Stilbene derivatives and their use for binding and imaging amyloid plaques

• US 7,807,135 B2
• Filed: 12/19/2005
• Issued: 10/05/2010
• 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
• Primary Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US11/305,333
• Publication Number:
  US 20060269473A1
• Time in Patent Office: 1,751 Days
• Field of Search: 424/1.11, 424/1.65, 424/1.81, 424/1.85, 424/1.89, 424/9.1, 424/9.2, 424/9.3, 424/9.4, 424/9.5, 424/9.6, 424/9.7, 424/9.8, 564/1, 564/305, 564/442
• US Class Current: 424/1.89
• 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 R⁷ and R⁸ are hydrogen or fluorine, wherein at least one of R⁷ and R⁸ is fluorine.

3. The compound of claim 1, wherein R² is

4. The compound of claim 3, wherein q is an integer from 2 to 5.

5. The compound of claim 4, wherein R³⁰, R³¹, R³² and R³³ are, in each instance, hydrogen.

6. The compound of claim 5, wherein q is an integer from 3 to 4.

7. The compound of claim 6, wherein Z is ¹⁸F.

8. The compound of claim 7, having the following formula:

9. The compound of claim 7, having the following formula:

10. The compound of claim 1, wherein R² is

11. The compound of claim 10, wherein Z is ¹⁸F.

12. The compound of claim 11, wherein R³⁰, R³¹, R³² and R³³ are, in each instance, hydrogen.

13. The compound of claim 1, wherein R² is

14. The compound of claim 13, wherein R³⁴, R³⁵, R³⁶, R³⁷, R³⁸, R³⁹ and R⁴⁰ are, in each instance, hydrogen.

15. The compound of claim 14, having the following structure:

33. A pharmaceutical composition comprising a compound of claim 1, 16 or 31.

34. A diagnostic composition for imaging amyloid deposits, comprising a radiolabeled compound of claim 1, 16 or 31.

35. A method of imaging amyloid deposits, comprising:

a. introducing into a mammal a detectable quantity of a diagnostic composition of claim 34;

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.

16. A compound of Formula II,

17. The compound of claim 16, wherein R¹ is NR^aR^b, wherein R^a and R^b are independently hydrogen or C_1-4 alkyl.

18. The compound of claim 17, wherein R² is

19. The compound of claim 18, wherein q is an integer from 2 to 5.

20. The compound of claim 19, wherein R⁷ and R⁸ are each hydrogen.

21. The compound of claim 20, wherein R³⁰, R³¹, R³² and R³³ are, in each instance, hydrogen.

22. The compound of claim 21, having the following formula:

23. The compound of claim 21, having the following formula:

24. The compound of claim 17, wherein R² is

25. The compound of claim 24, wherein Z is ¹⁸F.

26. The compound of claim 25, wherein R⁷ and R⁸ are each hydrogen.

27. The compound of claim 26, wherein R³⁰, R³¹, R³² and R³³ are, in each instance, hydrogen.

28. The compound of claim 17, wherein R² is

29. The compound of claim 28, wherein R³⁴, R³⁵, R³⁶, R³⁷, R³⁸, R³⁹ and R⁴⁰ are, in each instance, hydrogen.

30. The compound of claim 29, having the following structure:

31. A compound of Formula III:

32. The compound of claim 31, wherein n is one, and R⁴¹ is selected from the group consisting of hydroxy, methylamino and dimethylamino.