1,16-bis[4-((5-benzyloxy-7-methoxymethoxy)-4H-chromen-4-on-2-yl)phenyl]-1,4,7,10,13,16-hexaoxahexadecane | 916330-73-9

• 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: 1,16-bis[4-((5-benzyloxy-7-methoxymethoxy)-4H-chromen-4-on-2-yl)phenyl]-1,4,7,10,13,16-hexaoxahexadecane
• CAS: 916330-73-9
• 化学式: C₅₈H₅₈O₁₆
• 分子量: 1011.09
• InChiKey: HRBLSUWEJHTQIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.88
• 重原子数：
  74.0
• 可旋转键数：
  31.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  171.18
• 氢给体数：
  0.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  1,16-bis[4-((5-benzyloxy-7-methoxymethoxy)-4H-chromen-4-on-2-yl)phenyl]-1,4,7,10,13,16-hexaoxahexadecane 在 palladium on activated charcoal 氢气 作用下， 以 氯仿 为溶剂， 反应 12.0h， 以84%的产率得到1,16-bis[4-((5-hydroxy-7-methoxymethoxy)-4H-chromen-4-on-2-yl)phenyl]-1,4,7,10,13,16-hexaoxahexadecane
  参考文献：
  名称：

  Flavonoid Dimers as Bivalent Modulators for P-Glycoprotein-Based Multidrug Resistance:  Synthetic Apigenin Homodimers Linked with Defined-Length Poly(ethylene glycol) Spacers Increase Drug Retention and Enhance Chemosensitivity in Resistant Cancer Cells

  摘要：

  Much effort has been spent on searching for better P-glycoprotein- ( P-gp-) based multidrug resistance ( MDR) modulators. Our approach was to target the binding sites of P-gp using dimers of dietary flavonoids. A series of apigenin-based flavonoid dimers, linked by poly( ethylene glycol) chains of various lengths, have been synthesized. These flavonoid dimers modulate drug chemosensitivity and retention in breast and leukemic MDR cells with the optimal number of ethylene glycol units equal to 2-4. Compound 9d bearing four ethylene glycol units increased drug accumulation in drug-resistant cells and enhanced cytotoxicity of paclitaxel, doxorubicin, daunomycin, vincristine, and vinblastine in drug- resistant breast cancer and leukemia cells in vitro, resulting in reduction of IC50 by 5-50 times. This compound also stimulated P-gp's ATPase activity by 3.3-fold. Its modulating activity was presumably by binding to the substrate binding sites of P-gp and disrupting drug efflux.

  DOI：

  10.1021/jm060593+
• 作为产物：
  描述：

  1-[2-羟基-4,6-双(甲氧基甲氧基)苯基]乙酮,2',4'-双(甲氧基甲氧基)-6'-羟基苯乙酮 在 氢氧化钾 、 四(三苯基膦)钯 、 potassium carbonate 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 27.0h， 生成 1,16-bis[4-((5-benzyloxy-7-methoxymethoxy)-4H-chromen-4-on-2-yl)phenyl]-1,4,7,10,13,16-hexaoxahexadecane
  参考文献：
  名称：

  Flavonoid Dimers as Bivalent Modulators for P-Glycoprotein-Based Multidrug Resistance:  Synthetic Apigenin Homodimers Linked with Defined-Length Poly(ethylene glycol) Spacers Increase Drug Retention and Enhance Chemosensitivity in Resistant Cancer Cells

  摘要：

  Much effort has been spent on searching for better P-glycoprotein- ( P-gp-) based multidrug resistance ( MDR) modulators. Our approach was to target the binding sites of P-gp using dimers of dietary flavonoids. A series of apigenin-based flavonoid dimers, linked by poly( ethylene glycol) chains of various lengths, have been synthesized. These flavonoid dimers modulate drug chemosensitivity and retention in breast and leukemic MDR cells with the optimal number of ethylene glycol units equal to 2-4. Compound 9d bearing four ethylene glycol units increased drug accumulation in drug-resistant cells and enhanced cytotoxicity of paclitaxel, doxorubicin, daunomycin, vincristine, and vinblastine in drug- resistant breast cancer and leukemia cells in vitro, resulting in reduction of IC50 by 5-50 times. This compound also stimulated P-gp's ATPase activity by 3.3-fold. Its modulating activity was presumably by binding to the substrate binding sites of P-gp and disrupting drug efflux.

  DOI：

  10.1021/jm060593+