N-(4-acetylphenyl)-N-(2,2,2-trifluoroethyl)benzenesulfonamide | 932032-94-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(4-acetylphenyl)-N-(2,2,2-trifluoroethyl)benzenesulfonamide
• CAS: 932032-94-5
• 化学式: C₁₆H₁₄F₃NO₃S
• 分子量: 357.353
• InChiKey: SLRAFPZKYWAAMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  62.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(4-acetylphenyl)-N-(2,2,2-trifluoroethyl)benzenesulfonamide 在 乙烯基溴化镁 作用下， 以 四氢呋喃 为溶剂， 以30 mg的产率得到N-[4-(1-hydroxyethyl)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
• 作为产物：
  描述：

  4-氨基苯乙酮 在 吡啶 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 11.0h， 生成 N-(4-acetylphenyl)-N-(2,2,2-trifluoroethyl)benzenesulfonamide
  参考文献：
  名称：

  Functional induction of P-glycoprotein efflux pump by phenyl benzenesulfonamides: Synthesis and biological evaluation of T0901317 analogs

  摘要：

  N-(2,2,2-Trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyll-benzenesulfo- namide (T0901317, 6) is a potent activator of pregnane-X-receptor (PXR), which is a nuclear receptor controlling P-gp expression. Herein, we aimed to investigate P-gp induction activity of T0901317 and establish its structure-activity relationship. T0901317 along with a series of N-triazolyl-methylene-linked benzenesulfonamides were synthesized and screened for P-gp induction activity using a rhodamine-123 based efflux assay in the P-gp overexpressing human adenocarcinoma LS-180 cells, wherein several compounds showed potent P-gp induction activity at 5 mu M. Treatment with benzene sulphonamides led to the decrease in intracellular accumulation of a fluorescent P-gp substrate rhodamine-123 up to 48% (control 100%). In the western-blot studies, T0901317 (6) and its triazole linked analog 26e at 5 displayed induction of P-gp expression in LS180 cells. These compounds were non-toxic in LS-180 and human neuroblastoma SH-SY5Y cells (IC50 > 50 mu M). The compound 26e showed significant P-gp induction even at 0.3 mu M, indicating an excellent therapeutic window. These results clearly indicate promise of this class of compounds as potential agents to enhance amyloid-beta clearance in Alzheimers patients. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.07.005

文献信息

• Functional induction of P-glycoprotein efflux pump by phenyl benzenesulfonamides: Synthesis and biological evaluation of T0901317 analogs
  作者：Anil K. Padala、Abubakar Wani、Ram A. Vishwakarma、Ajay Kumar、Sandip B. Bharate

  DOI：10.1016/j.ejmech.2016.07.005

  日期：2016.10

  N-(2,2,2-Trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyll-benzenesulfo- namide (T0901317, 6) is a potent activator of pregnane-X-receptor (PXR), which is a nuclear receptor controlling P-gp expression. Herein, we aimed to investigate P-gp induction activity of T0901317 and establish its structure-activity relationship. T0901317 along with a series of N-triazolyl-methylene-linked benzenesulfonamides were synthesized and screened for P-gp induction activity using a rhodamine-123 based efflux assay in the P-gp overexpressing human adenocarcinoma LS-180 cells, wherein several compounds showed potent P-gp induction activity at 5 mu M. Treatment with benzene sulphonamides led to the decrease in intracellular accumulation of a fluorescent P-gp substrate rhodamine-123 up to 48% (control 100%). In the western-blot studies, T0901317 (6) and its triazole linked analog 26e at 5 displayed induction of P-gp expression in LS180 cells. These compounds were non-toxic in LS-180 and human neuroblastoma SH-SY5Y cells (IC50 > 50 mu M). The compound 26e showed significant P-gp induction even at 0.3 mu M, indicating an excellent therapeutic window. These results clearly indicate promise of this class of compounds as potential agents to enhance amyloid-beta clearance in Alzheimers patients. (C) 2016 Elsevier Masson SAS. All rights reserved.
• 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.