Imaging histone deacetylases with a radiotracer using positron emission tomography

Patent metadata

Field	Value
Publication number	US-10842891-B2
Application number	US-201816213358-A
Country	US
Kind code	B2
Filing date	Dec 7, 2018
Priority date	Oct 18, 2013
Publication date	Nov 24, 2020
Grant date	Nov 24, 2020

Abstract

Disclosed herein are histone deacetylase imaging agents for positron emission tomography and related imaging methods using the histone deacetylase imaging agents. The histone deacetylase imaging agents may be a compound of formula (I):

wherein R 1 is a moiety including a positron emitter; R 2 represents hydrogen, or substituted or unsubstituted alkyl, or substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and n is an integer selected from 0 or 1. In one version of the compound of formula (I), R 1 is a moiety including an adamantyl group.

First claim

What is claimed is:

1. A method for the treatment of a condition involving a histone deacetylase, the method comprising:
administering to a subject having the condition a therapeutically effective amount of a compound of formula (III):

wherein R 3 is

and
wherein R 4 represents hydrogen, or substituted or unsubstituted alkyl, or substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heterocyclic.

2. The method of claim 1 wherein:
the condition is a psychiatric disorder.

3. The method of claim 1 wherein:
the condition is a neurological disorder.

4. The method of claim 1 wherein:
the condition is cancer.

5. The method of claim 1 wherein:
the condition is heart disease.

6. The method of claim 1 wherein:
the condition is an inflammatory disease.

7. The method of claim 1 wherein:
R 3 is a moiety including a bridged carbocycle.

8. The method of claim 1 wherein:
R 3 is a moiety including a substituted or unsubstituted adamantyl group.

9. The method of claim 1 wherein R 4 is selected from the group consisting of

10. A compound of formula (III):

wherein R 3 is

and
wherein R 4 represents hydrogen, or substituted or unsubstituted alkyl, or substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heterocyclic.

11. The compound of claim 10 wherein R 4 is selected from the group consisting of

Assignees

• Massachusetts Gen Hospital

Inventors

• Hooker Jacob M
• Wang Changning
• Schroeder Frederick Albert

Classifications

• C07C259/06 Primary

  having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• C07C311/21

  having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring · CPC title

• C07C259/08

  having carbon atoms of hydroxamic groups bound to carbon atoms of rings other than six-membered aromatic rings · CPC title

• C07D209/14

  Radicals substituted by nitrogen atoms, not forming part of a nitro radical · CPC title