ethyl-2-(5-chloropyridin-3-yloxy)-5-(2,4-dichlorophenylsulfonamido)benzoate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl-2-(5-chloropyridin-3-yloxy)-5-(2,4-dichlorophenylsulfonamido)benzoate
• 英文别名: ethyl 5-(2,4-dichlorobenzene-sulfonamido)-2-(3-chloro-5-pyridyloxy)benzoate；Ethyl 2-(5-chloropyridin-3-yl)oxy-5-[(2,4-dichlorophenyl)sulfonylamino]benzoate
• 化学式: C₂₀H₁₅Cl₃N₂O₅S
• 分子量: 501.774
• InChiKey: FQFGYISGVMGYTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl-2-(5-chloropyridin-3-yloxy)-5-(2,4-dichlorophenylsulfonamido)benzoate 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 生成 2-(5-Chloropyridin-3-yl)oxy-5-[(2,4-dichlorophenyl)sulfonylamino]benzoic acid
  参考文献：
  名称：

  Discovery of INT131: A selective PPARγ modulator that enhances insulin sensitivity

  摘要：

  PPAR gamma is a member of the nuclear hormone receptor family and plays a key role in the regulation of glucose homeostasis. This Letter describes the discovery of a novel chemical class of diarylsulfonamide partial agonists that act as selective PPAR gamma modulators (SPPAR gamma Ms) and display a unique pharmacological profile compared to the thiazolidinedione (TZD) class of PPAR gamma full agonists. Herein we report the initial discovery of partial agonist 4 and the structure-activity relationship studies that led to the selection of clinical compound INT131 (3), a potent PPAR gamma partial agonist that displays robust glucose-lowering activity in rodent models of diabetes while exhibiting a reduced side-effects profile compared to marketed TZDs. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.058
• 作为产物：
  描述：

  2-氯-5-硝基苯甲酸乙酯 在 吡啶 、 tin(II) chloride dihdyrate 、 caesium carbonate 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl-2-(5-chloropyridin-3-yloxy)-5-(2,4-dichlorophenylsulfonamido)benzoate
  参考文献：
  名称：

  Discovery of INT131: A selective PPARγ modulator that enhances insulin sensitivity

  摘要：

  PPAR gamma is a member of the nuclear hormone receptor family and plays a key role in the regulation of glucose homeostasis. This Letter describes the discovery of a novel chemical class of diarylsulfonamide partial agonists that act as selective PPAR gamma modulators (SPPAR gamma Ms) and display a unique pharmacological profile compared to the thiazolidinedione (TZD) class of PPAR gamma full agonists. Herein we report the initial discovery of partial agonist 4 and the structure-activity relationship studies that led to the selection of clinical compound INT131 (3), a potent PPAR gamma partial agonist that displays robust glucose-lowering activity in rodent models of diabetes while exhibiting a reduced side-effects profile compared to marketed TZDs. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.058

文献信息

• PPARgamma modulators
  申请人：Tularik Inc.

  公开号：US20010027200A1

  公开（公告）日：2001-10-04

  Modulators of PPAR&ggr; activity are provided which are useful in pharmaceutical compositions and methods for the treatment of conditions such as type II diabetes and obesity.

  提供了PPAR&ggr;活性的调节剂，这些调节剂在制药组合物和治疗2型糖尿病和肥胖等疾病的方法中非常有用。
• PPAR-GAMMA MODULATORS
  申请人：TULARIK, INC.

  公开号：EP1053227A1

  公开（公告）日：2000-11-22
• US6200995B1
  申请人：——

  公开号：US6200995B1

  公开（公告）日：2001-03-13
• US6620827B2
  申请人：——

  公开号：US6620827B2

  公开（公告）日：2003-09-16
• US7439242B2
  申请人：——

  公开号：US7439242B2

  公开（公告）日：2008-10-21