5044-23-5Relevant academic research and scientific papers
An inhibitor of the proteasomal deubiquitinating enzyme USP14 induces tau elimination in cultured neurons
Boselli, Monica,Lee, Byung-Hoon,Robert, Jessica,Prado, Miguel A.,Min, Sang-Won,Cheng, Chialin,Catarina Silva,Seong, Changhyun,Elsasser, Suzanne,Hatle, Ketki M.,Gahman, Timothy C.,Gygi, Steven P.,Haggarty, Stephen J.,Gan, Li,King, Randall W.,Finley, Daniel
, p. 19209 - 19225 (2017)
The ubiquitin-proteasome system (UPS) is responsible for most selective protein degradation in eukaryotes and regulates numerous cellular processes, including cell cycle control and protein quality control. A component of this system, the deubiquitinating enzyme USP14, associates with the proteasome where it can rescue substrates from degradation by removal of the ubiquitin tag. We previously found that a small-molecule inhibitor of USP14, known as IU1, can increase the rate of degradation of a subset of proteasome substrates. We report here the synthesis and characterization of 87 variants of IU1, which resulted in the identification of a 10-fold more potent USP14 inhibitor that retains specificity for USP14. The capacity of this compound, IU1-47, to enhance protein degradation in cells was tested using as a reporter the microtubule-associated protein tau, which has been implicated in many neurodegenerative diseases. Using primary neuronal cultures, IU1-47 was found to accelerate the rate of degradation of wild-type tau, the pathological tau mutants P301L and P301S, and the A152T tau variant. We also report that a specific residue in tau, lysine 174, is critical for the IU1-47–mediated tau degradation by the proteasome. Finally, we show that IU1-47 stimulates autophagic flux in primary neurons. In summary, these findings provide a powerful research tool for investigating the complex biology of USP14.
Flexible Construction of Functionalized-Pyrroles under Palladium or Copper Catalysis in the Presence of BF3 ? Et2O
Liu, Yin,Liu, Teng,Yan, Biwei,Wei, Kun,Guo, Wusheng
, p. 916 - 921 (2022/01/26)
We have developed a flexible approach enabling the access to highly functionalized pyrroles under palladium or copper catalysis in the presence of BF3 ? Et2O. This catalytic methodology utilizes commercially available amines as react
Amidosulfonic acid supported on graphitic carbon nitride: novel and straightforward catalyst for Paal–Knorr pyrrole reaction under mild conditions
Azhdari, Asieh,Azizi, Najmedin,Sanaeishoar, Haleh,Tahanpesar, Elham
, p. 625 - 634 (2021/05/12)
A novel heterogeneous acidic catalyst was prepared by in situ immobilization of amidosulfonic acid (NH2SO3H) on graphitic carbon nitride (g-C3N4) under hydrothermal conditions. The textural morphology of NH2SO3H/g-C3N4 nanocomposite was characterized via powder X-ray diffraction, FT-IR, TGA, EDX, and scanning electron microscopy. The spatial arrangement of the amidosulfonic acid on the surface of g-C3N4 leads to the construction of a unique solid acid structure, resulting in a substantial enhancement of catalytic activity toward a high efficient preparation of pyrroles by Paal–Knorr reaction. The reactions undergo completion readily with good to excellent yields, with simple purification in an environmentally friendly manner. The NH2SO3H/g-C3N4 nanocomposite can be readily recycled, and no noteworthy reduction in the catalytic activity detected after four runs. Graphic abstract: [Figure not available: see fulltext.]
Crystalline salicylic acid as an efficient catalyst for ultrafast Paal–Knorr pyrrole synthesis under microwave induction
Aghapoor, Kioumars,Mohsenzadeh, Farshid,Darabi, Hossein Reza,Sayahi, Hani
, (2021/04/19)
Abstract: In this study, the viability of a wide range of crystalline aromatic and aliphatic carboxylic acids as organocatalysts has been investigated for solvent-free Paal–Knorr pyrrole synthesis under microwave activation. Among these potential catalysts, crystalline salicylic acid proved to be a remarkable catalyst because its efficiency remained high even under low microwave power irradiation or a shorter reaction time for the model reaction. The outstanding catalytic activity of salicylic acid allowed the Paal–Knorr cyclocondensation with a turnover frequency up to 1472?h?1 which is unique in the context of a metal-free homogeneous catalysis. The attractive feature of this organocatalyst is its assistance in ultrafast pyrrole synthesis with no risk of metal contamination. Graphic abstract: [Figure not available: see fulltext.] Synopsis: A green and expeditious protocol for the synthesis of 2,5-dimethylpyrroles via combination of salicylic acid as catalyst (in its solid state) and microwaves has been introduced.
Facile fabrication of porous magnetic covalent organic frameworks as robust platform for multicomponent reaction
Azizi, Najmedin,Heidarzadeh, Fatemeh,Farzaneh, Fezeh
, (2021/07/26)
The design of cheap yet efficient nanoporous magnetic catalysts for the environmentally benign process's widespread application is an extremely attractive, challenging chemical research field. A novel porous magnetic covalent organic framework was prepared by the condensation reaction of melamine and terephthaladehyde on the surface of 3,4-dihydroxybenzaldehyde coated magnetic Fe3O4 nanoparticles COF@Fe3O4 under hydrothermal conditions for the first time. The high surface area magnetic COF could exhibit superior catalytic activity for sustainable synthesis of trisubstituted and tetrasubstituted imidazoles and pyrroles in good to excellent yields in PEG as solvent under environmentally friendly, ambient conditions and making the overall process economical, efficient, and green. The retrievable catalyst in PEG is general and applicable to a broad substrate scope and functional group compatibility. The structure and morphology of the COF@Fe3O4 were characterized by FTIR, XRD, EDX, and SEM spectroscopy. The COF@Fe3O4 magnetic catalyst was recovered by an external magnet and used for several cycles without significant catalytic activity loss.
Synthesis of Fe3O4@L-proline@SO3H as a novel and reusable acidic magnetic nanocatalyst and its application for the synthesis of N-substituted pyrroles at room temperature under ultrasonic irradiation and without solvent
Behbahani, Farahnaz K.,Shokri, Fatemeh
, (2021/08/18)
N-Substituted pyrroles have been prepared in high isolated yields (65–90%) by the reaction of hexane-2,5-dione with amines or diamines in the presence of Fe3O4@L-proline@SO3H at ambient temperature under ultrasonic irradiation and without solvent. The experimental procedure involves simple operations, and the products are readily separated by external magnet. The same reaction of hexane-2,5-dione with amines containing electron-acceptor substituents, such as 4-nitroaniline, resulted in fair yields of pyrrole derivatives.
A New FXR Ligand Chemotype with Agonist/Antagonist Switch
Helmst?dter, Moritz,Vietor, Jan,Sommer, Jana,Schierle, Simone,Willems, Sabine,Kaiser, Astrid,Schmidt, Jurema,Merk, Daniel
supporting information, p. 267 - 274 (2021/02/20)
Therapeutic modulation of the bile acid-sensing transcription factor farnesoid X receptor (FXR) is an appealing strategy to counteract hepatic and metabolic diseases. Despite the availability of several highly potent FXR agonists structural diversity of FXR modulators is limited, and new ligand scaffolds are needed. Here we report structure-activity relationship elucidation of a new FXR modulator chemotype whose activity can be tuned between agonism and antagonism by two minor structural modifications. Starting from a weak FXR/PPAR agonist, we have developed selective FXR activators and antagonists with nanomolar to low-micromolar potencies and binding affinities. The new FXR ligand chemotype modulates the FXR activity in the native cellular setting, is endowed with favorable metabolic stability, and lacks cytotoxicity. It valuably expands the collection of FXR modulators as a new scaffold for FXR-targeted drug discovery.
One-pot synthesis of cyclohexylamine and: N -aryl pyrroles via hydrogenation of nitroarenes over the Pd0.5Ru0.5-PVP catalyst
Chaudhari, Chandan,Sato, Katsutoshi,Ikeda, Yasuyuki,Terada, Kenji,Abe, Naoya,Nagaoka, Katsutoshi
supporting information, p. 9743 - 9746 (2021/06/15)
The direct synthesis of cyclohexylamine via the hydrogenation of nitrobenzene over monometallic (Pd, Ru or Rh) and bimetallic (PdxRu1-x) catalysts was studied. The Pd0.5Ru0.5-PVP catalyst was the most effective catalyst for this reaction. The catalyst can be reused and applied for the synthesis of N-aryl pyrroles and quinoxalines from nitrobenzenes.
Method for preparing N-aryl pyrrole compound
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Paragraph 0021; 0047, (2020/09/09)
The present invention relates to a method for preparing an N-aryl pyrrole compound. Furan containing different substituents, aromatic amine containing different substituents and a solid Lewis acid catalyst are mixed and placed in a closed reactor, and an N-aryl pyrrole compound with different substituents is prepared under certain catalytic conditions. The reaction temperature of the catalytic reaction condition is 140-210 DEG C. The solid Lewis acid catalyst is prepared by a sol-gel method, Hf is used as a core metal element, and a mesoporous molecular sieve SBA-15 is used as a carrier. According to the method, the catalyst is simple to prepare, low in cost, high in reaction activity, good in water resistance and structural stability and high in catalytic reaction yield; meanwhile, the Lewis acid type catalyst does not generate acid protons, the corrosion of the catalyst to equipment at high temperature is avoided, the post-reaction treatment is convenient, and the catalyst is renewable and environment-friendly.
Naturally occurring organic acids for organocatalytic synthesis of pyrroles via Paal–Knorr reaction
Mohsenzadeh, Farshid,Darabi, Hossein Reza,Alivand, Mahsa,Aghapoor, Kioumars,Balavar, Yadollah
, p. 5255 - 5262 (2020/09/09)
Abstract: In this study, common naturally occurring organic acids, namely oxalic, malonic, succinic, tartaric and citric acid (as safe, inexpensive, and biodegradable organocatalysts), have been employed for Paal–Knorr pyrrole synthesis. The organocatalyzed reaction proved to be effective in ethanol at 60?°C. However, the reaction rate is mainly dominated by the nature and position of functional groups on the aromatic ring of substrate. This metal-free procedure tolerates a series of functional groups and should be considered as an asset to the pharmaceutical industry since no metal contamination could take place during the synthesis of pyrrole scaffolds. Graphic abstract: [Figure not available: see fulltext.].
