Probes for imaging huntingtin protein

Patent metadata

Field	Value
Publication number	US-12258355-B2
Application number	US-202217881895-A
Country	US
Kind code	B2
Filing date	Aug 5, 2022
Priority date	Aug 29, 2014
Publication date	Mar 25, 2025
Grant date	Mar 25, 2025

Abstract

Provided are imaging agents comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, and methods of their use.

First claim

What is claimed is:

1. A compound which is:

or a pharmaceutically acceptable salt thereof.

2. A compound which is:

or a pharmaceutically acceptable salt thereof,
wherein the compound, or a pharmaceutically acceptable salt thereof, is labeled with one or more positron-emitting radionuclides.

3. The compound of claim 2 , wherein said one or more positron-emitting radionuclides are selected from: 11 C, 13 N, 15 O, and 18 F.

4. A pharmaceutical composition comprising the compound of claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

5. A method of generating diagnostic images in an individual comprising administering an effective amount of a compound of claim 2 , or a pharmaceutically acceptable salt thereof, to an individual, and generating an image of at least a part of said individual.

6. The method of claim 5 , wherein generating an image of at least a part of said individual comprises generating an image to detect a presence or absence of huntingtin protein (HTT protein) monomers or aggregates in a brain of said individual; and detecting a presence or absence of a pathologic process.

7. The method of claim 6 , wherein said HTT protein monomers or aggregates are present in the basal ganglia of said brain of said individual.

8. The method of claim 6 , wherein the pathologic process is a neurodegenerative disease.

9. The method of claim 8 , wherein the neurodegenerative disease is chosen from Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, Prion disease, and spinocerebellar ataxias.

10. The method of claim 9 , wherein the neurodegenerative disease is Huntington's disease (HD).

11. The method of claim 5 , wherein said effective amount of said compound comprises from about 0.1 to about 20 mCi.

12. The method of claim 11 , wherein said effective amount of said compound is about 10 mCi.

13. The method of claim 5 , wherein said generating an image comprises positron emission tomography (PET) imaging, PET with concurrent computed tomography imaging (PET/CT), PET with concurrent magnetic resonance imaging (PET/MRI), or a combination thereof.

14. The method of claim 13 , wherein said generating an image comprises PET imaging.

Assignees

• Chdi Foundation Inc

Inventors

• Dominguez Celia
• Coe Samuel
• Johnson Peter David
• Prime Michael Edward
• Brown Christopher John
• Galan Sébastien René Gabriel
• Giles Paul Richard
• Bard Jonathan
• Gadouleau Elise Lucienne Paulette
• Krülle Thomas Martin
• Clark-Frew Daniel
• Wityak John
• Kiselyov Alex
• Hayes Sarah

Classifications

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D413/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• A61K51/0463

  having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines · CPC title

• A61K51/0459

  having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine · CPC title