7-hydroxy-4-phenylnaphtho<2,3-c>furan-1(3H)-one | 144800-92-0

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 芳基萘木脂素
• 英文名称: 7-hydroxy-4-phenylnaphtho<2,3-c>furan-1(3H)-one
• 英文别名: 6-hydroxy-9-phenyl-1H-benzo[f][2]benzofuran-3-one
• CAS: 144800-92-0
• 化学式: C₁₈H₁₂O₃
• 分子量: 276.291
• InChiKey: XUOLHQIAHXFRHM-UHFFFAOYSA-N

物化性质

• 沸点：
  568.8±50.0 °C(Predicted)
• 密度：
  1.355±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-hydroxy-4-phenylnaphtho<2,3-c>furan-1(3H)-one 在 1,1'-双(二苯基膦)二茂铁 、 palladium diacetate 、 2,6-二叔丁基吡啶 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.67h， 生成 7-(methoxycarbonyl)-4-phenylnaphtho<2,3-c>furan-1(3H)-one
  参考文献：
  名称：

  Naphthalenic Lignan Lactones as Selective, Nonredox 5-Lipoxygenase Inhibitors. Synthesis and Biological Activity of (Methoxyalkyl)thiazole and Methoxytetrahydropyran Hybrids

  摘要：

  Combinations of structural elements found in (methoxyalkyl)thiazole 1a and methoxytetrahydropyran 2a with a naphthalenic lignan lactone produce the potent 5-lipoxygenase (5-LO) inhibitors 3 and 4. While the nature of link Y-Z has a major effect on the in vitro activity of compounds 1 and 2, inhibitors 3 and 4 retain their potencies with either an oxymethylene (Y = O, Z = CH2) or a methyleneoxy (Y = CH2, Z = O) link. Compound 4b inhibits the oxidation of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid by 5-LO (IC50 = 14 nM) and the formation of leukotriene Bq in human polymorphonuclear leukocytes (IC50 = 1.5 nM) as well as in human whole blood (IC50 = 50 nM). Compound 4b is a selective 5-LO inhibitor showing no significant inhibition of human 15-lipoxygenase or porcine 12-lipoxygenase or binding to human 5-lipoxygenase-activating protein up to 10 mu M and inhibits leukotriene biosynthesis by a direct, nonredox interaction with 5-LO. Compound 15, the open form of lactone 4b, is well absorbed in the rat and is transformed into the active species 4b. In addition, 15 is orally active in the rat pleurisy model (ED(50) = 0.6 mg/kg) and in the functional model of antigen-induced bronchoconstriction in allergic squirrel monkeys (95% inhibition at 0.3 mg/kg).

  DOI：

  10.1021/jm00030a010
• 作为产物：
  描述：

  3-[Hydroxy-(3-phenylmethoxyphenyl)methyl]-4-[phenyl-bis(phenylsulfanyl)methyl]oxolan-2-one 在 茴香硫醚 、 三氟乙酸 作用下， 反应 1.0h， 生成 7-hydroxy-4-phenylnaphtho<2,3-c>furan-1(3H)-one
  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

文献信息

• Pyranylphenyl hydroxyalkylnaphthoic acids as inhibitors of leukotriene biosynthesis
  申请人：MERCK FROSST CANADA INC.

  公开号：EP0501578A1

  公开（公告）日：1992-09-02

  Compounds having the formula I: are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis and allograft rejection and in preventing the formation of atherosclerotic plaques.

  具有式 I 的化合物： 是白三烯生物合成的抑制剂。这些化合物可用作抗哮喘、抗过敏、抗炎和细胞保护剂。它们还可用于治疗心绞痛、脑痉挛、肾小球肾炎、肝炎、内毒素血症、葡萄膜炎和异体移植排斥反应，以及预防动脉粥样硬化斑块的形成。
• Naphthalene lactones as inhibitors of leukotriene biosynthesis
  申请人：MERCK FROSST CANADA INC.

  公开号：EP0501579A1

  公开（公告）日：1992-09-02

  Compounds having the formula I: are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis and allograft rejection and in preventing the formation of atherosclerotic plaques.

  具有式 I 的化合物： 是白三烯生物合成的抑制剂。这些化合物可用作抗哮喘、抗过敏、抗炎和细胞保护剂、 抗过敏、抗炎和细胞保护剂。它们还可用于治疗心绞痛、脑痉挛、肾小球肾炎、肝炎、内毒素血症、葡萄膜炎和异体移植排斥反应，以及预防动脉粥样硬化斑块的形成。
• Ducharme Yves, Brideau Christine, Dube Daniel, Chan Chi-Chung, Falgueyret+, J. Med. Chem, 37 (1994) N 4, S 512-518
  作者：Ducharme Yves, Brideau Christine, Dube Daniel, Chan Chi-Chung, Falgueyret+

  DOI：——

  日期：——
• US5227399A
  申请人：——

  公开号：US5227399A

  公开（公告）日：1993-07-13
• US5281720A
  申请人：——

  公开号：US5281720A

  公开（公告）日：1994-01-25