2-(4-(4-((4-isopropylphenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-(4-((4-isopropylphenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 6,7-dimethoxy-2-[2-[4-[4-[(4-propan-2-ylphenoxy)methyl]triazol-1-yl]phenyl]ethyl]-3,4-dihydro-1H-isoquinoline
• 化学式: C₃₁H₃₆N₄O₃
• 分子量: 512.652
• InChiKey: KALANPZFAKSAHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  61.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-异丙基苯酚 在 Cu⁽²⁺⁾*CuO₄^(2-) 、 potassium carbonate 、 sodium ascorbate 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 4.0h， 生成 2-(4-(4-((4-isopropylphenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Design, synthesis and biological evaluation of LBM-A5 derivatives as potent P-glycoprotein-mediated multidrug resistance inhibitors

  摘要：

  A novel series of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) inhibitors with triazol-N-phenethyl-tetrahydroisoquinoline or triazol-N-ethyl-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 4 showed a comparable activity with the known potent P-gp inhibitor WK-X-34 with lower cytotoxicity toward K562 cells (IC50 > 100 mu M). Compared with VRP, compound 4 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 4 could significantly reverse MDR in a dose-dependent manner and also persist longer chemo-sensitizing effect than VRP with reversibility. Further mechanism studies revealed that compound 4 could remarkably increase the intracellular accumulation of Adriamycin (ADM) in K562/A02 cells as well as inhibit rhodamine-123 (Rh123) efflux from the cells. These results suggested that compound 4 may represent a promising candidate for developing P-gp-mediated MDR inhibitors. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.03.065

文献信息

• Design, synthesis and biological evaluation of LBM-A5 derivatives as potent P-glycoprotein-mediated multidrug resistance inhibitors
  作者：Yuxiang Wu、Miaobo Pan、Yuxuan Dai、Baomin Liu、Jian Cui、Wei Shi、Qianqian Qiu、Wenlong Huang、Hai Qian

  DOI：10.1016/j.bmc.2016.03.065

  日期：2016.5

  A novel series of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) inhibitors with triazol-N-phenethyl-tetrahydroisoquinoline or triazol-N-ethyl-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 4 showed a comparable activity with the known potent P-gp inhibitor WK-X-34 with lower cytotoxicity toward K562 cells (IC50 > 100 mu M). Compared with VRP, compound 4 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 4 could significantly reverse MDR in a dose-dependent manner and also persist longer chemo-sensitizing effect than VRP with reversibility. Further mechanism studies revealed that compound 4 could remarkably increase the intracellular accumulation of Adriamycin (ADM) in K562/A02 cells as well as inhibit rhodamine-123 (Rh123) efflux from the cells. These results suggested that compound 4 may represent a promising candidate for developing P-gp-mediated MDR inhibitors. (C) 2016 Elsevier Ltd. All rights reserved.