(5R,14S,19R,28S)-11,22-dibromo-4,4,29,29-tetramethyl-3,7,26,30-tetraoxaheptacyclo[16.12.0.02,15.05,14.08,13.019,28.020,25]triaconta-1(18),2(15),8(13),9,11,20(25),21,23-octaene-16,17-dione | 1082067-71-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (5R,14S,19R,28S)-11,22-dibromo-4,4,29,29-tetramethyl-3,7,26,30-tetraoxaheptacyclo[16.12.0.02,15.05,14.08,13.019,28.020,25]triaconta-1(18),2(15),8(13),9,11,20(25),21,23-octaene-16,17-dione
• CAS: 1082067-71-7
• 化学式: C₃₀H₂₆Br₂O₆
• 分子量: 642.341
• InChiKey: SOKWXPCDOOBVMZ-MTIDIVMFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  38
• 可旋转键数：
  0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,5-二羟基-1,4-苯喹酮 、 5-bromo-2-(3-methylbut-2-enyloxy)-benzaldehyde 在 ethylenediamine Tetraacetic Acid 作用下， 以 乙醇 为溶剂， 反应 0.42h， 以38.4%的产率得到(5R,14S,19S,28R)-11,22-dibromo-4,4,29,29-tetramethyl-3,7,26,30-tetraoxaheptacyclo[16.12.0.02,15.05,14.08,13.019,28.020,25]triaconta-1(18),2(15),8(13),9,11,20(25),21,23-octaene-16,17-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.