Imagining agents for diagnosis of Parkinson's disease

• US 6,515,131 B2
• Filed: 02/22/2001
• Issued: 02/04/2003
• Est. Priority Date: 02/22/2000
• Status: Expired due to Fees

• Current Assignee: Molecular Insight Pharmaceuticals Incorporated (Lantheus Holdings, Inc.)
• Original Assignee: Biostream Therapeutics, Inc.
• Inventors: Babich, John W., Smith, Miles P.
• Primary Examiner(s): Chang, Ceila
• Application Number:
  US09/790,320
• Publication Number:
  US 20010044543A1
• Time in Patent Office: 712 Days
• Field of Search: 546/193, 546/194, 546/232, 546/233, 546/234
• US Class Current: 546/194
• CPC Class Codes: A61K 51/0478 complexes from non-cyclic ligands, e.g. EDTA, MAG3
• CPC Class Codes: A61K 51/0497 conjugates with a carrier being an organic compounds

Abstract

Generally, the present invention is directed to central nervous system dopamine transporter-imaging agents and methods of use thereof. In certain embodiments, the present invention relates to radiolabeled piperidine derivatives for use as imaging agents in the diagnosis of Parkinson'"'"'s disease. Another aspect of the present invention relates to piperidine monoamine transporter ligands, comprising a functional group capable of chelating a radionuclide, e.g., technetium, and methods of use thereof.

Claims

1. A compound represented by A:

wherein

X represents O or (H)₂;

R represents H, alkyl, alkoxyl, alkylamino, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, alkoxycarbonyl, or alkylaminocarbonyl;

R₂ represents H;

R₃ represents optionally substituted aryl or heteroaryl;

R₄ represents H;

R₅ represents independently for each occurrence H, alkyl, alkoxyl, alkylamino, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, alkoxycarbonyl, or alkylaminocarbonyl; and

n is 0, 1, or 2.

2. The compound of claim 1, wherein X represents O.

3. The compound of claim 1, wherein R represents alkyl.

4. The compound of claim 1, wherein R₃ represents optionally substituted phenyl.

5. The compound of claim 1, wherein R₅ represents H or aralkyl.

6. The compound of claim 1, wherein n is 1.

7. The compound of claim 1, wherein X represents O;

and R represents alkyl.

8. The compound of claim 1, wherein X represents O;

and R₃ represents optionally substituted phenyl.

9. The compound of claim 1, wherein X represents O;

and R₅ represents independently for each occurrence H or aralkyl.

10. The compound of claim 1, wherein X represents O;

and n is 1.

11. The compound of claim 1, wherein X represents O;

R represents alkyl; and

R₃ represents optionally substituted phenyl.

12. The compound of claim 1, wherein X represents O;

R represents alkyl; and

R₅ represents independently for each occurrence H or aralkyl.

13. The compound of claim 1, wherein X represents O;

R represents alkyl;

R₃ represents optionally substituted phenyl; and

R₅ represents independently for each occurrence H or aralkyl.

14. The compound of claim 1, wherein X represents O;

R represents methyl;

R₃ represents 4-chlorophenyl;

R₅ represents independently for each occurrence H or 4-methoxybenzyl; and

n is 1.

15. A compound represented by B:

wherein

X represents O or (H)₂;

R represents H, alkyl, alkoxyl, alkylamino, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, alkoxycarbonyl, or alkylaminocarbonyl;

R₂ represents H;

R₃ represents H;

R₄ represents optionally substituted aryl or heteroaryl;

R₅ represents independently for each occurrence H, alkyl, alkoxyl, alkylamino, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, alkoxycarbonyl, or alkylaminocarbonyl; and

n is 0, 1, or 2.

16. The compound of claim 15, wherein X represents O.

17. The compound of claim 15, wherein R represents alkyl.

18. The compound of claim 15, wherein R₄ represents optionally substituted phenyl.

19. The compound of claim 15, wherein R₅ represents H or aralkyl.

20. The compound of claim 15, wherein n is 1.

21. The compound of claim 15, wherein X represents O;

and R represents alkyl.

22. The compound of claim 15, wherein X represents O;

and R₄ represents optionally substituted phenyl.

23. The compound of claim 15, wherein X represents O;

and R₅ represents independently for each occurrence H or aralkyl.

24. The compound of claim 15, wherein X represents O;

and n is 1.

25. The compound of claim 15, wherein X represents O;

R represents alkyl; and

R₄ represents optionally substituted phenyl.

26. The compound of claim 15, wherein X represents O;

R represents alkyl; and

R₅ represents independently for each occurrence H or aralkyl.

27. The compound of claim 15, wherein X represents O;

R represents alkyl;

R₄ represents optionally substituted phenyl; and

R₅ represents independently for each occurrence H or aralkyl.

28. The compound of claim 15, wherein X represents O;

R represents methyl;

R₄ represents 4-chlorophenyl;

R₅ represents independently for each occurrence H or 4-methoxybenzyl; and

n is 1.

29. A compound represented by C:

wherein

X represents O or (H)₂;

R represents H, alkyl, alkoxyl, alkylamino, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, alkoxycarbonyl, or alkylaminocarbonyl;

R₁ represents H;

R₃ represents optionally substituted aryl or heteroaryl;

R₄ represents H;

R₅ represents independently for each occurrence H, alkyl, alkoxyl, alkylamino, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, alkoxycarbonyl, or alkylaminocarbonyl; and

n is 0, 1, or 2.

30. The compound of claim 29, wherein X represents O.

31. The compound of claim 29, wherein R represents alkyl.

32. The compound of claim 29, wherein R₃ represents optionally substituted phenyl.

33. The compound of claim 29, wherein R₅ represents H or aralkyl.

34. The compound of claim 29, wherein n is 1.

35. The compound of claim 29, wherein X represents O;

and R represents alkyl.

36. The compound of claim 29, wherein X represents O;

and R₃ represents optionally substituted phenyl.

37. The compound of claim 29, wherein X represents O;

and R₅ represents independently for each occurrence H or aralkyl.

38. The compound of claim 29, wherein X represents O;

and n is 1.

39. The compound of claim 29, wherein X represents O;

R represents alkyl; and

R₃ represents optionally substituted phenyl.

40. The compound of claim 29, wherein X represents O;

R represents alkyl; and

R₅ represents independently for each occurrence H or aralkyl.

41. The compound of claim 29, wherein X represents O;

R represents alkyl;

R₃ represents optionally substituted phenyl; and

R₅ represents independently for each occurrence H or aralkyl.

42. The compound of claim 29, wherein X represents O;

R represents methyl;

R₃ represents 4-chlorophenyl;

R₅ represents independently for each occurrence H or 4-methoxybenzyl; and

n is 1.

43. A compound represented by D:

wherein

X represents O or (H)₂;

R represents H, alkyl, alkoxyl, alkylamino, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, alkoxycarbonyl, or alkylaminocarbonyl;

R₁ represents H;

R₃ represents H;

R₄ represents optionally substituted aryl or heteroaryl;

R₅ represents independently for each occurrence H, alkyl, alkoxyl, alkylamino, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, alkoxycarbonyl, or alkylaminocarbonyl; and

n is 0, 1, or 2.

44. The compound of claim 43, wherein X represents O.

45. The compound of claim 43, wherein R represents alkyl.

46. The compound of claim 43, wherein R₄ represents optionally substituted phenyl.

47. The compound of claim 43, wherein R₅ represents H or aralkyl.

48. The compound of claim 43, wherein n is 1.

49. The compound of claim 43, wherein X represents O;

and R represents alkyl.

50. The compound of claim 43, wherein X represents O;

and R₄ represents optionally substituted phenyl.

51. The compound of claim 43, wherein X represents O;

and R₅ represents independently for each occurrence H or aralkyl.

52. The compound of claim 43, wherein X represents O;

and n is 1.

53. The compound of claim 43, wherein X represents O;

R represents alkyl; and

R₄ represents optionally substituted phenyl.

54. The compound of claim 43, wherein X represents O;

R represents alkyl; and

R₅ represents independently for each occurrence H or aralkyl.

55. The compound of claim 43, wherein X represents O;

R represents alkyl;

R₄ represents optionally substituted phenyl; and

R₅ represents independently for each occurrence H or aralkyl.

56. The compound of claim 43, wherein X represents O;

R represents methyl;

R₄ represents 4-chlorophenyl;

R₅ represents independently for each occurrence H or 4-methoxybenzyl; and

n is 1.