Heteroarylbenzimidazole compounds

Patent metadata

Field	Value
Publication number	US-10894784-B2
Application number	US-201616063370-A
Country	US
Kind code	B2
Filing date	Dec 15, 2016
Priority date	Dec 18, 2015
Publication date	Jan 19, 2021
Grant date	Jan 19, 2021

Abstract

The present invention covers heteroarylbenzimidazole compounds of general formula (I) in which R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative and/or inflammatory disorders, as a sole agent or in combination with other active ingredients.

First claim

The invention claimed is:

1. A compound of formula (I):

wherein
R 1 represents a group selected from

in which “*” represents the point of attachment to the rest of the molecule, said group being optionally substituted one or two times, differently or identically, with a R 7 group;

R 2 represents a group

in which “*” represents the point of attachment to the rest of the molecule;

R 3 represents a hydrogen atom;
R 4 represents a hydrogen atom;
R 5 represents a hydrogen atom;
R 7 represents a group selected from the group consisting of methyl, (methoxy)-(methyl)-, ethylamino, isopropylamino, (cyclopropyl)-(methyl)-amino-, cyclopropylamino, cyclobutylamino, dimethylamino, azetidin-1-yl, 3,3-difluoroazetidin-1-yl, 3-trifluoromethylazetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, morpholinyl, methoxy, ethoxy, iso-propoxy, 2,2,2-trifluoroethoxy, 2,2-difluoropropoxy and (cyclopropyl)-(methoxy)-;
R 9 represents a methyl group;
R 10 represents a —C(═O)R 12 group;
R 12 represents a group selected from the group consisting of 2,2,2-trifluoroethyl, cyclopropyl, (1-trifluoromethyl)-(cyclopropyl)-, 2,2-difluorocyclopropyl and 2,2-difluoro-1-methylcyclopropyl,
or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.

2. The compound according to claim 1 , which is selected from the group consisting of:
(rac)-cyclobutyl{4-[1-(2-{[6-(pyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
(rac)-cyclopropyl{4-[1-(2-{[6-(pyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
(rac)-3,3,3-trifluoro-1-{4-[1-(2-{[6-(pyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}propan-1-one;
cyclopropyl{4-[(1R)-1-(2-{[6-(pyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
cyclopropyl{4-[(1S)-1-(2-{[6-(pyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
3,3,3-trifluoro-1-{4-[(1R)-1-(2-{[6-(pyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}propan-1-one;
3,3,3-trifluoro-1-{4-[(1S)-1-(2-{[6-(pyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}propan-1-one;
cyclobutyl{4-[(1R)-1-(2-{[6-(pyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
cyclobutyl{4-[(1S)-1-(2-{[6-(pyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
(rac)-cyclopropyl{4-[1-(2-{[6-(2-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
(rac)-cyclobutyl{4-[1-(2-{[6-(2-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
(rac)-3,3,3-trifluoro-1-{4-[1-(2-{[6-(2-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}propan-1-one;
3,3,3-trifluoro-1-{4-[(1R)-1-(2-{[6-(2-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}propan-1-one;
3,3,3-trifluoro-1-{4-[(1S)-1-(2-{[6-(2-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}propan-1-one;
cyclobutyl{4-[(1R)-1-(2-{[6-(2-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
cyclobutyl{4-[(1S)-1-(2-{[6-(2-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
cyclopropyl{4-[(1R)-1-(2-{[6-(2-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
cyclopropyl{4-[(1S)-1-(2-{[6-(2-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
(rac)-1-{4-[1-(2-{[6-(2-ethoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}-3,3,3-trifluoropropan-1-one;
1-{4-[(1R)-1-(2-{[6-(2-ethoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}-3,3,3-trifluoropropan-1-one;
1-{4-[(1S)-1-(2-{[6-(2-ethoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}-3,3,3-trifluoropropan-1-one;
(rac)-3,3,3-trifluoro-1-{4-[1-(2-{[6-(6-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}propan-1-one;
(rac)-cyclobutyl{4-[1-(2-{[6-(6-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
(rac)-cyclopropyl{4-[1-(2-{[6-(6-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
3,3,3-trifluoro-1-{4-[(1R)-1-(2-{[6-(6-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}propan-1-one;
3,3,3-trifluoro-1-{4-[(1S)-1-(2-{[6-(6-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}propan-1-one;
cyclobutyl{4-[(1R)-1-(2-{[6-(6-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
cyclobutyl{4-[(1S)-1-(2-{[6-(6-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
cyclopropyl{4-[(1R)-1-(2-{[6-(6-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
cyclopropyl{4-[(1S)-1-(2-{[6-(6-methylpyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
(rac)-3,3,3-trifluoro-1-{4-[1-(2-{[6-(6-methoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}propan-1-one;
(rac)-cyclopropyl{4-[1-(2-{[6-(6-methoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
3,3,3-trifluoro-1-{4-[(1R)-1-(2-{[6-(6-methoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}propan-1-one (single stereoisomer A);
3,3,3-trifluoro-1-{4-[(1S)-1-(2-{[6-(6-methoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}propan-1-one;
cyclopropyl{4-[(1R)-1-(2-{[6-(6-methoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
cyclopropyl{4-[(1S)-1-(2-{[6-(6-methoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
(rac)-3,3,3-trifluoro-1-{4-[1-(2-{[6-(5-methoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}propan-1-one;
(rac)-cyclopropyl{4-[1-(2-{[6-(5-methoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
(rac)-cyclobutyl{4-[1-(2-{[6-(5-methoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
3,3,3-trifluoro-1-{4-[(1R)-1-(2-{[6-(5-methoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}propan-1-one;
3,3,3-trifluoro-1-{4-[(1S)-1-(2-{[6-(5-methoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}propan-1-one;
cyclopropyl{4-[(1R)-1-(2-{[6-(5-methoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
cyclopropyl{4-[(1S)-1-(2-{[6-(5-methoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone;
cyclobutyl{4-[(1R)-1-(2-{[6-(5-methoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone);
cyclobutyl{4-[(1S)-1-(2-{[6-(5-methoxypyrimidin-4-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazin-1-yl}methanone (single stereoisomer B);
3,3,3-trifluoro-1-(4-{(1R or 1S)-1-[2-({6-[5-(propan-2-yloxy)pyrimidin-4-yl]-1H-benzimidazol-2-yl}amino)pyridin-4-yl]ethyl}piperazin-1-yl)propan-1-one (single stereoisomer A);

Assignees

• Bayer Pharma AG

Inventors

• Schulze Volker
• Heinrich Tobias
• Prinz Florian
• Lefranc Julien
• SCHRÖDER Jens
• Mengel Anne
• Bone Wilhelm
• Bálint Joszef
• Wengner Antje Margret
• Eis Knut
• Irlbacher Horst
• Koppitz Marcus
• Bömer Ulf
• Bader Benjamin
• Briem Hans
• Lienau Philip
• Christ Clara
• Stöckigt Detlef
• Hillig Roman

Classifications

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D401/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D471/08

  Bridged systems · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D409/14

  containing three or more hetero rings · CPC title