Compositions and methods for treating and preventing neurodegenerative disorders
Inventors
Kocis, Petr • TOLAR, Martin • Hey, John
Assignees
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Publication Number
US-10590070-B2
Publication Date
2020-03-17
Expiration Date
Abstract
Compounds, pharmaceutical compositions, methods and kits are described for treating or preventing neurodegenerative diseases such as Alzheimer's disease.
Core Innovation
The invention relates to compounds defined by Formula IV-3a or Formula IV-3b, or pharmaceutically acceptable salts of any of the foregoing. The compounds include specific substituent selections in which R a1 is selected from hydrogen and a C1-C3 alkyl optionally substituted with one or more hydroxyl, R b1 is selected from hydrogen, R7 and R8 are each hydrogen, and ring A is selected from optionally substituted pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl.
The substituent framework further specifies that C1-C5 alkyl is substituted with one or more substituents independently selected from carboxy, amino, optionally substituted heteroaryl, optionally substituted aryl, alkylthio, aminocarbonyl, hydroxy, dialkylamino, alkylamino, and arylalkylamino. Cycloalkyl is optionally substituted with amino, and heterocyclyl is optionally substituted with amino. The partial content also includes related compound structures and intermediates with diamine, deprotection, and sulfonyl or sulfur-oxo motifs, together with labeled products and structural variants.
The invention is positioned in the context of treatment of Alzheimer’s disease. The provided text refers to an amyloid-beta binding and anti-aggregation/clearance rationale, including plaque clearance and neurofibrillary tangles context, and also describes patient subgroup embodiments based on ApoE4 allele status, including ApoE4-positive and homozygous for ApoE4.
Claims Coverage
The document includes two independent claim scopes covering compounds defined by Formula IV-3a/IV-3b with specified substituent and ring A selections, and a broader compound defined by a chemical Formula. Across these claims, the inventive coverage centers on 2 core compound-definition frameworks, with dependent coverage further adding pharmaceutical composition form and methods of treating Alzheimer’s disease, including ApoE4-positive and homozygous ApoE4 patient subgroups.
Formula IV-3a or Formula IV-3b compound with defined substituents
A compound having Formula IV-3a or Formula IV-3b, or a pharmaceutically acceptable salt of any of the foregoing, wherein R a1 is selected from hydrogen and a C1-C3 alkyl optionally substituted with one or more hydroxyl; R b1 is selected from hydrogen; the C1-C5 alkyl is substituted with one or more substituents independently selected from carboxy, amino, optionally substituted heteroaryl, optionally substituted aryl, alkylthio, aminocarbonyl, hydroxy, dialkylamino, alkylamino, and arylalkylamino; cycloalkyl is optionally substituted with amino; heterocyclyl is optionally substituted with amino; R7 and R8 are each hydrogen; and ring A is selected from optionally substituted pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl.
Compound of a defined chemical Formula
A compound of the Formula, or a pharmaceutically acceptable salt thereof.
Pharmaceutically acceptable carrier pharmaceutical composition
A pharmaceutical composition comprising the claimed compound or a pharmaceutically acceptable salt of it together with a pharmaceutically acceptable carrier.
Treating Alzheimer's disease by administering the compound
A method of treating Alzheimer’s disease comprising administering to a patient a compound specified in the claims.
Alzheimer’s treatment for ApoE4-positive patients
The method of treating Alzheimer’s disease according to the claim in which the patient is ApoE4-positive.
Alzheimer’s treatment for homozygous ApoE4 patients
The method of treating Alzheimer’s disease according to the claim in which the patient is homozygous for ApoE4.
Overall, claim coverage centers on formula-defined compounds with constrained substituent and ring-A selections, plus pharmaceutically acceptable salts. Dependent claims extend coverage to pharmaceutical compositions and to treatment of Alzheimer’s disease, including patient subgroup restrictions based on ApoE4 status.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating Alzheimer’s disease by administering the claimed compound or a pharmaceutically acceptable salt to a patient.
Treating Alzheimer’s disease in a patient who is ApoE4-positive.
Treating Alzheimer’s disease in a patient who is homozygous for ApoE4.
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