Compounds, compositions and methods for making the same

• US 9,486,441 B2
• Filed: 04/21/2009
• Issued: 11/08/2016
• Est. Priority Date: 04/21/2008
• Status: Active Grant

• Current Assignee: Signum Biosciences, Inc.
• Original Assignee: Signum Biosciences, Inc.
• Inventors: Vafai, Scott, Voronkov, Michael, Stock, Maxwell, Stock, Jeffry B., Lee, Seung-Yub, Li, Zhu, Gu, Haoming
• Primary Examiner(s): Pihonak, Sarah
• Application Number:
  US12/427,743
• Publication Number:
  US 20090264496A1
• Time in Patent Office: 2,758 Days
• Field of Search: 514/419, 548/496
• US Class Current: 1/1
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• 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 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• 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 5/50 for increasing or potentiating the activity of insulin

Abstract

The present invention provides compounds and/or compositions that modulate PP2A methylation and/or activity and methods for preparing the same, which are useful for modulating the demethylation of PP2A, modulating the methylation of PP2A and/or modulating the activity of PP2A.

Claims

1. A method for reducing the severity of symptoms in a subject suffering from a neurodegenerative disease or disorder, the method comprising administering to the subject a therapeutic amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises at least 8.0 mg of a composition consisting essentially of an at least 80% or above pure or synthetic compound selected from the group consisting of:

2. The method according to claim 1, wherein the neurodegenerative disease is a tauopathy.

3. The method according to claim 2, wherein the tauopathy is selected from the group consisting of Alzheimer'"'"'s disease, neurodegeneration in adult cases of Down'"'"'s syndrome, Dementia puglistica, Pick'"'"'s disease, Guam parkinsonism dementia complex, Fronto-temporal dementa, Cortico-Basal Degeneration, Pallido-Pontal-Nigral Degeneration, Progressive Nuclear Palsy and Parkinsonism of Chromosome 17 (FTDP-17), and a combination thereof.

4. The method according to claim 2, wherein the tauopathy is Alzheimer'"'"'s disease.

5. The method according to claim 1, wherein the neurodegenerative disease is a synucleopathy.

6. The method according to claim 5, wherein the synucleopathy is selected from the group consisting of Parkinson'"'"'s disease, Dementia with Lewy bodies, Multiple System Atrophy, and a combination thereof.

7. The method according to claim 5, wherein the synucleopathy is Parkinson'"'"'s disease.

8. The method according to claim 1, wherein modulation of the phosphatase activity of protein phosphatase 2A (PP2A) results in a changed pattern of phosphorylation of substrate Tau compared to a control.

9. The method according to claim 1, wherein modulation of the phosphatase activity of protein phosphatase 2A (PP2A) results in a changed pattern of phosphorylation of substrate alpha-synuclein compared to a control.

10. The method according to claim 1, wherein the therapeutic amount is at least 12.0 mg per day.

11. The method according to claim 1, wherein the therapeutic amount is at least 20.0 mg per day.

12. The method according to claim 1, wherein the therapeutic amount is at least 50.0 mg.

13. The method according to claim 1, wherein the therapeutic amount is at least 100.0 mg.