Histone deacetylase inhibitors and compositions and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9562021-B2
Application number	US-201414776039-A
Country	US
Kind code	B2
Filing date	Mar 10, 2014
Priority date	Mar 14, 2013
Publication date	Feb 7, 2017
Grant date	Feb 7, 2017

Abstract

Provided are certain histone deacetylase (HDAC) inhibitors of Formula I, compositions thereof, and methods of their use.

First claim

What is claimed:

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein
R is pyrimidine substituted with 1 or 2 groups independently chosen from halo, C 1 -C 4 alkyl, and C 1 -C 4 haloalkyl;
each R 1 is independently chosen from halo, C 1 -C 4 alkyl, and C 1 -C 4 haloalkyl; and
m is 1, 2 or 3.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R is

wherein each R 2 is independently chosen from halo, C 1 -C 4 alkyl, and C 1 -C 4 haloalkyl;
n is 1 or 2; and
represents the point of connection to the rest of the molecule.

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein n is 1.

4. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R is

5. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein each R 2 is independently C 1 -C 4 alkyl or C 1 -C 4 haloalkyl.

6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein each R 2 is independently methyl or trifluoromethyl.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R is

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 1.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein at least one R 1 is halo.

10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein at least one R 1 is fluoro.

11. The compound of claim 10 , or a pharmaceutically acceptable salt thereof, wherein m is 1, and R 1 is 2-fluoro.

12. A compound, which is 2-(2-fluorophenyl)-N-hydroxy-2-(4-(2-methylpyrimidin-5-yl)phenyl)acetamide, of the formula:

2-(2-fluorophenyl)-N-hydroxy-2-(4-(5-(trifluoromethyl)pyrimidin-2-yl)phenyl)acetamide, of the formula:

or a pharmaceutically acceptable salt thereof.

13. A pharmaceutically acceptable composition comprising a pharmaceutically acceptable carrier and at least one compound of claim 1 , or a pharmaceutically acceptable salt thereof.

14. A pharmaceutical composition of claim 13 , wherein the composition is formulated in a form chosen from tablets, capsules, powders, liquids, suspensions, suppositories, and aerosols.

15. A method for treating Huntington's disease in a patient in need of such treatment, wherein the method comprises administering to the patient a therapeutically effective amount of at least one compound of claim 1 , or a pharmaceutically accepatable salt thereof.

16. A new method for treating Huntington's disease in a patient in need of such treatment, wherein the method comprises administering to the patient a therapeutically effective amount of at least one compound of claim 12 , or a pharmaceutically acceptable salt thereof.

Assignees

• Chdi Foundation Inc

Inventors

• Dominguez Celia
• Beaumont Vahri
• Muñoz-Sanjuán Ignacio
• Bürli Roland W
• Haughan Alan F
• Luckhurst Christopher A
• Wall Michael
• Raphy Gilles
• Thomas Beth

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P43/00

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

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title