1,8-Dihydroxy-10-[methoxy-(4-trifluoromethyl-phenyl)-methyl]-10H-anthracen-9-one | 151562-81-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 1,8-Dihydroxy-10-[methoxy-(4-trifluoromethyl-phenyl)-methyl]-10H-anthracen-9-one
• 英文别名: 1,8-dihydroxy-10-[methoxy-[4-(trifluoromethyl)phenyl]methyl]-10H-anthracen-9-one
• CAS: 151562-81-1
• 化学式: C₂₃H₁₇F₃O₄
• 分子量: 414.381
• InChiKey: DDMWWVOMTCXEFT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1,8-Dihydroxy-10-[methoxy-(4-trifluoromethyl-phenyl)-methyl]-10H-anthracen-9-one 在 吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 生成 1,8-Dihydroxy-10-[(4-trifluoromethylphenyl)methylene]-9(10H)-anthracenone
  参考文献：
  名称：

  Synthesis, antiproliferative activity and inhibition of tubulin polymerization by 1,5- and 1,8-disubstituted 10H-anthracen-9-ones bearing a 10-benzylidene or 10-(2-oxo-2-phenylethylidene) moiety

  摘要：

  A novel series of 1,5- and 1,8-disubstituted 10-benzylidene-10H-anthracen-9-ones and 10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-ones was synthesized to assess the substituent effects on biological activity. The 3-hydroxy-2,4-dimethoxy-benzylidene analogue 16h displayed strong antiproliferative activity against several tumor cell lines, including multi-drug resistant phenotypes. Flow cytometric studies showed that KB/HeLa cells treated by elected compounds were arrested in the G2/M phases of the cell cycle. Among the compounds tested for inhibition of tubulin polymerization, 14 compounds proved to be exceptionally active with IC50 values < 1 mu M. In the 1,5-dichloro-derived series of benzylideneanthracenones, E/Z isomers were separated and biological effects were monitored. We found that the olefinic geometry had no significant effect on biological activity. Furthermore, the E isomeric 1,5-dichloro-substituted phenacylidenes entirely proved to be more potent inhibitors of tubulin polymerization than the recently described 10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-ones. In conclusion, the present study improves understanding of the action of anthracenone-based tubulin polymerization inhibitors and contributes to the design of further potent anti-tubulin drugs. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.04.032
• 作为产物：
  描述：

  4-三氟甲基苯甲醛二甲基缩醛 在 氯化亚砜 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 乙酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 1,8-Dihydroxy-10-[methoxy-(4-trifluoromethyl-phenyl)-methyl]-10H-anthracen-9-one
  参考文献：
  名称：

  Antipsoriatic anthrones with modulated redox properties. 1. Novel 10-substituted 1,8-dihydroxy-9(10H)-anthracenones as inhibitors of 5-lipoxygenase

  摘要：

  The syntheses, the biological evaluation, and the structure-activity relationships of a novel series of 1,8-dihydroxy-9(10H)-anthracenones bearing acyl-, alkyl-, or alkylidene-linked aromatic substituents in the 10-position are described. The phenylacyl and phenylalkylidene analogs were far more potent inhibitors of 5-lipoxygenase (5-LO) from bovine polymorphonuclear leukocytes (IC50 values in the 10(-7) M range) than the antipsoriatic drug anthralin, whereas phenylalkyl analogs were only weak inhibitors. Among the active compounds were both potent generators of hydroxyl radicals, as determined by deoxyribose degradation, and strong reducers of the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). However, several derivatives of this series maintained 5-LO inhibitory activity but did not generate hydroxyl radicals and were not reactive with DPPH. In particular, phenylacyl analogs were also 6 times more efficient in inhibition of lipid peroxidation in model membranes than anthralin. Structure-activity relationships have shown that the presence of free phenolic groups in the attached aromatic ring is beneficial but not required for 5-LO inhibitory potency. The inhibitory potency in the 10-phenylacyl series increased with the length of the acyl chain with three methylene units being the optimum, suggesting a specific enzyme interaction which would not be expected for nonspecific redox inhibitors.

  DOI：

  10.1021/jm00077a015

文献信息

• 10-SUBSTITUTED 1,8-DIHYDROXY-9(10H) ANTHRACENONE PHARMACEUTICALS
  申请人：TEVA PHARMACEUTICAL INDUSTRIES LTD.

  公开号：EP0664780A1

  公开（公告）日：1995-08-02
• US5426197A
  申请人：——

  公开号：US5426197A

  公开（公告）日：1995-06-20
• US5661187A
  申请人：——

  公开号：US5661187A

  公开（公告）日：1997-08-26
• US5844004A
  申请人：——

  公开号：US5844004A

  公开（公告）日：1998-12-01
• US5952390A
  申请人：——

  公开号：US5952390A

  公开（公告）日：1999-09-14