10-[2-(3-methoxyphenyl)-2-oxoethylidene]-10H-anthracen-9-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 10-[2-(3-methoxyphenyl)-2-oxoethylidene]-10H-anthracen-9-one
• 英文别名: 10-[2-(3-methoxy-phenyl)-2-oxo-ethylidene]-10H-anthracen-9-one；10-[2-(3-Methoxyphenyl)-2-oxoethylidene]anthracen-9-one
• 化学式: C₂₃H₁₆O₃
• 分子量: 340.378
• InChiKey: SBRPPUGOMDHGCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  蒽酮 、 3-甲氧基苯基乙二醛水合物 在 乙酸酐 作用下， 以 水 为溶剂， 以22%的产率得到10-[2-(3-methoxyphenyl)-2-oxoethylidene]-10H-anthracen-9-one
  参考文献：
  名称：

  10-(2-oxo-2-Phenylethylidene)-10H-anthracen-9-ones as Highly Active Antimicrotubule Agents: Synthesis, Antiproliferative Activity, and Inhibition of Tubulin Polymerization

  摘要：

  A series of 10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-ones were synthesized and evaluated for interactions with tubulin and for antiproliferative activity against a panel of human and rodent tumor cell lines. The 4-methoxy analogue 17b was most potent, displaying IC50 values ranging from 40 to 80 nM, including multidrug resistant phenotypes, and had excellent activity as an inhibitor of tubulin polymerization (IC50 = 0.52 mu M). Concentration-dependent flow cytometric studies showed that KB/HeLa cells treated with 17b were arrested in the G2/M phases of the cell cycle (EC50 = 90 nM). In competition experiments, 17b strongly displaced [H-3]-colchicine from its binding site in the tubulin. The results obtained demonstrate that the anti proliferative activity is related to the inhibition of tubulin polymerization.

  DOI：

  10.1021/jm801338r

文献信息

• ANTHRACENE COMPOUNDS AND THEIR USE FOR TREATING BENIGN AND MALIGNANT TUMOR DISORDERS
  申请人：Gerlach Matthias

  公开号：US20080051463A1

  公开（公告）日：2008-02-28

  The present invention provides novel anthracene compounds according to the formulae (I) and (II) and also selected anthracene compound compounds. The present invention furthermore provides a process for preparing such anthracene compounds. Also provided are pharmaceutical formulations comprising these anthracene compounds. The anthracene compounds provided are particularly suitable for the treatment and/or prophylaxis of physiological and/or pathophysiological conditions which can be treated by inhibiting tubulin polymerization and/or by inhibiting microtubuli-based motor proteins, in particular various tumor disorders.

  本发明提供了根据式(I)和(II)的新型蒽醌化合物，还提供了选定的蒽醌化合物。本发明还提供了制备这些蒽醌化合物的方法。还提供了包含这些蒽醌化合物的药物配方。提供的蒽醌化合物特别适用于治疗和/或预防可以通过抑制微管聚合和/或抑制微管基础马达蛋白来治疗的生理和/或病理生理状况，特别是各种肿瘤疾病。
• [DE] ANTHRACEN-DERIVATE UND DEREN VERWENDUNG ZUR BEHANDLUNG GUTARTIGER UND BÖSARTIGER TUMORERKRANKUNGEN<br/>[EN] ANTHRACEN DERIVATIVES AND THEIR USE FOR THE TREATMENT OF BENIGN AND MALIGNANT TUMOROUS DISEASES<br/>[FR] DÉRIVÉS DE L'ANTHRACÈNE ET LEUR UTILISATION POUR LE TRAITEMENT D'AFFECTIONS TUMORALES BÉNIGNES ET MALIGNES
  申请人：AETERNA ZENTARIS GMBH

  公开号：WO2008015265A1

  公开（公告）日：2008-02-07

  [EN] The present invention provides anthracen derivatives according to the general formulas (I) and (II), as well as selected anthracen derivative compounds. Further, the present invention provides a method for the production of such anthracen derivatives. Further, pharmaceutical formulations containing these anthracen derivatives are provided. The anthracen derivatives provided are particularly suited to be used for the treatment or prophylaxis of physiological and/or pathophysiological conditions that can be treated by means of the inhibition of the tubulin polymerization, and/or by means of the inhibition of microtubuli-based motor proteins, particularly of diverse tumorous diseases.
  [FR] La présente invention concerne des dérivés de l'anthracène selon les formules générales (I) et (II), ainsi que des composés choisis des dérivés de l'anthracène. En outre, la présente invention concerne un procédé pour la préparation de tels dérivés de l'anthracène. En outre, l'invention concerne des formulations pharmaceutiques qui contiennent ces dérivés de l'anthracène. Les dérivés de l'anthracène selon l'invention conviennent en particulier au traitement ou à la prophylaxie d'états physiologiques et/ou pathophysiologiques pouvant être traités par l'inhibition de la polymérisation des tubulines et/ou par l'inhibition de protéines motrices à base de microtubules, en particulier de diverses affections tumorales.
  [DE] Die vorliegende Erfindung stellt Anthracen-Derivate gemäß der allgemeinen Formel (I) und (II) sowie ausgewählte Anthracen-Derivat-Verbindungen bereit. Ferner stellt die vorliegende Erfindung ein Verfahren zur Herstellung solcher Anthracen-Derivate bereit. Des Weiteren werden diese Anthracen-Derivate enthaltenden pharmazeutischen Formulierungen bereitgestellt. Die bereitgestellten Anthracen-Derivate sind insbesondere geeignet zur Behandlung oder Prophylaxe von durch die Inhibition der Tubulin-Polymerisation und/oder von durch die Inhibition Microtubuli-basierten Motorproteinen behandelbaren physiologischen und/oder pathophysiologischen Zuständen, insbesondere diverser Tumorerkrankungen, eingesetzt zu werden.
• 10-(2-<i>oxo</i>-2-Phenylethylidene)-10<i>H</i>-anthracen-9-ones as Highly Active Antimicrotubule Agents: Synthesis, Antiproliferative Activity, and Inhibition of Tubulin Polymerization
  作者：Helge Prinz、Peter Schmidt、Konrad J. Böhm、Silke Baasner、Klaus Müller、Eberhard Unger、Matthias Gerlach、Eckhard G. Günther

  DOI：10.1021/jm801338r

  日期：2009.3.12

  A series of 10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-ones were synthesized and evaluated for interactions with tubulin and for antiproliferative activity against a panel of human and rodent tumor cell lines. The 4-methoxy analogue 17b was most potent, displaying IC50 values ranging from 40 to 80 nM, including multidrug resistant phenotypes, and had excellent activity as an inhibitor of tubulin polymerization (IC50 = 0.52 mu M). Concentration-dependent flow cytometric studies showed that KB/HeLa cells treated with 17b were arrested in the G2/M phases of the cell cycle (EC50 = 90 nM). In competition experiments, 17b strongly displaced [H-3]-colchicine from its binding site in the tubulin. The results obtained demonstrate that the anti proliferative activity is related to the inhibition of tubulin polymerization.