50337-85-4

Usage

Uses

Used in Pharmaceutical Industry:
4,4-bis(4-fluorophenyl)butan-1-ol is used as an intermediate in the synthesis of various compounds with potential pharmaceutical applications. One such example is its role in the production of 1,1''-(4-Chlorobutylidene)bis(4-fluorobenzene) (C364775), a derivative of Zerumbone. This derivative has demonstrated potential anti-tumor effects, particularly towards HeLa cancer cells, making it a promising candidate for further research and development in cancer treatment.

InChI:InChI=1/C16H16F2O/c17-14-7-3-12(4-8-14)16(2-1-11-19)13-5-9-15(18)10-6-13/h3-10,16,19H,1-2,11H2

Upstream product

• 20662-52-6 4,4-bis(4-fluorophenyl)butanoic acid 
• 3312-04-7 4-chloro-1,1-bis(4-fluorophenyl)butane 
• 54314-85-1 (3-benzyloxypropyl)triphenylphosphonium bromide 
• 345-92-6 4,4'-Difluorobenzophenone 
• 1765-93-1 4-fluoroboronic acid 
• 352-13-6 4-flourophenylmagnesium bromide 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 51787-96-3 5-(4-fluorophenyl)dihydrofuran-2(3H)-one 
• 462-06-6 fluorobenzene 
• 293729-65-4 5,5-bis-(4-fluoro-phenyl)-tetrahydro-furan-2-ol 
• 99734-06-2 α,α-bis(4-fluorophenyl)allyl alcohol 
• 357-77-7 1,1-bis(4-fluorophenyl)prop-2-yn-1-ol 
• 337506-83-9 1,1-bis(4-fluorophenyl)butane-1,4-diol 

Downstream Products

• 51787-79-2 1,1-bis(-4-fluorophenyl)-4-iodobutane 
• 1266656-43-2 8-(4,4-bis(4-fluorophenyl)butanoyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one 
• 3312-04-7 4-chloro-1,1-bis(4-fluorophenyl)butane 
• 20662-52-6 4,4-bis(4-fluorophenyl)butanoic acid 
• 1841-19-6 fluspirilene 
• 26864-56-2 penfluridol 
• 57668-61-8 4,4'-(4-bromobutane-1,1-diyl)bis(fluorobenzene) 

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.

Design, synthesis and structure-activity relationship study of novel urea compounds as FGFR1 inhibitors to treat metastatic triple-negative breast cancer

Triple-negative breast cancer (TNBC) is an aggressive type of cancer characterized by higher metastatic and reoccurrence rates, where approximately one-third of TNBC patients suffer from the metastasis in the brain. At the same time, TNBC shows good responses to chemotherapy, a feature that fuels the search for novel compounds with therapeutic potential in this area. Recently, we have identified novel urea-based compounds with cytotoxicity against selected cell lines and with the ability to cross the blood-brain barrier in vivo. We have synthesized and analyzed a library of more than 40 compounds to elucidate the key features responsible for the observed activity. We have also identified FGFR1 as a molecular target that is affected by the presence of these compounds, confirming our data using in silico model. Overall, we envision that these compounds can be further developed for the potential treatment of metastatic breast cancer.

Improved method for preparing penfuridol

The invention discloses an improved method for preparing penfuridol, comprising the following steps: using 4, 4-bis (4-fluorophenyl) butyric acid as a starting material, carrying out reduction synthesis to synthesize an intermediate I [4, 4-bis (4-fluorophenyl)-1-butanol]; carrying out esterification with a sulfonyl chloride compound to synthesize an intermediate II [4, 4-bis (4-fluorophenyl)-1 (4-methyl-phenyl)-butyl sulfonate] or [4, 4-bis (4-fluorophenyl)-1-methyl-butyl sulfonate]; and condensing with pipradrol to obtain penfuridol. According to the preparation method, 4, 4-bis (4-fluorophenyl) butyric acid is used as a raw material, penfuridol is obtained through a reduction reaction, an esterification reaction and a condensation reaction, the total yield is 81.3%, the whole process isconvenient to operate and mild in reaction, the obtained product is high in yield and purity, and the preparation method is more economical and more suitable for industrial application. The technicalproblems that an existing method is low in yield and poor in purity are solved. The reaction general formula is as shown in the specification.

Remote C(sp3)?H Arylation and Vinylation of N-Alkoxypyridinium Salts to δ-Aryl and δ-Vinyl Alcohols

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.

A Non-Competitive Inhibitor of VCP/p97 and VPS4 Reveals Conserved Allosteric Circuits in Type I and II AAA ATPases

AAA ATPases have pivotal functions in diverse cellular processes essential for survival and proliferation. Revealing strategies for chemical inhibition of this class of enzymes is therefore of great interest for the development of novel chemotherapies or chemical tools. Here, we characterize the compound MSC1094308 as a reversible, allosteric inhibitor of the type II AAA ATPase human ubiquitin-directed unfoldase (VCP)/p97 and the type I AAA ATPase VPS4B. Subsequent proteomic, genetic and biochemical studies indicate that MSC1094308 binds to a previously characterized drugable hotspot of p97, thereby inhibiting the D2 ATPase activity. Our results furthermore indicate that a similar allosteric site exists in VPS4B, suggesting conserved allosteric circuits and drugable sites in both type I and II AAA ATPases. Our results may thus guide future chemical tool and drug discovery efforts for the biomedically relevant AAA ATPases.

PROCESS FOR THE PREPARATION OF A FLUSPIRILENE INTERMEDIATE

The present invention relates to a process for the preparation of a 4,4'- bis(fluorobenzene) derivative, which is an intermediate compound in the synthesis of some drugs, for example in the synthesis of fluspirilene. The invention further relates to new synthetic intermediate compounds.

Studies on a novel safety-catch linker cleaved by Pummerer rearrangement

(Equation Presented) We describe the use of a sulfide linkage as a safety-catch linker. This linker is significantly stable to acidic as well as basic conditions and allows transformations to be carried out on solid supports. Moreover, its cleavage is facile by applying Pummerer rearrangement after transforming it to sulfoxide.

Rhodium catalyzed hydroformylation of 1,1-bis(p-fluorophenyl)allyl or propargyl alcohol: A key step in the synthesis of Fluspirilen and Penfluridol

Fluspirilen (1) and Penfluridol (2), two neuroleptic agents, belong to a wide class of pharmaceuticals that contain in their molecules a 4,4-bis(p-fluorophenyl)butyl group bound to a nitrogen atom of a pyrrolidine, piperidine or piperazine moiety. A key intermediate for the synthesis of compounds 1 and 2,4,4-bis(p-fluorophenyl)butylbromide (15), has been prepared starting from commercially available 4,4′-difluorobenzophenone (7) following a preparative route involving the rhodium catalyzed hydroformylation in toluene or in the biphasic system toluene/water or cyclohexane/water of 1,1-bis(p-fluorophenyl)-2-propenol (8) and/or 1,1-bis(p-fluorophenyl)-2-propynol (12). Fluspirilen and Penfluridol were obtained in 70-80% yield by reaction of bromide 15 with 1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one (16) and 4-[4-chloro-3-(trifluoromethyl)phenyl]-4-piperidinol (17), respectively. The overall yields of the two pharmaceuticals 1 and 2, based on starting ketone 7, were about 35-40%.