Methyl 6-bromo-4-(6-bromo-7-methoxy-5-methoxycarbonyl-1,3-benzodioxol-4-yl)-7-methoxy-1,3-benzodioxole-5-carboxylate | 114370-82-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 单宁
• 英文名称: Methyl 6-bromo-4-(6-bromo-7-methoxy-5-methoxycarbonyl-1,3-benzodioxol-4-yl)-7-methoxy-1,3-benzodioxole-5-carboxylate
• CAS: 114370-82-0
• 化学式: C₂₀H₁₆Br₂O₁₀
• 分子量: 576.149
• InChiKey: YVRFIROLGABNBD-UHFFFAOYSA-N

物化性质

• 沸点：
  632.2±55.0 °C(predicted)
• 密度：
  1.728±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  Methyl 6-bromo-4-(6-bromo-7-methoxy-5-methoxycarbonyl-1,3-benzodioxol-4-yl)-7-methoxy-1,3-benzodioxole-5-carboxylate 在 4-二甲氨基吡啶 、 二异丁基氢化铝 、 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 作用下， 以 氯仿 为溶剂， 生成 Methyl 6-bromo-4-(6-bromo-7-methoxy-5-methoxycarbonyl-1,3-benzodioxol-4-yl)-7-methoxy-1,3-benzodioxole-5-carboxylate
  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

• Anti-AIDS (Acquired Immune Deficiency Syndrome) Agents. 17. New Brominated Hexahydroxybiphenyl Derivatives as Potent Anti-HIV Agents
  作者：Lan Xie、Jing-Xi Xie、Yoshiki Kashiwada、L. Mark Cosentino、Shwu-Huey Liu、Rekha B. Pai、Yung-Chi Cheng、Kuo-Hsiung Lee

  DOI：10.1021/jm00016a002

  日期：1995.8

  Sixteen biphenyl derivatives were synthesized and evaluated for their inhibitory activity against HIV-1 replication in acutely infected H9 cells. 3-Bromo- (4) and 3,3'-dibromo-4,4'-dimethoxy-5,6,5',6'-bis(methylenedioxy)-2,2' -bis(methoxycarbonyl)biphenyl (5) demonstrated potent anti-HIV activity with EC(50) values of 0.52 and 0.23 mu g/mL and therapeutic index values of > 190 and > 480, respectively. A comparison, of the anti-HIV activity of these biphenyl derivatives suggested that the types of substituents on the phenolic hydroxy groups rather than the number of bromine(s) on the aromatic rings are important to the enhanced anti-HIV activity. Compounds 4 and 5 also showed potent inhibitory activity against HIV-1 reverse transcriptase in a template-primer dependent manner. The site of inhibition of HIV could be related to inhibition of this enzyme. Compounds 4 and 5 did not induce virus expression from the chronic HIV-1-infected cell lines ACH-2 and U1. Furthermore, these two agents did not inhibit an increase in virus production from the chronic HIV-1-infected cell lines when the phorbol ester PMA was present.
• 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.