(3E)-3-[(2,3,4,5-tetramethoxy-6-methylphenyl)methylidene]oxolan-2-one | 1136839-81-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (3E)-3-[(2,3,4,5-tetramethoxy-6-methylphenyl)methylidene]oxolan-2-one
• CAS: 1136839-81-0
• 化学式: C₁₆H₂₀O₆
• 分子量: 308.331
• InChiKey: BRDARAZFMOJHPG-CSKARUKUSA-N

物化性质

• 熔点：
  78-79 °C
• 沸点：
  494.2±45.0 °C(predicted)
• 密度：
  1.202±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3E)-3-[(2,3,4,5-tetramethoxy-6-methylphenyl)methylidene]oxolan-2-one 、 原甲酸三甲酯 在 硫酸 作用下， 以 甲醇 为溶剂， 以76%的产率得到methyl (2E)-4-methoxy-2-[(2,3,4,5-tetramethoxy-6-methylphenyl)methylidene]butanoate
  参考文献：
  名称：

  Design and Synthesis of Novel Quinone Inhibitors Targeted to the Redox Function of Apurinic/Apyrimidinic Endonuclease 1/Redox Enhancing Factor-1 (Ape1/Ref-1)

  摘要：

  The multifunctional enzyme apurinic endonuclease 1/redox enhancing factor 1 (Apel/ref-1) maintains genetic fidelity through the repair of apurinic sites and regulates transcription through redox-dependent activation of transcription factors. Apel can therefore serve as a therapeutic target in either a DNA repair or transcriptional context. Inhibitors of the redox function can be used as either therapeutics or novel tools for separating the two functions for in vitro study. Presently there exist only a few compounds that have been reported to inhibit Apel redox activity; here we describe a series of quinones that exhibit micromolar inhibition of the redox function of Apel. Benzoquinone and naphthoquinone analogues of the Apel-inhibitor E3330 were designed and synthesized to explore structural effects on redox function and inhibition of cell growth. Most of the naphthoquinones were low micromolar inhibitors of Apel redox activity, and the most potent analogues inhibited tumor cell growth with IC50 values in the 10-20 mu M range.

  DOI：

  10.1021/jm9014857
• 作为产物：
  描述：

  α-溴-γ-丁内酯 、 2,3,4,5-四甲氧基-6-甲基苯甲醛 在 sodium hydride 、 亚磷酸三乙酯 作用下， 以 甲苯 为溶剂， 以66%的产率得到(3E)-3-[(2,3,4,5-tetramethoxy-6-methylphenyl)methylidene]oxolan-2-one
  参考文献：
  名称：

  Design and Synthesis of Novel Quinone Inhibitors Targeted to the Redox Function of Apurinic/Apyrimidinic Endonuclease 1/Redox Enhancing Factor-1 (Ape1/Ref-1)

  摘要：

  The multifunctional enzyme apurinic endonuclease 1/redox enhancing factor 1 (Apel/ref-1) maintains genetic fidelity through the repair of apurinic sites and regulates transcription through redox-dependent activation of transcription factors. Apel can therefore serve as a therapeutic target in either a DNA repair or transcriptional context. Inhibitors of the redox function can be used as either therapeutics or novel tools for separating the two functions for in vitro study. Presently there exist only a few compounds that have been reported to inhibit Apel redox activity; here we describe a series of quinones that exhibit micromolar inhibition of the redox function of Apel. Benzoquinone and naphthoquinone analogues of the Apel-inhibitor E3330 were designed and synthesized to explore structural effects on redox function and inhibition of cell growth. Most of the naphthoquinones were low micromolar inhibitors of Apel redox activity, and the most potent analogues inhibited tumor cell growth with IC50 values in the 10-20 mu M range.

  DOI：

  10.1021/jm9014857

文献信息

• QUINONE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF
  申请人：Kelley Mark R.

  公开号：US20100297113A1

  公开（公告）日：2010-11-25

  This application describes quinone derivatives which target the redox site of Ape1/Ref1. Also included in the invention are pharmaceutical formulations containing the derivatives and therapeutic uses of the derivatives.

  这个应用描述了目标为Ape1/Ref1的氧化还原位点的醌衍生物。发明还包括含有这些衍生物的药物制剂和这些衍生物的治疗用途。
• US9089605B2
  申请人：——

  公开号：US9089605B2

  公开（公告）日：2015-07-28
• Design and Synthesis of Novel Quinone Inhibitors Targeted to the Redox Function of Apurinic/Apyrimidinic Endonuclease 1/Redox Enhancing Factor-1 (Ape1/Ref-1)
  作者：Rodney L. Nyland、Meihua Luo、Mark R. Kelley、Richard F. Borch

  DOI：10.1021/jm9014857

  日期：2010.2.11

  The multifunctional enzyme apurinic endonuclease 1/redox enhancing factor 1 (Apel/ref-1) maintains genetic fidelity through the repair of apurinic sites and regulates transcription through redox-dependent activation of transcription factors. Apel can therefore serve as a therapeutic target in either a DNA repair or transcriptional context. Inhibitors of the redox function can be used as either therapeutics or novel tools for separating the two functions for in vitro study. Presently there exist only a few compounds that have been reported to inhibit Apel redox activity; here we describe a series of quinones that exhibit micromolar inhibition of the redox function of Apel. Benzoquinone and naphthoquinone analogues of the Apel-inhibitor E3330 were designed and synthesized to explore structural effects on redox function and inhibition of cell growth. Most of the naphthoquinones were low micromolar inhibitors of Apel redox activity, and the most potent analogues inhibited tumor cell growth with IC50 values in the 10-20 mu M range.