5-(2-bromo-1-hydroxyethyl)-2-chloro-N,N-dimethylbenzenesulfonamide | 59816-01-2

• 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: 5-(2-bromo-1-hydroxyethyl)-2-chloro-N,N-dimethylbenzenesulfonamide
• 英文别名: 2-bromo-1-(4-chloro-3-dimethylsulfamoylphenyl)-ethanol
• CAS: 59816-01-2
• 化学式: C₁₀H₁₃BrClNO₃S
• 分子量: 342.641
• InChiKey: LFDMRYCZXABFFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(2-bromo-1-hydroxyethyl)-2-chloro-N,N-dimethylbenzenesulfonamide 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 24.0h， 以30%的产率得到2-chloro-N,N-dimethyl-5-(oxiran-2-yl)benzenesulfonamide
  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：

  4-chloro-3-(N,N-dimethylsulfamoyl)benzoic acid 在 吡啶 、 sodium tetrahydroborate 、 氯化亚砜 、 N,N-二甲基甲酰胺 、 copper(ll) bromide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 氯仿 、 乙酸乙酯 为溶剂， 生成 5-(2-bromo-1-hydroxyethyl)-2-chloro-N,N-dimethylbenzenesulfonamide
  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

• Thiazolidine derivatives
  申请人：Hoechst Aktiengesellschaft

  公开号：US04061761A1

  公开（公告）日：1977-12-06

  The invention relates to thiazolidine derivatives having in 4-position a hydroxy group and a 3'-sulphamyl-phenyl substituent, in 2-position an imino group and in 1-position an aliphatic or cycloaliphatic substituent. Said thiazolidines have diuretic activity. The invention also relates to a process for the manufacture of said compounds.

  本发明涉及在4位具有羟基和3'-磺酰氨基-苯基取代基，在2位具有亚氨基，在1位具有脂肪族或环脂肪族取代基的噻唑烷衍生物。所述噻唑烷具有利尿活性。本发明还涉及制造所述化合物的方法。
• US4061761A
  申请人：——

  公开号：US4061761A

  公开（公告）日：1977-12-06
• US4125614A
  申请人：——

  公开号：US4125614A

  公开（公告）日：1978-11-14