1841-17-4

Upstream product

• 59455-11-7 1-[4-bromo-1-(4-fluorophenyl)but-1-en-1-yl]-4-fluorobenzene 
• 1021-25-6 1-Phenyl-1,3,8-triaza-spiro[4.5]decan-4-one 
• 352-13-6 4-flourophenylmagnesium bromide 
• 337506-83-9 1,1-bis(4-fluorophenyl)butane-1,4-diol 
• 345-92-6 4,4'-Difluorobenzophenone 
• 99734-06-2 α,α-bis(4-fluorophenyl)allyl alcohol 
• 817642-33-4 8-[4,4-bis(p-fluorophenyl)-4-hydroxybutyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one 

Downstream Products

• 1841-19-6 fluspirilene 

Relevant academic research and scientific papers

Fluspirilene Analogs Activate the 20S Proteasome and Overcome Proteasome Impairment by Intrinsically Disordered Protein Oligomers

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.

Regioselective hydroaminomethylation of 1,1-diaryl-allyl-alcohols: A new access to 4,4-diarylbutylamines

Pharmacologically active 4,4-diarylbutylamines like Fluspirilene and 4-amino-1,1-diarylbutan-1-ols like Difenidol were prepared in high yields via rhodium catalysed hydroaminomethylation of 1,1-diaryl-allylalcohols. Conversion of these olefins with carbon monoxide, hydrogen and secondary amines proceeds with complete regioselectivity. This group can easily be removed under acidic and hydrogenating conditions, enabling the transformation of 4-amino-1,1-diarylbutan-1-ols to 4,4-diarylbutylamines in high yields. Thus Fluspirilene was synthesised in 88% yield in four steps starting from commercially available materials. Graphical Abstract.