1H-naphtho[1,2-c]chromene-1,4,5-trione | 1448692-59-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: 1H-naphtho[1,2-c]chromene-1,4,5-trione
• 英文别名: Naphtho[1,2-c]chromene-1,4,5-trione；naphtho[1,2-c]chromene-1,4,5-trione
• CAS: 1448692-59-8
• 化学式: C₁₇H₈O₄
• 分子量: 276.248
• InChiKey: HFHCEBAWIQEUHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-bromo-2H-chromen-2-one 在 1,1'-双(二苯基膦)二茂铁 、 tris-(dibenzylideneacetone)dipalladium(0) 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 16.0h， 生成 1H-naphtho[1,2-c]chromene-1,4,5-trione
  参考文献：
  名称：

  4-Vinyl-2H-1-benzopyran-2-ones 在 Diels-Alder 环加成反应中的反应性：获得具有 Cdc25 磷酸酶抑制活性的基于香豆素的多环

  摘要：

  4-(1-butoxyvinyl)-2H-chromen-2-one (1) 和 (E)-4-(2-butoxyvinyl)-2H-chromen-2-one (2) 在热 Diels 中作为二烯的反应性–报道了与几种缺电子亲二烯体的 Alder 环加成反应。在本研究中使用的几种亲二烯体中，1,4-苯醌提供环加合物 11-丁氧基-1H-萘并[1,2-c]色烯-1,4,5-三酮 (3e) 和 1H-萘并[1,2-c ]chromene-1,4,5-trione (4g) 在低微摩尔值下显示 Cdc25 磷酸酶抑制活性，这两种化合物对 Cdc25 A 和 Cdc25 C 异构体​​更有效。

  DOI：

  10.1002/ejoc.201201736

文献信息

• Reactivity of 4-Vinyl-2<i>H</i>-1-benzopyran-2-ones in Diels-Alder Cycloaddition Reactions: Access to Coumarin-Based Polycycles with Cdc25 Phosphatase-Inhibiting Activity
  作者：Sergio Valente、Zhanjie Xu、Emilie Bana、Clemens Zwergel、Antonello Mai、Claus Jacob、Peter Meiser、Denyse Bagrel、Artur M. S. Silva、Gilbert Kirsch

  DOI：10.1002/ejoc.201201736

  日期：2013.5

  The reactivity of 4-(1-butoxyvinyl)-2H-chromen-2-one (1) and (E)-4-(2-butoxyvinyl)-2H-chromen-2-one (2) as diene in thermal Diels–Alder cycloaddition reactions with several electron-poor dienophiles is reported. Among several dienophiles used in this study 1,4-benzoquinone afforded cycloadducts 11-butoxy-1H-naphtho[1,2-c]chromene-1,4,5-trione (3e) and 1H-naphtho[1,2-c]chromene-1,4,5-trione (4g) that

  4-(1-butoxyvinyl)-2H-chromen-2-one (1) 和 (E)-4-(2-butoxyvinyl)-2H-chromen-2-one (2) 在热 Diels 中作为二烯的反应性–报道了与几种缺电子亲二烯体的 Alder 环加成反应。在本研究中使用的几种亲二烯体中，1,4-苯醌提供环加合物 11-丁氧基-1H-萘并[1,2-c]色烯-1,4,5-三酮 (3e) 和 1H-萘并[1,2-c ]chromene-1,4,5-trione (4g) 在低微摩尔值下显示 Cdc25 磷酸酶抑制活性，这两种化合物对 Cdc25 A 和 Cdc25 C 异构体​​更有效。
• Novel coumarin- and quinolinone-based polycycles as cell division cycle 25-A and -C phosphatases inhibitors induce proliferation arrest and apoptosis in cancer cells
  作者：Clemens Zwergel、Brigitte Czepukojc、Emilie Evain-Bana、Zhanjie Xu、Giulia Stazi、Mattia Mori、Alexandros Patsilinakos、Antonello Mai、Bruno Botta、Rino Ragno、Denise Bagrel、Gilbert Kirsch、Peter Meiser、Claus Jacob、Mathias Montenarh、Sergio Valente

  DOI：10.1016/j.ejmech.2017.04.012

  日期：2017.7

  Cell division cycle phosphatases CDC25 A, B and C are involved in modulating cell cycle processes and are found overexpressed in a large panel of cancer typology. Here, we describe the development of two novel quinone-polycycle series of CDC25A and C inhibitors on the one hand la-k, coumarin-based, and on the other 2a-g, quinolinone-based, which inhibit either enzymes up to a sub-micro molar level and at single digit micro molar concentrations, respectively. When tested in six different cancer cell lines, compound 2c displayed the highest efficacy to arrest cell viability, showing in almost all cell lines sub-micro molar IC50 values, a profile even better than the reference compound NCS95397. To investigate the putative binding mode of the inhibitors and to develop quantitative structure-activity relationships, molecular docking and 3-D QSAR studies were also carried out. Four selected inhibitors, la, ld, 2a and 2c have been also tested in A431 cancer cells; among them, compound 2c was the most potent one leading to cell proliferation arrest and decreased CDC25C protein levels together with its splicing variant. Compound 2c displayed increased phosphorylation levels of histone H3, induction of PARP and caspase 3 cleavage, highlighting its contribution to cell death through pro-apoptotic effects. (C) 2017 Elsevier Masson SAS. All rights reserved.