US 12,473,288 B2
Treatment of neurodegenerative diseases through inhibiton of Hsp90
Gabriela Chiosis, New York, NY (US); Huazhong He, New York, NY (US); and Danuta Zatorska, Ericeira (PT)
Assigned to Sloan-Kettering Institute for Cancer Research, New York, NY (US)
Filed by Sloan-Kettering Institute for Cancer Research, New York, NY (US)
Filed on May 26, 2023, as Appl. No. 18/202,704.
Application 18/202,704 is a division of application No. 17/957,437, filed on Sep. 30, 2022, abandoned.
Application 17/957,437 is a division of application No. 17/502,563, filed on Oct. 15, 2021, abandoned.
Application 17/502,563 is a division of application No. 16/398,650, filed on Apr. 30, 2019, abandoned.
Application 16/398,650 is a division of application No. 12/307,063, granted, now 10,336,757, previously published as PCT/US2007/072671, filed on Jul. 2, 2007.
Claims priority of provisional application 60/806,427, filed on Jun. 30, 2006.
Prior Publication US 2024/0158397 A1, May 16, 2024
Int. Cl. A61K 31/52 (2006.01); C07D 473/40 (2006.01)
CPC C07D 473/40 (2013.01) [A61K 31/52 (2013.01)] 19 Claims
 
1. 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:

OG Complex Work Unit Chemistry
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.