3,3'-dibromo-4,4'-dimethoxy-5,6,5',6'-bis(methylenedioxy)-biphenyl-2,2'-dimethanol | 1377829-25-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 单宁
• 英文名称: 3,3'-dibromo-4,4'-dimethoxy-5,6,5',6'-bis(methylenedioxy)-biphenyl-2,2'-dimethanol
• 英文别名: [6-Bromo-4-[6-bromo-5-(hydroxymethyl)-7-methoxy-1,3-benzodioxol-4-yl]-7-methoxy-1,3-benzodioxol-5-yl]methanol
• CAS: 1377829-25-8
• 化学式: C₁₈H₁₆Br₂O₈
• 分子量: 520.128
• InChiKey: ROCOSVNAHDFLFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  95.8
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3,3'-dibromo-4,4'-dimethoxy-5,6,5',6'-bis(methylenedioxy)-biphenyl-2,2'-dimethanol 、 苯甲酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 (3,3'-dibromo-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2,2'-diyl)bis(methylene) dibenzoate
  参考文献：
  名称：

  Antitumor Agents. 293. Nontoxic Dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylenedioxybiphenyl-2,2′-dicarboxylate (DDB) Analogues Chemosensitize Multidrug-Resistant Cancer Cells to Clinical Anticancer Drugs

  摘要：

  Novel dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybipheny1-2,2'-dicarboxylate (DDB) analogues were designed and synthesized to improve their chemo-sensitizing action on KBvin (vincristine-resistant nasopharyngeal carcinoma) cells, a multidrug resistant cell line overexpressing P-glycoprotein (P-gp). Structure-activity relationship analysis showed that aromatic and bulky aliphatic side chains at the 2,2'-positions effectively and significantly sensitized P-gp overexpressing multidrug resistant (MDR) cells to anticancer drugs, such as paclitaxel (TAX), vincristine (VCR), and doxorubicin (DOX). DDB derivatives 16 and 23 showed 5-10 times more effective reversal ability than verapamil (VRP) for TAX and VCR. Analogue 6 also exhibited five times greater chemosensitizing effect against DOX than VRP. Importantly, no cytotoxicity was observed by the active DDB analogues against both non-MDR and MDR cells, suggesting that DDB analogues serve as novel lead compounds for the development of chemosensitizers to overcome the MDR phenotype. The mechanism of action studies demonstrated that effective inhibition of P-glycoprotein by DDB analogues dramatically elevated the cellular concentration of anticancer drugs.

  DOI：

  10.1021/jm300378k
• 作为产物：
  描述：

  联苯双酯 在 溴 、 二异丁基氢化铝 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 生成 3,3'-dibromo-4,4'-dimethoxy-5,6,5',6'-bis(methylenedioxy)-biphenyl-2,2'-dimethanol
  参考文献：
  名称：

  Antitumor Agents. 293. Nontoxic Dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylenedioxybiphenyl-2,2′-dicarboxylate (DDB) Analogues Chemosensitize Multidrug-Resistant Cancer Cells to Clinical Anticancer Drugs

  摘要：

  Novel dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybipheny1-2,2'-dicarboxylate (DDB) analogues were designed and synthesized to improve their chemo-sensitizing action on KBvin (vincristine-resistant nasopharyngeal carcinoma) cells, a multidrug resistant cell line overexpressing P-glycoprotein (P-gp). Structure-activity relationship analysis showed that aromatic and bulky aliphatic side chains at the 2,2'-positions effectively and significantly sensitized P-gp overexpressing multidrug resistant (MDR) cells to anticancer drugs, such as paclitaxel (TAX), vincristine (VCR), and doxorubicin (DOX). DDB derivatives 16 and 23 showed 5-10 times more effective reversal ability than verapamil (VRP) for TAX and VCR. Analogue 6 also exhibited five times greater chemosensitizing effect against DOX than VRP. Importantly, no cytotoxicity was observed by the active DDB analogues against both non-MDR and MDR cells, suggesting that DDB analogues serve as novel lead compounds for the development of chemosensitizers to overcome the MDR phenotype. The mechanism of action studies demonstrated that effective inhibition of P-glycoprotein by DDB analogues dramatically elevated the cellular concentration of anticancer drugs.

  DOI：

  10.1021/jm300378k

文献信息

• Antitumor Agents. 293. Nontoxic Dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylenedioxybiphenyl-2,2′-dicarboxylate (DDB) Analogues Chemosensitize Multidrug-Resistant Cancer Cells to Clinical Anticancer Drugs
  作者：Hsin-Yi Hung、Emika Ohkoshi、Masuo Goto、Kenneth F. Bastow、Kyoko Nakagawa-Goto、Kuo-Hsiung Lee

  DOI：10.1021/jm300378k

  日期：2012.6.14

  Novel dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybipheny1-2,2'-dicarboxylate (DDB) analogues were designed and synthesized to improve their chemo-sensitizing action on KBvin (vincristine-resistant nasopharyngeal carcinoma) cells, a multidrug resistant cell line overexpressing P-glycoprotein (P-gp). Structure-activity relationship analysis showed that aromatic and bulky aliphatic side chains at the 2,2'-positions effectively and significantly sensitized P-gp overexpressing multidrug resistant (MDR) cells to anticancer drugs, such as paclitaxel (TAX), vincristine (VCR), and doxorubicin (DOX). DDB derivatives 16 and 23 showed 5-10 times more effective reversal ability than verapamil (VRP) for TAX and VCR. Analogue 6 also exhibited five times greater chemosensitizing effect against DOX than VRP. Importantly, no cytotoxicity was observed by the active DDB analogues against both non-MDR and MDR cells, suggesting that DDB analogues serve as novel lead compounds for the development of chemosensitizers to overcome the MDR phenotype. The mechanism of action studies demonstrated that effective inhibition of P-glycoprotein by DDB analogues dramatically elevated the cellular concentration of anticancer drugs.