1,13-bis[4-(4H-chromen-4-on-2-yl)phenyl]-7-(3,4,5-trifluorobenzyl)-1,4,10,13-tetraoxa-7-azatridecane | 1346227-28-8

• 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-(4H-chromen-4-on-2-yl)phenyl]-7-(3,4,5-trifluorobenzyl)-1,4,10,13-tetraoxa-7-azatridecane
• 英文别名: 1,13-bis[4'-(4H-chromen-4-on-2-yl)phenyl]-7-(3,4,5-trifluorobenzyl)-1,4,10,13-tetraoxa-7-azatridecane；2-[4-[2-[2-[2-[2-[4-(4-Oxochromen-2-yl)phenoxy]ethoxy]ethyl-[(3,4,5-trifluorophenyl)methyl]amino]ethoxy]ethoxy]phenyl]chromen-4-one；2-[4-[2-[2-[2-[2-[4-(4-oxochromen-2-yl)phenoxy]ethoxy]ethyl-[(3,4,5-trifluorophenyl)methyl]amino]ethoxy]ethoxy]phenyl]chromen-4-one
• CAS: 1346227-28-8
• 化学式: C₄₅H₃₈F₃NO₈
• 分子量: 777.794
• InChiKey: JEULJLJVJVTBJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  57
• 可旋转键数：
  18
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  92.8
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  4-羟基黄烷酮 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 7.0h， 生成 1,13-bis[4-(4H-chromen-4-on-2-yl)phenyl]-7-(3,4,5-trifluorobenzyl)-1,4,10,13-tetraoxa-7-azatridecane
  参考文献：
  名称：

  [EN] FLAVONOID DIMERS AND THEIR USE
  [FR] DIMÈRES FLAVONOÏDES ET LEURS APPLICATIONS

  摘要：

  这项发明涉及到公式为黄酮素-连接子-Y-连接子-黄酮素的双黄酮类化合物，它们的合成以及在化疗和原虫感染中抑制多药耐药性的用途。

  公开号：

  WO2011137516A1

文献信息

• [EN] FLAVONOID DIMERS AND THEIR USE<br/>[FR] DIMÈRES FLAVONOÏDES ET LEURS APPLICATIONS
  申请人：UNIV MCGILL

  公开号：WO2011137516A1

  公开（公告）日：2011-11-10

  This invention relates to bis-flavonoid compounds of formula Flavonoid-Linker-Y-Linker-Flavonoid, their synthesis and use for inhibiting multidrug resistance in chemotherapy and protozoan infection.

  这项发明涉及到公式为黄酮素-连接子-Y-连接子-黄酮素的双黄酮类化合物，它们的合成以及在化疗和原虫感染中抑制多药耐药性的用途。
• 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.