Amyloid targeting agents and methods of using the same

Patent metadata

Field	Value
Publication number	US-11718596-B2
Application number	US-202117171947-A
Country	US
Kind code	B2
Filing date	Feb 9, 2021
Priority date	Mar 19, 2014
Publication date	Aug 8, 2023
Grant date	Aug 8, 2023

Abstract

Provided herein is the design and synthesis of novel molecular rotor fluorophores useful for detection of amyloid or amyloid like proteins. The fluorophores are designed to exhibit enhanced fluorescence emission upon associating with amyloid or amyloid like proteins as compared to unbound compound. Also disclosed herein are methods for treating diseases associated with amyloid or amyloid like proteins.

First claim

What is claimed is:

1. A compound of Formula (Ie):

wherein
EDG is heterocycloalkyl of no more than 10 carbons optionally substituted with one or more R 17 ;
each R 17 is independently halogen, —OR 18 , —NR 19 R 20 , C 1 -C 10 alkyl, or C 1 -C 10 heteroalkyl;
each of R 18 , R 19 and R 20 is independently hydrogen, C 1 -C 10 alkyl, C 1 -C 10 heteroalkyl, or cycloalkyl of no more than 10 carbon atoms, each of which except for hydrogen is optionally substituted with one or more R 21 ;
each R 21 is independently halogen, —OR 22 , —NR 23 R 24 , C 1 -C 10 alkyl, C 1 -C 10 heteroalkyl, cycloalkyl of no more than 10 carbon atoms, heterocycloalkyl of no more than 10 carbon atoms, aryl of no more than 10 carbon atoms, or heteroaryl of no more than 10 carbon atoms;
each of R 22 , R 23 and R 24 is independently hydrogen or C 1 -C 10 alkyl;

Ar is naphthylene optionally substituted with one or more R 1 ; each R 1 is independently halogen, —OR 2 , —NR 3 R 4 , C 1 -C 10 alkyl, or C 1 -C 10 heteroalkyl, each of R 2 , R 3 and R 4 is independently hydrogen, C 1 -C 10 alkyl, or C 1 -C 10 heteroalkyl;
R 84 is hydrogen or optionally substituted C 1 -C 10 alkyl;
EWG is —CN; and
WSG is:

wherein n is an integer from 2-50, and R 81 is hydrogen or C 1 -C 10 alkyl.

2. The compound of claim 1 , wherein Ar is

3. The compound of claim 1 , wherein EDG is

wherein each of which is optionally substituted with one or more C 1 -C 10 alkyl.

4. The compound of claim 3 , wherein EDG is

optionally substituted with one or more C 1 -C 10 alkyl.

5. The compound of claim 4 , wherein EDG is

substituted with methyl or ethyl.

6. The compound of claim 1 , wherein:
WSG is

n is an integer of value 1-10; and
R 81 is hydrogen or C 1 -C 10 alkyl.

7. The compound of claim 6 , wherein R 81 is methyl.

8. The compound of claim 7 , wherein WSG is

9. The compound of claim 1 , wherein R 84 is hydrogen, C 1 -C 4 alkyl or substituted C 1 -C 4 alkyl.

10. The compound of claim 9 , wherein R 84 is substituted C 1 -C 4 alkyl.

11. The compound of claim 10 , wherein R 84 is substituted methyl.

12. The compound of claim 1 , wherein:
Ar is

 and
EDG is

 optionally substituted with one or more C 1 -C 10 alkyl.

13. The compound of claim 12 , wherein EDG is

substituted with methyl or ethyl.

14. The compound of claim 13 , wherein:
WSG is

n is an integer of value 1-10; and
R 81 is hydrogen or C 1 -C 10 alkyl.

15. The compound of claim 14 , wherein R 81 is methyl.

16. The compound of claim 15 , wherein WSG is

17. The compound of claim 16 , wherein R 84 is optionally substituted C 1 -C 4 alkyl.

18. The compound of claim 17 , wherein R 84 is substituted C 1 -C 4 alkyl.

19. The compound of claim 17 , wherein R 84 is substituted methyl.

20. A pharmaceutical composition comprising a compound of according to claim 1 and a pharmaceutically acceptable carrier.

Assignees

• Univ California
• Amydis Inc

Inventors

• Yang Jerry
• Theodorakis Emmanuel A
• Sarraf Stella

Classifications

• Y02E10/549

  Organic PV cells · CPC title

• C07D295/155 Primary

  with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings · CPC title

• A61B5/0075

  by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy (A61B5/0071 takes precedence) · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• C07C255/42 Primary

  the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms · CPC title