(2E)-1-(2,4-di(methoxymethoxy)-6-methoxyphenyl)-3-(4-methoxyphenyl)-2-propen-1-one | 1082076-62-7

• 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: (2E)-1-(2,4-di(methoxymethoxy)-6-methoxyphenyl)-3-(4-methoxyphenyl)-2-propen-1-one
• 英文别名: (e)-1-(2-Methoxy-4,6-bis(methoxymethoxy)phenyl)-3-(4-methoxyphenyl)prop-2-en-1-one；(E)-1-[2-methoxy-4,6-bis(methoxymethoxy)phenyl]-3-(4-methoxyphenyl)prop-2-en-1-one
• CAS: 1082076-62-7
• 化学式: C₂₁H₂₄O₇
• 分子量: 388.417
• InChiKey: YGRFFDBPFUVUSZ-JXMROGBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2E)-1-(2,4-di(methoxymethoxy)-6-methoxyphenyl)-3-(4-methoxyphenyl)-2-propen-1-one 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 0.5h， 以65%的产率得到2',4'-二羟基-4,6'-二甲氧基查尔酮
  参考文献：
  名称：

  Synthesis of Xanthohumol Analogues and Discovery of Potent Thioredoxin Reductase Inhibitor as Potential Anticancer Agent

  摘要：

  The selenoprotein thioredoxin reductases (TrxRs) are attractive targets for anticancer drugs development. Xanthohumol (Xn), a naturally occurring polyphenol chalcone from hops, has received increasing attention because of its multiple pharmacological activities. We synthesized Xn and its 43 analogues and discovered that compound 13n displayed the highest cytotoxicity toward HeLa cells (IC50 = 1.4 mu M). Structure-activity relationship study indicates that the prenyl group is not necessary for cytotoxicity, and introducing electron-withdrawing group, especially on the meta-position, is favored. In addition, methylation of the phenoxyl groups generally improves the potency. Mechanistic study revealed that 13n selectively inhibits TrxR and induces reactive oxygen species and apoptosis in HeLa cells. Cells overexpressing TrxR are resistant to 13n insult, while knockdown of TrxR sensitizes cells to 13n treatment, highlighting the physiological significance of targeting TrxR by 13n. The clarification of the structural determinants for the potency would guide the design of novel potent molecules for future development.

  DOI：

  10.1021/jm5016507
• 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 在 potassium carbonate 、 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.08h， 生成 (2E)-1-(2,4-di(methoxymethoxy)-6-methoxyphenyl)-3-(4-methoxyphenyl)-2-propen-1-one
  参考文献：
  名称：

  Synthesis of Xanthohumol Analogues and Discovery of Potent Thioredoxin Reductase Inhibitor as Potential Anticancer Agent

  摘要：

  The selenoprotein thioredoxin reductases (TrxRs) are attractive targets for anticancer drugs development. Xanthohumol (Xn), a naturally occurring polyphenol chalcone from hops, has received increasing attention because of its multiple pharmacological activities. We synthesized Xn and its 43 analogues and discovered that compound 13n displayed the highest cytotoxicity toward HeLa cells (IC50 = 1.4 mu M). Structure-activity relationship study indicates that the prenyl group is not necessary for cytotoxicity, and introducing electron-withdrawing group, especially on the meta-position, is favored. In addition, methylation of the phenoxyl groups generally improves the potency. Mechanistic study revealed that 13n selectively inhibits TrxR and induces reactive oxygen species and apoptosis in HeLa cells. Cells overexpressing TrxR are resistant to 13n insult, while knockdown of TrxR sensitizes cells to 13n treatment, highlighting the physiological significance of targeting TrxR by 13n. The clarification of the structural determinants for the potency would guide the design of novel potent molecules for future development.

  DOI：

  10.1021/jm5016507

文献信息

• [EN] COMPOUNDS, THEIR SYNTHESES, AND THEIR USES<br/>[FR] COMPOSÉS, LEUR SYNTHÈSE ET LEURS UTILISATIONS
  申请人：UNIV LOUISVILLE RES FOUND

  公开号：WO2010019861A1

  公开（公告）日：2010-02-18

  Embodiments of the present invention provide compounds (such as Formula (I) compounds, Formula (II) compounds, and various embodiments thereof). Compositions comprising those compounds are also provided. Methods for their preparation are included. Also, uses of the compounds are included, such as administering and treating diseases (e.g., cancer and infections).

  本发明实施例提供化合物（如式（I）化合物、式（II）化合物及其各种实施例）。还提供包含这些化合物的组合物。包括它们的制备方法。此外，还包括化合物的用途，如给药和治疗疾病（例如癌症和感染）。
• COMPOUNDS, THEIR SYNTHESES, AND THIER USES
  申请人：Hammond Gerald B.

  公开号：US20110190325A1

  公开（公告）日：2011-08-04

  Embodiments of the present invention provide compounds (such as Formula (I) compounds, Formula (II) compounds, and various embodiments thereof). Compositions comprising those compounds are also provided. Methods for their preparation are included. Also, uses of the compounds are included, such as administering and treating diseases (e.g., cancer and infections).

  本发明实施例提供化合物（例如公式（I）化合物、公式（II）化合物及其各种实施例）。还提供包含这些化合物的组合物。其中包括它们的制备方法。此外，还包括这些化合物的用途，例如用于治疗疾病（例如癌症和感染）的给药和治疗。
• In vitro and in vivo anti-Leishmania activity of polysubstituted synthetic chalcones
  作者：José C. Aponte、Denis Castillo、Yannick Estevez、German Gonzalez、Jorge Arevalo、Gerald B. Hammond、Michel Sauvain

  DOI：10.1016/j.bmcl.2009.11.033

  日期：2010.1

  The in vitro screening of 43 polysubstituted chalcones against Leishmania amazonensis axenic amastigotes, led to the evaluation of 9 of them in a macrophage-infected model with the two other most infectious Leishmania species prevalent in Peru (L. braziliensis and L. peruviana). The five most active and selective chalcones were studied in vivo, resulting on the identification of two chalcones with high reduction parasite burden percentages. (C) 2009 Elsevier Ltd. All rights reserved.
• US9061984B2
  申请人：——

  公开号：US9061984B2

  公开（公告）日：2015-06-23
• Synthesis of Xanthohumol Analogues and Discovery of Potent Thioredoxin Reductase Inhibitor as Potential Anticancer Agent
  作者：Baoxin Zhang、Dongzhu Duan、Chunpo Ge、Juan Yao、Yaping Liu、Xinming Li、Jianguo Fang

  DOI：10.1021/jm5016507

  日期：2015.2.26

  The selenoprotein thioredoxin reductases (TrxRs) are attractive targets for anticancer drugs development. Xanthohumol (Xn), a naturally occurring polyphenol chalcone from hops, has received increasing attention because of its multiple pharmacological activities. We synthesized Xn and its 43 analogues and discovered that compound 13n displayed the highest cytotoxicity toward HeLa cells (IC50 = 1.4 mu M). Structure-activity relationship study indicates that the prenyl group is not necessary for cytotoxicity, and introducing electron-withdrawing group, especially on the meta-position, is favored. In addition, methylation of the phenoxyl groups generally improves the potency. Mechanistic study revealed that 13n selectively inhibits TrxR and induces reactive oxygen species and apoptosis in HeLa cells. Cells overexpressing TrxR are resistant to 13n insult, while knockdown of TrxR sensitizes cells to 13n treatment, highlighting the physiological significance of targeting TrxR by 13n. The clarification of the structural determinants for the potency would guide the design of novel potent molecules for future development.