Methods and compositions for treating amyloid-related diseases

• US 7,244,764 B2
• Filed: 06/18/2004
• Issued: 07/17/2007
• Est. Priority Date: 06/23/2003
• Status: Expired due to Fees

• Current Assignee: Bellus Health (Interational) Limited (GSK plc), Queen's University At Kingston
• Original Assignee: Neurochem (International) Limited (GSK plc)
• Inventors: Kong, Xianqi, Szarek, Walter A., Gervais, Francine
• Primary Examiner(s): Saeed; Kamal A.
• Assistant Examiner(s): CHUNG, SUSANNAH LEE
• Application Number:
  US10/871,365
• Publication Number:
  US 20050038117A1
• Time in Patent Office: 1,124 Days
• Field of Search: 514/554, 562/43
• US Class Current: 514/554
• 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: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07C 2601/02 with a three-membered ring
• CPC Class Codes: C07C 2601/04 with a four-membered ring
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 2601/18 with a ring being at least seven-membered
• CPC Class Codes: C07C 2602/08 the other ring being five-membered, e.g. indane
• CPC Class Codes: C07C 2602/10 the other ring being six-membered, e.g. tetraline
• CPC Class Codes: C07C 2602/42 the bicyclo ring system containing seven carbon atoms
• CPC Class Codes: C07C 2603/74 Adamantanes
• CPC Class Codes: C07C 307/02 Monoamides of sulfuric acids or esters thereof, e.g. sulfamic acids
• CPC Class Codes: C07C 309/13 containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton
• CPC Class Codes: C07C 309/14 containing amino groups bound to the carbon skeleton
• CPC Class Codes: C07C 309/15 the nitrogen atom of at least one of the amino groups being part of any of the groups , X being a hetero atom, Y being any atom
• CPC Class Codes: C07C 309/46 having the sulfo groups bound to carbon atoms of non-condensed six-membered aromatic rings
• CPC Class Codes: C07C 309/69 of a carbon skeleton substituted by nitrogen atoms, not being part of nitro or nitroso groups
• CPC Class Codes: C07C 311/32 : of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 311/46 : Y being a hydrogen or a carbon atom
• CPC Class Codes: C07C 335/32 : having sulfur atoms of isothiourea groups bound to acyclic carbon atoms
• CPC Class Codes: C07C 381/02 : Thiosulfates
• CPC Class Codes: C07D 295/084 : with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/088 : to an acyclic saturated chain
• CPC Class Codes: C07F 9/1651 : with hydroxyalkyl compounds with further substituents on alkyl
• CPC Class Codes: C07F 9/2458 : of aliphatic amines

Abstract

Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-+related disease.

Claims

1. A compound of Formula I:

3. The compound of claim 1 or 2, wherein R² is hydrogen.

4. The compound of claim 1 or 2, wherein R¹ is indolyl.

5. The compound of claim 1, wherein L¹ is CH₂CH₂.

6. The compound of claim 1 or 2, wherein R¹ is tetrahydronaphthyl.

7. The compound of claim 1, wherein L¹ is absent.

8. The compound of claim 1, wherein said compound is:

9. A method of treating Alzheimer'"'"'s disease in a subject comprising administering to a subject in need thereof an effective amount or a compound of claim 1.

10. The method according to claim 9, wherein said subject is a human.

11. The method according to claim 9, wherein the compound is administered orally.

12. The method according to claim 9, wherein said compound is administered in a pharmaceutically acceptable vehicle.

13. A pharmaceutical composition comprising a compound according to claim 1, and a pharmaceutically acceptable carrier.

14. The method of claim 9, wherein said subject is a human over 40 years old.

15. The method of claim 9, wherein said subject is a human over 50 years old.

16. The method of claim 9, wherein said subject is a human over 60 years old.

17. The method of claim 9, wherein said subject is a human over 70 years old.

18. The method of claim 9, wherein said subject is a human over 80 years old.

19. The method of claim 9, wherein said subject is a human over 85 years old.

20. The method of claim 9, wherein said subject is a female human.

21. The method of claim 9, wherein said subject is a postmenopausal female human.

22. The method of claim 9, wherein said subject is on hormone replacement therapy.

23. The method of claim 9, wherein said subject is a male human.

24. The method of claim 9, wherein said subject has familial, sporadic, or idiopathic Alzheimer'"'"'s disease.

25. The method of claim 9, wherein said subject'"'"'s brain has amyloid-β

.

26. The pharmaceutical composition of claim 13, wherein said pharmaceutical composition further comprises a pharmaceutically acceptable acid, base, buffering agent, inorganic salt, solvent, or preservative.

27. The pharmaceutical composition of claim 13, wherein said compound is dissolved in a liquid pharmaceutically acceptable vehicle.

28. The pharmaceutical composition of claim 13, wherein said compound is present as a homogenous mixture in a capsule or pill.

29. The compound of claim 1, wherein said compound is:

37. The compound of claim 1, wherein said compound is:

2. A compound of Formula II:

42. A method of treating Alzheimer'"'"'s disease in a subject comprising administering to a subject in need thereof an effective amount of a compound of claim 2.

43. The method according to claim 42, wherein said subject is a human.

44. The method according to claim 42, wherein the compound is administered orally.

45. A pharmaceutical composition comprising a compound according to claim 2 and a pharmaceutically acceptable carrier.

30. A compound of Formula II:

31. The compound of claim 30, wherein R² is hydrogen.

32. The compound of claim 30, wherein said bicyclic ring group is indolyl.

33. The compound of claim 30, wherein L is CH₂CH₂.

34. The compound of claim 30, wherein R¹ is tetrahydronaphthyl.

35. The compound claim 30, wherein L is absent.

36. The compound of claim 30, wherein said compound is:

38. The compound of claim 30, wherein said compound is:

39. The compound of claim 30, wherein said compound is:

40. The compound of claim 30, wherein said compound is:

41. The compound of claim 30, wherein said compound is:

46. A method of treating Alzheimer'"'"'s disease in a subject comprising administering to a subject in need thereof an effective amount of a compound of claim 30.

47. The method according to claim 46, wherein said subject is a human.

48. The method according to claim 46, wherein the compound is administered orally.

49. A pharmaceutical composition comprising a compound according to claim 30 and a pharmaceutically acceptable carrier.

50. A compound selected from the group consisting of: