Compounds and probes for imaging huntingtin protein

Patent metadata

Field	Value
Publication number	US-11992535-B2
Application number	US-202017125905-A
Country	US
Kind code	B2
Filing date	Dec 17, 2020
Priority date	Dec 18, 2019
Publication date	May 28, 2024
Grant date	May 28, 2024

Abstract

Provided herein are certain compounds and imaging agents useful for detecting a condition or disorder associated with protein aggregation, compositions thereof, and methods of their use.

First claim

What is claimed:

1. A compound of Formula (I):

or an isotopically labeled analog, pharmaceutically acceptable salt, solvate, stereoisomer, or mixture of stereoisomers thereof,
wherein:
Z 1 and Z 2 are each independently CH, or one of Z 1 and Z 2 is N and the other is CH;
Z 3 is N or CH;
L 1 is —O—C 1-4 alkylene;
one of X 1 and X 2 is N-L 2 -R 2 and the other is CH 2 ;
X 3 is CH 2 or —O—CH 2 —;
L 2 is —C(═O)—;
R 1 is heteroaryl optionally substituted with one or two substituents independently selected from hydroxy, alkyl, alkoxy, haloalkoxy, and —N(R 4 ) 2 ;
R 2 is aryl, heteroaryl, heterocycloalkyl, or heterocycloalkenyl, each of which is substituted with one or two substituents independently selected from halogen, haloalkyl, hydroxy, alkyl, alkoxy, haloalkoxy, heteroaryl, and —N(R 4 ) 2 ;
wherein when R 2 is substituted with alkyl, the alkyl is optionally substituted with alkenyl or alkoxy;
wherein when R 2 is substituted with alkoxy, the alkoxy is optionally substituted with alkenyl or alkoxy;

p is 0, 1, or 2;
each R 3 is independently C 1-4 alkyl; and
each R 4 is independently H or C 1-4 alkyl.

2. The compound of claim 1 , of Formula (Ha):

or an isotopically labeled analog, pharmaceutically acceptable salt, solvate, stereoisomer, or mixture of stereoisomers thereof.

3. The compound of claim 1 , of Formula (IIb):

or an isotopically labeled analog, pharmaceutically acceptable salt, solvate, stereoisomer, or mixture of stereoisomers thereof.

4. The compound of claim 1 , of Formula (Ma):

or an isotopically labeled analog, pharmaceutically acceptable salt, solvate, stereoisomer, or mixture of stereoisomers thereof.

5. The compound of claim 1 , of Formula (Mb):

or an isotopically labeled analog, pharmaceutically acceptable salt, solvate, stereoisomer, or mixture of stereoisomers thereof.

6. The compound of claim 1 , of Formula (Mc):

or an isotopically labeled analog, pharmaceutically acceptable salt, solvate, stereoisomer, or mixture of stereoisomers thereof.

7. The compound of claim 1 , wherein R 1 is pyridinyl optionally substituted with one or two substituents independently selected from hydroxy, alkyl, alkoxy, and haloalkoxy.

8. The compound of claim 1 , wherein R 1 is pyridinyl optionally substituted with methoxy.

9. The compound of claim 1 , wherein R 1 is

10. The compound of claim 1 , wherein -L 1 -R 1 is

11. The compound of claim 1 , wherein Z 1 and Z 2 are each independently CH.

12. The compound of claim 1 , wherein one of Z 1 and Z 2 is N and the other is CH.

13. The compound of claim 12 , wherein Z 1 is N and Z 2 is CH.

14. The compound of claim 12 , wherein Z 2 is N and Z 1 is CH.

15. The compound of claim 1 , wherein R 2 is a substituted heteroaryl.

16. The compound of claim 1 , wherein R 2 is a substituted 6-membered heteroaryl ring containing one or two N.

17. The compound of claim 1 , wherein R 2 is selected from

each of which is substituted with one or two substituents independently selected from hydroxy, alkyl optionally substituted with alkoxy, haloalkyl, alkoxy optionally substituted with alkenyl or alkoxy, haloalkoxy, —N(R 4 ) 2 , and heteroaryl.

18. The compound of claim 1 , wherein R 2 is a substituted heterocycloalkyl or heterocycloalkenyl.

19. The compound of claim 18 , wherein R 2 is selected from

each of which is substituted with one or two substituents independently selected from hydroxy, alkyl optionally substituted with alkoxy, haloalkyl, alkoxy optionally substituted with alkenyl or alkoxy, haloalkoxy, —N(R 4 ) 2 , and heteroaryl.

20. The compound of claim 1 , wherein Z 3 is CH.

21. The compound of claim 1 , wherein X 3 is CH 2 .

22. A compound selected from

Example
Structure

1

1.1

1.2

1.3

1.4

1.5

1.6

1.8

Assignees

• Chdi Foundation Inc

Inventors

• Liu Longbin
• Lee Matthew
• Dominguez Celia
• Johnson Peter David
• Brown Christopher John
• Hayes Sarah
• Kotey Adrian
• Mills Matthew Robert
• Prime Michael Edward

Classifications

• C07D491/107

  with only one oxygen atom as ring hetero atom in the oxygen-containing ring · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title