[(R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methyl] 9-[1-[9-[(R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]-9-oxononyl]triazol-4-yl]nonanoate | 1383809-59-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 金鸡纳生物碱
• 英文名称: [(R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methyl] 9-[1-[9-[(R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]-9-oxononyl]triazol-4-yl]nonanoate
• CAS: 1383809-59-3
• 化学式: C₆₀H₇₉N₇O₆
• 分子量: 994.331
• InChiKey: KAILNJQNHIGTNA-VWTKTFGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.7
• 重原子数：
  73
• 可旋转键数：
  30
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  134
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  (1R)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl 9-azidononanoate 、 (1R)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl undec-10-ynoate 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 12.0h， 生成 [(R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methyl] 9-[1-[9-[(R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]-9-oxononyl]triazol-4-yl]nonanoate
  参考文献：
  名称：

  Click chemistry-derived bivalent quinine inhibitors of P-glycoprotein-mediated cellular efflux

  摘要：

  P-glycoprotein (P-gp) effluxes a diverse set of drug substrates out of cells in an ATP dependent manner, thereby limiting the effective accumulation of therapeutic agents. Herein we demonstrate the use of click chemistry to rapidly generate bivalent quinine dimers, containing an intervening triazole ring, as potential inhibitors of P-gp mediated efflux. Calcein-AM substrate accumulation assays were performed in an MCF7/DX1 cell line that overexpresses P-gp to monitor the inhibitory activity of the clicked quinine dimers. A small library of potent P-gp inhibitors with varying tether lengths is reported, with the best dimer demonstrating low micromolar efficacy. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.125

文献信息

• Click chemistry-derived bivalent quinine inhibitors of P-glycoprotein-mediated cellular efflux
  作者：Jerrin Kuriakose、Christine A. Hrycyna、Jean Chmielewski

  DOI：10.1016/j.bmcl.2012.04.125

  日期：2012.7

  P-glycoprotein (P-gp) effluxes a diverse set of drug substrates out of cells in an ATP dependent manner, thereby limiting the effective accumulation of therapeutic agents. Herein we demonstrate the use of click chemistry to rapidly generate bivalent quinine dimers, containing an intervening triazole ring, as potential inhibitors of P-gp mediated efflux. Calcein-AM substrate accumulation assays were performed in an MCF7/DX1 cell line that overexpresses P-gp to monitor the inhibitory activity of the clicked quinine dimers. A small library of potent P-gp inhibitors with varying tether lengths is reported, with the best dimer demonstrating low micromolar efficacy. (C) 2012 Elsevier Ltd. All rights reserved.