1,13-bis[4-(3-benzyloxy-4H-chromen-4-on-2-yl)phenyl]-1,4,10,13-tetraoxa-7-azatridecane | 1346227-02-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 1,13-bis[4-(3-benzyloxy-4H-chromen-4-on-2-yl)phenyl]-1,4,10,13-tetraoxa-7-azatridecane
• 英文别名: 2-[4-[2-[2-[2-[2-[4-(4-Oxo-3-phenylmethoxychromen-2-yl)phenoxy]ethoxy]ethylamino]ethoxy]ethoxy]phenyl]-3-phenylmethoxychromen-4-one；2-[4-[2-[2-[2-[2-[4-(4-oxo-3-phenylmethoxychromen-2-yl)phenoxy]ethoxy]ethylamino]ethoxy]ethoxy]phenyl]-3-phenylmethoxychromen-4-one
• CAS: 1346227-02-8
• 化学式: C₅₂H₄₇NO₁₀
• 分子量: 845.946
• InChiKey: XMJXZCIKAHQGOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.7
• 重原子数：
  63
• 可旋转键数：
  22
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  1,13-bis[4-(3-benzyloxy-4H-chromen-4-on-2-yl)phenyl]-7-(tert-butyloxycarbonyl)-1,4,10,13-tetraoxa-7-azatridecane 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以93%的产率得到1,13-bis[4-(3-benzyloxy-4H-chromen-4-on-2-yl)phenyl]-1,4,10,13-tetraoxa-7-azatridecane
  参考文献：
  名称：

  Amine Linked Flavonoid Dimers as Modulators for P-Glycoprotein-Based Multidrug Resistance: Structure–Activity Relationship and Mechanism of Modulation

  摘要：

  Here we report a great improvement in reversal potency of cancer drug resistance when flavonoid dimers possess a functionally substituted aminopolyethylene glycol linker. The most potent compound, 18, contains a N-benzyl group at the linker. It has many advantages including (1) high potencies in reversing P-glycoprotein (P-gp) mediated resistance in LCC6MDR cells to various anticancer drugs with EC50 in the nanomolar range, (2) low toxicity and high therapeutic index, and (3) preferential inhibition of P-gp over multidrug resistance protein 1 and breast cancer resistance protein. Compound 18 stimulates P-gp-ATPase activity by 2.7-fold and mediates a dose-dependent inhibition of doxorubicin (DOX) transport activity. Lineweaver-Burk and Dixon plots suggest that 18 is a competitive inhibitor to DOX in binding to P-gp with a K-i of 0.28-0.34 mu M and a Hill coefficient of 1.17. Moreover, the LCC6MDR cell displays about 2.1-fold lower intracellular accumulation of 18 compared to the wild type, suggesting that 18 is a P-gp substrate as well.

  DOI：

  10.1021/jm201121b

文献信息

• Amine Linked Flavonoid Dimers as Modulators for P-Glycoprotein-Based Multidrug Resistance: Structure–Activity Relationship and Mechanism of Modulation
  作者：Kin-Fai Chan、Iris L. K. Wong、Jason W. Y. Kan、Clare S. W. Yan、Larry M. C. Chow、Tak Hang Chan

  DOI：10.1021/jm201121b

  日期：2012.3.8

  Here we report a great improvement in reversal potency of cancer drug resistance when flavonoid dimers possess a functionally substituted aminopolyethylene glycol linker. The most potent compound, 18, contains a N-benzyl group at the linker. It has many advantages including (1) high potencies in reversing P-glycoprotein (P-gp) mediated resistance in LCC6MDR cells to various anticancer drugs with EC50 in the nanomolar range, (2) low toxicity and high therapeutic index, and (3) preferential inhibition of P-gp over multidrug resistance protein 1 and breast cancer resistance protein. Compound 18 stimulates P-gp-ATPase activity by 2.7-fold and mediates a dose-dependent inhibition of doxorubicin (DOX) transport activity. Lineweaver-Burk and Dixon plots suggest that 18 is a competitive inhibitor to DOX in binding to P-gp with a K-i of 0.28-0.34 mu M and a Hill coefficient of 1.17. Moreover, the LCC6MDR cell displays about 2.1-fold lower intracellular accumulation of 18 compared to the wild type, suggesting that 18 is a P-gp substrate as well.