Neurodegenerative therapies
Inventors
SVENDSEN, John S. • Stensen, Wenche • LEESON, Frederick A.
Assignees
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Publication Number
US-10231954-B2
Publication Date
2019-03-19
Expiration Date
Abstract
The present invention provides a compound of formula (I) wherein: Y represents a C or N atom which may be substituted or form a cyclic group with R″′ but may not be a quaternary C atom; R′ is —OR1, —CONH2, —CF3, F, —OH, —NO2, —CN or —OCOR1 in which R1, is C1-3 alkyl and each may be in the beta or gamma position; R″ is C1-3 alkyl or H; and R″′ is H or a group consisting of 1-12 non-hydrogen atoms and may be linear, branched and/or incorporate one or more cyclic groups, cyclic groups may be aromatic and/or heterocyclic and 2 or more cyclic groups may be linked or fused and each may be substituted; or a salt, hydrate or solvate of a compound of formula (I) for use in the treatment or prevention of a neurodegenerative disorder by inhibiting formation of neurofibrillary (tau) tangles and/or by inhibiting Dyrk 1A. The invention further relates to non-therapeutic uses of these compounds.
Core Innovation
The invention relates to neurodegenerative therapy using compounds of formula (I), including salts, hydrates, and solvates, for the treatment or prevention of neurodegenerative disorders, particularly Alzheimer’s disease, including Alzheimer’s disease in Down syndrome. The compounds are used by administering a therapeutically effective amount such that neurofibrillary (tau) tangle formation is inhibited.
The disclosure identifies Dyrk1A as dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A and links inhibition of Dyrk1A activity with suppression of neurofibrillary (tau) tangle formation. The invention is based on inhibiting neurofibrillary (tau) tangle formation and/or inhibiting Dyrk1A activity.
Formula (I) is defined by variables including Y, R2', R3', and R3'', with allowed substitutions and optional cyclic or heterocyclic group systems. The description includes benzothiazole carboxamide/urea derivatives with defined ring and substituent variants, preferred structural features, and excluded prior example compounds.
Claims Coverage
Two independent claims are present. The claims cover a formula (I) Dyrk1A-inhibiting compound definition with multiple structural constraints, and methods using that compound to inhibit Dyrk1A activity and/or inhibit formation of neurofibrillary (tau) tangles.
Treatment method for Alzheimer's disease or Parkinson's disease using a compound of formula (I)
Administering to a subject a therapeutically effective amount of a compound of formula (I), including a salt, hydrate or solvate, wherein the amount is such as to inhibit formation of neurofibrillary (tau) tangles.
In vitro inhibition of Dyrk1A using a compound of formula (I)
An in vitro method comprising contacting Dyrk1A or a reaction catalysed by Dyrk1A with a compound of formula (I), including a salt, hydrate or solvate of that compound.
Across the independent claims, coverage is directed to compounds of formula (I) defined by detailed structural variables and applied either as an administered therapeutically effective treatment inhibiting neurofibrillary (tau) tangle formation, or as an in vitro Dyrk1A inhibition by contacting the kinase or its catalytic reaction with the compound.
Stated Advantages
Inhibiting formation of neurofibrillary (tau) tangles.
Inhibiting Dyrk1A or a reaction catalysed by Dyrk1A.
Treatment or prevention of neurodegenerative disorders, particularly Alzheimer’s disease, including Alzheimer’s disease in Down syndrome.
Documented Applications
Treatment of Alzheimer's disease or Parkinson's disease in a subject by administering a therapeutically effective amount of a compound of formula (I).
Treatment of Alzheimer's disease in a subject having Down syndrome.
In vitro inhibition of Dyrk1A or a reaction catalysed by Dyrk1A by contacting Dyrk1A with a compound of formula (I).
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