N-(2-((1-(4-(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-4-methoxybenzamide | 1610804-88-0

• 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-(2-((1-(4-(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-4-methoxybenzamide
• 英文别名: N-[2-[[1-[4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]phenyl]triazol-4-yl]methoxy]phenyl]-4-methoxybenzamide
• CAS: 1610804-88-0
• 化学式: C₃₆H₃₇N₅O₅
• 分子量: 619.72
• InChiKey: SWZYKVPIUGCFSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  46
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-硝基-2-丙炔-2-氧基苯 在 铁粉 、 氯化铵 、 copper(II) sulfate 、 sodium ascorbate 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 27.5h， 生成 N-(2-((1-(4-(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-4-methoxybenzamide
  参考文献：
  名称：

  Discovery of Novel P-Glycoprotein-Mediated Multidrug Resistance Inhibitors Bearing Triazole CoreviaClick Chemistry

  摘要：

  A novel series of P‐glycoprotein (P‐gp)‐mediated multidrug resistance (MDR) inhibitors bearing a triazol‐phenethyl‐tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 5 showed a comparable activity with the known potent P‐gp inhibitor WK‐X‐34 with lower cytotoxicity (IC50s > 100 μm). Compared with VRP, compound 5 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 5 persisted longer chemo‐sensitizing effect (>24 h) than VRP (<6 h) with reversibility. Given the low intrinsic cytotoxicity and the potent reversal activity, compound 5 may represent a promising candidate for developing P‐gp‐mediated MDR inhibitor.

  DOI：

  10.1111/cbdd.12301

文献信息

• Discovery of Novel P-Glycoprotein-Mediated Multidrug Resistance Inhibitors Bearing Triazole Core<i>via</i>Click Chemistry
  作者：Baomin Liu、Qianqian Qiu、Tianxiao Zhao、Lei Jiao、Jianyu Hou、Yunman Li、Hai Qian、Wenlong Huang

  DOI：10.1111/cbdd.12301

  日期：2014.8

  A novel series of P‐glycoprotein (P‐gp)‐mediated multidrug resistance (MDR) inhibitors bearing a triazol‐phenethyl‐tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 5 showed a comparable activity with the known potent P‐gp inhibitor WK‐X‐34 with lower cytotoxicity (IC50s > 100 μm). Compared with VRP, compound 5 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 5 persisted longer chemo‐sensitizing effect (>24 h) than VRP (<6 h) with reversibility. Given the low intrinsic cytotoxicity and the potent reversal activity, compound 5 may represent a promising candidate for developing P‐gp‐mediated MDR inhibitor.