(E)-3-(5,6-dimethoxy-3-methyl-1,4-dioxocyclohexa-2,5-dien-2-yl)-2-methyl-2-propenoic acid | 1136838-66-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (E)-3-(5,6-dimethoxy-3-methyl-1,4-dioxocyclohexa-2,5-dien-2-yl)-2-methyl-2-propenoic acid
• 英文别名: (E)-3-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)-2-methylpropenoic acid；(E)-3-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)-2-methylprop-2-enoic acid
• CAS: 1136838-66-8
• 化学式: C₁₃H₁₄O₆
• 分子量: 266.251
• InChiKey: HLCWUWGXJOLZGX-AATRIKPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (E)-3-(6-methyl-2,3,4,5-tetramethoxyphenyl)-2-methylpropenoic acid 在 硝酸 、 溶剂黄146 作用下， 以 乙酸乙酯 为溶剂， 反应 4.0h， 以31%的产率得到(E)-3-(5,6-dimethoxy-3-methyl-1,4-dioxocyclohexa-2,5-dien-2-yl)-2-methyl-2-propenoic acid
  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：US09089605B2

  公开（公告）日：2015-07-28

  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.

  本申请描述了靶向Ape1/Ref1的氧化还原位点的醌衍生物。本发明还包括含有该衍生物的药物配方和该衍生物的治疗用途。
• 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。
• Benzoquinone derivative E3330 in combination with chemotherapeutic agents for the treatment of bladder cancer
  申请人：Indiana University Research and Technology Corporation

  公开号：US11331294B2

  公开（公告）日：2022-05-17

  Disclosed are novel methods for the therapeutic treatment of cancer and angiogenesis. The enzyme Ape1/Ref-1, via its redox function, enhances the DNA binding activity of transcription factors that are associated with the progression of cancer. The present disclosure describes the use of agents to selectively inhibit the redox function of Ape1/Ref-1 and thereby reduce tumor cell growth, survival, migration and metastasis. In addition, Ape1/Ref-1 inhibitory activity is shown to augment the therapeutic effects of other therapeutics and protect normal cells against toxicity. Further, Ape1/Ref-1 inhibition is shown to decrease angiogenesis, for use in the treatment of cancer as well other pathologic conditions of which altered angiogenesis is a component.

  所公开的是治疗癌症和血管生成的新方法。Ape1/Ref-1 酶通过其氧化还原功能增强与癌症进展相关的转录因子的 DNA 结合活性。本公开描述了如何使用药剂选择性地抑制 Ape1/Ref-1 的氧化还原功能，从而减少肿瘤细胞的生长、存活、迁移和转移。此外，Ape1/Ref-1 抑制活性还能增强其他疗法的治疗效果，保护正常细胞免受毒性影响。此外，Ape1/Ref-1 抑制剂还能减少血管生成，可用于治疗癌症及其他以血管生成改变为组成部分的病理状况。
• BENZOQUINONE DERIVATIVE E3330 FOR THE TREATMENT OF EYE DISEASES
  申请人：Indiana University Research & Technology Corporation

  公开号：EP3725309B1

  公开（公告）日：2022-11-23
• BENZOQUINONE DERIVATIVES FOR THE TREATMENT OF BLADDER CANCER
  申请人：Indiana University Research and Technology Corporation

  公开号：US20220249421A1

  公开（公告）日：2022-08-11

  Disclosed are novel methods for the therapeutic treatment of cancer and angiogenesis. The enzyme Ape1/Ref-1, via its redox function, enhances the DNA binding activity of transcription factors that are associated with the progression of cancer. The present disclosure describes the use of agents to selectively inhibit the redox function of Ape1/Ref-1 and thereby reduce tumor cell growth, survival, migration and metastasis. In addition, Ape1/Ref-1 inhibitory activity is shown to augment the therapeutic effects of other therapeutics and protect normal cells against toxicity. Further, Ape1/Ref-1 inhibition is shown to decrease angiogenesis, for use in the treatment of cancer as well other pathologic conditions of which altered angiogenesis is a component.