933-01-7Relevant academic research and scientific papers
Identification of the New Covalent Allosteric Binding Site of Fructose-1,6-bisphosphatase with Disulfiram Derivatives toward Glucose Reduction
Huang, Yunyuan,Xu, Yixiang,Song, Rongrong,Ni, Shuaishuai,Liu, Jiaqi,Xu, Yanhong,Ren, Yanliang,Rao, Li,Wang, Yingjie,Wei, Lin,Feng, Lingling,Su, Chen,Peng, Chao,Li, Jian,Wan, Jian
, p. 6238 - 6247 (2020)
Fructose 1,6-bisphosphatase (FBPase) has attracted substantial interest as a target associated with cancer and type 2 diabetes. Herein, we found that disulfiram and its derivatives can potently inhibit FBPase by covalently binding to a new C128 allosteric
Development of disulfide-derived fructose-1,6-bisphosphatase (FBPase) covalent inhibitors for the treatment of type 2 diabetes
Xu, Yi-xiang,Huang, Yun-yuan,Song, Rong-rong,Ren, Yan-liang,Chen, Xin,Zhang, Chao,Mao, Fei,Li, Xiao-kang,Zhu, Jin,Ni, Shuai-shuai,Wan, Jian,Li, Jian
, (2020/07/25)
Fructose-1,6-bisphosphatase (FBPase), as a key rate-limiting enzyme in the gluconeogenesis (GNG) pathway, represents a practical therapeutic strategy for type 2 diabetes (T2D). Our previous work first identified cysteine residue 128 (C128) was an important allosteric site in the structure of FBPase, while pharmacologically targeting C128 attenuated the catalytic ability of FBPase. Herein, ten approved cysteine covalent drugs were selected for exploring FBPase inhibitory activities, and the alcohol deterrent disulfiram displayed superior inhibitory efficacy among those drugs. Based on the structure of lead compound disulfiram, 58 disulfide-derived compounds were designed and synthesized for investigating FBPase inhibitory activities. Optimal compound 3a exhibited significant FBPase inhibition and glucose-lowering efficacy in vitro and in vivo. Furthermore, 3a covalently modified the C128 site, and then regulated the N125–S124–S123 allosteric pathway of FBPase in mechanism. In summary, 3a has the potential to be a novel FBPase inhibitor for T2D therapy.
Trichloroisocyanuric acid-promoted thiolation of phosphites by thiols
Chen, Yingying,Li, Meichao,Gong, Zhangshui,Shen, Zhenlu
, p. 19 - 27 (2020/08/06)
A simple and convenient method for the synthesis of thiophosphates by coupling of phosphites with thiols under mild conditions has been developed. The reactions were promoted by trichloroisocyanuric acid (TCCA) and were carried out at room temperature in
Interaction of difluoromethylene phosphobetaine with heteroatom-centered electrophiles
Trifonov, Alexey L.,Panferova, Liubov I.,Levin, Vitalij V.,Volodin, Alexander D.,Korlyukov, Alexander A.,Dilman, Alexander D.
, p. 78 - 82 (2019/03/19)
A series of difluorinated phosphonium salts were obtained by reaction of difluoromethylene phosphobetaine with halogenating reagents, as well as arylsulfenyl and arylselenyl chlorides. The reaction proceeds via decarboxylation of the phosphobetaine followed by trapping of the difluorinated phosphorus ylide by heteroatom-centered electrophiles. The crystal structures of the phosphonium salts were studied by X-ray diffraction analysis. For the salt containing the CF2I group and iodide counterion, the I?I interaction was identified in the solid state. The nature of this halogen bond was evaluated by quantum chemical calculations.
Synthetic method of aryl sulfur chlorine or aryl selenium chlorine
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Paragraph 0029-0032, (2019/06/27)
The invention discloses a synthetic method of aryl sulfur chlorine or aryl selenium chlorine. The synthetic method comprises the following steps that diaryl disulfide or diaryl diselenide II is dissolved in a solvent and reacts under the action of dichloro-iodobenzene III to obtain aryl sulfur chlorine or aryl selenium chlorine I. In the formula shown in the description, R refers to hydrogen, methyl or halogen, and Y refers to sulfur or selenium. The method has the advantages that the operation is simple, the raw materials are cheap and easy to obtain, the yield is relatively ideal and the cost is low.
In Situ Formation of RSCl/ArSeCl and Their Application to the Synthesis of 4-Chalcogenylisocumarins/Pyrones from o-(1-Alkynyl)benzoates and (Z)-2-Alken-4-ynoates
Xing, Linlin,Zhang, Yong,Li, Bing,Du, Yunfei
supporting information, p. 3620 - 3624 (2019/05/24)
The reaction of diorganyl disulfides or diselenides with PhICl2 in acetonitrile was found for the first time to lead to the in situ formation of organosulfenyl chloride or selenenyl chloride, which enables the regioselective intramolecular chalcogenylacyloxylation of alkynes resulting in the formation of 4-chalcogenylisocumarins/pyrones in good to excellent yields under metal-free conditions.
Unsymmetrical difunctionalization of cyclooctadiene under continuous flow conditions: Expanding the scope of ring opening metathesis polymerization
Shen, Xianwang,Gong, Honghong,Zhou, Yang,Zhao, Yucheng,Lin, Jun,Chen, Mao
, p. 1846 - 1853 (2018/02/23)
Functionalized cyclooctenes (FCOEs) are important monomers in ring-opening metathesis polymerization (ROMP). Herein, a new library of disubstituted FCOEs bearing adjacent heteroatoms were synthesized and applied in ROMP. To address the issues associated w
Generation of 1,2-oxathiolium ions from (arysulfonyl)- and (arylsulfinyl)allenes in Br?nsted acids. NMR and DFT study of these cations and their reactions
Lozovskiy, Stanislav V.,Ivanov, Alexander Yu.,Khoroshilova, Olesya V.,Vasilyev, Aleksander V.
, p. 2897 - 2906 (2018/12/13)
In strong Br?nsted acids (CF3SO3H, FSO3H, D2SO4), (arysulfonyl)allenes (ArSO2-CR1=C=CR2R3) and (arylsulfinyl)allenes (ArSO-CR1=C=CR2R3) undergo cyclization into the corresponding stable 1,2-oxathiolium ions, which were studied by means of NMR and DFT calculations. Quenching of solutions of these cations with low nucleophilic media, aqueous HCl, leads to their deprotonation with a stereoselective formation of (arysulfonyl)butadienes (for instance, ArSO2-CR1=C-C(Me)=CH2, for R2 = R3 = Me, yields of 87-98%). Reactions of (arysulfonyl)allenes in the system TfOH (0.1 equiv)-HFIP (hexafluoropropan-2-ol) followed by hydrolysis give rise to allyl alcohols (ArSO2-CR1=CH-C(OH)R2R3, yields of 78-99%). Reflux of solutions of (arysulfonyl)allenes in the presence of TfOH (1 equiv) in 1,2-dichlorobenzene leads to the cyclization into thiochromene 1,1-diox-ides in high yields. Under the action of TfOH or AlX3 (X = Cl, Br) followed by hydrolysis of reaction mixtures, (arylsulfinyl)allenes give allyl alcohols (ArSO2-CR1=CH-C(OH)R2R3). Plausible reaction mechanisms have been proposed for all studied reactions.
Generation of Oxazolidine-2,4-diones Bearing Sulfur-Substituted Quaternary Carbon Atoms by Oxothiolation/Cyclization of Ynamides
Huang, Hai,Fan, Junzhen,He, Guangke,Yang, Zhimin,Jin, Xiaodong,Liu, Qi,Zhu, Hongjun
supporting information, p. 2532 - 2538 (2016/02/12)
A novel method for metal-free oxothiolation of ynamides to construct oxazolidine-2,4-diones bearing sulfur-substituted quaternary carbon atoms has been developed. It represents a rare C-O bond cleavage of ynamides, as well as a facile and tandem approach for the formation of C-O, C-S, and C-Cl bonds. This redox-neutral protocol can be applied to the synthesis of multisubstituted oxazolidine-2,4-diones with good chemoselectivity and good yields of isolated products under mild conditions.
Formation of α-chalcogenyl acrylamides through unprecedented chalcogen-mediated metal-free oxyfunctionalization of ynamides with DMSO as an oxidant
Huang, Hai,Tang, Luning,Liu, Qi,Xi, Yang,He, Guangke,Zhu, Hongjun
supporting information, p. 5605 - 5608 (2016/05/09)
A novel chalcogen-mediated oxyfunctionalization mode of ynamides for the synthesis of α-chalcogenyl acrylamides has been developed. Independent of metal catalysts, external oxidants and additives, this mild process afforded a range of structurally diverse
