(4R,6R,9R,15R,17R,20R)-6,10,10,17,21,21-hexamethyl-11,22-dioxapentacyclo[12.8.0.03,12.04,9.015,20]docosa-1(14),3(12)-diene-2,13-dione | 1082067-65-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 乙烯酯类
• 英文名称: (4R,6R,9R,15R,17R,20R)-6,10,10,17,21,21-hexamethyl-11,22-dioxapentacyclo[12.8.0.03,12.04,9.015,20]docosa-1(14),3(12)-diene-2,13-dione
• CAS: 1082067-65-9
• 化学式: C₂₆H₃₆O₄
• 分子量: 412.569
• InChiKey: PREXAGWWLAMIAK-TYENPDHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  30
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (-)-香茅醛 、 2,5-二羟基-1,4-苯喹酮 在 ethylenediamine Tetraacetic Acid 作用下， 以 乙醇 为溶剂， 反应 0.37h， 以48.5%的产率得到(5S,8R,10S,15S,17S,20S)-4,4,8,17,21,21-hexamethyl-3,22-dioxapentacyclo[12.8.0.02,11.05,10.015,20]docosa-1(14),2(11)-diene-12,13-dione
  参考文献：
  名称：

  Bis-pyranobenzoquinones as a New Family of Reversal Agents of the Multidrug Resistance Phenotype Mediated by P-Glycoprotein in Mammalian Cells and the Protozoan Parasite Leishmania

  摘要：

  We have synthesized a set of bis-pyranobenzoquinones through a direct and highly efficient approach based on a double intramolecular domino Knoevenagel hetero Diels-Alder reaction. These bis-pyranobenzoquinone derivatives are compounds whose skeletons have similarities to those of some anticancerous and leishmanicidal drugs. Considering that these drugs are substrates for some members of the ATP-binding cassette (ABC) family of proteins that confers a multidrug resistance (MDR) phenotype, we have carried out the biological evaluation of 20 bis-pyranobenzoquinones as modulators of the MDR phenotype in mammalian cell lines overexpressing P-glycoprotein, MRP1, or BCRP. Moreover, we also tested some of these compounds as potential MDR modulators in a Leishmania tropica line overexpressing a P-glycoprotein-like transporter. Compounds 9 and 10 are, in this work, the most promising reversal agents of MDR in human cancer cell lines, while compounds 4 and 20 showed potent reversal activity of MDR phenotype in the protozoan parasite Leishmania.

  DOI：

  10.1021/jm800403b

文献信息

• Bis-pyranobenzoquinones as a New Family of Reversal Agents of the Multidrug Resistance Phenotype Mediated by P-Glycoprotein in Mammalian Cells and the Protozoan Parasite <i>Leishmania</i>
  作者：Sandra Jiménez-Alonso、Antonio L. Pérez-Lomas、Ana Estévez-Braun、Francisco Muñoz Martinez、Haydee Chávez Orellana、Angel G. Ravelo、Francisco Gamarro、Santiago Castanys、Matías López

  DOI：10.1021/jm800403b

  日期：2008.11.27

  We have synthesized a set of bis-pyranobenzoquinones through a direct and highly efficient approach based on a double intramolecular domino Knoevenagel hetero Diels-Alder reaction. These bis-pyranobenzoquinone derivatives are compounds whose skeletons have similarities to those of some anticancerous and leishmanicidal drugs. Considering that these drugs are substrates for some members of the ATP-binding cassette (ABC) family of proteins that confers a multidrug resistance (MDR) phenotype, we have carried out the biological evaluation of 20 bis-pyranobenzoquinones as modulators of the MDR phenotype in mammalian cell lines overexpressing P-glycoprotein, MRP1, or BCRP. Moreover, we also tested some of these compounds as potential MDR modulators in a Leishmania tropica line overexpressing a P-glycoprotein-like transporter. Compounds 9 and 10 are, in this work, the most promising reversal agents of MDR in human cancer cell lines, while compounds 4 and 20 showed potent reversal activity of MDR phenotype in the protozoan parasite Leishmania.