Compositions and methods for inhibiting n-smase2
AssigneeThe Regents of the University of California
InventorsTina Bilousova, Barbara Jagodzinska, Varghese John
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Abstract
Provided herein are compounds of Formula (I) and (II) and their salts, and compositions comprising such compounds that are useful for useful for modulating neutral sphingomyelinase 2 (n-SMase2) in cells. Also disclosed herein are methods of using the disclosed compounds and compositions for inhibiting the spread of Tau seeds from donor cells to recipient cells. Moreover, disclosed herein are methods of using the disclosed compounds and compositions for treating or preventing a neurodegenerative disorder, such as a tauopathy, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Lewy body dementia, frontotemporal dementia, and amyotrophic lateral sclerosis (ALS).
Claims31
A compound having a structure of Formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- X1 and X2 are each independently O or S;
- and
- R1 and R2 are each, independently alkyl, —C(O)-alkyl, haloalkyl, alkoxy, cycloalkyl, aryl, —C(O)-aryl, aralkyl, or haloalkyl, each of which is unsubstituted or substituted with one or more substituents;
- provided that the compound of Formula (I) is not a compound of Formula (A):
- or a pharmaceutically acceptable salt thereof.
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A compound having a structure of Formula (II):
- or a pharmaceutically acceptable salt thereof, wherein:
- X1 is O or S;
- R1 is alkyl, alkenyl, aryl, aralkyl, heteroaryl, —O-alkyl, —O-alkenyl, —O-haloalkyl, —O-cycloalkyl, —O-aralkyl, —O-aralkoxy, —O-aryl, 13 O-heteroaryl, —S-alkyl, —S-alkenyl, —S-haloalkyl, —S-cycloalkyl, —S-aralkyl, —S-aralkoxy, —S-aryl, or —S-heteroaryl, each of which is unsubstituted or substituted with one or more substituents;
- and
- R2 and R3 are each, independently CN, C(O)-alkyl, alkyl, haloalkyl, alkoxy, cycloalkyl, aryl, aralkyl, alkyl-O-aryl, or heteroaryl, wherein each of —C(O)-alkyl, alkyl, haloalkyl, alkoxy, cycloalkyl, aryl, aralkyl, aryl-O-alkyl, or heteroaryl is unsubstituted or substituted with one or more substituents.
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Dependencies are inferred from the claim text.