74243-85-9Relevant academic research and scientific papers
Benchtop-Stabssle Hypervalent Bromine(III) Compounds: Versatile Strategy and Platform for Air- And Moisture-Stable λ3-Bromanes
Miyamoto, Kazunori,Saito, Motomichi,Tsuji, Shunsuke,Takagi, Taisei,Shiro, Motoo,Uchiyama, Masanobu,Ochiai, Masahito
supporting information, p. 9327 - 9331 (2021/07/01)
We present the first synthesis of air/moisture-stable λ3-bromanes (9and10) by using a cyclic 1,2-benzbromoxol-3-one (BBX) strategy. X-ray crystallography and NMR and IR spectroscopy ofN-triflylimino-λ3-bromane (12) revealed that the bromine(III) center is effectively stabilized by intramolecular R-Br-O hypervalent bonding. This strategy enables the synthesis of a variety of air-, moisture-, and benchtop-stable Br-hydroxy, -acetoxy, -alkynyl, -aryl, and bis[(trifluoromethyl)sulfonyl]methylide λ3-bromane derivatives.
2,3-EPOXY SUCCINYL DERIVATIVE, PREPARATION METHOD THEREFOR, AND USES THEREOF
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Paragraph 0220; 0221; 0222, (2019/01/17)
The present invention relates to a 2,3-epoxy succinyl derivative, a preparation method and a use thereof, in particular, the present invention relates to a compound represented by Formula (1), a racemate or an optical isomer thereof, a solvate thereof, or
Approaching an experimental electron density model of the biologically active trans-epoxysuccinyl amide group—Substituent effects vs. crystal packing
Shi, Ming W.,Stewart, Scott G.,Sobolev, Alexandre N.,Dittrich, Birger,Schirmeister, Tanja,Luger, Peter,Hesse, Malte,Chen, Yu-Sheng,Spackman, Peter R.,Spackman, Mark A.,Grabowsky, Simon
, (2017/10/17)
The trans-epoxysuccinyl amide group as a biologically active moiety in cysteine protease inhibitors such as loxistatin acid E64c has been used as a benchmark system for theoretical studies of environmental effects on the electron density of small active i
Design, synthesis, and structure–activity relationship study of epoxysuccinyl–peptide derivatives as cathepsin B inhibitors
Zhang, Xiaoye,Yang, Xiaohong,Wang, Hongqiang,Li, Song,Guo, Kun,Jiang, Dan,Xiao, Junhai,Liang, Di
, p. 1240 - 1246 (2017/08/09)
Cathepsin B is a lysosomal cysteine protease involved in many diseases. The present research demonstrates that derivatives of epoxysuccinyl–peptide are effective and selective cathepsin B inhibitors. We synthesized a series of epoxysuccinyl–peptide deriva
Cysteine protease inhibitors and uses thereof
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Page/Page column 39, (2016/08/29)
The invention provides for novel cysteine protease inhibitors and compositions comprising novel cysteine protease derivatives. The invention further provides for methods for treatment of neurodegenerative diseases comprising administration novel cysteine
2, 3-Butanediamide Epoxide Compound and Preparation Method and Use Thereof
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Paragraph 0161, (2016/05/19)
Provided are a compound of formula I which can be used as a drug against small RNA virus infections, and optical isomers, pharmaceutically acceptable salts, solvates or hydrates thereof. Also provided are the preparation method of the compound, the method for using the compound for treating bacterial infections and the use of the compound in the preparation of a drug for preventing and/or treating viral diseases caused by small RNA viruses.
Design, synthesis, and optimization of novel epoxide incorporating peptidomimetics as selective calpain inhibitors
Schiefer, Isaac T.,Tapadar, Subhasish,Litosh, Vladislav,Siklos, Marton,Scism, Rob,Wijewickrama, Gihani T.,Chandrasena, Esala P.,Sinha, Vaishali,Tavassoli, Ehsan,Brunsteiner, Michael,Fa', Mauro,Arancio, Ottavio,Petukhov, Pavel,Thatcher, Gregory R. J.
supporting information, p. 6054 - 6068 (2013/09/02)
Hyperactivation of the calcium-dependent cysteine protease calpain 1 (Cal1) is implicated as a primary or secondary pathological event in a wide range of illnesses and in neurodegenerative states, including Alzheimer's disease (AD). E-64 is an epoxide-containing natural product identified as a potent nonselective, calpain inhibitor, with demonstrated efficacy in animal models of AD. By use of E-64 as a lead, three successive generations of calpain inhibitors were developed using computationally assisted design to increase selectivity for Cal1. First generation analogues were potent inhibitors, effecting covalent modification of recombinant Cal1 catalytic domain (Cal1cat), demonstrated using LC-MS/MS. Refinement yielded second generation inhibitors with improved selectivity. Further library expansion and ligand refinement gave three Cal1 inhibitors, one of which was designed as an activity-based protein profiling probe. These were determined to be irreversible and selective inhibitors by kinetics studies comparing full length Cal1 with the general cysteine protease papain.
Design, synthesis, and screen of cathepsin K inhibitors
Yu, Ying-Ying,Sun, Wei,Dong, Lei,Liu, Hai-Dong,Jiang, Dan,Xiao, Jun-Hai,Yang, Xiao-Hong,Li, Song
, p. 715 - 718 (2013/07/26)
We synthesized a series of epoxysuccinic acid derivatives and evaluated their in vitro cathepsin K inhibitory activity The screening results show that the potency of compounds 9e, 9d, 9p, 9j and 9k (IC50 ≤ 0.005 μmol/L) were equal to or greater than that of the lead compound 9a. Less hydrophobic compounds showed weaker potency, which can be explained by the hydrophobic nature of the cathepsin K binding pockets.
3-Fluoroaspartate and pyruvoyl-dependant aspartate decarboxylase: Exploiting the unique characteristics of fluorine to probe reactivity and binding
De Villiers, Jandre,Koekemoer, Lizbe,Strauss, Erick
experimental part, p. 10030 - 10041 (2011/01/13)
Fluorine-containing amino acids have been used with great success as mechanism-based inhibitors of pyridoxal phosphate (PLP)-dependent enzymes, and the influence of fluorine on the conformation of molecules has also been extensively studied and practically exploited. In this study, we sought to use these unique characteristics to probe the reactivity and binding of aspartate decarboxylase (ADC) enzymes, which are members of the small class of pyruvoyl-dependant decarboxylases. Since ADC activity has been shown to be essential to the virulence of Mycobacterium tuberculosis, information gained in this manner could be used for the development of inhibitors that selectively target pyruvoyl-dependent enzymes such as ADC, without affecting PLP-dependent enzymes in the host. For this purpose, we synthesized the L-erythro and L-threo isomers of 3-fluoroaspartate and tested their ability to act as substrates and/or inhibitors of the M. tuberculosis and Escherichia coli ADC enzymes. Trapping and MS-based binding analysis was additionally used to confirm that both isomers enter the enzymes' active sites. Our studies show that both isomers undergo single turnover decarboxylation and fluorine elimination reactions to give enamine products that can be trapped within the active site. Interestingly, the enamine/ADC complex that forms from the lerythro (but not the L-threo) isomer is sufficiently stable that it can be observed even without any trapping. This finding suggests that the two 3-fluoroaspartates maintain different conformations within the ADC active site, which leads to the enamine products with configurations of different stabilities. Taken together, our results provide new insights for the development of cofactor-specific inhibitors, and confirm the utility of fluorine as a unique tool for probing reactivity and binding profiles within enzymes.
Two-step labeling of endogenous enzymatic activities by Diels-Alder ligation
Willems, Lianne I.,Verdoes, Martijn,Florea, Bogdan I.,Van Der Marel, Gijsbert A.,Overkleeft, Herman S.
experimental part, p. 1769 - 1781 (2011/04/18)
A ligation strategy based on the Diels-Alder [4+2] cycloaddition for the two-step activity-based labeling of endogenously expressed enzymes in complex biological samples has been developed. A panel of four diene-derivatized proteasome probes was synthesized, along with a dienophile-functionalized BODIPY(TMR) tag. These probes were applied in a Diels-Alder labeling procedure that enabled us to label active proteasome β-subunits selectively in cellular extracts and in living cells. We were also able to label the activity of cysteine proteases in cell extracts by utilizing a diene-derivatized cathepsin probe. Importantly, the Diels-Alder strategy described here is fully orthogonal with respect to the Staudinger-Bertozzi ligation, as demonstrated by the independent labeling of different proteolytic activities by the two methods in a single experiment.
