trans-3-(4-allyloxyphenyl)-1-[2,4-bis(methoxymethoxy)-6-hydroxyphenyl]prop-2-en-1-one | 916331-01-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: trans-3-(4-allyloxyphenyl)-1-[2,4-bis(methoxymethoxy)-6-hydroxyphenyl]prop-2-en-1-one
• 英文别名: trans-3-(4-allyloxyphenyl)-1-[2,4-bis(methoxymethoxy)-6-hydroxyphenyl]propenone；(E)-1-[2-hydroxy-4,6-bis(methoxymethoxy)phenyl]-3-(4-prop-2-enoxyphenyl)prop-2-en-1-one
• CAS: 916331-01-6
• 化学式: C₂₂H₂₄O₇
• 分子量: 400.428
• InChiKey: XVZDBOAEUKZDFG-JXMROGBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  83.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  trans-3-(4-allyloxyphenyl)-1-[2,4-bis(methoxymethoxy)-6-hydroxyphenyl]prop-2-en-1-one 在 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 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 11.0h， 生成 1,7-bis[4-((5-benzyloxy-7-methoxymethoxy)-4H-chromen-4-on-2-yl)phenyl]-1,4,7-trioxaheptane
  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 、 4-烯丙氧基苯甲醛 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以95%的产率得到trans-3-(4-allyloxyphenyl)-1-[2,4-bis(methoxymethoxy)-6-hydroxyphenyl]prop-2-en-1-one
  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+

文献信息

• Flavonoid Dimers and Methods of Making and Using Such
  申请人：Chan Tak-Hang

  公开号：US20090197943A1

  公开（公告）日：2009-08-06

  Multidrug resistance (MDR) is a major problem in cancer chemotherapy. The best characterized resistance mechanism is the one mediated by the over-expression of drug efflux transporters, permeability-glycoprotein (P-gp), which pump a variety of anticancer drugs out of the cells, resulting in lowered intracellular drug accumulation. A series of flavonoid dimers are developed in this invention, which are linked together by linker groups of various lengths. These flavonoid dimers are found to be efficient P-gp modulators that increase cytotoxicity of anticancer drugs in vitro and dramatically enhance their intracellular drug accumulation. It is found that the flavonoid dimers of this invention is also useful in reducing drug resistance in treating parasitic diseases.

  多药耐药性（MDR）是癌症化疗中的主要问题。最好表征的耐药机制是通过过度表达药物外流转运蛋白、渗透性糖蛋白（P-gp）介导的耐药机制，它将各种抗癌药物泵出细胞，导致细胞内药物积累降低。本发明开发了一系列由不同长度的连接基团连接在一起的类黄酮二聚体。发现这些类黄酮二聚体是有效的P-gp调节剂，可以增加抗癌药物在体外的细胞毒性并显著提高它们的细胞内药物积累。同时，发现本发明的类黄酮二聚体也有助于减少治疗寄生虫病的耐药性。
• WO2007/135592
  申请人：——

  公开号：——

  公开（公告）日：——
• US8710097B2
  申请人：——

  公开号：US8710097B2

  公开（公告）日：2014-04-29
• 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
  作者：Kin-Fai Chan、Yunzhe Zhao、Brendan A. Burkett、Iris L. K. Wong、Larry M. C. Chow、Tak Hang Chan

  DOI：10.1021/jm060593+

  日期：2006.11.1

  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.