5,7-bis(phenylmethoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-one | 701284-21-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 5,7-bis(phenylmethoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-one
• CAS: 701284-21-1
• 化学式: C₃₂H₃₀O₇
• 分子量: 526.586
• InChiKey: DHJHAXQAMWVOKZ-UHFFFAOYSA-N

物化性质

• 沸点：
  693.1±55.0 °C(Predicted)
• 密度：
  1.226±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.12
• 重原子数：
  39.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  72.45
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  5,7-bis(phenylmethoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-one 在 吡啶 、 4-二甲氨基吡啶 、 L-Selectride 、 lithium bromide 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 5,7-bis(benzyloxy)-2-(3,4,5-trimethoxyphenyl)chroman-3-yl 3′,6-dimethoxy-[1,1′-biphenyl]-3-carboxylate
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of EGCG Analogues, a Recently Identified Hsp90 Inhibitor

  摘要：

  Epigallocatechin-3-gallate (EGCG), the principal polyphenol isolated from green tea, was recently shown to inhibit Hsp90; however, structure activity relationships for this natural product have not yet been produced. Herein, we report the synthesis and biological evaluation of EGCG analogues to establish structure activity relationships between EGCG and Hsp90. All four rings as well as the linker connecting the C- and the D-rings were systematically investigated, which led to the discovery of compounds that inhibit Hs90 and display improvement in efficacy over EGCG. Antiproliferative activity of all the analogues was determined against MCF-7 and SKBr3 cell lines and Hsp90 inhibitory activity of the four most potent analogues was further evaluated by Western blot analyses and degradation of Hsp90-dependent client proteins. The prenyl-substituted aryl ester of 3,5-dihydroxychroman-3-ol ring system was identified as a novel scaffold that exhibits Hsp90 inhibitory activity.

  DOI：

  10.1021/jo401027r
• 作为产物：
  描述：

  (E)-3,5-bis(benzyloxy)-2-(3-(3,4,5-trimethoxyphenyl)allyl)-phenol 在 甲醇 、 三氟化硼乙醚 、 4-甲基苯磺酸吡啶 、 potassium carbonate 、 戴斯-马丁氧化剂 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 21.0h， 生成 5,7-bis(phenylmethoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-one
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of EGCG Analogues, a Recently Identified Hsp90 Inhibitor

  摘要：

  Epigallocatechin-3-gallate (EGCG), the principal polyphenol isolated from green tea, was recently shown to inhibit Hsp90; however, structure activity relationships for this natural product have not yet been produced. Herein, we report the synthesis and biological evaluation of EGCG analogues to establish structure activity relationships between EGCG and Hsp90. All four rings as well as the linker connecting the C- and the D-rings were systematically investigated, which led to the discovery of compounds that inhibit Hs90 and display improvement in efficacy over EGCG. Antiproliferative activity of all the analogues was determined against MCF-7 and SKBr3 cell lines and Hsp90 inhibitory activity of the four most potent analogues was further evaluated by Western blot analyses and degradation of Hsp90-dependent client proteins. The prenyl-substituted aryl ester of 3,5-dihydroxychroman-3-ol ring system was identified as a novel scaffold that exhibits Hsp90 inhibitory activity.

  DOI：

  10.1021/jo401027r

文献信息

• Analogs of green tea polyphenols as chemotherapeutic and chemopreventive agents
  申请人：——

  公开号：US20040110790A1

  公开（公告）日：2004-06-10

  Novel compounds useful as chemotherapeutic and chemopreventive agents are provided. The compounds are analogs of polyphenol catechins that occur in green tea, such as epigallocatichin-3-gallate (EGCG), and have the structure of formula (I) 1 wherein R 1 through R 11 are defined herein. Preferred R 4 moieties are selected from O, S, NH and CH 2 , and in exemplary compounds, R 4 is O and R 5 is a tri-substituted aroyloxy substituent, such as a 3,4,5-substituted benzoyloxy group. Pharmaceutical compositions are provided as well, as are methods of chemotherapy and chemoprevention.

  提供了作为化疗和化学预防剂有用的新型化合物。这些化合物是绿茶中存在的多酚儿茶素的类似物，如表儿茶素-3-没食子酸酯（EGCG），其结构如式（I）1所示，其中R1至R11在此处定义。首选的R4基团从O、S、NH和CH2中选择，在示例化合物中，R4为O，R5为三取代芳酰氧基取代基，如3,4,5-取代苯甲酰氧基基团。还提供了药物组合物，以及化疗和化学预防的方法。