Compounds, Compositions, and Methods for the Treatment of Beta-Amyloid Diseases and Synucleinopathies

• US 20100331380A1
• Filed: 06/29/2009
• Published: 12/30/2010
• Est. Priority Date: 06/29/2009
• Status: Abandoned Application

• Current Assignee: Proteotech Inc
• Original Assignee: Proteotech Inc
• Inventors: Weigele, Manfred, Lake, Thomas, Cummings, Joel, Snow, Alan, Hudson, F. Michael, Esposito, Luke A., Larsen, Lesley
• Application Number:
  US12/493,856
• Publication Number:
  US 20100331380A1
• Time in Patent Office: Days
• US Class Current: 514/383
• 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: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 233/58 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
• CPC Class Codes: C07D 249/08 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles

Abstract

Dihydroxyaryl compounds and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of β-amyloid diseases, such as observed in Alzheimer'"'"'s disease, and synucleinopathies, such as observed in Parkinson'"'"'s disease, and the manufacture of medicaments for such treatment.

Claims

1. A compound selected from the group consisting of:

2. The compound of claim 1 where R is an imidazole.

3. The compound of claim 1 where R is a triazole.

4. The compound of claim 1 where R is a pyrazoles.

5. The compound of claim 1 where the compound is selected from the group consisting of:

2,4-bis(3,4-dihydroxyphenyl)imidazole;

3,5-bis(3,4 dihydroxyphenyl) 1,2,4 triazole;

3,5-bis(3,4 dihydroxyphenyl)pyrazole and pharmaceutically acceptable salts thereof.

6. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

7. A method of inhibiting the formation, deposition, accumulation, or persistence of Aβ

amyloid or α

-synuclein aggregatess, comprising treating the aggregatess with an effective amount of the compound of claim 1.

8. The method of claim 7 where the compound is selected from the group consisting of:

2,4-bis(3,4 dihydroxyphenyl) imidazole,

3,5-bis(3,4 dihydroxyphenyl) 1,2,4 triazole, and

3,5-bis(3,4 dihydroxyphenyl) pyrazole, and pharmaceutically acceptable salts thereof.

9. A method of treating a β

-amyloid disease or a synucleinopathy in a mammal suffering therefrom, comprising administration of a therapeutically effective amount of the compound of claim 1.

10. The method of claim 9 where the β

-amyloid disease is selected from the group of diseases consisting of Alzheimer'"'"'s disease, Down'"'"'s syndrome, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, and cerebral β

-amyloid angiopathy.

11. The method of claim 10 where the β

-amyloid disease is Alzheimer'"'"'s disease.

12. The method of claim 9 where the synucleinopathy is selected from the group consisting of Parkinson'"'"'s disease, familial Parkinson'"'"'s disease, Lewy body disease, the Lewy body variant of Alzheimer'"'"'s disease, dementia with Lewy bodies, multiple system atrophy, and the Parkinsonism-dementia complex of Guam.

13. The method of claim 12 where the synucleinopathy is Parldnson'"'"'s disease.

14. The method of claim 9 where the compound is selected from the group consisting of

2,4-bis(3,4 dihydroxyphenyl)imidazole,

3,5-bis(3,4 dihydroxyphenyl)1,2,4 triazole, and

3,5-bis(3,4 dihydroxyphenyl)pyrazole, and pharmaceutically acceptable salts thereof.

15. A method of improving motor performance in a mammal suffering from a synucleinopathy, comprising administration of a therapeutically effective amount of the compound of claim 1.

16. A method of arresting the progression of motor deficits in a mammal suffering from Parkinson'"'"'s disease, comprising administration of a therapeutically effective amount of the compound of claim 1.