2-((4-bromophenyl)disulfanyl)thiazole

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-((4-bromophenyl)disulfanyl)thiazole
• 英文别名: acs.jmedchem.1c00409_ST.339；2-[(4-bromophenyl)disulfanyl]-1,3-thiazole
• 化学式: C₉H₆BrNS₃
• 分子量: 304.255
• InChiKey: KQZVIMICGAXAJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  91.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-溴苯硫酚 在 磺酰氯 、 乙醚 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 13.0h， 生成 2-((4-bromophenyl)disulfanyl)thiazole
  参考文献：
  名称：

  Development of disulfide-derived fructose-1,6-bisphosphatase (FBPase) covalent inhibitors for the treatment of type 2 diabetes

  摘要：

  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. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112500

文献信息

• Discovery of unsymmetrical aromatic disulfides as novel inhibitors of SARS-CoV main protease: Chemical synthesis, biological evaluation, molecular docking and 3D-QSAR study
  作者：Li Wang、Bo-Bo Bao、Guo-Qing Song、Cheng Chen、Xu-Meng Zhang、Wei Lu、Zefang Wang、Yan Cai、Shuang Li、Sheng Fu、Fu-Hang Song、Haitao Yang、Jian-Guo Wang

  DOI：10.1016/j.ejmech.2017.05.045

  日期：2017.9

  outbreak of severe acute respiratory syndrome (SARS) in 2003 had caused a high rate of mortality. Main protease (Mpro) of SARS-associated coronavirus (SARS-CoV) is an important target to discover pharmaceutical compounds for the therapy of this life-threatening disease. During the course of screening new anti-SARS agents, we have identified that a series of unsymmetrical aromatic disulfides inhibited SARS-CoV

  2003年，世界范围内的严重急性呼吸道综合症（SARS）爆发导致了很高的死亡率。SARS相关冠状病毒（SARS-CoV）的主要蛋白酶（M pro）是发现用于治疗这种威胁生命的疾病的药物的重要靶标。在筛选新的抗SARS药物的过程中，我们发现一系列不对称的芳香族二硫化物首次显着抑制了SARS-CoV M pro。本文中，化学合成了40种新型不对称芳族二硫化物，并在体外评估了它们对SARS-CoV M pro的生物学活性。这些新型化合物显示出优异的IC 50数据范围为0.516–5.954μM。初步研究表明，这些二硫化物是可逆的和竞争性抑制剂。通过分子对接模拟生成了可能的结合模式，并构建了一个比较场分析（CoMFA）模型来理解结构-活性关系。因此，本研究为设计和鉴定具有全新化学结构的抗SARS药物提供了有意义的指导。
• Development of disulfide-derived fructose-1,6-bisphosphatase (FBPase) covalent inhibitors for the treatment of type 2 diabetes
  作者：Yi-xiang Xu、Yun-yuan Huang、Rong-rong Song、Yan-liang Ren、Xin Chen、Chao Zhang、Fei Mao、Xiao-kang Li、Jin Zhu、Shuai-shuai Ni、Jian Wan、Jian Li

  DOI：10.1016/j.ejmech.2020.112500

  日期：2020.10

  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. (C) 2020 Elsevier Masson SAS. All rights reserved.