imidazo[2,1·b]thiazolyl or benzoisoxazolyl group, where said groups are independently unsubstituted or monosubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl; or R1 is a 2,3-dihydrobenzofuranyl group; or a pharmaceutically acceptable salt. The 2-aza-bicyclo[3.3.0]octane derivative of formula (I) is as a medicinal agent having the activity of orexin receptor antagonists.

EFFECT: obtaining novel 2-aza-bicyclo[3,3,0]octane derivatives as orexin receptor antagonists.

8 cl, 1 tbl, 26 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted N-phenylbipyrrolidine carboxamides of formula , where values of R, R1, R2, R3 and R4 are given in claim 1.

EFFECT: compounds have activity which binds to the H3 ligand, which allows use thereof in pharmaceutical compositions for treating sleep disorder.

10 cl, 1 tbl, 4 dwg, 153 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a biologically active substance possessing the antiaggregant properties. The technical effect: what is produced is a drug preparation of a new compound of (2E)-3-[1-(2-hydroxy-3-piperidin-1-ylpropyl)-1 H-indol-3-yl]-1-(2-thienyl)prop-2-en-1-one hydrochloride of formula I possessing antiaggregant action:

.

EFFECT: substance may be used in medicine for producing a drug preparation for preventing the conditions associated with a high thrombogenic potential of blood.

1 cl, 2 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula I, enantiomers and pharmaceutically acceptable salts thereof having the properties of AKT/protein kinase inhibitors. In formula 1 G represents phenyl, naphthalene, 5-member heteroaryl with 1 sulphur atom in a ring or 9-member bicyclic heteroaryl specified in indolyl wherein phenyl, naphthalene, 5-member heteroaryl is optionally substituted by one of three Ra groups; R1 and R1a are independently specified in H, Me, Et, -CH2OH, CF3, CHF2 or CH2F; R2 represents H, -OH, -OMe or F; R2a representsH, Me or F; R3 represents H, Me, Et; R4 represents H, 6-member heterocyclyl containing an oxygen atom as a heteroatom, cyclopropyl methyl or C1-C4 alkyl is optionally substituted F,-OH or -O(C1-C3 alkyl); R5 and R5a are independently specified in H and C1-C4 alkyl, or R5 and R5a together with an atom whereto attached form a carbonyl group or 5-6-member cycloalkyl; each Ra independently represents halogen, C1-C6-alkyl, C3-C6-cycloalkyl,-O-(C1-C6-alkyl), CF3, CN, phenyl, pyrazole, CH2F, CHF2, -OCH2F, -OCHF2, -OH, -SO2(C1-C6-alkyl), C(O)NH2; and j represents 1 or 2; and provided j represents 2, j-ring carbon atom, opposite NR4, may be substituted by heteroatom O.

EFFECT: compounds may be used for treating hyperproliferative diseases, such as cancer.

35 cl, 9 dwg, 4 tbl, 141 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula I, enantiomers and pharmaceutically acceptable salts thereof which have selective inhibitory action on AKT protein kinase, in particular protein kinase B. In formula I: A represents R1 and R1a are independently specified in H, Me, Et. vinyl, CF3, CHF2 or CH2F:R2 represents H, OH, OMe or F; R2a represents H, Me or F; R3 represents H. Me. Et or CF3; G represents phenyl optionally substituted by one to four groups Rc, or 5-6-member heteroaryl containing one heteroatom specified in sulphur optionally substituted by halogen; R5 and R6 independently represent H, OCH3, C3-C6-cycloalkyl independently substituted by F, OH, C1-C3alkyl or O(C1-C3alkyl), 4-6-member heterocyclyl containing one heteroatom specified in nitrogen optionally substituted by F, OH, C1-C3alkyl, cyclopropylmethyl or -C(=O)(C1-C3alkyl), or C1-C6-alkyl optionally substituted by one or more groups independently specified in OH, oxo O(C1-C6-alkyl), CN, F, NH2. NH(C1-C6-alkyl), O(C1-C6-alkyl)2. cyclopropyl. phenyl, imidazolyl, piperidinyl, pyrrolidinyl, morpholinyl, tetrahydrofuranyl, oxetanil or tetrahydropyranyl. The other radical values are specified in the patent claim.

EFFECT: compounds may be used treating the conditions selected from inflammatory, hyperproliferative, cardiovascular, neurodegenerative, gynaecological and dermatological diseases and disorders, preferentially in treating cancer.

15 cl, 2 tbl, 8 dwg, 14 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

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to organic chemistry, namely new 3,8-diaminotetrahydroquinoline derivatives of formula (1a) or to their pharmaceutically acceptable salts wherein X represents CH2, C=O or CH-OR; m is 1 or 2; Ar represents a phenyl group or a 5-merous or 6-merous aromatic heterocyclic group having one element specified in S and N, (wherein the phenyl group may be substituted by 1-2 halogen atoms); each R1 and R2 represents a hydrogen atom; R3 represents a C1-C6 alkyl group or indolyl-C1-4 alkyl group (the indolyl group is optionally substituted by a C1-C6 alkyl group or a halogen atom), n is 0; R4 and R5 which may be identical or different, each represents a hydrogen atom or a C1-C6 linear or branched alkyl group; each R6 and R7 represents a hydrogen atom; and R represents a hydrogen atom. Also, the present invention refers to a drug preparation and a pharmaceutical composition of the basis of the compound of formula (1a), to the compound of formula (F1), to a method for preparing an intermediate compound (e).

EFFECT: there are prepared new 3,8-diaminotetrahydroquinoline derivatives which possess high GHS-R antagonist activity.

10 cl, 1 tbl, 124 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: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of general formula (I), (the radical values are presented in the patent claim) including their split enantiomers, split diastereomers, solvates and pharmaceutically acceptable salts. What is also described is a method for preparing new compounds, a pharmaceutical composition containing them.

EFFECT: use of the compounds as protein kinase inhibitors and a method of treating cancer.

113 cl, 49 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to substituted N-phenylbipyrrolidine carboxamides of formula , where values of R, R1, R2, R3 and R4 are given in claim 1.

EFFECT: compounds have activity which binds to the H3 ligand, which allows use thereof in pharmaceutical compositions for treating sleep disorder.

10 cl, 1 tbl, 4 dwg, 153 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to compounds of formula I

,

wherein radicals and symbols assume values given in the claim, or pharmaceutically acceptable salts thereof. The disclosed compounds inhibit serine protease activity, especially activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, compounds of the present invention inhibit the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to a pharmaceutical composition containing said compounds for administering to a patient suffering from HCV infection.

EFFECT: invention also relates to a method of treating HCV infection in a patient and a method of inhibiting replication of hepatitis C virus by administering a pharmaceutical composition containing compounds of the present invention.

7 cl, 7 tbl, 158 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to particular compounds, which demonstrate inhibiting activity with respect to ERK, whose structure formula is given in description, to their pharmaceutically acceptable salts, based on them pharmaceutical composition and their application for treatment of cancer, mediated by ERK activity.

EFFECT: obtaining compounds, which demonstrate inhibiting activity with respect to ERK.

5 cl

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

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