Therapeutics for central nervous system disorders
Inventors
Li, Chiang J. • CHEN, Suzhen • Liu, Jifeng
Assignees
GLOBE BIOMEDICAL Co Ltd • 1Globe Biomedical Co Ltd • Globe Health Institute LLC • 1Globe Health Institute LLC
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12091378-B2
Publication Date
2024-09-17
Expiration Date
Abstract
The invention provides novel compounds, pharmaceutical compositions and methods of preparation and use thereof for treating disease affecting the central nervous system such as multiple sclerosis.
Core Innovation
The invention provides central nervous system therapeutics for multiple sclerosis and other demyelinating diseases using novel compounds of Formulas (I)–(III). The compounds include variable substituents defined by R1–R3, Z, Y, and X, and the embodiments encompass enantiomers, diastereomers, tautomers, and pharmaceutically acceptable salts or solvates.
The invention also provides related pharmaceutical compositions that include the compound and pharmaceutically acceptable excipients or carriers, including hydrochloride and other acid-addition salts as salt forms. The described scope links the chemical structures to therapeutic use in central nervous system disorders, in particular multiple sclerosis.
The document reports experimental evidence that representative compounds promote remyelination and oligodendrocyte maturation, suppress microglia activation and TNF-α release, induce microglia cell death, and show little toxicity to adult cerebellar granule neurons. Additional evaluations include efficacy in cuprizone (CPZ) regimens, Experimental Autoimmune Encephalomyelitis (EAE), and changes in myelin, axon, gliosis, and neuroinflammation markers.
Claims Coverage
The independent claim provides coverage for a compound of formula (II) defined by selectable substituents R1, R2, R3, Y, and X, with allowance for enantiomers, diastereomers, tautomers, and pharmaceutically acceptable salts or solvates. Across dependent claims, the coverage is further narrowed by fixed structural options, particular salt forms, and therapeutic method context.
Formula (II) substituent-defined compound
A compound of formula (II) wherein each of R1, R2, and R3 is independently selected from hydrogen, alkyl or substituted alkyl, alkoxy or substituted alkoxy, and heteroalkyl or substituted heteroalkyl; Y is selected from alkyl or substituted alkyl, alkoxy or substituted alkoxy, heteroalkyl or substituted heteroalkyl, aryl or substituted aryl, and heteroaryl or substituted heteroaryl; and X is selected from CR'R'', NR', O, and S, wherein each of R' and R'' is independently selected from hydrogen and alkyl.
Enantiomers, diastereomers, tautomers, and pharmaceutically acceptable salts or solvates
The compound is also claimed as an enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt or solvate thereof.
X fixed to oxygen
The compound is specified such that X is O.
Substituted group substituent limits
The claim specifies that each substituted alkyl, substituted alkoxy, or substituted aryl group has 1 to 3 substituents, each independently selected from hydrogen, halogen, methyl, methoxyl, ethyl, and ethoxyl.
Inorganic acid addition salt
The claim specifies that the salt is an acid addition salt of an inorganic acid.
Hydrochloride salt
The claim specifies that the compound is present as a hydrochloride salt.
Therapeutic method for multiple sclerosis by administration
It claims a method for treating or reducing multiple sclerosis by administering to a subject a therapeutically effective amount of the pharmaceutical composition.
Overall, the claim set covers a formula (II) compound with defined substituent sets for R1–R3, Y, and X, further extending to enantiomers, diastereomers, tautomers, and pharmaceutically acceptable salts or solvates. Dependent coverage narrows structure by selecting X as oxygen and constraining substituted-group substituent counts and types, and also narrows salt forms, including hydrochloride, and ties the pharmaceutical composition to a method of treating or reducing multiple sclerosis by administration.
Stated Advantages
Promote remyelination and oligodendrocyte maturation.
Suppress microglia activation and TNF-α release.
Induce microglia cell death.
Show little toxicity to adult cerebellar granule neurons.
Provide efficacy in cuprizone (CPZ) regimens and Experimental Autoimmune Encephalomyelitis (EAE).
Documented Applications
Central nervous system therapeutics for multiple sclerosis.
Therapeutic use in other demyelinating diseases.
Methods of treatment for multiple sclerosis by administration of the pharmaceutical composition.
Interested in licensing this patent?