pyranoxanthone | 1241391-92-3

• 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: pyranoxanthone
• 英文别名: Dihydro-12-hydroxy-2,2-dimethyl-2H,6H-pyrano[3,2-B]xanthen-6-one；12-hydroxy-2,2-dimethyl-3,4-dihydropyrano[3,2-b]xanthen-6-one
• CAS: 1241391-92-3
• 化学式: C₁₈H₁₆O₄
• 分子量: 296.323
• InChiKey: MLFQPQKMYSPJGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  pyranoxanthone 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 3,4-dihydro-2,2-dimethyl-2H,6H-pyrano[3,2-b]xanthen-6-one-12-O-butyl 5,6-dimethylxanthone-4-acetate
  参考文献：
  名称：

  DMXAA-pyranoxanthone hybrids enhance inhibition activities against human cancer cells with multi-target functions

  摘要：

  Four 5,6-dimethylxanthone-4-acetic acid (D) and pyranoxanthone (P) hybrids (D-P-n) were design-synthesized based on multi-target-addressed strategy. D-P-4 was confirmed as the most active agent against HepG-2 cell line growth with an IC50 of 0.216 +/- 0.031 mu M. Apoptosis analysis indicated different contributions of early/late apoptosis/necrosis to cell death for both monomers, the combination (D + P in 1:1 mol ratio) and D-P-4. They all arrested more cells on S phase. Western Blot implied that D-P-4 regulated p53/MDM2 to a better healthy state. Moreover, it improved Bax/Bcl-2 signaling pathway to increase cancer cell apoptosis. In all cases studied, D-P-4 showed the best activity and synergistic effect. All the evidences support that D-P-4 is a better anti-cancer therapy with multi-target functions. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.10.074
• 作为产物：
  描述：

  (8-hydroxy-7-methoxy-2,2-dimethyl-3,4-dihydrobenzopyran-6-yl)(2-hydroxyphenyl)methanone 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 以92%的产率得到pyranoxanthone
  参考文献：
  名称：

  Multidimensional optimization of promising antitumor xanthone derivatives

  摘要：

  A promising antitumor xanthone derivative was optimized following a multidimensional approach that involved the synthesis of 17 analogues, the study of their lipophilicity and solubility, and the evaluation of their growth inhibitory activity on four human tumor cell lines. A new synthetic route for the hit xanthone derivative was also developed and applied for the synthesis of its analogues. Among the used cell lines, the HL-60 showed to be in general more sensitive to the compounds tested, with the most potent compound having a GI(50) of 5.1 mu M, lower than the hit compound. Lipophilicity was evaluated by the partition coefficient (K-p) of a solute between buffer and two membrane models, namely liposomes and micelles. The compounds showed a log K-p between 3 and 5 and the two membrane models showed a good correlation (r(2) = 0.916) between each other. Studies concerning relationship between solubility and structure were developed for the hit compound and 5 of its analogues. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.079

文献信息

• 一种DMXAA-Pyranoxanthone杂合体化合物 及其制备方法与用途
  申请人：广州药本君安医药科技股份有限公司

  公开号：CN107445970B

  公开（公告）日：2020-02-07

  本发明公开了一种具有抗肿瘤作用的DMXAA‑Pyranoxanthone杂合体化合物及其制备方法与用途。该化合物的结构如式I所示。其制备方法包括：三个步骤制备DMXAA，两个步骤制备pyranoxanthone，两个步骤将DMXAA和pyranoxanthone骈合为DMXAA‑Pyranoxanthone杂合体化合物。本发明所述DMXAA‑Pyranoxanthone杂合体化合物以及DMXAA/pyranoxanthone联合药物对乳腺癌、肝癌、白血病细胞具有优良的体外肿瘤细胞增殖抑制活性，并且能多靶点诱导肿瘤细胞的凋亡。本发明所述DMXAA‑Pyranoxanthone杂合体化合物以及DMXAA/pyranoxanthone联合药物可以应用于制备治疗癌症药物。
• p53 DEGRADATION INDUCING MOLECULE AND PHARMACEUTICAL COMPOSITION
  申请人：Tokyo University of Science Foundation

  公开号：EP3542821A1

  公开（公告）日：2019-09-25

  A p53 degradation inducing molecule which can induce degradation of p53 proteins or p53 composites, and a pharmaceutical composition containing said p53 degradation inducing molecule are provided. This p53 degradation inducing molecule is a conjugate of a p53 affinity molecule which has affinity for p53 proteins or p53 composites, and a proteolysis induction tag which has affinity for protease and which does not inhibit proteolysis of proteins by protease.

  本发明提供了一种可诱导 p53 蛋白或 p53 复合物降解的 p53 降解诱导分子，以及一种含有所述 p53 降解诱导分子的药物组合物。这种 p53 降解诱导分子是对 p53 蛋白质或 p53 复合物具有亲和力的 p53 亲和分子与对蛋白酶具有亲和力且不抑制蛋白酶对蛋白质的蛋白水解的蛋白水解诱导标签的共轭物。
• P53 degradation inducing molecule and pharmaceutical composition
  申请人：Tokyo University of Science Foundation

  公开号：US11007269B2

  公开（公告）日：2021-05-18

  A p53 degradation inducing molecule which can induce degradation of p53 proteins or p53 composites, and a pharmaceutical composition containing said p53 degradation inducing molecule are provided. This p53 degradation inducing molecule is a conjugate of a p53 affinity molecule which has affinity for p53 proteins or p53 composites, and a proteolysis induction tag which has affinity for protease and which does not inhibit proteolysis of proteins by protease.

  本发明提供了一种可诱导 p53 蛋白或 p53 复合物降解的 p53 降解诱导分子，以及一种含有所述 p53 降解诱导分子的药物组合物。这种 p53 降解诱导分子是对 p53 蛋白质或 p53 复合物具有亲和力的 p53 亲和分子与对蛋白酶具有亲和力且不抑制蛋白酶对蛋白质的蛋白水解的蛋白水解诱导标签的共轭物。
• Insights into the In Vitro Antitumor Mechanism of Action of a New Pyranoxanthone
  作者：Andreia Palmeira、Ana Paiva、Emília Sousa、Hugo Seca、Gabriela M. Almeida、Raquel T. Lima、Miguel X. Fernandes、Madalena Pinto、M. Helena Vasconcelos

  DOI：10.1111/j.1747-0285.2010.00978.x

  日期：——

  Naturally occurring xanthones have been documented as having antitumor properties, with some of them presently undergoing clinical trials. In an attempt to improve the biological activities of dihydroxyxanthones, prenylation and other molecular modifications were performed. All the compounds reduced viable cell number in a leukemia cell line K‐562, with the fused xanthone 3,4‐dihydro‐12‐hydroxy‐2,2‐dimethyl‐2H,6H‐pyrano[3,2‐b]xanthen‐6‐one (5) being the most potent. The pyranoxanthone 5 was particularly effective in additional leukemia cell lines (HL‐60 and BV‐173). Furthermore, the pyranoxanthone 5 decreased cellular proliferation and induced an S‐phase cell cycle arrest. In vitro, the pyranoxanthone 5 increased the percentage of apoptotic cells which was confirmed by an appropriate response at the protein level (e.g., PARP cleavage). Using a computer screening strategy based on the structure of several anti‐ and pro‐apoptotic proteins, it was verified that the pyranoxanthone 5 may block the binding of anti‐apoptotic Bcl‐xL to pro‐apoptotic Bad and Bim. The structure‐based screening revealed the pyranoxanthone 5 as a new scaffold that may guide the design of small molecules with better affinity profile for Bcl‐xL.
• P53 DEGRADATION INDUCING MOLECULE AND PHARMACEUTICAL COMPOSITION
  申请人：Tokyo University of Science Foundation

  公开号：US20190314508A1

  公开（公告）日：2019-10-17

  A p53 degradation inducing molecule which can induce degradation of p53 proteins or p53 composites, and a pharmaceutical composition containing said p53 degradation inducing molecule are provided. This p53 degradation inducing molecule is a conjugate of a p53 affinity molecule which has affinity for p53 proteins or p53 composites, and a proteolysis induction tag which has affinity for protease and which does not inhibit proteolysis of proteins by protease.