N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)-N-((1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)benzenesulfonamide

• 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-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)-N-((1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)benzenesulfonamide
• 英文别名: N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-[[1-(4-nitrophenyl)triazol-4-yl]methyl]benzenesulfonamide
• 化学式: C₂₄H₁₇F₆N₅O₅S
• 分子量: 601.486
• InChiKey: YBQDFKDUAPYQKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  41
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  143
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  2-(4-氨基苯)-1,1,1,3,3,3-六氟-2-丙醇 在 吡啶 、 copper(ll) sulfate pentahydrate 、 potassium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium ascorbate 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 、 叔丁醇 为溶剂， 反应 21.0h， 生成 N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)-N-((1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)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.