(E)-1,8-Dihydroxy-10-[3-(3-methoxyphenyl)-1-oxo-2-propenyl]-9(10H)-anthracenone

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: (E)-1,8-Dihydroxy-10-[3-(3-methoxyphenyl)-1-oxo-2-propenyl]-9(10H)-anthracenone
• 英文别名: (E)-1,8-Dihydroxy-10-[3-(3-methoxy-phenyl)-acryloyl]-10H-anthracen-9-one；1,8-dihydroxy-10-[(E)-3-(3-methoxyphenyl)prop-2-enoyl]-10H-anthracen-9-one
• 化学式: C₂₄H₁₈O₅
• 分子量: 386.404
• InChiKey: BCLNDDOCALUAHU-VAWYXSNFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  地蒽酚 、 (E)-3-methoxycinnamoyl chloride 在 吡啶 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以36%的产率得到(E)-1,8-Dihydroxy-10-[3-(3-methoxyphenyl)-1-oxo-2-propenyl]-9(10H)-anthracenone
  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
• US6127426A
  申请人：——

  公开号：US6127426A

  公开（公告）日：2000-10-03
• [EN] 10-SUBSTITUTED 1,8-DIHYDROXY-9(10H) ANTHRACENONE PHARMACEUTICALS<br/>[FR] PRODUITS PHARMACEUTIQUES A BASE D'ANTHRACENONES 1,8-DIHYDROXY-9(10H) SUBSTITUEES EN POSITION 10
  申请人：——

  公开号：WO1995003266A1

  公开（公告）日：1995-02-02

  [EN] Therapeutic compositions comprising 1,8-dihydroxy-9(10H) anthracenones substituted at position 10 thereof with phenylalkylidene or arylacyl blocking moieties, said compounds having substantial therapeutic activity and minimal inflammatory effect.
  [FR] Compositions thérapeutiques comprenant des anthracénones 1,8-dihydroxy-9 (10H) substituées en position 10, avec des fractions de blocage du phénylalkylidène ou de l'arylacyle, ces composés présentant une importante activité thérapeutique et un effet inflammatoire minime.