58287-80-2Relevant academic research and scientific papers
An Exploration of Chemical Properties Required for Cooperative Stabilization of the 14-3-3 Interaction with NF-κB—Utilizing a Reversible Covalent Tethering Approach
Wolter, Madita,Valenti, Dario,Cossar, Peter J.,Hristeva, Stanimira,Levy, Laura M.,Genski, Thorsten,Hoffmann, Torsten,Brunsveld, Luc,Tzalis, Dimitrios,Ottmann, Christian
supporting information, p. 8423 - 8436 (2021/06/28)
Protein-protein modulation has emerged as a proven approach to drug discovery. While significant progress has been gained in developing protein-protein interaction (PPI) inhibitors, the orthogonal approach of PPI stabilization lacks established methodologies for drug design. Here, we report the systematic ″bottom-up″ development of a reversible covalent PPI stabilizer. An imine bond was employed to anchor the stabilizer at the interface of the 14-3-3/p65 complex, leading to a molecular glue that elicited an 81-fold increase in complex stabilization. Utilizing protein crystallography and biophysical assays, we deconvoluted how chemical properties of a stabilizer translate to structural changes in the ternary 14-3-3/p65/molecular glue complex. Furthermore, we explore how this leads to high cooperativity and increased stability of the complex.
PROTEIN-PROTEIN INTERACTION STABILIZERS
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Paragraph 0041; 1043-1044; 1046, (2021/10/11)
Provided herein, inter alia, are stabilizers of protein-protein interactions and methods of identifying and using the same.
Discovery and optimization of 4-oxo-2-thioxo-thiazolidinones as NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inhibitors
Chen, Yun,Deng, Xianming,He, Hongbin,Hu, Zhiyu,Huang, Huiying,Jiang, Hua,Li, Li,Xu, Qingyan,Zhou, Rongbin
supporting information, (2020/02/15)
Aberrant activation of NLRP3 inflammasome is present in a subset of acute and chronic inflammatory diseases. The NLRP3 inflammasome has been recognized as an attractive therapeutic target for developing novel and specific anti-inflammatory inhibitors. Cellular structure-activity relationship-guided optimization resulted in the identification of 4-oxo-2-thioxo-thiazolidinone derivative 9 as a selective and direct small-molecule inhibitor of NLRP3 with IC50 of 2.4 μM, possessing favorable ex vivo and in vivo pharmacokinetic properties. Compound 9 may represent a lead for the development of anti-inflammatory therapeutics for treating NLRP3-driven diseases.
COMPOUND USED AS AUTOPHAGY REGULATOR, AND PREPARATION METHOD THEREFOR AND USES THEREOF
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Paragraph 0266-0267, (2020/07/07)
It is related to compounds used as autophagy modulators and a method for preparing and using the same, specifically providing a compound of general formula (I), or pharmaceutically acceptable salts thereof, which is a type of autophagy modulators, particularly mammalian ATG8 homologues modulators.
Supported Palladium Nanoparticles that Catalyze Aminocarbonylation of Aryl Halides with Amines using Oxalic Acid as a Sustainable CO Source
Bal Reddy,Ram, Shankar,Kumar, Ajay,Bharti, Richa,Das, Pralay
supporting information, p. 4067 - 4071 (2019/02/27)
Polystyrene-supported palladium (Pd@PS) nanoparticles (NPs) have been used to catalyze the aminocarbonylation of aryl halides with amines using oxalic acid as a CO source for the first-time for the synthesis of amides. Furthermore, o-iodoacetophenones participated in amidation and cyclization reactions to give isoindolinones in a single step following a concerted approach. Oxalic acid has been used as a safe, environmentally benign and operationally simple ex situ sustainable CO source under double-layer-vial (DLV) system for different aminocarbonylation reactions. Catalyst stability under a CO environment is a challenging task, however, Pd@PS was found to be recyclable and applicable for a vast substrate scope avoiding regeneration steps. Easy handling of oxalic acid, additive and base-free CO generation, catalyst stability and effortless catalyst separation from the reaction mixture by filtration and introduce of DLV are the added advantages to make the overall process a sustainable approach.
COMPOUNDS AND METHOD OF USE
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Paragraph 0950, (2019/09/06)
This present disclosure relates to compounds with ferroptosis inducing activity, a method of treating a subject with cancer with the compounds, and combination treatments with a second therapeutic agent.
An efficient procedure for chemoselective amidation from carboxylic acid and amine (ammonium salt) under mild conditions
Li, Jianhui,He, Shaopo,Fu, Haiqing,Chen, Xin,Tang, Min,Zhang, Dela,Wang, Bo
, p. 2289 - 2303 (2017/12/26)
Presented here is an efficient one-pot and catalyst-free procedure for the synthesis of amides starting from carboxylic acids and amine/ammonium salts using 2,2-dichloro-1,3-diisopropylimidazolidine-4,5-dione as the coupling agent. Reactions can proceed smoothly even with those bearing thermosensitive group(s) at ambient temperature, and the corresponding products of primary, secondary and tertiary amides can be afforded in moderate to excellent yields of up to 96%.
HETEROARYL COMPOUNDS AS BTK INHIBITORS AND USES THEREOF
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Paragraph 0229, (2016/05/02)
The present invention relates to imidazo pyridine compounds, and pharmaceutically acceptable compositions thereof, useful as BTK inhibitors.
Co2(CO)8 as a convenient in situ CO source for the direct synthesis of benzamides from aryl halides (Br/I) via aminocarbonylation
Baburajan, Poongavanam,Elango, Kuppanagounder P.
supporting information, p. 1006 - 1010 (2014/02/14)
A fast, mild, and functional group tolerant method for the direct synthesis of benzamides from aryl halides (Br, I) via aminocarbonylation, using solid Co2(CO)8 as a convenient CO source, has been demonstrated. The developed method is applicable to a wide variety of 1 and cyclic and acyclic 2 amines. Nitro substituted (o, m and p) aryl halides have easily been converted to the corresponding benzamides, without the reduction of the nitro group, in high yields using this in situ carbonylation methodology under microwave irradiation.
Co2(CO)8 as a convenient in situ CO source for the direct synthesis of benzamides from aryl halides (Br/I) via aminocarbonylation
Baburajan, Poongavanam,Elango, Kuppanagounder P.
supporting information, p. 1006 - 1010 (2015/02/19)
A fast, mild, and functional group tolerant method for the direct synthesis of benzamides from aryl halides (Br, I) via aminocarbonylation, using solid Co2(CO)8 as a convenient CO source, has been demonstrated. The developed method is applicable to a wide variety of 1° and cyclic and acyclic 2°amines. Nitro substituted (o, m and p) aryl halides have easily been converted to the corresponding benzamides, without the reduction of the nitro group, in high yields using this in situ carbonylation methodology under microwave irradiation.
