Claims
- 1. A method for modulating the processing of an amyloid precursor protein (APP), said method comprising contacting a composition containing said APP with an aspartyl protease inhibitor having the general formula:
- 2. The method according to claim 1, wherein:
R1 is a member selected from the group consisting of substituted alkylaryl, substituted aryl, substituted alkyl and substituted heterocyclic groups.
- 3. The method according to claim 2, wherein:
R1 is a member selected from the group consisting of: 67
- 4. The method according to claim 1, wherein:
R2 is a member selected from the group consisting of substituted alkyl, heterocyclic and substituted heterocyclic groups.
- 5. The method according to claim 4, wherein R2 is a member selected from the group consisting of:
- 6. The method according to claim 1, wherein:
R3 is a member selected from the group consisting of substituted alkyl and substituted aryl groups.
- 7. The method according to claim 6, wherein R3 is a member selected from the group consisting of:
- 8. The method according to claim 1, wherein R5 and R6 and the carbons to which they are bound form an optionally substituted napthalene ring.
- 9. The method according to claim 1, wherein R5 and R6 are both hydrogen.
- 10. The method in accordance with claim 1, wherein R5 is hydrogen and R6 is meta or para to R5 and is a member selected from the group consisting of halogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, aryloxyalkyl and substituted aryloxyalkyl.
- 11. The method according to claim 1, wherein said aspartyl protease inhibitor is a member selected from the group consisting of:
- 12. The method according to claim 1, wherein said aspartyl protease inhibitor is a member selected from the group consisting of:
- 13. The method in accordance with claim 1, wherein said aspartyl protease inhibitor is a member selected from the group consisting of CEL5-A, CEL5-G and EA-1, which are illustrated in FIG. 12.
- 14. The method in accordance with claim 1, where in said composition is a body fluid.
- 15. The method in accordance with claim 13, 14, wherein said body fluid is cerebral spinal fluid.
- 16. The method in accordance with claim 1, whereby formation of amyloidogenic Aβ peptides (Aβ) is decreased compared to the amount formed in the absence of said aspartyl protease inhibitor.
- 17. The method in accordance with claim 1, whereby formation of α-sAPP is increased compared to the amount formed in the absence of said aspartyl protease inhibitor.
- 18. The method in accordance with claim 1, wherein the modulation is effected by modulating the activity of cathepsin D.
- 19. A method for modulating the processing of a tau-protein (τ-protein), said method comprising contacting a composition containing said τ-protein with an aspartyl protease inhibitor having the general formula:
- 20. The method according to claim 19, wherein:
R1 is a member selected from the group consisting of substituted alkylaryl, substituted aryl, substituted alkyl and substituted heterocyclic groups.
- 21. The method according to claim 20, wherein:
R1 is a member selected from the group consisting of: 84
- 22. The method according to claim 19, wherein:
R2 is a member selected from the group consisting of substituted alkyl, heterocyclic and substituted heterocyclic groups.
- 23. The method according to claim 22, wherein R2 is a member selected from the group consisting of:
- 24. The method according to claim 19, wherein:
R3 is a member selected from the group consisting of substituted alkyl and substituted aryl groups.
- 25. The method according to claim 24, wherein R3 is a member selected from the group consisting of:
- 26. The method according to claim 19, wherein R5 and R6 and the carbons to which they are bound form an optionally substituted napthalene ring.
- 27. The method according to claim 19, wherein R5 and R6 are both hydrogen.
- 28. The method in accordance with claim 19, wherein R5 is hydrogen and R6 is meta or para to R5 and is a member selected from the group consisting of halogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, aryloxyalkyl and substituted aryloxyalkyl.
- 29. The method according to claim 19, wherein said aspartyl protease inhibitor is a member selected from the group consisting of:
- 30. The method according to claim 19, wherein said aspartyl protease inhibitor is a member selected from the group consisting of:
- 31. The method in accordance with claim 19, wherein said aspartyl protease inhibitor is a member selected from the group consisting of CEL5-A, CEL5-G and EA-1, which are illustrated in FIG. 12.
- 32. The method in accordance with claim 19, wherein said composition is a body fluid.
- 33. The method in accordance with claim 31, 32, wherein said body fluid is cerebral spinal fluid.
- 34. The method in accordance with claim 19, whereby formation of τ-fragments is decreased compared to the amount formed in the absence of said aspartyl protease inhibitor.
- 35. The method in accordance with claim 19, wherein the modulation is effected by modulating the activity of cathepsin D.
- 36. A method for treating a neurodegenerative disorder, said method comprising: administering to a mammal a therapeutically effective amount of an aspartyl protease inhibitor having the general formula:
- 37. The method in accordance with claim 36, wherein said neurodegenerative disorder is characterized by the accumulation of amyloid plaques.
- 38. The method in accordance with claim 36, wherein said neurodegenerative disorder is characterized by the accumulation of τ-fragments.
- 39. The method in accordance with claim 36, wherein said neurodegenerative disorder is a member selected from the group consisting of Alzheimer's disease, Parkinson's disease, cognition defects, Downs Syndrome, cerebral hemorrhage with amyloidosis, dementia and head trauma.
- 40. The method according to claim 36, wherein:
R1 is a member selected from the group consisting of substituted alkylaryl, substituted aryl, substituted alkyl and substituted heterocyclic groups.
- 41. The method according to claim 40, wherein:
R1 is a member selected from the group consisting of: 101
- 42. The method according to claim 36, wherein:
R2 is a member selected from the group consisting of substituted alkyl, heterocyclic and substituted heterocyclic groups.
- 43. The method according to claim 42, wherein R2 is a member selected from the group consisting of:
- 44. The method according to claim 36, wherein:
R3 is a member selected from the group consisting of substituted alkyl and substituted aryl groups.
- 45. The method according to claim 44, wherein R3 is a member selected from the group consisting of:
- 46. The method according to claim 36, wherein R5 and R6 and the carbons to which they are bound form an optionally substituted napthalene ring.
- 47. The method according to claim 36, wherein R5 and R6 are both hydrogen.
- 48. The method in accordance with claim 36, wherein R5 is hydrogen and R6 is meta or para to R5 and is a member selected from the group consisting of halogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, aryloxyalkyl and substituted aryloxyalkyl.
- 49. The method in accordance with claim 36, wherein said aspartyl protease inhibitor is a member selected from the group consisting of:
- 50. The method in accordance with claim 36, wherein said aspartyl protease inhibitor is a member selected from the group consisting of CEL5-A, CEL5-G and EA-1, which are illustrated in FIG. 12.
GOVERNMENT RIGHTS
[0001] This invention was made with Government support under Grant (Contract) Nos. RO1 GM53696 and RO1 GM50353 awarded by the National Institutes of Health. The Government has certain rights in this invention.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60125958 |
Mar 1999 |
US |
|
60036903 |
Feb 1997 |
US |
Continuations (1)
|
Number |
Date |
Country |
Parent |
09534706 |
Mar 2000 |
US |
Child |
10774262 |
Feb 2004 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
09018226 |
Feb 1998 |
US |
Child |
10774262 |
Feb 2004 |
US |