Pharmaceutical compounds and use of same in cancer and tauopathies
AssigneesThe Regents of the University of Michigan, University of South Florida
InventorsJason E. Gestwicki, Chad Dickey
Life of this patent
Estimating the term…
Abstract
Disclosed are compounds of formula (l)-(V): where the substituents are as provided herein. Further disclosed are methods of inhibiting tau aggregation, treating or ameliorating a tauopathy or cancer by administration of such a compound. Tau is a microtubule-binding protein that accumulates in a number of neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease (AD). The presence of abnormal tau correlates with neuron loss and memory deficits in patients with AD and other neurodegenerative disorders that involve tau accumulation.
Claims18
A method of treating a subject suffering from cancer comprising administering to the subject a compound or salt thereof in an amount effective to treat the cancer, wherein the compound or salt thereof has a structure of Formula (I) or (III):
- R1, R2, and R3 are each selected from the group consisting of hydrogen, fluoro, chloro, methoxy, and trifluoromethyl,
- R4 and R5 are each selected from the group consisting of hydrogen, fluoro, and chloro,
- R6 is C1-C4 alkyl or CH2Ar;
- Ar is aryl;
- R7 is ethyl, allyl, or benzyl;
- X is a pharmaceutically acceptable anion, and m is 1, 2, or 3;
- with the proviso that
- (1) if R6 is alkyl, R7 is ethyl, and each of R4 and R5 is hydrogen, then at least one of R1, R2, and R3 is other than hydrogen;
- (2) when each of R1, R2, R3, R4, and R5 is hydrogen R6 is CH2Ar;
- and
- (3) when the compound has a structure of Formula (III) and R7 is ethyl, at least one of R4 and R5 is other than hydrogen.
A method of inhibiting tau protein aggregate formation in a cell comprising contacting the cell with a compound or salt thereof in an amount effective to inhibit tau protein aggregate formation,
- wherein the compound or salt thereof has a structure of Formula (I) or (III):
- R1, R2, and R3 are each selected from the group consisting of hydrogen, fluoro, chloro, methoxy, and trifluoromethyl,
- R4 and R5 are each selected from the group consisting of hydrogen, fluoro, and chloro,
- R6 is C1-C4 alkyl or CH2Ar;
- Ar is aryl;
- R7 is ethyl, allyl, or benzyl;
- X is a pharmaceutically acceptable anion, and m is 1, 2, or 3;
- with the proviso that
- (1) if R6 is alkyl, R7 is ethyl, and each of R4 and R5 is hydrogen, then at least one of R1, R2, and R3 is other than hydrogen;
- (2) when each of R1, R2, R3, R4, and R5 is hydrogen R6 is CH2Ar;
- and
- (3) when the compound has a structure of Formula (III) and R7 is ethyl, at least one of R4 and R5 is other than hydrogen.
A method of inhibiting tau protein aggregate formation in a cell or a method of inhibiting a cancer cell comprising contacting the cell with a compound having a structure of formula (IV) to inhibit tau protein aggregate formation or to inhibit the cancer cell:
- wherein
- R1, R2, R3, and R5 are each selected from the group consisting of hydrogen, fluoro, chloro, methoxy, and trifluoromethyl;
- R4 and R5 are each selected from the group consisting of hydrogen, fluoro, chloro, methyl, and;
- R7 is methyl, ethyl, or benzyl,
- or a salt thereof.
A method of inhibiting tau protein aggregate formation in a cell or a method of inhibiting a cancer cell comprising contacting the cell with a compound or salt thereof selected from the group consisting of
Dependencies are inferred from the claim text.