N-(1-benzyl-1H-indol-5-yl)(2-chlorophenyl)methanesulfonamide | 1026754-66-4

• 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-(1-benzyl-1H-indol-5-yl)(2-chlorophenyl)methanesulfonamide
• 英文别名: N-(1-benzylindol-5-yl)-1-(2-chlorophenyl)methanesulfonamide
• CAS: 1026754-66-4
• 化学式: C₂₂H₁₉ClN₂O₂S
• 分子量: 410.924
• InChiKey: QMZRZSBKTJMQOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  59.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (2-氯苯基)甲基磺酰氯 、 1-苄基-1H-吲哚-5-甲胺 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以80%的产率得到N-(1-benzyl-1H-indol-5-yl)(2-chlorophenyl)methanesulfonamide
  参考文献：
  名称：

  N-1H-Benzimidazol-5-ylbenzenesulfonamide derivatives as potent hPXR agonists

  摘要：

  The Human Pregnane X Receptor (hPXR) is a nuclear receptor that regulates the expression of phase I and phase II drug-metabolizing enzymes, as well as that of drug transporters. Because this receptor plays a critical role in protecting tissues from potentially toxic endo-and xenobiotics, highly active agonists could represent novel therapeutic tools in treating several human diseases. Using an in vitro screening reporter system that allow to characterize hPXR activators and a first step of chemical modifications of an original agonist ligand (C2BA-4, 1-(2-chlorophenyl)-N-[1-(1-phenylethyl)-1H-benzimidazol-5-yl] methanesulfonamide), we identified compounds with a N-1H-benzimidazol-5-ylbenzenesulfonamide scaffold as a potent family of hPXR agonists. Further chemical modi. cations allowed us to identify enhanced activators, notably N-(1-benzyl-1H-benzimidazol-5-yl)-2,3,4,5,6-pentamethylbenzenesulfonamide (6n) with an EC50 value in the subnanomolar range. Accordingly to their potent EC50, these compounds induced an efficient protection of hPXR against proteolytic digestion by trypsin even at very low ligand concentrations and were able to induce the expression of the main target genes of hPXR, CYP3A4 and CYP2B6, in primary cultures of human hepatocytes. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.02.020

文献信息

• N-1H-Benzimidazol-5-ylbenzenesulfonamide derivatives as potent hPXR agonists
  作者：Cindy Benod、Guy Subra、Virginie Nahoum、Aude Mallavialle、Jean-François Guichou、Julien Milhau、Samuel Roblés、William Bourguet、Jean-Marc Pascussi、Patrick Balaguer

  DOI：10.1016/j.bmc.2008.02.020

  日期：2008.4.1

  The Human Pregnane X Receptor (hPXR) is a nuclear receptor that regulates the expression of phase I and phase II drug-metabolizing enzymes, as well as that of drug transporters. Because this receptor plays a critical role in protecting tissues from potentially toxic endo-and xenobiotics, highly active agonists could represent novel therapeutic tools in treating several human diseases. Using an in vitro screening reporter system that allow to characterize hPXR activators and a first step of chemical modifications of an original agonist ligand (C2BA-4, 1-(2-chlorophenyl)-N-[1-(1-phenylethyl)-1H-benzimidazol-5-yl] methanesulfonamide), we identified compounds with a N-1H-benzimidazol-5-ylbenzenesulfonamide scaffold as a potent family of hPXR agonists. Further chemical modi. cations allowed us to identify enhanced activators, notably N-(1-benzyl-1H-benzimidazol-5-yl)-2,3,4,5,6-pentamethylbenzenesulfonamide (6n) with an EC50 value in the subnanomolar range. Accordingly to their potent EC50, these compounds induced an efficient protection of hPXR against proteolytic digestion by trypsin even at very low ligand concentrations and were able to induce the expression of the main target genes of hPXR, CYP3A4 and CYP2B6, in primary cultures of human hepatocytes. (C) 2008 Elsevier Ltd. All rights reserved.