1-allyl-1,3,3a,4,4a,11a-hexahydro-10,12-dioxo-1,4a-methano-furo[3,4-b]xanthene | 786705-89-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 1-allyl-1,3,3a,4,4a,11a-hexahydro-10,12-dioxo-1,4a-methano-furo[3,4-b]xanthene
• 英文别名: 13-Prop-2-enyl-2,14-dioxapentacyclo[11.4.1.01,10.03,8.012,16]octadeca-3,5,7,10-tetraene-9,18-dione
• CAS: 786705-89-3
• 化学式: C₁₉H₁₆O₄
• 分子量: 308.334
• InChiKey: VKVHRFPOPZNKAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,4-bis(allyloxy)-9H-xanthen-9-one 以 萘烷 为溶剂， 反应 3.0h， 以32%的产率得到1-allyl-1,3,3a,4,5,12a-hexahydro-7,13-dioxo-1,5-methano-furo[3,4-d]xanthene
  参考文献：
  名称：

  Synthesis and evaluation of novel aza-caged Garcinia xanthones

  摘要：

  受简化笼型呫吨酮治疗潜力的启发，我们开发了一种化学策略，通过区域选择性Claisen/Diels-Alder串联反应合成新颖的氮笼型藤黄模拟物。区域选择性的起源已通过DFT方法解释。我们进一步评估了这些化合物的细胞增殖和IKKβ抑制活性，并通过分子对接研究了它们与IKKβ的结合模式。结果表明，氮笼型骨架提供了合适的修饰位点，疏水基团的引入提高了细胞毒性和IKKβ抑制活性。氮笼型化合物6c对HepG2、A549细胞和IKKβ的IC50值分别为2.68、2.10、8.02 μM。6c的机理研究表明，氮笼型化合物诱导A549细胞凋亡和细胞周期S期阻滞。

  DOI：

  10.1039/c2ob07088j

文献信息

• SMALL MOLECULE THERAPEUTICS, SYNTHESIS OF ANALOGUES AND DERIVATIVES AND METHODS OF USE
  申请人：Theodorakis Emmanuel

  公开号：US20100137421A1

  公开（公告）日：2010-06-03

  Provided herein are compounds that are inducers of apoptosis activators of caspases and pharmaceutically acceptable derivatives thereof. Also provided are methods of synthesis of the compounds and methods for treatment of diseases in which there is uncontrolled cell growth and spread of abnormal cells, such as cancers, by administering the compounds.

  本文提供的化合物是凋亡激活剂和半胱氨酸蛋白酶的诱导剂，以及其药用可接受的衍生物。还提供了合成这些化合物的方法，以及通过给予这些化合物来治疗细胞生长失控和异常细胞扩散等疾病的方法，如癌症。
• Methods of treating diseases responsive to induction of Apoptosis and screening assays
  申请人：Kasibhatla Shailaja

  公开号：US20050004026A1

  公开（公告）日：2005-01-06

  The present invention pertains to a method of treating, preventing or ameliorating a disease responsive to induction of the caspase cascade in an animal, comprising administering to the animal a compound which binds specifically to one or more Apoptosis Inducing Proteins (AIPs). AIPs include Transferrin Receptor Related Apoptosis Inducing Proteins (TRRAIPs), Clathrin Heavy Chain Related Apoptosis Inducing Proteins (CHCRAIPs), IQ motif containing GTPase Activating Protein Related Apoptosis Inducing Proteins (IQGAPRAIPs), and Heat Shock Protein Related Apoptosis Inducing Proteins (HSPRAIPs). The present invention also relates to screening methods useful for drug discovery of apoptosis inducing compounds. In particular, the screening methodology relates to using AIPs as a target for the discovery of apoptosis activators useful as anticancer agents. The screening methods of the present invention can employ homogenous or heterogenous binding assays using purified or partially purified AIPs; or whole cell assays using cells with altered levels of one or more AIPs. The invention also contemplates use of gambogic acid or GA-related compounds which bind AIPs and can accordingly be used to raise antibodies useful for drug discovery. Alternatively, labeled GA is used for competitive binding assays for drug discovery. Such assays afford high throughput screening of chemical libraries for apoptosis activators.

  本发明涉及一种治疗、预防或改善动物中对caspase级联诱导敏感的疾病的方法，包括向动物中注射一种与一种或多种凋亡诱导蛋白（AIPs）特异结合的化合物。AIPs包括转铁蛋白受体相关凋亡诱导蛋白（TRRAIPs）、衣蛋白重链相关凋亡诱导蛋白（CHCRAIPs）、IQ基序含有GTP酶激活蛋白相关凋亡诱导蛋白（IQGAPRAIPs）和热休克蛋白相关凋亡诱导蛋白（HSPRAIPs）。本发明还涉及用于药物发现凋亡诱导化合物的筛选方法。特别地，筛选方法涉及使用AIPs作为发现凋亡激活剂用于抗癌药物的靶点。本发明的筛选方法可以使用纯化或部分纯化的AIPs进行同质或异质结合分析的细胞分析，或使用具有改变一种或多种AIPs水平的细胞进行整个细胞分析。本发明还考虑使用结合AIPs的苦参酸或GA相关化合物，可用于制备用于药物发现的抗体。或者，标记的GA可用于竞争性结合分析，用于药物发现。这种分析可用于高通量筛选化学库以寻找凋亡激活剂。
• US7592143B2
  申请人：——

  公开号：US7592143B2

  公开（公告）日：2009-09-22
• Synthesis and evaluation of novel aza-caged Garcinia xanthones
  作者：Xiaojin Zhang、Xiang Li、Haopeng Sun、Zhengyu Jiang、Lei Tao、Yuan Gao、Qinglong Guo、Qidong You

  DOI：10.1039/c2ob07088j

  日期：——

  Inspired by the therapeutic potential of the simplified caged xanthones, we have developed a chemical strategy for synthesizing novel aza-caged Garcinia analogues through a regioselective Claisen/Diels–Alder cascade reaction. The origin of regioselectivity has been explained using the DFT method. We have further evaluated the cell proliferation and IKKβ inhibitory activities of these compounds and studied their binding mode with IKKβ by molecular docking. The results suggested that the aza-caged scaffold provides a suitable modification site and the introduction of a hydrophobic moiety leads to improvement in the cytotoxicity and IKKβ inhibitory activity. The aza-caged compound 6c exhibited an IC50 value of 2.68, 2.10, 8.02 μM against the HepG2, A549 cells and IKKβ, respectively. Mechanism studies with 6c showed that the aza-caged compounds induce apoptosis and cell cycle S phase arrest in A549 cells.

  受简化笼型呫吨酮治疗潜力的启发，我们开发了一种化学策略，通过区域选择性Claisen/Diels-Alder串联反应合成新颖的氮笼型藤黄模拟物。区域选择性的起源已通过DFT方法解释。我们进一步评估了这些化合物的细胞增殖和IKKβ抑制活性，并通过分子对接研究了它们与IKKβ的结合模式。结果表明，氮笼型骨架提供了合适的修饰位点，疏水基团的引入提高了细胞毒性和IKKβ抑制活性。氮笼型化合物6c对HepG2、A549细胞和IKKβ的IC50值分别为2.68、2.10、8.02 μM。6c的机理研究表明，氮笼型化合物诱导A549细胞凋亡和细胞周期S期阻滞。