1-(benzyloxy)-4-ethyl-5-<(6-methyl-6-cyanoheptyl)oxy>-2-phenylbenzene | 152609-41-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(benzyloxy)-4-ethyl-5-<(6-methyl-6-cyanoheptyl)oxy>-2-phenylbenzene
• 英文别名: 1-benzyloxy-2-phenyl-4-ethyl-5-(6-methyl-6-cyanoheptyloxy)benzene；7-(2-Ethyl-4-phenyl-5-phenylmethoxyphenoxy)-2,2-dimethylheptanenitrile
• CAS: 152609-41-1
• 化学式: C₃₀H₃₅NO₂
• 分子量: 441.613
• InChiKey: IQPSIXOOUUIENF-UHFFFAOYSA-N

物化性质

• 沸点：
  584.2±50.0 °C(Predicted)
• 密度：
  1.047±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(benzyloxy)-4-ethyl-5-<(6-methyl-6-cyanoheptyl)oxy>-2-phenylbenzene 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 以79%的产率得到4-ethyl-5-<(6-methyl-6-cyanoheptyl)oxy>-2-phenylphenol
  参考文献：
  名称：

  Synthetic and Structure/Activity Studies on Acid-Substituted 2-Arylphenols: Discovery of 2-[2-Propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]- propoxy]phenoxy]benzoic Acid, a High-Affinity Leukotriene B4 Receptor Antagonist

  摘要：

  Structural derivatives of LY255283 have been studied as receptor antagonists of leukotriene B-4. Substitution of the 2-hydroxyacetophenone subunit of 1 (LY255283) with a 2-arylphenol group provided entry into several new series that feature various mono- and diacidic core functionality. These new analogues, the subject of a broad structure-activity investigation, displayed significantly increased in vitro and in vivo activity as receptor antagonists of LTB(4). A series of diaryl ether carboxylic acids demonstrated especially interesting activity and led to the discovery of compound 43b, 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]- propoxy]phenoxy]benzoic acid (LY293111), a 2-arylphenol-substituted diaryl ether carboxylic acid which displayed potent binding to human neutrophils (IC50 = 17 +/- 14.6 nM) and guinea pig lung membranes (IC50 6.6 +/- 0.71 nM), inhibition of LTB(4)-induced expression of the CD11b/CD18 receptor on human neutrophils (IC50 - 3.3 +/- 0.81 nM), and inhibition of LTB(4)-induced contraction of guinea pig lung parenchyma (pK(B) = 8.7 +/- 0.16). In vivo, 43b demonstrated potent activity in inhibiting LTB(4)-induced airway obstruction in the guinea pig when dosed by the oral (ED(50) = 0.40 mg/kg) or intravenous (ED(50) = 0.014 mg/kg) routes. A specific LTB(4) receptor antagonist, 43b had little effect on inhibiting contractions of guinea pig lung parenchyma induced by leukotriene D-4 (LTD(4)), histamine, carbachol, or U46619. Compound 43b has been chosen as a clinical candidate and is currently in phase I studies for a variety of inflammatory diseases.

  DOI：

  10.1021/jm00022a006
• 作为产物：
  描述：

  6-cyano-1-chloro-6-methylheptane 在 三乙基硅烷 、 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 、 三氟乙酸 、 potassium iodide 作用下， 以 四氯化碳 、 乙醇 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 47.5h， 生成 1-(benzyloxy)-4-ethyl-5-<(6-methyl-6-cyanoheptyl)oxy>-2-phenylbenzene
  参考文献：
  名称：

  Synthetic and Structure/Activity Studies on Acid-Substituted 2-Arylphenols: Discovery of 2-[2-Propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]- propoxy]phenoxy]benzoic Acid, a High-Affinity Leukotriene B4 Receptor Antagonist

  摘要：

  Structural derivatives of LY255283 have been studied as receptor antagonists of leukotriene B-4. Substitution of the 2-hydroxyacetophenone subunit of 1 (LY255283) with a 2-arylphenol group provided entry into several new series that feature various mono- and diacidic core functionality. These new analogues, the subject of a broad structure-activity investigation, displayed significantly increased in vitro and in vivo activity as receptor antagonists of LTB(4). A series of diaryl ether carboxylic acids demonstrated especially interesting activity and led to the discovery of compound 43b, 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]- propoxy]phenoxy]benzoic acid (LY293111), a 2-arylphenol-substituted diaryl ether carboxylic acid which displayed potent binding to human neutrophils (IC50 = 17 +/- 14.6 nM) and guinea pig lung membranes (IC50 6.6 +/- 0.71 nM), inhibition of LTB(4)-induced expression of the CD11b/CD18 receptor on human neutrophils (IC50 - 3.3 +/- 0.81 nM), and inhibition of LTB(4)-induced contraction of guinea pig lung parenchyma (pK(B) = 8.7 +/- 0.16). In vivo, 43b demonstrated potent activity in inhibiting LTB(4)-induced airway obstruction in the guinea pig when dosed by the oral (ED(50) = 0.40 mg/kg) or intravenous (ED(50) = 0.014 mg/kg) routes. A specific LTB(4) receptor antagonist, 43b had little effect on inhibiting contractions of guinea pig lung parenchyma induced by leukotriene D-4 (LTD(4)), histamine, carbachol, or U46619. Compound 43b has been chosen as a clinical candidate and is currently in phase I studies for a variety of inflammatory diseases.

  DOI：

  10.1021/jm00022a006

文献信息

• Leukotriene antagonists for use in the treatment or prevention of alzheimer's disease
  申请人：ELI LILLY AND COMPANY

  公开号：EP0743064A1

  公开（公告）日：1996-11-20

  This invention provides methods for the treatment or prevention of Alzheimer's disease which comprises administering to a mammal in need thereof an effective amount of a compound having activity as a leukotriene antagonist.

  这项发明提供了治疗或预防阿尔茨海默病的方法，包括向需要的哺乳动物施用具有白三烯拮抗活性的化合物的有效量。
• [EN] USE OF PLA2 INHIBITORS AS TREATMENT FOR ALZHEIMER'S DISEASE<br/>[FR] UTILISATION D'INHIBITEURS DE PLA2 POUR TRAITER LA MALADIE D'ALZHEIMER
  申请人：ELI LILLY AND COMPANY

  公开号：WO1995017183A1

  公开（公告）日：1995-06-29

  (EN) This invention provides methods for the treatment or prevention of Alzheimer's disease in a mammal which comprises administering to a mammal in need thereof an effective amount of an inhibitor of phospholipase A2. This invention also provides a series of compounds which are useful as inhibitors of phospholipases A2, especially cytosolic phospholipase A2.(FR) L'invention se rapporte à des procédés de traitement ou de prévention de la maladie d'Alzheimer chez un mammifère, ce procédé consistant à administrer à un mammifère nécessitant un tel traitement une dose efficace d'un inhibiteur de phospholipase A2 (PLA2). L'invention se rapporte également à une série de composés aptes à être utilisés comme inhibiteurs de phospholipases A2, en particulier de la phospholipase A2 cytosolique.

  该发明提供了一种治疗或预防哺乳动物阿尔茨海默病的方法，该方法包括向需要治疗的哺乳动物施用有效量的磷脂酶A2抑制剂。该发明还提供了一系列化合物，这些化合物可用作磷脂酶A2的抑制剂，特别是细胞质磷脂酶A2。
• o-Phenylphenols: potent and orally active leukotriene B4 receptor antagonists
  作者：Michael J. Sofia、Paul Floreancig、Nicholas J. Bach、S. Richard Baker、Sandra L. Cockerham、Jerome H. Fleisch、Larry L. Froelich、William T. Jackson、Philip Marder

  DOI：10.1021/jm00076a029

  日期：1993.11
• Substituted phenyl phenol leukotriene antagonists
  申请人：ELI LILLY AND COMPANY

  公开号：EP0544488B1

  公开（公告）日：1998-03-11
• USE OF PLA 2? INHIBITORS AS TREATMENT FOR ALZHEIMER'S DISEASE
  申请人：ELI LILLY AND COMPANY

  公开号：EP0735870A1

  公开（公告）日：1996-10-09