Stilbene derivatives and their use for binding and imaging amyoid plaques

• US 20060269473A1
• Filed: 12/19/2005
• Published: 11/30/2006
• Est. Priority Date: 12/17/2004
• Status: Active Grant

• Current Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Kung, Mei-Ping, Kung, Hank F., Zhuang, Zhi-Ping
• Granted Patent: US 7,807,135 B2
• Time in Patent Office: Days
• US Class Current: 424/1.110
• CPC Class Codes: A61K 51/04 Organic compounds
• 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: C07B 59/001 Acyclic or carbocyclic compounds
• CPC Class Codes: C07C 217/80 having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings

Abstract

This invention relates to a method of imaging amyloid deposits and to labeled compounds, and methods of making labeled compounds useful in imaging amyloid deposits. This invention also relates to compounds, and methods of making compounds for inhibiting the aggregation of amyloid proteins to form amyloid deposits, and a method of delivering a therapeutic agent to amyloid deposits.

Claims

1. A compound of Formula I,

2. The compound of claim 1, wherein R^1′

is hydrogen and R¹ is NR^aR^b, wherein R^a and R^b are independently hydrogen or C_1-4 alkyl.

3. The compound of claim 2 wherein R⁷ and R⁸ are hydrogen or fluorine, wherein at least one of R⁷ and R⁸ is fluorine.

4. The compound of claim 2, wherein R² is

5. The compound of claim 4, wherein q is an integer from 2 to 5.

6. The compound of claim 5, wherein R³⁰, R³¹, R³² and R³³ are, in each instance, hydrogen.

7. The compound of claim 6, wherein q is an integer from 3 to 4.

8. The compound of claim 7, wherein Z is ¹⁸F.

9. The compound of claim 8, having the following formula:

10. The compound of claim 8, having the following formula:

11. The compound of claim 2, wherein R² is

12. The compound of claim 11, wherein Z is ¹⁸F.

13. The compound of claim 12, wherein R³⁰, R³¹, R³² and R³³ are, in each instance, hydrogen.

14. The compound of claim 2, wherein R² is

15. The compound of claim 14, wherein R³⁴, R³⁵, R³⁶, R³⁷, R³⁸R³⁹ and R⁴⁰ are, in each instance, hydrogen.

16. The compound of claim 15, having the following structure:

34. A pharmaceutical composition comprising a compound of claim 1, 17 or 32.

35. A diagnostic composition for imaging amyloid deposits, comprising a radiolabeled compound of claim 1, 17 or 32.

36. A method of imaging amyloid deposits, comprising:

a. introducing into a mammal a detectable quantity of a diagnostic composition of claim 35;

b. allowing sufficient time for the labeled compound to be associated with amyloid deposits; and

c. detecting the labeled compound associated with one or more amyloid deposits.

37. A method of inhibiting amyloid plaque aggregation in a mammal, comprising administering a composition of claim 34 in an amount effective to inhibit amyloid plaque aggregation.

17. A compound of Formula II,

18. The compound of claim 17, wherein R¹ is NR^aR^b, wherein R^a and R^b are independently hydrogen or C_1-4 alkyl.

19. The compound of claim 18, wherein R² is

20. The compound of claim 19, wherein q is an integer from 2 to 5.

21. The compound of claim 20, wherein R⁷ and R⁸ are each hydrogen.

22. The compound of claim 21, wherein R³⁰, R³¹, R³² and R³³ are, in each instance, hydrogen.

23. The compound of claim 22, having the following formula:

24. The compound of claim 22, having the following formula:

25. The compound of claim 18, wherein R² is

26. The compound of claim 25, wherein Z is ¹⁸F.

27. The compound of claim 26, wherein R⁷ and R⁸ are each hydrogen.

28. The compound of claim 27, wherein R³⁰, R³¹, R³² and R³³ are, in each instance, hydrogen.

29. The compound of claim 18, wherein R² is

30. The compound of claim 29, wherein R³⁴, R³⁵, R³⁶, R³⁷, R³⁸, R³⁹ and R⁴⁰ are, in each instance, hydrogen.

31. The compound of claim 30, having the following structure:

32. A compound of Formula III:

33. The compound of claim 32, wherein n is one, and R⁴¹ is selected from the group consisting of hydroxy, methylamino and dimethylamino.