14575-10-1Relevant academic research and scientific papers
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
A metal free chlorothiolation strategy for synthesis of vinyl sulfides from internal alkynoates
Surineni, Naresh,Buragohain, Pori,Saikia, Bishwajit,Barua, Nabin C.,Baruah, Rajani K.
supporting information, p. 6965 - 6969 (2015/11/27)
A metal free chlorothiolation approach has been developed for conversion of internal alkynoates to vinyl sulfides and also utilized mild PIDA mediated oxidation to yield the corresponding sulfoxides.
Novel pyrrolobenzoxaboroles: Design, synthesis, and biological evaluation against Trypanosoma brucei
Wu, Puhua,Zhang, Jiong,Meng, Qingqing,Nare, Bakela,Jacobs, Robert T.,Zhou, Huchen
, p. 59 - 75 (2014/06/09)
Human African trypanosomiasis is a fatal parasitic infection caused by the protozoan Trypanosoma brucei. The development of novel antitrypanosomal agents is urgently needed. Here we report the synthesis and structure-activity relationship of a new class of benzoxaboroles as antitrypanosomal agents. These compounds showed antiparasitic IC50 values ranging from 4.02 to 0.03 μg/mL and satisfactory cytotoxicity profile. Three of the lead compounds were demonstrated to cure the parasitic infection in a murine acute infection model. The structure-activity relationship of the pyrrolobenzoxaboroles are also discussed.
The Reaction of 9-(2',3'-Dideoxy-β-D-glycero-pent-2-Enofuranosyl)-adenine Derivatives with Arene- and Alkenesulfenyl Chlorides. An Unusual Ring Opening Reaction of Thiiranium Ions
Welch, C. J.,Bazin, H.,Chattopadhyaya, J.
, p. 343 - 357 (2007/10/02)
A series of arenesulfenyl chlorides and methanesulfenyl chloride were reacted in pyridine solution with 6-N-dibenzoyl-9-(2',3'-dideoxy-β-D-glycero-pent-2-enofuranosyl)adenine (1b).In each case, the relative abundance of isomeric β-chloroarene/alkene sulfides was estimated and used to assess the relative thermodynamic stabilities of the lyxo and ribo thiiranium ion intermediates and their steric susceptibilities to attack by nucleophile (Cl-).Subsequently, the β-chloroarene/alkene sulfides 8a-d to 13 a-d, upon alkaline treatment, underwent an unprecedented ylide-mediated β elimination of the intermediary lyxo and ribo thiiranium ions, to give only 2'-ene-thiol ethers 14-19.
Antidiabetic furancarboxylic and thiphenecarboxylic acids
-
, (2008/06/13)
Compounds of the structure STR1 wherein Z is oxygen or sulfur; R is (C1 -C2)alkoxy; phenoxy; benzyl; phenylthiomethyl; phenylthio; phenylthio monosubstituted in the 2-, 3- or 4-position with (C1 -C3)alkyl, pheny
Antidiabetic pyrrolecarboxylic acids
-
, (2008/06/13)
Certain pyrrolecarboxylic and pyrroleacetic acid derivatives substituted on the pyrrole ring with thioether groups, acyl groups, phenyl, substituted phenyl, phenoxy, substituted phenoxy, benzyl or halo and optionally substituted on the pyrrole nitrogen with alkyl, and the pharmaceutically acceptable salts thereof, are useful in lowering the blood glucose levels of hyperglycemic animals.
