52578-66-2Relevant articles and documents
Discovery of Cell-Permeable O-GlcNAc Transferase Inhibitors via Tethering in Situ Click Chemistry
Wang, Yue,Zhu, Jingjing,Zhang, Lianwen
, p. 263 - 272 (2017/04/26)
O-GlcNAc transferase (OGT) is a key enzyme involved in dynamic O-GlcNAcylation of nuclear and cytoplasmic proteins similar to phosphorylation. Discovery of cell-permeable OGT inhibitors is significant to clarify the function and regulatory mechanism of O-GlcNAcylation. This will establish the foundation for the development of therapeutic drugs for relevant diseases. Here, we report two cell-permeable OGT inhibitors (APNT and APBT), developed from low-activity precursors (IC50 > 1 mM) via “tethering in situ click chemistry (TISCC)”. Both of them were able to inhibit O-GlcNAcylation in cells without significant effects on cell viability. Unusual noncompetitive inhibition of OGT was helpful to discover novel inhibitors and explore the regulatory mechanism of OGT. The development of these molecules validates that TISCC can be utilized to discover novel lead compounds from components that exhibited very weak binding to the target.
One-pot synthesis of 1,4-disubstituted 1,2,3-triazoles from nitrobenzenes
Zhao, Fen,Chen, Zhen,Xie, Kai,Yang, Rui,Jiang, Yu-Bo
, p. 109 - 113 (2016/01/25)
A facile synthesis of 1,4-disubstituted 1,2,3-triazoles was achieved from nitrobenzenes and terminal alkynes under mild conditions. The reactions were successful for nitrobenzenes and terminal alkynes bearing various functionalities, from which the 1,2,3-triazole derivatives were smoothly synthesized through a four-step one-pot sequence.
Synthesis of α-santonin derived acetyl santonous acid triazole derivatives and their bioevaluation for T and B-cell proliferation
Dangroo, Nisar A.,Singh, Jasvinder,Dar, Alamgir A.,Gupta, Nidhi,Chinthakindi, Praveen K.,Kaul, Anpurna,Khuroo, Mohmmed A.,Sangwan, Payare L.
, p. 160 - 169 (2016/05/24)
A new series of α-santonin derived acetyl santonous acid 1,2,3-triazole derivatives were synthesised using Huisgen 1,3-dipolar cyclo-addition reaction (click chemistry approach) and evaluated for their in vitro inhibition activity on concanavalin A (ConA) induced T cell proliferation and lipopolysaccharide (LPS) induced B cell proliferation. Among the synthesised series, compounds 2-10 and 19 exhibited significant inhibition against ConA and LPS stimulated T-cell and B-cell proliferation in a dose dependent manner. More significantly compounds 4, 9-10 and 19 exhibited potent inhibition activity with remarkably lower cytotoxicity on the mitogen-induced T cell and B cell proliferation at 1 μM concentration. The compound 6 displayed potent immunosuppressive effects with ～89% against LPS induced B-cell and ～83% against ConA stimulated T-cell proliferation at 100 μM concentration without cytotoxicity. Compound 10 was more selective against B cell proliferation and exhibited 81% and 69% suppression at 100 and 1 μM concentration respectively. The present study led to the identification of several santonin analogs with reduced cytotoxicity and strong inhibition activity against the cell proliferation induced by the mitogens.
Copper catalyzed synthesis of aryl azides from aryl bromides and sodium azide
Zeng, Ming,Yang, Yu Hua,Li, Jin Jing,Chen, Ying,Cui, Dong Mei,Zhang, Chen
, p. 1698 - 1700 (2015/03/04)
Aryl azides were synthesized using heterogeneous porous Cu catalyst via a coupling reaction of aryl bromides with sodium azide under mild conditions. The catalyst can be recycled in five times without significant loss of their catalytic activity.
Copper catalyzed synthesis of 1-aryl-1,2,3-triazoles from aryl iodides, alkynes, and sodium azide
Chen, Ying,Zhuo, Zi-Jian,Cui, Dong-Mei,Zhang, Chen
, p. 215 - 218 (2013/11/06)
Aryl azides were synthesized using heterogeneous porous Cu (0) catalyst via a coupling reaction of aryl iodides with sodium azide under mild conditions. Under the same conditions, one-pot Cu-catalyzed azide-alkyne cycloaddition of aryl iodides, alkynes, and sodium azide yielded 1-aryl-1,2,3-triazoles.
Rates of thermolysis of azidobenzenes in solution: Large stabilizations of transition states by charge transfer from electron-donor substituents
Dyall, Leonard K.,L'abbe, Gerrit,Dehaen, Wim
, p. 971 - 975 (2007/10/03)
Introduction of +R type para substituents into azidobenzenes causes very large increases in rate of thermolysis, up to 225-fold. The rates of nitrobenzene solutions at 120°C follow a Hammett-type linear free energy relationship log k = -5.44 - 2.33σ1 - 1.48R+ which indicates conjugative stabilization of a nitrene-like transition state. ortho-Substituents of the +R type causes still larger rate enhancements, up to 456-fold for 2-amino, which identify a special resonance proximity effect. It is suggested that the very high rates reported for such α-azidoheterocycles as 2-azidothiophene are due to similar resonance stabilizations and not to ring-opening concerted with nitrogen loss.
Involvement of Free Nitrenium Ions, Ion Pairs, and Preassociation Trapping in the Reactions of Ester Derivatives of N-Arylhydroxylamines and N-Arylhydroxamic Acids in Aqueous Solution
Novak, Michael,Kahley, Mary Jo,Lin, Jing,Kennedy, Sonya A.,James, Tishia G.
, p. 8294 - 8304 (2007/10/03)
Rate and product yield data for the decomposition of the ester derivatives of N-arylhydroxylamines and N-arylhydroxamic acids 1a-i in aqueous solution in the presence of N3- support a mechanistic scheme (Scheme 5) in which the trapping by N3- changes from trapping of the free ion, to trapping of an ion pair, to a preassociation process as the ion becomes more reactive.When the rate constant for trapping of the free ion by solvent, ks, 8 s-1, trapping by both N3- and solvent occurs almost exclusively at the free ion.When 108 s-1 s 10 s-1, a change in the mechanism occurs, and trapping of the ion pair by both solvent and N3- becomes important.In this range of reactivity there is also evidence, based on the apparent magnitude of kaz', the rate constant for N3- trapping of the ion pair, that some of the reaction with N3- occurs through a preassociation process.When ks > ca. 1010 s-1 essentially all of the observed N3- trapping occurs by a preassociation process because N3-, which cannot react with the ion pair faster than the diffusion limit, can no longer compete with solvent for the ion pair.This progression in trapping mechanisms as the ion becomes more reactive with solvent is apparently an important factor in determining the carcinogenic potential of aromatic amines and amides which are metabolized into sulfuric and carboxylic acid esters of N-arylhydroxylamines and N-arylhydroxamic acids.Nitrenium ions which undergo slow reactions with solvent are selectively trapped by biologically relevant nucleophiles such as 2'-deoxyguanosine.As the rate constant for reaction with solvent increases, the nitrenium ion is no longer capable of undergoing selective trapping by nonsolvent nucleophiles because these reactions are limited by diffusion, but solvent trapping is not.
