Treatment of neurodegenerative diseases through inhibiton of Hsp90
AssigneeSloan-Kettering Institute for Cancer Research
InventorsGabriela Chiosis, Huazhong He, Danuta Zatorska
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Abstract
Treatment of neurodegenerative diseases is achieved using small molecule purine scaffold compounds that inhibit Hsp90 and that possess the ability to cross the blood-brain barrier or are otherwise delivered to the brain.
Claims19
A method for treatment of a neurodegenerative disease, comprising administering to an individual in need of such treatment a therapeutically effective amount of a compound having the structure:
- wherein
- R is hydrogen, or a C1 to C10 alkyl, C2 to C10 alkenyl, C2 to C10 alkynyl, or C2 to C10 alkoxyalkyl group, optionally including heteroatoms;
- Y1 and Y2 are independently C or N;
- X4 is hydrogen or halogen;
- X3 is CH2, CF2, S, SO, SO2, O, NH, or NR2, wherein R2 is alkyl;
- and
- X2 is halogen, alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, pyrollyl, optionally substituted aryloxy, alkylamino, dialkylamino, carbamyl, amido, alkylamido, dialkylamido, acylamino, alkylsulfonylamido, trihalomethoxy, trihalocarbon, thioalkyl, SO2-alkyl, COO-alkyl, NH2, OH, or CN;
- and
- X1 has the formula —X—Y—Z— wherein X, Y and Z are independently C, N, S or O, connected by single or double bonds and with appropriate hydrogen substitution to satisfy valence, or Y may be (CH2)2, wherein one of X and Z is bonded at the 5-position of the aryl ring and the other is bonded to the 4-position;
- and
- wherein the compound is optionally in the form of an acid addition salt;
- and
- wherein the neurodegenerative disease is selected from the group consisting of complete androgen insensitivity syndrome (CAIS), spinal and bulbar muscular atrophy (SBMA or Kennedy's disease), Alzheimer's Disease (AD), sporadic frontotemporal dementia with parkinsonism (FTDP), familial FTDP-17 syndromes, Parkinson's disease, and Huntington disease.
A method for treatment of a neurodegenerative disease, comprising administering to an individual in need of such treatment a therapeutically effective amount of a compound of formula:
- wherein
- X4 is hydrogen or halogen;
- X6 is amino;
- X3 is C, O, N, or S with hydrogens as necessary to satisfy valence, or CF2, SO, SO2 or NR3 where R3 is alkyl;
- R1 is hydrogen, a C1 to C10 alkyl, alkenyl, alkynyl, or an alkoxyalkyl group, optionally including heteroatoms;
- R2 is selected from the group consisting of
- where the squiggly line represents the attachment point to X3;
- and
- X2 is halogen, alkyl, halogenated alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, pyrollyl, optionally substituted aryloxy, alkylamino, dialkylamino, carbamyl, amido, alkylamido dialkylamido, acylamino, alkylsulfonylamido, trihalomethoxy, trihalocarbon, thioalkyl, SO2-alkyl, COO-alkyl, NH2, OH, or CN;
- wherein the compound is optionally in the form of an acid addition salt;
- and
- wherein the neurodegenerative disease is selected from the group consisting of complete androgen insensitivity syndrome (CAIS), spinal and bulbar muscular atrophy (SBMA or Kennedy's disease), Alzheimer's Disease (AD), sporadic frontotemporal dementia with parkinsonism (FTDP), familial FTDP-17 syndromes, Parkinson's disease, and Huntington disease.
A method for treatment of a neurodegenerative disease, comprising administering to an individual in need of such treatment a therapeutically effective amount of a compound of formula:
- wherein
- X4 is hydrogen or halogen;
- X6 is amino;
- X3 is C, O, N, or S with hydrogens as necessary to satisfy valence, or CF2, SO, SO2 or NR3 where R3 is alkyl;
- R1 is hydrogen, a C1 to C10 alkyl, alkenyl, alkynyl, or an alkoxyalkyl group, optionally including heteroatoms;
- R2 is
- where the squiggly line represents the attachment point to X3;
- and
- X2 is ethylene;
- wherein the compound is optionally in the form of an acid addition salt;
- and
- wherein the neurodegenerative disease is selected from the group consisting of complete androgen insensitivity syndrome (CAIS), spinal and bulbar muscular atrophy (SBMA or Kennedy's disease), Alzheimer's Disease (AD), sporadic frontotemporal dementia with parkinsonism (FTDP), familial FTDP-17 syndromes, Parkinson's disease, and Huntington disease.
Dependencies are inferred from the claim text.