N-[4-(hydroxymethyl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide | 932032-90-1

• 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: N-[4-(hydroxymethyl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide
• CAS: 932032-90-1
• 化学式: C₁₅H₁₄F₃NO₃S
• 分子量: 345.342
• InChiKey: GNQJQTSRHDQFTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-[4-(hydroxymethyl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以85%的产率得到N-(4-formylphenyl)-N-(2,2,2-trifluoroethyl)benzenesulfonamide
  参考文献：
  名称：

  Crystal structure of the PXR–T1317 complex provides a scaffold to examine the potential for receptor antagonism

  摘要：

  The human pregnane X receptor (PXR) recognizes a range of structurally and chemically distinct ligands and plays a key role in regulating the expression of protective gene products involved in the metabolism and excretion of potentially harmful compounds. The identification and development of PXR antagonists is desirable as a potential way to control the up-regulation of drug metabolism pathways during the therapeutic treatment of disease. We present the 2.8 angstrom resolution crystal structure of the PXR ligand binding domain (LBD) in complex with T0901317 (T 1317), which is also an agonist of another member of the orphan class of the nuclear receptor superfamily, the liver X receptor (LXR). In spite of differences in the size and shape of the receptors' ligand binding pockets, key interactions with this ligand are conserved between human PXR and human LXR. Based on the PXR-T1317 structure, analogues of T 1317 were generated with the goal of designing an PXR antagonist effective via the receptor's ligand binding pocket. We find that selectivity in activating PXR versus LXR was achieved; such compounds may be useful in addressing neurodegenerative diseases like Niemann-Pick C. We were not successful, however, in producing a PXR antagonist. Based on these observations, we conclude that the generation of PXR antagonists targeted to the ligand binding pocket may be difficult due to the promiscuity and structural conformability of this xenobiotic sensor. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.026
• 作为产物：
  描述：

  对氨基苯甲醇 在 吡啶 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 N-[4-(hydroxymethyl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide
  参考文献：
  名称：

  Crystal structure of the PXR–T1317 complex provides a scaffold to examine the potential for receptor antagonism

  摘要：

  The human pregnane X receptor (PXR) recognizes a range of structurally and chemically distinct ligands and plays a key role in regulating the expression of protective gene products involved in the metabolism and excretion of potentially harmful compounds. The identification and development of PXR antagonists is desirable as a potential way to control the up-regulation of drug metabolism pathways during the therapeutic treatment of disease. We present the 2.8 angstrom resolution crystal structure of the PXR ligand binding domain (LBD) in complex with T0901317 (T 1317), which is also an agonist of another member of the orphan class of the nuclear receptor superfamily, the liver X receptor (LXR). In spite of differences in the size and shape of the receptors' ligand binding pockets, key interactions with this ligand are conserved between human PXR and human LXR. Based on the PXR-T1317 structure, analogues of T 1317 were generated with the goal of designing an PXR antagonist effective via the receptor's ligand binding pocket. We find that selectivity in activating PXR versus LXR was achieved; such compounds may be useful in addressing neurodegenerative diseases like Niemann-Pick C. We were not successful, however, in producing a PXR antagonist. Based on these observations, we conclude that the generation of PXR antagonists targeted to the ligand binding pocket may be difficult due to the promiscuity and structural conformability of this xenobiotic sensor. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.026

文献信息

• Crystal structure of the PXR–T1317 complex provides a scaffold to examine the potential for receptor antagonism
  作者：Yu Xue、Esther Chao、William J. Zuercher、Timothy M. Willson、Jon L. Collins、Matthew R. Redinbo

  DOI：10.1016/j.bmc.2006.12.026

  日期：2007.3

  The human pregnane X receptor (PXR) recognizes a range of structurally and chemically distinct ligands and plays a key role in regulating the expression of protective gene products involved in the metabolism and excretion of potentially harmful compounds. The identification and development of PXR antagonists is desirable as a potential way to control the up-regulation of drug metabolism pathways during the therapeutic treatment of disease. We present the 2.8 angstrom resolution crystal structure of the PXR ligand binding domain (LBD) in complex with T0901317 (T 1317), which is also an agonist of another member of the orphan class of the nuclear receptor superfamily, the liver X receptor (LXR). In spite of differences in the size and shape of the receptors' ligand binding pockets, key interactions with this ligand are conserved between human PXR and human LXR. Based on the PXR-T1317 structure, analogues of T 1317 were generated with the goal of designing an PXR antagonist effective via the receptor's ligand binding pocket. We find that selectivity in activating PXR versus LXR was achieved; such compounds may be useful in addressing neurodegenerative diseases like Niemann-Pick C. We were not successful, however, in producing a PXR antagonist. Based on these observations, we conclude that the generation of PXR antagonists targeted to the ligand binding pocket may be difficult due to the promiscuity and structural conformability of this xenobiotic sensor. (c) 2006 Elsevier Ltd. All rights reserved.