Activators of autophagic flux and phospholipase D and clearance of protein aggregates including tau and treatment of proteinopathies
AssigneesThe Trustees of Columbia University in they City of New York, NY State Psychiatric Institute
InventorsKirsten Alison Rinderspacher, Wai Yu, Karen Duff, Donald Landry, Shi-Xian Deng
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Abstract
The present application discloses compounds which are activators of autophagic flux and pharmaceutical compositions comprising said activators. It further discloses use of said compounds and pharmaceutical compositions in the treatment of neurodegenerative diseases, particularly proteinopathies and tauopathies such as Alzheimer's disease. It further discloses methods of enhancing autophagic flux.
Claims19
A compound having the formula (IV):
- wherein X is halide;
- wherein R1 is selected from the group consisting of optionally substituted thioheteroaryl, optionally substituted (2-aminoethyl)aryl, halide, optionally substituted thiocycloalkyl wherein 1-3 carbon atoms of the cycloalkyl is optionally replaced with a heteroatom selected from the group consisting of O, S and N, and thioaryl,
- or a salt, enantiomer, racemate, mixture thereof, or combination thereof.
A compound having the formula (V):
- wherein X is H;
- wherein R1 is selected from the group consisting of optionally substituted thioheteroaryl, optionally substituted thiocycloalkyl wherein 1-3 carbon atoms of the cycloalkyl is optionally replaced with a heteroatom selected from the group consisting of O, S and N, and thioaryl,
- or a salt, enantiomer, racemate, mixture thereof, or combination thereof.
A compound having the formula (VI):
- wherein X is H;
- wherein R1 is selected from the group consisting of optionally substituted thioheteroaryl, halide, optionally substituted thiocycloalkyl wherein 1-3 carbon atoms of the cycloalkyl is optionally replaced with a heteroatom selected from the group consisting of O, S and N, and thioaryl,
- or a salt, enantiomer, racemate, mixture thereof, or combination thereof.
A method of treating a proteinopathy comrising administering to a subject in need thereof an effective amount of the pharmaceutical composition of cliam 7.
Dependencies are inferred from the claim text.