1-{7-[3-(4-Hydroxy-tetrahydro-pyran-4-yl)-benzyloxy]-4-phenyl-naphthalen-2-yl}-ethanone | 156151-04-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-{7-[3-(4-Hydroxy-tetrahydro-pyran-4-yl)-benzyloxy]-4-phenyl-naphthalen-2-yl}-ethanone
• 英文别名: 1-[7-[[3-(4-hydroxyoxan-4-yl)phenyl]methoxy]-4-phenylnaphthalen-2-yl]ethanone
• CAS: 156151-04-1
• 化学式: C₃₀H₂₈O₄
• 分子量: 452.55
• InChiKey: CTSJGJBJQLBSTN-UHFFFAOYSA-N

物化性质

• 沸点：
  667.5±55.0 °C(Predicted)
• 密度：
  1.214±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 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：

  1-{7-[3-(4-Hydroxy-tetrahydro-pyran-4-yl)-benzyloxy]-4-phenyl-naphthalen-2-yl}-ethanone 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以90%的产率得到4-{3-[7-(1-Hydroxy-ethyl)-5-phenyl-naphthalen-2-yloxymethyl]-phenyl}-tetrahydro-pyran-4-ol
  参考文献：
  名称：

  Dioxabicyclooctanyl Naphthalenenitriles as Nonredox 5-Lipoxygenase Inhibitors:  Structure−Activity Relationship Study Directed toward the Improvement of Metabolic Stability

  摘要：

  Naphthalenic lignan lactone 3a (L-702,539), a potent and selective 5-lipoxygenase (5-LO) inhibitor, is extensively metabolized at two different sites: the tetrahydropyran and the lactone rings. Early knowledge of the metabolic pathways triggered and directed a structure-activity relationship study aimed toward the improvement of metabolic stability in this series. The best modifications discovered, i.e., replacement of the lactone ring by a nitrile group, replacement of the tetrahydropyran ring by a 6,8-dioxabicydo[3.2.1]octanyl moiety, and replacement of the pendant phenyl ring by a 3-furyl ring, were incorporated in a single molecule to produce inhibitor 9ac (L-708,780). Compound 9ac inhibits the oxidation of arachidonic acid to 5-hydroperoxy-eicosatetraenoic acid by 5-LO (IC50 = 190 nM) and the formation of leukotriene B-4 in human polymorphonuclear leukocytes (IC50 = 3 nM) as well as in human whole blood (IC50 = 150 nM). The good inhibitory profile shown by naphthalenenitrile 9ac is accompanied by an improved resistance to oxidative metabolism. In addition, 9ac is orally active in the functional model of antigen-induced bronchoconstriction in allergic squirrel monkeys (95% inhibition at 0.1 mg/kg).

  DOI：

  10.1021/jm960301c
• 作为产物：
  描述：

  1-phenyl-3-carboxy-6-naphthol 在 caesium carbonate 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 1-{7-[3-(4-Hydroxy-tetrahydro-pyran-4-yl)-benzyloxy]-4-phenyl-naphthalen-2-yl}-ethanone
  参考文献：
  名称：

  Dioxabicyclooctanyl Naphthalenenitriles as Nonredox 5-Lipoxygenase Inhibitors:  Structure−Activity Relationship Study Directed toward the Improvement of Metabolic Stability

  摘要：

  Naphthalenic lignan lactone 3a (L-702,539), a potent and selective 5-lipoxygenase (5-LO) inhibitor, is extensively metabolized at two different sites: the tetrahydropyran and the lactone rings. Early knowledge of the metabolic pathways triggered and directed a structure-activity relationship study aimed toward the improvement of metabolic stability in this series. The best modifications discovered, i.e., replacement of the lactone ring by a nitrile group, replacement of the tetrahydropyran ring by a 6,8-dioxabicydo[3.2.1]octanyl moiety, and replacement of the pendant phenyl ring by a 3-furyl ring, were incorporated in a single molecule to produce inhibitor 9ac (L-708,780). Compound 9ac inhibits the oxidation of arachidonic acid to 5-hydroperoxy-eicosatetraenoic acid by 5-LO (IC50 = 190 nM) and the formation of leukotriene B-4 in human polymorphonuclear leukocytes (IC50 = 3 nM) as well as in human whole blood (IC50 = 150 nM). The good inhibitory profile shown by naphthalenenitrile 9ac is accompanied by an improved resistance to oxidative metabolism. In addition, 9ac is orally active in the functional model of antigen-induced bronchoconstriction in allergic squirrel monkeys (95% inhibition at 0.1 mg/kg).

  DOI：

  10.1021/jm960301c