76694-24-1Relevant 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.
Copper(I)-Catalyzed Enantioselective Intramolecular Aminotrifluoromethylation of O-Homoallyl Benzimidates
Mou, Xue-Qing,Rong, Feng-Ming,Zhang, Heng,Chen, Gong,He, Gang
supporting information, p. 4657 - 4661 (2019/06/17)
In the present paper, the Cu(I)-catalyzed intramolecular aminotrifluoromethylation of O-homoallyl benzimidates with Togni reagent I was reported. O-Homoallyl benzimidates equipped with terminal alkenes produced chiral 1,3-oxazines with high enantioselectivity in the presence of a chiral BOX ligand, and racemic tetrahydro-1,3-oxazepines were obtained in high yields from internal alkene derivatives with a monoprotected amino acid additive under similar conditions.
Alkene Oxyamination Using Malonoyl Peroxides: Preparation of Pyrrolidines and Isoxazolidines
Alamillo-Ferrer, Carla,Curle, Jonathan M.,Davidson, Stuart C.,Lucas, Simon C. C.,Atkinson, Stephen J.,Campbell, Matthew,Kennedy, Alan R.,Tomkinson, Nicholas C. O.
, p. 6728 - 6740 (2018/06/26)
Treatment of homoallylic N-tosyl amines or allylic N-tosyl hydroxylamines with 1.5 equiv of a malonoyl peroxide provides a stereoselective method to access functionalized pyrrolidines and isoxazolidines. This metal free alkene oxyamination proceeds in 50-
Analogs of penfluridol as chemotherapeutic agents with reduced central nervous system activity
Ashraf-Uz-Zaman, Md,Sajib, Md Sanaullah,Cucullo, Luca,Mikelis, Constantinos M.,German, Nadezhda A.
, p. 3652 - 3657 (2018/11/03)
Several recent reports have highlighted the feasibility of the use of penfluridol, a well-known antipsychotic agent, as a chemotherapeutic agent. In vivo experiments have confirmed the cytotoxic activity of penfluridol in triple-negative breast cancer model, lung cancer model, and further studies have been proposed to assess its anticancer activity and viability for the treatment of glioblastomas. However, penfluridol anticancer activity was observed at a dosage significantly higher than that administered in antipsychotic therapy, thus raising the concern for the potential onset of CNS side effects in patients undergoing intensive pharmacological treatment. In this study, we evaluate the potential CNS toxicity of penfluridol side by side with a set of analogs.
Copper-Catalyzed Diastereoselective Synthesis of Trifluoromethylated Tetrahydrofurans
Wang, Yanan,Jiang, Min,Liu, Jin-Tao
supporting information, p. 1322 - 1327 (2016/04/26)
The copper-catalyzed intramolecular diastereoselective trifluoromethylcycloetherification of homoallylic alcohols with Togni's reagent as trifluoromethylating reagent was realized under mild conditions. Various trifluoromethylated tetrahydrofurans were synthesized in moderate to good yields. Moreover, a wide range of common functional groups was tolerated.
Hot water-promoted cyclopropylcarbinyl rearrangement facilitates construction of homoallylic alcohols
Li, Pei-Fang,Yi, Cheng-Bo,Qu, Jin
, p. 5012 - 5021 (2015/05/05)
In refluxing 9 : 1 (v/v) H2O-1,4-dioxane and without an additional catalyst, the rearrangements of various types of cyclopropyl carbinols were attempted. It was found that the reactions generally gave homoallylic alcohols in good to very high chemical yields. Rearrangements of bicyclic or tricyclic cyclopropyl carbinols readily gave the desired ring-expanded cyclic homoallylic alcohols which are difficult to synthesize by other means.
Simple and efficient 1,3-isomerization of allylic alcohols using a supported monomeric vanadium-oxide catalyst
Mitsudome, Takato,Sueoka, Shoichiro,Ikeda, Satoshi,Mizugaki, Tomoo,Jitsukawa, Koichiro,Kaneda, Kiyotomi
, p. 2879 - 2882 (2013/10/21)
Promotion by group high five: Silica-supported monomeric vanadium-oxide promoted the isomerization of various allylic alcohols, including under scaled-up and solvent-free reaction conditions. This catalyst also exhibited high reusability with no drop in activity.
Rapid access to halohydrofurans via bronsted acid-catalyzed hydroxylation/halocyclization of cyclopropyl methanols with water and electrophilic halides
Mothe, Srinivasa Reddy,Kothandaraman, Prasath,Rao, Weidong,Chan, Philip Wai Hong
experimental part, p. 2521 - 2531 (2011/05/14)
A one-pot, two-step method to prepare 3-halohydrofurans efficiently by TfOH-catalyzed hydroxylation/halocyclization of cyclopropyl methanols with H2O and N-halosuccinimide (NXS, X=1, Br, Cl) or Selectfluor is described. The reactions proceed rapidly under mild and operationally straightforward conditions with a catalyst loading as low as 1 mol % and afford the 3-halohydrofuran products in moderate to excellent yields and, in most cases, with preferential cis diastereoselectivity. The method was shown to be applicable to cyclopropyl methanols containing electron-withdrawing, electron-donating, and sterically demanding functional groups and electrophilic halide sources. The mechanism is suggested to involve protonation of the alcohol substrate by the Bronsted acid catalyst and ionization of the starting material. This results in ring-opening of the cyclopropane moiety and in situ formation of a homoallylic alcohol intermediate, which undergoes subsequent intramolecular halocyclization on treating with the electrophilic halide source to give the halohydrofuran. The observed cis product selectivity is thought to be determined by the reaction proceeding through an in situ generated unsaturated alcohol intermediate that contains a (Z)-alkene moiety under the kinetically controlled conditions.
DIPHENYLBUTYPIPERIDINE AUTOPHAGY INDUCERS
-
, (2011/12/02)
Autophagy inducing compounds, methods of their preparation and use, and kits containg said compounds are disclosed herein.
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.
