2-(2,3,4-三羟基苯基)-4H-1-苯并吡喃-4-酮 | 144707-18-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 中文名称: 2-(2,3,4-三羟基苯基)-4H-1-苯并吡喃-4-酮
• 中文别名: 化合物2-D08
• 英文名称: 2-D08
• 英文别名: 2',3',4'-trihydroxyflavone；2′,3′,4′ -trihydroxyflavone；2-(2,3,4-trihydroxyphenyl)chromen-4-one
• CAS: 144707-18-6
• 化学式: C₁₅H₁₀O₅
• 分子量: 270.241
• InChiKey: JJAXTFSPCLZPIW-UHFFFAOYSA-N

物化性质

• 沸点：
  517.9±50.0 °C(Predicted)
• 密度：
  1.548±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO 中≥74.6 mg/mL； ≥1.76 mg/mL，溶于乙醇，温和加热并超声；不溶于水

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

制备方法与用途

生物活性

生物活性 2-D08（2',3',4'-三羟基黄酮）是一种具有细胞透过性的蛋白类泛素化抑制剂。它还能抑制Axl、IRAK4、ROS1、MLK4、GSK3β、RET (c-RET)、KDR和PI3Kα，对应的IC50值分别为0.49 nM、3.9 nM、5.3 nM、9.8 nM、11 nM、11 nM、17 nM 和 35 nM。

靶点

• 泛素化 (Cell-free assay)
• Axl (细胞自由测定) — 0.49 nM
• IRAK4 (细胞自由测定) — 3.9 nM
• ROS1 (细胞自由测定) — 5.3 nM

体外研究

2-D08通过组织SUMO从UBC9-SUMO硫酯转移到底物上，从而抑制泛素化。该化合物以浓度依赖性方式降低p-Axl/Axl的比值，并通过抑制Axl激酶活性破坏细胞骨架和肌动蛋白微丝，导致细胞连接重组。2-D08还能促使β-catenin易位到细胞连接处，上调E-cadherin表达。在肺多潜能干细胞系中，2D08也能以浓度依赖性方式降低其迁移能力。

反应信息

• 作为产物：
  描述：

  2',3',4'-trimethoxyflavone 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以46%的产率得到2-(2,3,4-三羟基苯基)-4H-1-苯并吡喃-4-酮
  参考文献：
  名称：

  Synthesis of 2′,3′,4′-trihydroxyflavone (2-D08), an inhibitor of protein sumoylation

  摘要：

  Protein sumoylation is a dynamic posttranslational modification involved in diverse biological processes during cellular homeostasis and development. Recently sumoylation has been shown to play a critical role in cancer, although to date there are few small molecule probes available to inhibit enzymes involved in the SUMO conjugation process. As part of a program to identify and study inhibitors of sumoylation we recently reported the discovery that 2',3',4'-trihydroxyflavone (2-D08) is a cell permeable, mechanistically unique inhibitor of protein sumoylation. The work reported herein describes an efficient synthesis of 2-D08 as well as a structurally related but inactive isomer. We also report an unanticipated Wessely-Moser rearrangement that occurs under vigorous methyl ether deprotection conditions. This rearrangement likely gave rise to 2-D08 during a deprotection step, resulting in 2-D08 appearing as a contaminant in a screening well from a commercial supplier. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2014.01.010

文献信息

• Flavonoid Compounds and Uses Thereof
  申请人：Jarrott Bevyn

  公开号：US20090130051A1

  公开（公告）日：2009-05-21

  Novel flavonoid compounds having anti-oxidant activity are described. The compounds and compositions have been shown to exhibit anti-oxidant properties and are particularly useful in the treatment of ischemia and reperfusion injuries. The invention also describes a method to chemically synthesize such flavonoid compounds and test their efficacy. Such compounds and corresponding pharmaceutically acceptable derivatives and/or salts have uses in the areas of pharmaceuticals, nutraceutical, and veterinary applications.

  本发明描述了具有抗氧化活性的新型黄酮类化合物。这些化合物和组合物已被证明具有抗氧化性质，特别适用于缺血和再灌注损伤的治疗。本发明还描述了一种化学合成这种黄酮类化合物并测试其功效的方法。这些化合物及其对应的药学上可接受的衍生物和/或盐在制药、保健品和兽医应用领域中有用。
• CROMOLYN DERIVATIVES AND RELATED METHODS OF IMAGING AND TREATMENT
  申请人：ELMALEH David R.

  公开号：US20160263257A1

  公开（公告）日：2016-09-15

  Novel cromolyn analogs useful as imaging agents for detecting atherosclerotic plaques and for treating atherosclerosis and Alzheimer's Disease, and methods of making the cromolyn analogs, are disclosed. The cromolyn analogs have the general formula; wherein X is OH, C 1 -C 6 alkoxyl; Y and Z are independently selected from a C 1 -C 6 alkyl, C 1 -C 6 alkoxyl, halogen, mi-substituted or C 1 -C 6 substituted amine, 18 F, 19 F, or H; and n is 1, 2, or 3; and wherein for structure (I), if n are both 1 and Y and Z are both H and X is OH.

  揭示了作为检测动脉粥样硬化斑块和治疗动脉硬化和阿尔茨海默病的成像剂的新型克罗莫林类似物以及制备克罗莫林类似物的方法。克罗莫林类似物具有一般式;其中X为OH，C1-C6烷氧基; Y和Z分别选自C1-C6烷基，C1-C6烷氧基，卤素，mi-取代或C1-C6取代胺，18F，19F或H; n为1，2或3;对于结构（I），如果n都为1且Y和Z都为H且X为OH。
• Tire with rubber containing flavone
  申请人：THE GOODYEAR TIRE & RUBBER COMPANY

  公开号：EP1391327A1

  公开（公告）日：2004-02-25

  The invention relates to a rubber composition and a pneumatic tire having a component comprising a rubber containing the reaction product of a flavone and a methylene donor.

  本发明涉及一种橡胶组合物和充气轮胎，其成分包括含有黄酮和亚甲基供体反应产物的橡胶。
• Rubber composition and tire with rubber containing flavone
  申请人：The Goodyear Tire & Rubber Company

  公开号：EP2730431A1

  公开（公告）日：2014-05-14

  A rubber composition comprising a diene based elastomer and an adhesion promoter derived from a flavone, a methylene donor and a methylene acceptor is disclosed. The rubber composition is essentially free of cobalt. Also, a pneumatic tire comprising such a rubber composition is disclosed.

  本发明公开了一种橡胶组合物，该组合物包含一种二烯基弹性体和一种由黄酮、亚甲基供体和亚甲基受体衍生的附着力促进剂。该橡胶组合物基本上不含钴。此外，还公开了一种包含这种橡胶组合物的充气轮胎。
• Cromolyn derivatives and related methods of imaging and treatment
  申请人：The General Hospital Corporation

  公开号：US10188757B2

  公开（公告）日：2019-01-29

  Novel cromolyn analogs useful as imaging agents for detecting atherosclerotic plaques and for treating atherosclerosis and Alzheimer's Disease, and methods of making the cromolyn analogs, are disclosed. The cromolyn analogs have the general formula; wherein X is OH, C1-C6 alkoxyl; Y and Z are independently selected from a C1-C6 alkyl, C1-C6 alkoxyl, halogen, mi-substituted or C1-C6 substituted amine, 18F, 19F, or H; and n is 1, 2, or 3; and wherein for structure (I), if n are both 1 and Y and Z are both H and X is OH.

  本发明公开了可用作检测动脉粥样硬化斑块和治疗动脉粥样硬化及阿尔茨海默氏症的成像剂的新型色瑞林类似物，以及制造色瑞林类似物的方法。色甘宁类似物具有通式； 其中 X 是 OH、C1-C6 烷氧基；Y 和 Z 独立选自 C1-C6 烷基、C1-C6 烷氧基、卤素、mi-取代或 C1-C6 取代的胺、18F、19F 或 H；n 是 1、2 或 3；对于结构 (I)，如果 n 均为 1 且 Y 和 Z 均为 H，则 X 是 OH。