Treatment of friedreich's ataxia using histone deacetylase inhibitors

Patent metadata

Field	Value
Publication number	US-9957225-B2
Application number	US-201414480899-A
Country	US
Kind code	B2
Filing date	Sep 9, 2014
Priority date	Nov 11, 2005
Publication date	May 1, 2018
Grant date	May 1, 2018

Abstract

The invention provides methods of treating Friedreich's ataxia and other neurodegenerative or neuromuscular conditions using histone deacetylase inhibitors.

First claim

What is claimed is:

1. A method of treating, or delaying the onset of Huntington's disease in a mammal comprising administering to the mammal a compound of formula I in an amount effective to alter the level of histone acetylation in the mammal and increase frataxin mRNA in lymphocytes from Friedreich's ataxia patients, wherein formula I is:

wherein:
n is 2 to about 10;
R 1 is aryl or heteroaryl;
R 2 is aryl or heteroaryl;
R a and R b are each independently H, alkyl, aryl, heteroaryl, or a nitrogen protecting group;
wherein any alkyl, aryl or heteroaryl is optionally substituted with 1 to 3 substituents selected from the group consisting of hydroxy, amino, nitro, cyano, halo, alkyl, trifluoromethyl, alkoxy, aryl, and NR c R d ;
wherein R c and R d are each independently hydrogen, alkyl, or C(═O)OR e wherein R e is H or alkyl;
or a salt thereof.

2. The method of claim 1 , further comprising identifying the mammal as one suffering from, or at risk for, Huntington's disease.

3. The method of claim 1 , wherein the mammal is a human.

4. The method of claim 1 , wherein the compound of formula I has a structure selected from the group consisting of:
a salt of a compound thereof; and
any combination thereof.

Assignees

• Scripps Research Inst

Inventors

• Gottesfeld Joel M
• Jenssen Ann-Kristin
• Herman David M
• Burnett Ryan
• Chou C James

Classifications

• C07C233/44

  having the carbon atom of the carboxamide group bound to a carbon atom of an unsaturated carbon skeleton · CPC title

• C07C233/29

  having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings · CPC title

• C07C231/02

  from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines · CPC title

• A61K31/167

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title

• C07C231/00

  Preparation of carboxylic acid amides · CPC title