Compounds for treating Huntington's disease

Patent metadata

Field	Value
Publication number	US-11407753-B2
Application number	US-201816617450-A
Country	US
Kind code	B2
Filing date	Jun 5, 2018
Priority date	Jun 5, 2017
Publication date	Aug 9, 2022
Grant date	Aug 9, 2022

Abstract

The present description relates to compounds, forms, and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington's disease. In particular, the present description relates to substituted bicyclic heteroaryl compounds of Formula (I), forms and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington's disease.

First claim

What is claimed is:

1. A compound selected from the group consisting of:
2-(2-methyl-2H-indazol-5-yl)-6-(piperidin-4-yl)quinoline,
6-(1-ethylpiperidin-4-yl)-2-(2-methyl-2H-indazol-5-yl)quinoline,
6-(2-methyl-2H-indazol-5-yl)-2-(piperidin-4-yl)quinolone,
3-(2-methyl-2H-indazol-5-yl)-7-(1,2,3,6-tetrahydropyridin-4-yl)cinnoline,
4-methyl-6-(2-methyl-2H-indazol-5-yl)-2-(piperidin-4-yl)quinoline,
6-(2-methyl-2H-indazol-5-yl)-2-(1-methylpiperidin-4-yl)quinoline,
2-(2-methyl-2H-indazol-5-yl)-6-(piperazin-1-yl)quinoline,
2-(1-ethylpiperidin-4-yl)-6-(2-methyl-2H-indazol-5-yl)quinoline,
2-(2-methyl-2H-indazol-5-yl)-6-(piperidin-4-yl)quinazoline,
6-(2,7-dimethyl-2H-indazol-5-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)quinolin-2-amine,
N-methyl-6-(2-methyl-2H-indazol-5-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)quinolin-2-amine,
6-(2,7-dimethyl-2H-indazol-5-yl)-2-(2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)quinoline,
6-(2,7-dimethyl-2H-indazol-5-yl)-2-(2,2,6,6-tetramethylpiperidin-4-yl)quinoline,
6-(2,7-dimethyl-2H-indazol-5-yl)-2-(piperidin-4-yl)quinoline,
7-(2,7-dimethyl-2H-indazol-5-yl)-3-(piperidin-4-yl)-1,2,4-benzotriazine,
3-(2,7-dimethyl-2H-indazol-5-yl)-7-(piperidin-4-yl)-1,2,4-benzotriazine,
6-(2,8-dimethylimidazo[1,2-a]pyrazin-6-yl)-2-(piperidin-4-yl)quinoline,
6-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-2-(piperidin-4-yl)quinoline,
6-(2,7-dimethyl-2H-indazol-5-yl)-8-fluoro-2-(piperidin-4-yl)quinoline,
6-(2,7-dimethyl-2H-indazol-5-yl)-2-(piperidin-4-yl)quinazoline,
6-[2-methyl-7-(trifluoromethyl)-2H-indazol-5-yl]-2-(piperidin-4-yl)quinoxaline,
3-(7-fluoro-2-methyl-2H-indazol-5-yl)-7-(piperidin-4-yl)-1,2,4-benzotriazine,
2-methyl-5-[7-(piperidin-4-yl)-1,2,4-benzotriazin-3-yl]-2H-indazole-7-carbonitrile,
3-(2,8-dimethylimidazo[1,2-a]pyridin-6-yl)-7-(piperidin-4-yl)-1,2,4-benzotriazine,
3-(1,3-dimethylpyrrolo[1,2-a]pyrazin-7-yl)-7-(piperidin-4-yl)-1,2,4-benzotriazine,
3-(2,7-dimethyl-2H-indazol-5-yl)-7-(piperidin-4-yl)quinoline,
7-(2,7-dimethyl-2H-indazol-5-yl)-3-(piperidin-4-yl)isoquinoline,
6-(2,7-dimethyl-2H-indazol-5-yl)-2-(piperidin-4-yl)quinoxaline,
5-fluoro-7-(7-fluoro-2-methyl-2H-indazol-5-yl)-3-(piperidin-4-yl)-1,2,4-benzotriazine,
7-(2,7-dimethyl-2H-indazol-5-yl)-5-fluoro-3-(piperidin-4-yl)-1,2,4-benzotriazine,
6-(2,7-dimethyl-2H-indazol-5-yl)-8-fluoro-2-(piperidin-4-yl)quinazoline,
5-[8-fluoro-2-(piperidin-4-yl)quinazolin-6-yl]-2-methyl-2H-indazole-7-carbonitrile,
8-fluoro-6-(7-fluoro-2-methyl-2H-indazol-5-yl)-2-(piperidin-4-yl)quinazoline,
6-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-8-fluoro-2-(piperidin-4-yl)quinazoline,
6-(2,7-dimethyl-2H-indazol-5-yl)-5-fluoro-2-(piperidin-4-yl)quinazoline,
6-(2,7-dimethyl-2H-indazol-5-yl)-7-fluoro-2-(piperidin-4-yl)quinazoline,
3-(2,8-dimethylimidazo[1,2-a]pyridin-6-yl)-5-fluoro-7-(piperidin-4-yl)-1,2,4-benzotriazine,
5-fluoro-3-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-(piperidin-4-yl)-1,2,4-benzotriazine,
7-(2,7-dimethyl-2H-indazol-5-yl)-5-fluoro-N-methyl-N-(piperidin-4-yl)-1,2,4-benzotriazin-3-amine,
3-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-(piperidin-4-yl)-1,2,4-benzotriazine,
3-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-7-(piperidin-4-yl)-1,2,4-benzotriazine,
6-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-8-fluoro-2-(piperidin-4-yl)quinoline,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-5-fluoro-3-(piperidin-4-yl)-1,2,4-benzotriazine,
6-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-8-fluoro-2-(1-methylpiperidin-4-yl)quinoline,
6-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-2-(1-ethylpiperidin-4-yl)-8-fluoroquinoline,
8-fluoro-6-(7-methoxy-2-methyl-2H-indazol-5-yl)-2-(piperidin-4-yl)quinoline,
8-fluoro-6-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-2-(piperidin-4-yl)quinoline,
8-fluoro-6-(8-methoxy-2-methylimidazo[1,2-b]pyridazin-6-yl)-2-(piperidin-4-yl)quinoline,
3-(7-methoxy-2-methyl-2H-indazol-5-yl)-7-(piperidin-4-yl)-1,2,4-benzotriazine,
8-fluoro-6-[8-(2-methoxyethoxy)-2-methylimidazo[1,2-b]pyridazin-6-yl]-2-(piperidin-4-yl)quinoline,
6-[8-fluoro-2-(piperidin-4-yl)quinolin-6-yl]-N-(2-methoxyethyl)-2-methylimidazo[1,2-b]pyridazin-8-amine,
7-(2,7-dimethyl-2H-indazol-5-yl)-5-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)cinnoline,
7-(8-azabicyclo[3.2.1]oct-3-yl)-3-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-1,2,4-benzotriazine,
3-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-5-fluoro-7-(piperidin-4-yl)-1,2,4-benzotriazine,
5-fluoro-7-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-3-(piperidin-4-yl)-1,2,4-benzotriazine,
7-(8-ethoxy-2-methylimidazo[1,2-b]pyridazin-6-yl)-5-fluoro-3-(piperidin-4-yl)-1,2,4-benzotriazine,
7-(2,8-dimethylimidazo[1,2-a]pyridin-6-yl)-5-fluoro-3-(piperidin-4-yl)-1,2,4-benzotriazine,
5-fluoro-7-[2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-6-yl]-3-(piperidin-4-yl)-1,2,4-benzotriazine,
7-(2,4-dimethyl-1,3-benzoxazol-6-yl)-5-fluoro-3-(piperidin-4-yl)-1,2,4-benzotriazine,
7-(2,4-dimethyl-1H-benzimidazol-6-yl)-5-fluoro-3-(piperidin-4-yl)-1,2,4-benzotriazine,
7-(1,3-dimethylpyrrolo[1,2-a]pyrazin-7-yl)-5-fluoro-3-(piperidin-4-yl)-1,2,4-benzotriazine,
7-(2,7-dimethylpyrazolo[1,5-a]pyridin-5-yl)-5-fluoro-3-(piperidin-4-yl)-1,2,4-benzotriazine,
7-(2,7-dimethyl-2H-pyrazolo[4,3-b]pyridin-5-yl)-5-fluoro-3-(piperidin-4-yl)-1,2,4-benzotriazine,
7-(2,7-dimethyl-2H-pyrazolo[3,4-c]pyridin-5-yl)-5-fluoro-3-(piperidin-4-yl)-1,2,4-benzotriazine,
5-fluoro-7-(4-fluoro-2-methyl-1,3-benzoxazol-6-yl)-3-(piperidin-4-yl)-1,2,4-benzotriazine,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-5-fluoro-3-(1-methylpiperidin-4-yl)-1,2,4-benzotriazine,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-3-(1-ethylpiperidin-4-yl)-5-fluoro-1,2,4-benzotriazine,
7-(2,7-dimethyl-2H-indazol-5-yl)-5-fluoro-3-(piperidin-4-yl)isoquinoline,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-5-fluoro-3-(piperidin-4-yl)isoquinoline,
7-(2,7-dimethyl-2H-indazol-5-yl)-5-fluoro-3-(piperidin-4-yl)cinnoline,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-5-fluoro-3-(piperidin-4-yl)cinnoline,
2-{4-[7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-5-fluorocinnolin-3-yl]piperidin-1-yl}ethanol,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-3-(1-ethylpiperidin-4-yl)-5-fluorocinnoline,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-5-fluoro-3-(1-propylpiperidin-4-yl)cinnoline,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-5-fluoro-3-[1-(propan-2-yl)piperidin-4-yl]cinnoline,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-5-fluoro-3-(1-methylpiperidin-4-yl)cinnoline,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-5-fluoro-3-(piperazin-1-yl)cinnoline,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-3-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-5-fluorocinnoline,
6-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-8-fluoro-2-(piperidin-4-yl)quinoxaline,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-5-fluoro-3-[1-(2-fluoroethyl)piperidin-4-yl]cinnoline,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-3-(piperidin-4-yl)cinnoline,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-3-(1-ethylpiperidin-4-yl)cinnoline,
1-[7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-5-fluorocinnolin-3-yl]-N,N-dimethylpyrrolidin-3-amine,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-3-[(2S,6S)-2,6-dimethylpiperidin-4-yl]-5-fluorocinnoline,
1-[7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-5-fluorocinnolin-3-yl]-N,N-dimethylpiperidin-4-amine,
(3R)-1-[7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-5-fluorocinnolin-3-yl]-N,N-dimethylpyrrolidin-3-amine,
7-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-3-[(2R,4r,6S)-2,6-dimethylpiperidin-4-yl]-5-fluorocinnoline,
5-fluoro-7-(2-methylimidazo[1,2-a]pyrimidin-6-yl)-3-(piperidin-4-yl)cinnoline,
5-fluoro-7-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-3-(piperidin-4-yl)cinnoline,
6-[5-fluoro-3-(piperidin-4-yl)cinnolin-7-yl]-2-methylimidazo[1,2-a]pyridine-8-carbonitrile,
5-fluoro-7-(2-methyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-(piperidin-4-yl)cinnoline,
5-fluoro-7-(2-methy

Assignees

• Ptc Therapeutics Inc

Inventors

• Woll Matthew G
• Amedzo Lukiana
• Babu Suresh
• Barraza Scott J
• Bhattacharyya Anuradha
• Karp Gary Mitchell
• Mazzotti Anthony R
• Narasimhan Jana
• Patel Jigar
• Turpoff Anthony
• Xu Zhenrong

Classifications

• A61P25/14

  for treating abnormal movements, e.g. chorea, dyskinesia · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• C07D491/048

  the oxygen-containing ring being five-membered · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title