Heteroaryl compounds for treating Huntington's disease

Patent metadata

Field	Value
Publication number	US-12139499-B2
Application number	US-201917254828-A
Country	US
Kind code	B2
Filing date	Jun 25, 2019
Priority date	Jun 27, 2018
Publication date	Nov 12, 2024
Grant date	Nov 12, 2024

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 benzothiazole 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 method for treating or ameliorating Huntington's Disease in a subject in need thereof comprising administering to the subject an effective amount of a compound of Formula (I):

or a form thereof, wherein:
W 1 , W 2 and W 3 are independently C—R a or N;
R a is, in each instance, independently selected from the group consisting of hydrogen, cyano, halogen, hydroxy, C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 alkyl-carbonyl, C 1-6 alkoxy, halo-C 1-6 alkoxy, C 1-6 alkoxy-C 1-6 alkyl, C 1-6 alkoxy-carbonyl, amino, C 1-6 alkyl-amino, (C 1-6 alkyl) 2 -amino, amino-C 1-6 alkyl, and hydroxy-C 1-6 alkyl;
X is selected from the group consisting of N—R b , O, and a bond;
R b is selected from the group consisting of hydrogen and C 1-6 alkyl;
R 1 is selected from the group consisting of C 3-10 cycloalkyl and heterocyclyl,
wherein heterocyclyl is a saturated or partially unsaturated 3-7 membered monocyclic, 6-10 membered bicyclic or 13-16 membered polycyclic ring system having 1, 2, or 3 heteroatom ring members independently selected from N, O, or S, and
wherein each instance of C 3-10 cycloalkyl and heterocyclyl is optionally substituted with one, two three, or four R 3 substituents and optionally, with one additional R 4 substituent, or,
wherein, alternatively, each instance of C 3-10 cycloalkyl and heterocyclyl is optionally substituted with one, two, three, four, or five R 3 substituents;

R 2 is selected from the group consisting of phenyl and heteroaryl,
wherein heteroaryl is selected from the group consisting of furanyl, 1H-imidazolyl, 1H -1,2,3-triazolyl, 4H-1,2,4-triazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1H-indolyl, 2H-indolyl, 1H-indazolyl, 2H-indazolyl, indolizinyl, benzofuranyl, 1H-benzimidazolyl, 1,3-benzoxazolyl, furo[2,3-b]pyridinyl, furo[2,3-c]pyridinyl, furo[3,2-b]pyridinyl, furo[3,2-c]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, 1H-pyrrolo[2,3-c]pyridinyl, pyrrolo[1,2-a]pyrimidinyl, pyrrolo[1,2-a]pyrazinyl, pyrrolo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl, 2H-pyrazolo[4,3-b]pyridinyl, 2H-pyrazolo[4,3-c]pyridinyl, pyrazolo[1,5-a]pyrazinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, imidazo[1,2-a]pyrimidinyl, imidazo[1,2-a]pyraziny, imidazo[1,2-b]pyridazinyl, imidazo[1,2-c]pyrimidinyl, imidazo[1,5-a]pyridinyl, imidazo[2,1-b][1,3]thiazolyl, imidazo[2,1-b][1,3,4]thiadiazoly, [1,3]oxazolo[4,5-b]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, [1,2,4]triazolo[1,5-b]pyridazinyl, and quinolinyl,
wherein each instance of phenyl and heteroaryl is optionally substituted with one, two or three R 5 substituents and optionally, with one additional R 6 substituent, or,
wherein, alternatively, each instance of phenyl and heteroaryl is optionally substituted with one, two, three or four R 5 substituents;

R 3 is, in each instance, independently selected from the group consisting of cyano, halogen, hydroxy, C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 alkyl-carbonyl, C 1-6 alkoxy, halo-C 1-6 alkoxy, C 1-6 alkoxy-C 1-6 alkyl, C 1-6 alkoxy-carbonyl, amino, C 1-6 alkyl-amino, amino-C 1-6 alkyl, and hydroxy-C 1-6 alkyl;
R 4 is selected from the group consisting of C 3-10 cycloalkyl, phenyl, heterocyclyl, and heteroaryl;
wherein heterocyclyl is a saturated or partially unsaturated 3-7 membered monocyclic, 6-10 membered bicyclic or 13-16 membered polycyclic ring system having 1, 2, or 3 heteroatom ring members independently selected from N, O, or S,
wherein heteroaryl is a 3-7 membered monocyclic or 6-10 membered bicyclic ring system having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, or S, and
wherein each instance of C 3-10 cycloalkyl, phenyl, heterocyclyl, and heteroaryl is optionally substituted with one, two or three R 7 substituents;

R 5 is, in each instance, independently selected from the group consisting of cyano, halogen, hydroxy, C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 alkyl-carbonyl, C 1-6 alkoxy, halo-C 1-6 alkoxy, C 1-6 alkoxy-C 1-6 alkyl, C 1-6 alkoxy-carbonyl, C 1-6 alkoxy-carbonyl-C 1-6 alkyl, carboxyl, C 1-6 alkyl-carboxyl, amino, C 1-6 alkyl-amino, (C 1-6 alkyl) 2 -amino, amino-C 1-6 alkyl, amino-carbonyl, and hydroxy-C 1-6 alkyl;
R 6 is selected from the group consisting of C 3-10 cycloalkyl, phenyl, phenyl-C 1-6 alkoxy, phenyl-oxy, heterocyclyl, and heteroaryl;
wherein heterocyclyl is a saturated or partially unsaturated 3-7 membered monocyclic, 6-10 membered bicyclic or 13-16 membered polycyclic ring system having 1, 2, or 3 heteroatom ring members independently selected from N, O, or S,
wherein heteroaryl is a 3-7 membered monocyclic or 6-10 membered bicyclic ring system having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, or S, and
wherein, each instance of C 3-10 cycloalkyl, phenyl, heterocyclyl, and heteroaryl is optionally substituted with one, two or three R 7 substituents; and

R 7 is, in each instance, independently selected from the group consisting of cyano, halogen, hydroxy, C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 alkyl-carbonyl, C 1-6 alkoxy, halo-C 1-6 alkoxy, C 1-6 alkoxy-C 1-6 alkyl, C 1-6 alkoxy-carbonyl, amino, C 1-6 alkyl-amino, (C 1-6 alkyl) 2 -amino, amino-C 1-6 alkyl, and hydroxy-C 1-6 alkyl;

wherein a form of the compound is selected from the group consisting of a salt, hydrate, solvate, racemate, enantiomer, diastereomer, stereoisomer, and tautomer form thereof.

2. The method of claim 1 , wherein R 1 is heterocyclyl selected from the group consisting of azetidinyl, tetrahydrofuranyl, pyrrolidinyl, piperidinyl, piperazinyl, 1H-azepinyl, 2,3,6,7-tetrahydro-1H-azepinyl, azepanyl, 1,4-diazepanyl, 1,2,5,6-tetrahydropyridinyl, 1,2,3,6-tetrahydropyridinyl, octahydroindolizinyl, octahydro-1H-pyrrolo[3,2-c]pyridinyl, (3aS,7aR)-octahydro-1H-pyrrolo[3,2-c]pyridinyl, 1-azabicyclo[2.2.2]octyl, 3-azabicyclo[3.1.0]hexyl, (1R,5S)-3-azabicyclo[3.1.0]hexyl, 3-azabicyclo[3.2.1]octyl, 8-azabicyclo[3.2.1]octyl, (1R,5S)-8-azabicyclo[3.2.1]octyl, 8-azabicyclo[3.2.1]oct-2-en-yl, (1R,5S)-8-azabicyclo[3.2.1]oct-2-en-yl, 9-azabicyclo[3.3.1]nonyl, (1R,5S)-9-azabicyclo[3.3.1]nonyl, 2,5-diazabicyclo[2.2.1]heptyl, (1S,4S)-2,5-diazabicyclo[2.2.1]heptyl, 1,4-diazabicyclo[3.1.1]heptyl, 3,6-diazabicyclo[3.2.0]heptyl, 2,5-diazabicyclo[2.2.2]octyl, 1,4-diazabicyclo[3.2.1]octyl, 3,8-diazabicyclo[3.2.1]octyl, (1R,5S)-3,8-diazabicyclo[3.2.1]octyl, 1,4-diazabicyclo[3.2.2]nonyl, 3,8-diazabicyclo[4.2.0]octyl, (1S,6R)-3,8-diazabicyclo[4.2.0]octyl, (1R,6S)-3,8-diazabicyclo[4.2.0]octyl, 2-azaspiro[3.3]heptyl, 4,7-diazaspiro[2.5]octyl, 2,6-diazaspiro[3.3]heptyl, 2,6-diazaspiro[3.4]octyl, 1,6-diazaspiro[3.5]nonyl, 1,7-diazaspiro[3.5]nonyl, 2,6-diazaspiro[3.5]nonyl, 2,7-diazaspiro[3.5]nonyl, 5,8-diazaspiro[3.5]nonyl, 1,7-diazaspiro[4.4]nonyl, 2,7-diazaspiro[4.4]nonyl, 2,7-diazaspiro[4.5]decyl, and 6,9-diazaspiro[4.5]decyl, wherein heterocyclyl is optionally substituted with one, two three, or four R 3 substituents and optionally, with one additional R 4 substituent, or, alternatively, wherein heterocyclyl is optionally substituted with one, two, three, four, or five R 3 substituents.

3. The method of claim 1 , wherein R 2 is heteroaryl selected from the group consisting of furanyl, 1H-imidazolyl, 1H-1,2,3-triazolyl, 4H-1,2,4-triazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1H-indolyl, 2H-indolyl, 1H-indazolyl, 2H-indazolyl, indolizinyl, benzofuranyl, 1H-benzimidazolyl, 1,3-benzoxazolyl, furo[2,3-b]pyridinyl, furo[2,3-c]pyridinyl, furo[3,2-b]pyridinyl, furo[3,2-c]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, 1H-pyrrolo[2,3-c]pyridinyl, pyrrolo[1,2-a]pyrimidinyl, pyrrolo[1,2-a]pyrazinyl, pyrrolo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl, 2H-pyrazolo[4,3-b]pyridinyl, 2H-pyrazolo[4,3-c]pyridinyl, pyrazolo[1,5-a]pyr

Assignees

• Ptc Therapeutics Inc

Inventors

• Zhang Nanjing
• Babu Suresh
• Barraza Scott J
• Bhattacharyya Anuradha
• Chen Guangming
• Karp Gary Mitchell
• Kassick Andrew J
• Mazzotti Anthony R
• Moon Young-Choon
• Narasimhan Jana
• Sydorenko Nadiya
• Turpoff Anthony
• Woll Matthew G
• Yan Wuming

Classifications

• C07D513/04

  Ortho-condensed systems · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D417/14 Primary

  containing three or more hetero rings · CPC title

• C07D498/04

  Ortho-condensed systems · CPC title