2-(3,4-dimethoxy-phenyl)-5-{[2-(4-hydroxy-phenyl)-ethyl]-methyl-amino}-2-isopropyl-pentanenitrile | 1246457-17-9

• 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: 2-(3,4-dimethoxy-phenyl)-5-{[2-(4-hydroxy-phenyl)-ethyl]-methyl-amino}-2-isopropyl-pentanenitrile
• 英文别名: 2-(3,4-Dimethoxyphenyl)-5-[2-(4-hydroxyphenyl)ethyl-methylamino]-2-propan-2-ylpentanenitrile
• CAS: 1246457-17-9
• 化学式: C₂₅H₃₄N₂O₃
• 分子量: 410.557
• InChiKey: YFDUPXJIAHNMMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  65.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(3,4-dimethoxy-phenyl)-5-{[2-(4-hydroxy-phenyl)-ethyl]-methyl-amino}-2-isopropyl-pentanenitrile 在 氨 、 碘 作用下， 以 乙腈 为溶剂， 反应 48.0h， 以41%的产率得到2-(3,4-dimethoxy-phenyl)-5-{[2-(4-hydroxy-3,5-diiodophenyl)-ethyl]-methyl-amino}-2-isopropyl-pentanenitrile
  参考文献：
  名称：

  Iodination of verapamil for a stronger induction of death, through GSH efflux, of cancer cells overexpressing MRP1

  摘要：

  The multidrug resistance protein 1 (MRP1), involved in multidrug resistance (MDR) of cancer cells, was found to be modulated by verapamil, through stimulation of GSH transport, leading to apoptosis of MRP1-overexpressing cells. In this study, various iodinated derivatives of verapamil were synthesized, including iodination on the B ring, known to be involved in verapamil cardiotoxicity, and assayed for the stimulation of GSH efflux by MRP1. The iodination, for nearly all compounds, led to a higher stimulation of GSH efflux. However, determination of concomitant cytotoxicity is also important for selecting the best compound, which was found to be 10-fold more potent than verapamil. This will then allow us to design original anti-cancer compounds which could specifically kill the resistant cancer cells. (C) 2010 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2010.07.031
• 作为产物：
  描述：

  methanesulfonic acid 2-(4-ethoxycarbonyloxy-phenyl)-ethyl ester 、 N-甲基-4-(3,4-二甲氧基苯基)-4-氰基-5-己基甲胺 在 碳酸氢钠 、 potassium iodide 、 盐酸 、 氨 作用下， 以 甲醇 、 水 为溶剂， 反应 72.0h， 以30%的产率得到2-(3,4-dimethoxy-phenyl)-5-{[2-(4-hydroxy-phenyl)-ethyl]-methyl-amino}-2-isopropyl-pentanenitrile
  参考文献：
  名称：

  Iodination of verapamil for a stronger induction of death, through GSH efflux, of cancer cells overexpressing MRP1

  摘要：

  The multidrug resistance protein 1 (MRP1), involved in multidrug resistance (MDR) of cancer cells, was found to be modulated by verapamil, through stimulation of GSH transport, leading to apoptosis of MRP1-overexpressing cells. In this study, various iodinated derivatives of verapamil were synthesized, including iodination on the B ring, known to be involved in verapamil cardiotoxicity, and assayed for the stimulation of GSH efflux by MRP1. The iodination, for nearly all compounds, led to a higher stimulation of GSH efflux. However, determination of concomitant cytotoxicity is also important for selecting the best compound, which was found to be 10-fold more potent than verapamil. This will then allow us to design original anti-cancer compounds which could specifically kill the resistant cancer cells. (C) 2010 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2010.07.031

文献信息

• Iodination of verapamil for a stronger induction of death, through GSH efflux, of cancer cells overexpressing MRP1
  作者：Régis Barattin、Thomas Perrotton、Doriane Trompier、Doriane Lorendeau、Attilio Di Pietro、Amaury du Moulinet d’Hardemare、Hélène Baubichon-Cortay

  DOI：10.1016/j.bmc.2010.07.031

  日期：2010.9

  The multidrug resistance protein 1 (MRP1), involved in multidrug resistance (MDR) of cancer cells, was found to be modulated by verapamil, through stimulation of GSH transport, leading to apoptosis of MRP1-overexpressing cells. In this study, various iodinated derivatives of verapamil were synthesized, including iodination on the B ring, known to be involved in verapamil cardiotoxicity, and assayed for the stimulation of GSH efflux by MRP1. The iodination, for nearly all compounds, led to a higher stimulation of GSH efflux. However, determination of concomitant cytotoxicity is also important for selecting the best compound, which was found to be 10-fold more potent than verapamil. This will then allow us to design original anti-cancer compounds which could specifically kill the resistant cancer cells. (C) 2010 Published by Elsevier Ltd.