4-((2-氯-5-硝基苯基)磺酰基)吗啉 | 40833-68-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-((2-氯-5-硝基苯基)磺酰基)吗啉
• 中文别名: 4-[(2-氯-5-硝基苯)磺酰基]吗啉
• 英文名称: 4-((2-chloro-5-nitrophenyl)sulfonyl)morpholine
• 英文别名: 4-(2-chloro-5-nitrophenyl)sulfonylmorpholine
• CAS: 40833-68-9
• 化学式: C₁₀H₁₁ClN₂O₅S
• mdl: MFCD00654510
• 分子量: 306.727
• InChiKey: HZUSSXQFEXYNEA-UHFFFAOYSA-N

物化性质

• 沸点：
  476.7±55.0 °C(Predicted)
• 密度：
  1.536±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  4-((2-氯-5-硝基苯基)磺酰基)吗啉 在 氯化铵 、 三乙胺 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 2-chloro-N-(4-chloro-3-(morpholinosulfonyl)phenyl)acetamide
  参考文献：
  名称：

  Development of Benzenesulfonamide Derivatives as Potent Glutathione Transferase Omega-1 Inhibitors

  摘要：

  Glutathione transferase omega-1 (GSTO1-1) is an enzyme whose function supports the activation of interleukin (IL)-1 beta and IL-18 that are implicated in a variety of inflammatory disease states for which small-molecule inhibitors are sought. The potent reactivity of the active-site cysteine has resulted in reported inhibitors that act by covalent labeling. In this study, structure-activity relationship (SAR) elaboration of the reported GSTO1-1 inhibitor C1-27 was undertaken. Compounds were evaluated for inhibitory activity toward purified recombinant GSTO1-1 and for indicators of target engagement in cell-based assays. As covalent inhibitors, the k(inact)/K-I values of selected compounds were determined, as well as in vivo pharmacokinetics analysis. Cocrystal structures of key novel compounds in complex with GSTO1-1 were also solved. This study represents the first application of a biochemical assay for GSTO1-1 to determine k(inact)/K-I values for tested inhibitors and the most extensive set of cell-based data for a GSTO1-1 inhibitor SAR series reported to date. Our research culminated in the discovery of 25, which we propose as the preferred biochemical tool to interrogate cellular responses to GSTO1-1 inhibition.

  DOI：

  10.1021/acs.jmedchem.9b01391
• 作为产物：
  描述：

  2-氯-5-硝基苯磺酸 在 氯化亚砜 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 生成 4-((2-氯-5-硝基苯基)磺酰基)吗啉
  参考文献：
  名称：

  Development of Benzenesulfonamide Derivatives as Potent Glutathione Transferase Omega-1 Inhibitors

  摘要：

  Glutathione transferase omega-1 (GSTO1-1) is an enzyme whose function supports the activation of interleukin (IL)-1 beta and IL-18 that are implicated in a variety of inflammatory disease states for which small-molecule inhibitors are sought. The potent reactivity of the active-site cysteine has resulted in reported inhibitors that act by covalent labeling. In this study, structure-activity relationship (SAR) elaboration of the reported GSTO1-1 inhibitor C1-27 was undertaken. Compounds were evaluated for inhibitory activity toward purified recombinant GSTO1-1 and for indicators of target engagement in cell-based assays. As covalent inhibitors, the k(inact)/K-I values of selected compounds were determined, as well as in vivo pharmacokinetics analysis. Cocrystal structures of key novel compounds in complex with GSTO1-1 were also solved. This study represents the first application of a biochemical assay for GSTO1-1 to determine k(inact)/K-I values for tested inhibitors and the most extensive set of cell-based data for a GSTO1-1 inhibitor SAR series reported to date. Our research culminated in the discovery of 25, which we propose as the preferred biochemical tool to interrogate cellular responses to GSTO1-1 inhibition.

  DOI：

  10.1021/acs.jmedchem.9b01391

文献信息

• US3957860A
  申请人：——

  公开号：US3957860A

  公开（公告）日：1976-05-18
• Development of Benzenesulfonamide Derivatives as Potent Glutathione Transferase Omega-1 Inhibitors
  作者：Yiyue Xie、Padmaja Tummala、Aaron J. Oakley、Girdhar Singh Deora、Yuji Nakano、Melissa Rooke、Matthew E. Cuellar、Jessica M. Strasser、Jayme L. Dahlin、Michael A. Walters、Marco G. Casarotto、Philip G. Board、Jonathan B. Baell

  DOI：10.1021/acs.jmedchem.9b01391

  日期：2020.3.26

  Glutathione transferase omega-1 (GSTO1-1) is an enzyme whose function supports the activation of interleukin (IL)-1 beta and IL-18 that are implicated in a variety of inflammatory disease states for which small-molecule inhibitors are sought. The potent reactivity of the active-site cysteine has resulted in reported inhibitors that act by covalent labeling. In this study, structure-activity relationship (SAR) elaboration of the reported GSTO1-1 inhibitor C1-27 was undertaken. Compounds were evaluated for inhibitory activity toward purified recombinant GSTO1-1 and for indicators of target engagement in cell-based assays. As covalent inhibitors, the k(inact)/K-I values of selected compounds were determined, as well as in vivo pharmacokinetics analysis. Cocrystal structures of key novel compounds in complex with GSTO1-1 were also solved. This study represents the first application of a biochemical assay for GSTO1-1 to determine k(inact)/K-I values for tested inhibitors and the most extensive set of cell-based data for a GSTO1-1 inhibitor SAR series reported to date. Our research culminated in the discovery of 25, which we propose as the preferred biochemical tool to interrogate cellular responses to GSTO1-1 inhibition.