36265-55-1Relevant articles and documents
Fluspirilene Analogs Activate the 20S Proteasome and Overcome Proteasome Impairment by Intrinsically Disordered Protein Oligomers
Fiolek, Taylor J.,Keel, Katarina L.,Tepe, Jetze J.
, p. 1438 - 1448 (2021/05/04)
Oligomerization of aggregation-prone intrinsically disordered proteins (IDPs), such as α-synuclein, amyloid β, and tau, has been shown to be associated with the pathogenesis of several neurodegenerative diseases, including Parkinson's and Alzheimer's disease. The proteasome is charged with regulating cellular levels of IDPs, but this degradation pathway can become dysregulated leading to their accumulation and subsequent aggregation. Although the pathogenesis of these neurodegenerative diseases is still under intense investigation, it has been shown that the oligomeric forms of IDPs, including α-synuclein and amyloid β, can impair proteasome function. This leads to additional accumulation of the IDPs, further promoting disease progression. Herein, we report the use of small molecule activators of the 20S subcomplex of the proteasome to restore impaired 20S proteasome activity and prevent IDP accumulation and oligomerization. We found that fluspirilene and its new synthetic analog (16) show strong 20S proteasome enhancement (doubling 20S proteolytic activity at μ2 μM, with maximum fold enhancement of μ1000%), overcome impaired proteasome function, and prevent the accumulation of pathogenic IDPs. These findings provide support for the use of 20S enhancers as a possible therapeutic strategy to combat neurodegenerative diseases.
Synthesis and SAR study of diphenylbutylpiperidines as cell autophagy inducers
Chen, Gang,Xia, Hongguang,Cai, Yu,Ma, Dawei,Yuan, Junying,Yuan, Chengye
scheme or table, p. 234 - 239 (2011/02/26)
A novel series of diphenylbutylpiperidines as autophagy inducers was described and extensive SAR studies resulted in derivatives (15d-e, 15i-j) with 10-fold greater activity than the lead compounds 1 and 2. Meanwhile, a new synthetic route to diphenylbutyl bromide (6) from bromobenzene and γ-butyrolactone was also reported here.
SIP3 RECEPTOR ANTAGONIST
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Page/Page column 22, (2010/02/14)
PROBLEM TO BE SOLVED: To obtain a compound having selective SIP3 receptor antagonism and a medicine containing the same. SOLUTION: The medicine comprises an aminopropionic acid derivative represented by general formula (1) (R1 is a hydrogen atom or a lower alkyl group; R2 is formula A; A is CO or CH2; E is an oxygen atom or an NR4; R3 is a lower alkyl group or formula B; G is CH, a nitrogen atom or a phosphorus atom; J is an oxygen atom or a sulfur atom; R4 is a hydrogen atom or a lower alkyl group; R5, R6 and R7 are each the same or different and a hydrogen atom, a lower alkyl group, a lower alkoxy group, a halogen atom, a nitro group or a haloalkyl group; m is an integer of 1-8; n is an integer of 1-5) or its pharmaceutically permissible salt as an active ingredient.