Histone deacetylase 6 selective inhibitors for the treatment of bone disease

Patent metadata

Field	Value
Publication number	US-9512083-B2
Application number	US-201214233228-A
Country	US
Kind code	B2
Filing date	Jul 20, 2012
Priority date	Jul 20, 2011
Publication date	Dec 6, 2016
Grant date	Dec 6, 2016

Abstract

This invention relates to methods for treating bone disease associated with osteoclast activation using HDAC6 selective inhibitors, e.g., small molecule inhibitors such as reverse amide compounds.

First claim

What is claimed is:

1. A method of treating, or reducing risk of, osteoporosis associated with abnormally high bone catabolism in a subject, the method comprising administering to the subject a therapeutically effective amount of a reverse amide compound of formula IVa:

or a pharmaceutically acceptable salt thereof, wherein, ring B is phenyl;
R 1 is phenyl, which may be optionally substituted by OH or halo; and
R is H or C1-8-alkyl.

2. The method of claim 1 , wherein the reverse amide compound is 2-(diphenylamino)-N-(7-(hydroxyamino)-7-oxoheptyl)pyrimidine-5-carboxamide, (Compound A):

3. The method of claim 1 , wherein the abnormally high bone catabolism is associated with increased osteoclastogenesis in the subject, decreased osteoblastogenesis in the subject, increased osteoclast activity in the subject, decreased osteoblast activity in the subject, an imbalance of osteoclastogenesis and osteoblastogenesis in the subject, or an imbalance of osteoclast and osteoblast activity in the subject.

4. The method of claim 1 , further comprising administering an additional active agent selected from the group consisting of bisphosphates, RANK ligands, bortezomib, Carfilzomib, lenalidomide, and Pomalidomide.

5. The method of claim 1 , wherein the methods further include administering a bisphosphate.

6. The method of claim 1 , wherein the reverse amide compound is 2-((2-chlorophenyl)(phenyl)amino)-N-(7-(hydroxyamino)-7-oxoheptyl)pyrimidine-5-carboxamide, (Compound C):

Assignees

• Raje Noopur
• Santo Loredana
• Massachusetts Gen Hospital

Inventors

• Raje Noopur
• Santo Loredana

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/505

  Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim · CPC title

• A61P19/00

  Drugs for skeletal disorders · CPC title