Compounds for treating Huntington's disease

Patent metadata

Field	Value
Publication number	US-11780839-B2
Application number	US-201917040104-A
Country	US
Kind code	B2
Filing date	Mar 27, 2019
Priority date	Mar 27, 2018
Publication date	Oct 10, 2023
Grant date	Oct 10, 2023

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 monocyclic heteroaryl compounds of Formula (I) or Formula (II), 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:
5-(5-methyl-1,3-oxazol-2-yl)-2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenol;
5-(2-methoxypyridin-4-yl)-2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(1H-1,2,3-triazol-4-yl)phenol;
4-(3-hydroxy-4-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenyl)pyridin-2-ol;
5-(3-methyl-1H-pyrazol-4-yl)-2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(1,3-oxazol-2-yl)phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(pyridin-4-yl)phenol;
5-(2-methylpyridin-4-yl)-2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenol;
5-(4-methyl-1H-imidazol-1-yl)-2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenol;
5-(1H-pyrazol-4-yl)-2-{3-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]-1,2,4-triazin-6-yl}phenol;
5-(3-fluoro-1H-pyrazol-4-yl)-2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenol;
5-(1H-pyrazol-4-yl)-2-{3-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenol;
5-[1-( 2 H 3 )methyl-1H-pyrazol-4-yl]-2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(1H-pyrazol-4-yl)phenol;
5-(1-methyl-1H-pyrazol-4-yl)-2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(1H-pyrazol-1-yl)phenol;
5-(3-fluoro-1-methyl-1H-pyrazol-4-yl)-2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenol;
2-{3-[methyl(piperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(1H-pyrazol-4-yl)phenol;
2-{3-[methyl(piperidin-3-yl)amino]-1,2,4-triazin-6-yl}-5-(1H-pyrazol-4-yl)phenol;
2-(3-{[(1R,3S,5S)-8-azabicyclo[3.2.1]octan-3-yl](methyl)amino}-1,2,4-triazin-6-yl)-5-(1H-pyrazol-4-yl)phenol;
2-(3-{[(1R,3S,5S)-9-azabicyclo[3.3.1]nonan-3-yl](methyl)amino}-1,2,4-triazin-6-yl)-5-(1H-pyrazol-4-yl)phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(2-methyl-2H-1,2,3-triazol-4-yl)phenol;
2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-3-yl}-5-(1H-pyrazol-4-yl)phenol;
(6-(2-hydroxy-4-(1H-pyrazol-4-yl)phenyl)-1,2,4-triazin-3-yl)(2,2,6,6-tetramethylpiperidin-4-yl)methanone;
(3-(2-hydroxy-4-(1H-pyrazol-4-yl)phenyl)-1,2,4-triazin-6-yl)(2,2,6,6-tetramethylpiperidin-4-yl)methanone;
2-(6-(2-hydroxy-4-(1H-pyrazol-4-yl)phenyl)-1,2,4-triazin-3-yl)-2-(2,2,6,6-tetramethylpiperidin-4-yl)acetonitrile;
2-(3-(2-hydroxy-4-(1H-pyrazol-4-yl)phenyl)-1,2,4-triazin-6-yl)-2-(2,2,6,6-tetramethylpiperidin-4-yl)acetonitrile;
2-(3-(amino(2,2,6,6-tetramethylpiperidin-4-yl)methyl)-1,2,4-triazin-6-yl)-5-(1H-pyrazol-4-yl)phenol;
2-(6-(amino(2,2,6,6-tetramethylpiperidin-4-yl)methyl)-1,2,4-triazin-3-yl)-5-(1H-pyrazol-4-yl)phenol;
2-(3-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-6-yl)-5-(1,3,5-triazin-2-yl)phenol;
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-3-yl)-5-(1,3,5-triazin-2-yl)phenol;
4-(3-hydroxy-4-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenyl)-1,3,5-triazin-2-ol;
4-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-3-yl)phenyl)-1,3,5-triazin-2-ol;
5-(4-amino-1,3,5-triazin-2-yl)-2-(3-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-6-yl)phenol;
5-(4-amino-1,3,5-triazin-2-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-3-yl)phenol;
5-(4-chloro-1,3,5-triazin-2-yl)-2-(3-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-6-yl)phenol
5-(4-chloro-1,3,5-triazin-2-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-3-yl)phenol;
2-(3-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-6-yl)-5-(5-methyl-1H-pyrazol-4-yl)phenol;
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-3-yl)-5-(5-methyl-1H-pyrazol-4-yl)phenol;
5-(5-chloro-1H-pyrazol-4-yl)-2-(3-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-6-yl)phenol;
5-(5-chloro-1H-pyrazol-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-3-yl)phenol;
4-(3-hydroxy-4-(3-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-6-yl)phenyl)-1H-pyrazole-5-carbonitrile;
4-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-3-yl)phenyl)-1H-pyrazole-5-carbonitrile;
5-(1,5-dimethyl-1H-pyrazol-4-yl)-2-(3-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-6-yl)phenol;
5-(1,5-dimethyl-1H-pyrazol-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-3-yl)phenol;
5-(5-chloro-1-methyl-1H-pyrazol-4-yl)-2-(3-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-6-yl)phenol;
5-(5-chloro-1-methyl-1H-pyrazol-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-3-yl)phenol;
4-(3-hydroxy-4-(3-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-6-yl)phenyl)-1-methyl-1H-pyrazole-5-carbonitrile;
4-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,2,4-triazin-3-yl)phenyl)-1-methyl-1H-pyrazole-5-carbonitrile;
5-(4-fluoro-1H-imidazol-1-yl)-2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(3-methyl-1H-1,2,4-triazol-1-yl)phenol;
2-{3-[(1-methylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(1H-pyrazol-4-yl)phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(thiophen-2-yl)phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(4-methylthiophen-2-yl)phenol;
5-(4-methoxy-1H-pyrazol-1-yl)-2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenol;
4-(3-hydroxy-4-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenyl)-1-methylpyridin-2(1H)-one;
5-(3-chloro-1H-pyrazol-4-yl)-2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(1,3-thiazol-2-yl)phenol;
5-(4-chloro-1H-imidazol-1-yl)-2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(pyridazin-4-yl)phenol;
5-(6-methylpyridazin-4-yl)-2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(1-methyl-1H-1,2,4-triazol-3-yl)phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(2H-1,2,3-triazol-2-yl)phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(2-methyl-1,3-thiazol-5-yl)phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(1,2,4-thiadiazol-5-yl)phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(3-methyl-1,2,4-thiadiazol-5-yl)phenol;
2-{3-[(3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl)(methyl)amino]-1,2,4-triazin-6-yl}-5-(1H-pyrazol-4-yl)phenol;
1-[1-(3-hydroxy-4-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}phenyl)-1H-pyrazol-4-yl]ethan-1-one;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(4-methyl-2H-1,2,3-triazol-2-yl)phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(pyridin-3-yl)phenol;
2-{3-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-yl}-5-(pyridin-2-yl)phenol;
5-(3-fluoro-1H-pyrazol-4-yl)-2-{3-[(2,

Assignees

• Ptc Therapeutics Inc

Inventors

• Sydorenko Nadiya
• Alam Md Rauful
• Amedzo Lukiana
• Babu Suresh
• Baiazitov Ramil Y
• Barraza Scott J
• Bhattacharyya Anuradha
• Karp Gary Mitchell
• Kenton Nathaniel T
• Mazzotti Anthony R
• Moon Young-Choon
• Mszar Nicholas W
• Narasimhan Jana
• Pal Sudipta
• Patel Jigar S
• Turpoff Anthony
• Woll Matthew G
• Xu Zhenrong
• Zhang Nanjing

Classifications

• C07D471/08 Primary

  Bridged systems · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• C07D401/12

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

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title