2-(3,4-dimethoxy-phenyl)-5-{[3-(4-hydroxy-phenyl)-propyl]-methyl-amino}-2-isopropyl-pentanenitrile | 1246457-19-1

• 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: 2-(3,4-dimethoxy-phenyl)-5-{[3-(4-hydroxy-phenyl)-propyl]-methyl-amino}-2-isopropyl-pentanenitrile
• 英文别名: 2-(3,4-Dimethoxyphenyl)-5-[3-(4-hydroxyphenyl)propyl-methylamino]-2-propan-2-ylpentanenitrile
• CAS: 1246457-19-1
• 化学式: C₂₆H₃₆N₂O₃
• 分子量: 424.583
• InChiKey: YMYZOCBBTKXUKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  31
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 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-{[3-(4-hydroxy-phenyl)-propyl]-methyl-amino}-2-isopropyl-pentanenitrile 在 氨 、 碘 作用下， 以 乙腈 为溶剂， 反应 48.0h， 以27%的产率得到2-(3,4-dimethoxy-phenyl)-5-{[3-(4-hydroxy-3-iodophenyl)-propyl]-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 3-(4-ethoxycarbonyloxy-phenyl)-propyl 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33%的产率得到2-(3,4-dimethoxy-phenyl)-5-{[3-(4-hydroxy-phenyl)-propyl]-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.