Casein kinase 1δ (CK 1δ) inhibitors
Inventors
Sheridan, Joseph M. • Heal, Jonathan R. • Hamilton, William D. O. • PIKE, IAN H.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9789111-B2
Publication Date
2017-10-17
Expiration Date
Abstract
The invention relates to pharmaceutical compositions having casein kinase 1 delta (CK1δ) inhibitors and to the use of the inhibitors in the treatment of neurodegenerative disorders such as Alzheimer's disease.
Core Innovation
The invention relates to treating Alzheimer’s disease in a subject by administering a therapeutically effective amount of a pharmaceutical composition comprising 5-(1,3-benzoxazol-2-yl)-4-(pyridine-4-yl)pyrimidin-2-amine (Compound 324), or a pharmaceutically acceptable salt or solvate thereof. The disclosed chemical structures depict related small-molecule candidates within the Compound 324 family, including variations in heteroaromatic cores, linkers, and substituents.
The document relates to pharmaceutical compositions containing casein kinase 1 delta (CK1δ) inhibitors based on compounds of formula (IB), including Compound 324. The compositions are for treating neurodegenerative disorders and tauopathies, including Alzheimer’s disease, and the therapeutic concept is directed to administering a therapeutically effective amount of the pharmaceutical composition to a subject.
The document reports CK1δ inhibition and kinase selectivity results for exemplary compounds, including results indicating >90% CK1δ inhibition and selectivity versus other kinases. It further reports cell-based findings in which lead compounds protect cell viability and reduce tau phosphorylation at Ser396 and Thr391.
Claims Coverage
The independent claim coverage centers on treating Alzheimer’s disease by administering a therapeutically effective amount of a pharmaceutical composition comprising Compound 324, with dependent refinements for administration route, dosage form, formulation components, and a Tau phosphorylation outcome. Six inventive features are identified across the merged claim set.
Compound 324 pharmaceutical composition for treating Alzheimer’s disease
Administering a therapeutically effective amount of a pharmaceutical composition comprising 5-(1,3-benzoxazol-2-yl)-4-(pyridine-4-yl)pyrimidin-2-amine (Compound 324), or a pharmaceutically acceptable salt or solvate thereof, to a subject; and treating Alzheimer’s disease in the subject.
Oral administration of the Compound 324 pharmaceutical composition
The pharmaceutical composition is intended for oral administration.
Solid or liquid dosage forms for the Compound 324 pharmaceutical composition
Using a pharmaceutical composition formulated as a tablet, capsule, powder or liquid.
Pharmaceutically acceptable excipient/carrier/buffer/stabilizer in the composition
The pharmaceutical composition includes at least one pharmaceutically acceptable excipient, carrier, buffer, or stabilizer.
Selected administration routes for the Compound 324 pharmaceutical composition
Using a pharmaceutical composition intended for intravenous, cutaneous, subcutaneous, nasal, intramuscular, or intraperitoneal routes.
Reducing Tau S396 phosphorylation in cells after administration
Administering Compound 324 at an amount sufficient to reduce phosphorylation on S396 of a Tau protein in at least one cell of the patient.
Overall, the claim coverage is directed to administering a Compound 324-containing pharmaceutical composition to treat Alzheimer’s disease, with dependent claims narrowing the route, dosage form, and formulation components. One dependent feature further requires reducing Tau phosphorylation on S396 in at least one cell of the patient.
Stated Advantages
CK1δ inhibition and kinase selectivity, including >90% CK1δ inhibition and selectivity versus other kinases.
Protect cell viability.
Reduce tau phosphorylation at Ser396 and Thr391.
Documented Applications
Treating Alzheimer’s disease in a subject using a therapeutically effective amount of a pharmaceutical composition comprising Compound 324, or a pharmaceutically acceptable salt or solvate thereof.
Treating neurodegenerative disorders and tauopathies.
Interested in licensing this patent?