4-(3-甲氧基苯基)-2,4-二氧丁酸 | 105356-66-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 4-(3-甲氧基苯基)-2,4-二氧丁酸
• 英文名称: 4-(3-methoxyphenyl)-2,4-dioxobutanoic acid
• CAS: 105356-66-9
• 化学式: C₁₁H₁₀O₅
• 分子量: 222.197
• InChiKey: VSUAIOMDWMRIAK-UHFFFAOYSA-N

物化性质

• 沸点：
  390.8±22.0 °C(Predicted)
• 密度：
  1.309±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2918990090

反应信息

• 作为反应物：
  描述：

  5-氯邻甲苯胺 、 4-(3-甲氧基苯基)-2,4-二氧丁酸 在 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以66%的产率得到N-(5-chloro-2-methylphenyl)-4-(3-methoxyphenyl)-2,4-dioxobutanamide
  参考文献：
  名称：

  [EN] SMALL MOLECULES FOR DISRUPTING THE SUPER ELONGATION COMPLEX AND INHIBITING TRANSCRIPTION ELONGATION FOR CANCER THERAPY
  [FR] PETITES MOLÉCULES PERMETTANT DE PERTURBER LE COMPLEXE DE SUPER-ALLONGEMENT ET D'INHIBER L'ALLONGEMENT DE LA TRANSCRIPTION POUR UNE CANCÉROTHÉRAPIE

  摘要：

  本文揭示了可用于抑制RNA聚合酶II（Pol II）转录的化合物，特别是破坏超级延伸复合物（SEC）的化合物。这些化合物可用于制备药物组合物和治疗与SEC生物活性相关的疾病和紊乱的方法，特别是与高水平表达SEC依赖基因相关的促进、支持或其他对疾病或紊乱必要的疾病和紊乱，如癌症。

  公开号：

  WO2019183373A1
• 作为产物：
  描述：

  3-甲氧基苯乙酮 在 正丁基锂 、 水 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 4-(3-甲氧基苯基)-2,4-二氧丁酸
  参考文献：
  名称：

  [EN] SMALL MOLECULES FOR DISRUPTING THE SUPER ELONGATION COMPLEX AND INHIBITING TRANSCRIPTION ELONGATION FOR CANCER THERAPY
  [FR] PETITES MOLÉCULES PERMETTANT DE PERTURBER LE COMPLEXE DE SUPER-ALLONGEMENT ET D'INHIBER L'ALLONGEMENT DE LA TRANSCRIPTION POUR UNE CANCÉROTHÉRAPIE

  摘要：

  本文揭示了可用于抑制RNA聚合酶II（Pol II）转录的化合物，特别是破坏超级延伸复合物（SEC）的化合物。这些化合物可用于制备药物组合物和治疗与SEC生物活性相关的疾病和紊乱的方法，特别是与高水平表达SEC依赖基因相关的促进、支持或其他对疾病或紊乱必要的疾病和紊乱，如癌症。

  公开号：

  WO2019183373A1

文献信息

• [EN] SMALL MOLECULES FOR DISRUPTING THE SUPER ELONGATION COMPLEX AND INHIBITING TRANSCRIPTION ELONGATION FOR CANCER THERAPY<br/>[FR] PETITES MOLÉCULES PERMETTANT DE PERTURBER LE COMPLEXE DE SUPER-ALLONGEMENT ET D'INHIBER L'ALLONGEMENT DE LA TRANSCRIPTION POUR UNE CANCÉROTHÉRAPIE
  申请人：UNIV NORTHWESTERN

  公开号：WO2019183373A1

  公开（公告）日：2019-09-26

  Disclosed are compounds which may be utilized to inhibit transcription by RNA Polymerase II (Pol II), and in particular to disrupt the Super Elongation Complex (SEC). The compounds may be utilized in pharmaceutical compositions and methods for treating diseases and disorders associated with the biological activity of SEC, and in particular, diseases and disorders that are associated with high levels of expression of genes whose expression is SEC-dependent and that promote, support, or otherwise are required for the disease or disorder such as cancers.

  本文揭示了可用于抑制RNA聚合酶II（Pol II）转录的化合物，特别是破坏超级延伸复合物（SEC）的化合物。这些化合物可用于制备药物组合物和治疗与SEC生物活性相关的疾病和紊乱的方法，特别是与高水平表达SEC依赖基因相关的促进、支持或其他对疾病或紊乱必要的疾病和紊乱，如癌症。
• Slow-binding inhibition of 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase
  作者：Rémi Braga、Laurence Hecquet、Casimir Blonski

  DOI：10.1016/j.bmc.2004.03.039

  日期：2004.6

  2-Keto-3-deoxy-6-phosphogluconate (KDPG) aldolase is a key enzyme in the Entner-Doudoroff pathway of bacteria. It catalyzes the reversible production of KDPG from pyruvate and D-glyceraldehyde 3-phosphate through a class I Schiff base mechanism. On the basis of aldolase mechanistic pathway, various pyruvate analogues bearing beta-diketo structures were designed and synthesized as potential inhibitors. Their capacity to inhibit aldolase catalyzed reaction by forming stabilized iminium ion or conjugated enamine were investigated by enzymatic kinetics and UV-vis difference spectroscopy. Depending of the substituent R (methyl or aromatic ring), a competitive or a slow-binding inhibition takes place. These results were examined on the basis of the three-dimensional structure of the enzyme. (C) 2004 Elsevier Ltd. All rights reserved.
• SMALL MOLECULES FOR DISRUPTING THE SUPER ELONGATION COMPLEX AND INHIBITING TRANSCRIPTION ELONGATION FOR CANCER THERAPY
  申请人：NORTHWESTERN UNIVERSITY

  公开号：US20210094907A1

  公开（公告）日：2021-04-01

  Disclosed are compounds which may be utilized to inhibit transcription by RNA Polymerase II (Pol II), and in particular to disrupt the Super Elongation Complex (SEC). The compounds may be utilized in pharmaceutical compositions and methods for treating diseases and disorders associated with the biological activity of SEC, and in particular, diseases and disorders that are associated with high levels of expression of genes whose expression is SEC-dependent and that promote, support, or otherwise are required for the disease or disorder such as cancers.
• Targeting Processive Transcription Elongation via SEC Disruption for MYC-Induced Cancer Therapy
  作者：Kaiwei Liang、Edwin R. Smith、Yuki Aoi、Kristen L. Stoltz、Hiroaki Katagi、Ashley R. Woodfin、Emily J. Rendleman、Stacy A. Marshall、David C. Murray、Lu Wang、Patrick A. Ozark、Rama K. Mishra、Rintaro Hashizume、Gary E. Schiltz、Ali Shilatifard

  DOI：10.1016/j.cell.2018.09.027

  日期：2018.10

  The super elongation complex (SEC) is required for robust and productive transcription through release of RNA polymerase II (Pol II) with its P-TEFb module and promoting transcriptional processivity with its ELL2 subunit. Malfunction of SEC contributes to multiple human diseases including cancer. Here, we identify peptidomimetic lead compounds, KL-1 and its structural homolog KL-2, which disrupt the interaction between the SEC scaffolding protein AFF4 and P-TEFb, resulting in impaired release of Pol II from promoter-proximal pause sites and a reduced average rate of processive transcription elongation. SEC is required for induction of heat-shock genes and treating cells with KL-1 and KL-2 attenuates the heat-shock response from Drosophila to human. SEC inhibition downregulates MYC and MYC-dependent transcriptional programs in mammalian cells and delays tumor progression in a mouse xenograft model of MYC-driven cancer, indicating that small-molecule disruptors of SEC could be used for targeted therapy of MYC-induced cancer.