4-ethyl-5-<(6-methyl-6-cyanoheptyl)oxy>-2-(2-pyridinyl)phenol | 153227-15-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-ethyl-5-<(6-methyl-6-cyanoheptyl)oxy>-2-(2-pyridinyl)phenol
• 英文别名: 7-(2-Ethyl-5-hydroxy-4-pyridin-2-ylphenoxy)-2,2-dimethylheptanenitrile；7-(2-ethyl-5-hydroxy-4-pyridin-2-ylphenoxy)-2,2-dimethylheptanenitrile
• CAS: 153227-15-7
• 化学式: C₂₂H₂₈N₂O₂
• 分子量: 352.477
• InChiKey: YHYBAULRIUNJOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  66.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-ethyl-5-<(6-methyl-6-cyanoheptyl)oxy>-2-(2-pyridinyl)phenol 在 sodium azide 、 (dimethylamino)ethanol hydrochloride 作用下， 以 二乙二醇二甲醚 为溶剂， 生成 4-Ethyl-5-[6-methyl-6-(1H-tetrazol-5-yl)-heptyloxy]-2-pyridin-2-yl-phenol
  参考文献：
  名称：

  邻苯酚：有效和口服的白三烯B4受体拮抗剂。

  摘要：

  DOI：

  10.1021/jm00076a029
• 作为产物：
  描述：

  1-bromo-2-benzyloxy-4-(6-methyl-6-cyanoheptyloxy)-5-ethylbenzene 在 四(三苯基膦)钯 、 叔丁基锂 、 三溴化硼 、 zinc(II) chloride 作用下， 以 二氯甲烷 为溶剂， 反应 1.17h， 生成 4-ethyl-5-<(6-methyl-6-cyanoheptyl)oxy>-2-(2-pyridinyl)phenol
  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

• 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
• 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
  作者：J. Scott Sawyer、Nicholas J. Bach、S. Richard Baker、Ronald F. Baldwin、Peter S. Borromeo、Sandra L. Cockerham、Jerome H. Fleisch、Paul Floreancig、Larry L. Froelich

  DOI：10.1021/jm00022a006

  日期：1995.10

  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.