Curcumin Analogs

• US 20150158841A1
• Filed: 08/06/2013
• Published: 06/11/2015
• Est. Priority Date: 08/06/2012
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Ran, Chongzhao, Moore, Anna, Zhang, Xueli
• Granted Patent: US 9,738,623 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61P 25/28 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 Class Codes: C07C 225/16 and containing six-membered aromatic rings
• CPC Class Codes: C07C 225/22 having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
• CPC Class Codes: C07C 49/248 having unsaturation outside the aromatic rings
• CPC Class Codes: C07C 49/252 containing six-membered aromatic rings and other rings
• CPC Class Codes: C07D 213/74 Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 213/89 with hetero atoms directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 233/60 with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
• CPC Class Codes: C07D 277/64 with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/06 Peri-condensed systems
• CPC Class Codes: C07F 5/022 without C-boron linkages

Abstract

Provided herein are curcumin analogues that are able to interact with amyloid β (Aβ) and to attenuate the copper-induced crosslinking of Aβ. Also provided herein are methods of using the compounds in the treatment of Alzheimer'"'"'s Disease or a related disorder.

Claims

1. A compound of Formula (I)

2. The compound of claim 1, wherein X is —

BR⁴R⁵.

3. The compound of claim 1, wherein R⁴ and R⁵ are halo.

4. The compound of claim 3 or II, wherein R⁴ and R⁵ are F.

5. The compound of claim 1, wherein R¹ and R² are each independently a substituted aryl.

6. The compound of claim 1, wherein R¹ and R² are independently:

7. The compound of claim 6, wherein R¹ and R² are independently:

8. The compound of claim 7, wherein R^a and R^b is independently selected from H and C_1-6 alkyl.

9. The compound of claim 7, wherein R^1a is a substituted or unsubstituted heteroaryl.

10. The compound of claim 9, wherein the heteroaryl is a N-containing heteroaryl.

11. The compound of claim 10, wherein the N-containing heteroaryl is selected from the group consisting of:

12. The compound of claim 1, wherein R¹ and R² are the same.

13. The compound of claim 1, wherein at least one of R¹ and R² is a substituted or unsubstituted heteroaryl.

14. The compound of claim 13, wherein the heteroaryl is a N-containing heteroaryl.

15. The compound of claim 14, wherein the N-containing heteroaryl is an imidazolyl.

16. The compound of claim 15, wherein the N-containing heteroaryl is selected from the group consisting of:

17. The compound of claim 1, wherein the compound of Formula (I) is selected from the group consisting of:

18. The compound of claim 17, wherein the compound of Formula (I) is selected from the group consisting of

21. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

22. A method for treating Alzheimer'"'"'s Disease or a related disorder in a patient, the method comprising administering to the patient a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

19. A compound of Formula (II):

20. A compound of Formula (III)