Tetrahydroquinoline derivatives useful as bromodomain inhibitors

Patent metadata

Field	Value
Publication number	US-9315487-B2
Application number	US-201214114545-A
Country	US
Kind code	B2
Filing date	May 2, 2012
Priority date	May 4, 2011
Publication date	Apr 19, 2016
Grant date	Apr 19, 2016

Abstract

Tetrahydroquinoline compounds pharmaceutical compositions containing such compounds and their use in therapy.

First claim

What is claimed is:

1. A compound selected from the group consisting of
1-methylethyl ((2S,4R)-1-acetyl-2-methyl-6-{1-[2-(methyloxy)ethyl]-1H-pyrazol-4-yl}-1,2,3,4-tetrahydro-4-quinolinyl)carbamate;
6-(((2S,4R)-1-acetyl-6-(1-(2-methoxyethyl)-1H-1,2,3-triazol-4-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile;
6-(((2S,4R)-1-acetyl-6-(2-(2-methoxyethyl)-2H-1,2,3-triazol-4-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile;
1-((2S,4R)-4-((5-chloropyridin-2-yl)amino)-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone;
1-((2S,4R)-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-4-((5-methylpyridin-2-yl)amino)-3,4-dihydroquinolin-1(2H)-yl)ethanone;
1-((2S,4R)-4-((3-chlorophenyl)amino)-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone;
1-((2S,4R)-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-4-((5-methylpyrazin-2-yl)amino)-3,4-dihydroquinolin-1(2H)-yl)ethanone;
6-(((2S,4R)-1-acetyl-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile; and
salts thereof.

2. A compound which is 6-(((2S,4R)-1-acetyl-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile or a salt thereof.

3. A compound according to claim 1 or a pharmaceutically acceptable salt thereof.

4. A pharmaceutical composition which comprises a compound or a pharmaceutically acceptable salt thereof as defined in claim 3 and one or more pharmaceutically acceptable carriers, diluents or excipients.

5. A combination pharmaceutical product comprising a compound or a pharmaceutically acceptable salt thereof as defined in claim 3 together with one or more other therapeutically active agents.

6. A method of treating diseases or conditions mediated by BET family bromodomain proteins in a subject in need thereof which comprises administering a therapeutically effective amount of compound or a pharmaceutically acceptable salt thereof as defined in claim 3 .

7. A method of treatment according to claim 6 , wherein the disease or condition is a chronic autoimmune and/or inflammatory condition.

8. A method of treatment according to claim 6 , wherein the disease or condition is cancer.

Assignees

• Amans Dominique
• Demont Emmanuel Hubert
• Jones Katherine Louise
• Seal Jonathan Thomas
• Walker Ann Louise
• Glaxosmithkline Llc

Inventors

• Amans Dominique
• Demont Emmanuel Hubert
• Jones Katherine Louise
• Seal Jonathan Thomas
• Walker Ann Louise

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title