56740-71-7Relevant 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.
Remote C(sp3)?H Arylation and Vinylation of N-Alkoxypyridinium Salts to δ-Aryl and δ-Vinyl Alcohols
Bao, Xu,Wang, Qian,Zhu, Jieping
supporting information, (2019/08/21)
The reaction of readily available and bench-stable N-alkoxypyridinium salts with arylboronic and vinylboronic acids afforded δ-aryl and δ-vinyl alcohols, respectively, in the presence of fac-Ir(ppy)3 and Cu(OTf)2 dual catalysts. The reaction takes place through a domino process involving the reductive generation of alkoxyl radicals, 1,5-hydrogen atom transfer (1,5-HAT) and the copper-catalyzed cross-coupling reaction of the resulting translocated carbon radicals with boronic acids. Complementary to the Minisci reaction, this method allows for the arylation of nucleophilic alkyl radicals with both electron-rich and electron-poor arenes under mild reaction conditions.
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.
