Treating nervous system disorders such as mild cognitive impairment, Alzheimer's disease or dementia associated with Down syndrome; e.g. use of 5,7-dichloro-8-hydroxy-2-(2-pyridyl)-quinoline (PBT 1052)
Inventors
Barnham, Kevin Jeffrey • Gautier, Elisabeth Colette Louise • Kok, Gaik Beng • Krippner, Guy
Assignees
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Publication Number
US-7619091-B2
Publication Date
2009-11-17
Expiration Date
Abstract
The present invention relates to a method for the treatment, amelioration and/or prophylaxis of a neurological condition, in particular neurodegenerative disorders which comprises the administration of an effective amount of a compound of formula (I): to a subject in need thereof. The present invention also relates to a compound of formula (II) and processes for its preparation.
Core Innovation
The invention relates to compounds of a formula, or pharmaceutically acceptable salts thereof, in which R1 is H and the remaining substituent groups are selected from specified optionally substituted alkyl, alkenyl, aryl, heterocyclyl, and functional group patterns. The formula includes options such as COR6, CSR6, CN, CH2NR9R10, HCNOR9, HCNNR9R10, OR11, SR11, NR11R12, and SO2NR13R14, with further restrictions on R4 and R5 being chloro in some claims.
The disclosed compounds include substituted aromatic and heteroaromatic scaffolds, including phenolic OH-containing structures and multiple halogen, methoxy, amino, nitro, and carbonyl-linked substituent patterns. The document also refers to specific named examples and structural series, together with associated numeric values, spectroscopic characterization, and mass spectral information.
The claim context further covers pharmaceutically acceptable salts, pharmaceutical compositions comprising a therapeutically effective amount of the compound with a pharmaceutically acceptable carrier, compositions including medicaments that are an inhibitor of the acetyl cholinesterase active site, an antioxidant, an anti-inflammatory agent, or an estrogenic agent, and hydrate forms of the formula-defined compound.
Claims Coverage
The consolidated claim coverage centers on one broad formula-defined compound family with R1 fixed as H and multiple R-group substitutions constrained to specified options. The inventive coverage includes 5 inventive features: the formula-defined compound family, a further refined substituent selection, a pharmaceutical composition with carrier, a pharmaceutical composition including specified medicament categories, and a hydrate form.
Formula-defined compound family with fixed R1 and constrained substituent groups
A compound of the formula, or pharmaceutically acceptable salts thereof, in which R1 is H and the remaining groups are selected from specified optionally substituted alkyl, alkenyl, aryl, heterocyclyl, and functional group patterns, including COR6, CSR6, CN, CH2NR9R10, HCNOR9, HCNNR9R10, OR11, SR11, NR11R12, and SO2NR13R14, with R4 and R5 being chloro.
Refined substituent options for aromatic and heterocyclic groups
A compound of the formula in which selected substituent groups are further restricted to options including phenyl, naphthyl, tetrahydronaphthyl, biphenyl, optionally substituted heterocyclyl, and related CH2NR9R10 or NR7R8/NR11R12-linked forms.
Pharmaceutical composition with therapeutically effective amount and carrier
A pharmaceutical composition comprising a therapeutically effective amount of a compound as defined in the formula claims together with a pharmaceutically acceptable carrier.
Pharmaceutical composition including specified medicament categories
A pharmaceutical composition comprising a medicament that is an inhibitor of the acetyl cholinesterase active site, an antioxidant, an anti-inflammatory agent, or an estrogenic agent.
Hydrate form of the compound
A hydrate form of the compound defined by the formula claims.
Overall, the claims cover a structurally defined compound family with fixed R1 and constrained substituent options, and extend to pharmaceutical compositions, specified medicament categories, and a hydrate solid form.
Stated Advantages
Improved metal chelation.
Improved aqueous solubility.
Reduced cell toxicity.
Amyloid dispersion.
CNS membrane permeability.
Metabolic stability.
Neuroprotective and antiamyloidogenic effects.
Documented Applications
Alzheimer’s disease and related conditions.
Neurodegenerative amyloidosis.
Pharmacodynamic, plasma, and CSF endpoints.
In vivo studies.
Therapeutic and veterinary compositions.
Compounds of Formula I/II directed to Alzheimer’s-related treatment screening, including peroxide inhibition and cell viability metrics.
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