2-benzyloxy-1-(4-fluorophenyl)-5-ethyl-4-(3-chloro-1-propyloxy)benzene | 152120-07-5

• 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: 2-benzyloxy-1-(4-fluorophenyl)-5-ethyl-4-(3-chloro-1-propyloxy)benzene
• 英文别名: 1-benzyloxy-5-(3-chloropropoxy)-4-ethyl-2-(4-fluorophenyl)benzene；4-(benzyloxy)-2-(3-chloropropoxy)-5-(4-fluorophenyl)ethylbenzene；5-(4-fluorophenyl)-4-benzyloxy-2-(3-chloropropoxy)ethylbenzene；2-benzyloxy-1-(4-fluorophenyl)-5-ethyl-4-(3-chloro-l-propyloxy)benzene；3-(2-ethyl-4-(4-fluorophenyl)-5-benzyloxyphenoxy)propyl chloride；1-(3-chloropropoxy)-2-ethyl-4-(4-fluorophenyl)-5-phenylmethoxybenzene
• CAS: 152120-07-5
• 化学式: C₂₄H₂₄ClFO₂
• 分子量: 398.905
• InChiKey: VLNMEZVULMYSMQ-UHFFFAOYSA-N

物化性质

• 熔点：
  63-65 °C
• 沸点：
  499.7±45.0 °C(Predicted)
• 密度：
  1.156±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-benzyloxy-1-(4-fluorophenyl)-5-ethyl-4-(3-chloro-1-propyloxy)benzene 在 sodium azide 、 三乙胺盐酸盐 、 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 46.0h， 生成 3-<2-<3-<5-(benzyloxy)-2-ethyl-4-(4-fluorophenyl)phenoxy>propoxy>-6-<<4-(1H-tetrazol-5-yl)butyl>oxy>phenyl>propanoic acid ethyl ester
  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：

  1-bromo-2-(phenylmethoxy)-4-[(3-chloropropyl)oxy]-5-ethylbenzene 以100%的产率得到2-benzyloxy-1-(4-fluorophenyl)-5-ethyl-4-(3-chloro-1-propyloxy)benzene
  参考文献：
  名称：

  Substituted phenyl phenol leukotriene antagonists

  摘要：

  具有取代苯酚或取代酚联苯结构以及各种衍生物的拮抗剂是特定的白三烯拮抗剂。它们的结构、用途和合成已被披露。此外，还公开了用于治疗由花生四烯酸代谢物之一白三烯B.sub.4过度释放所特征的疾病或症状的药物配方。主要的LTB.sub.4拮抗结构表示为：##STR1##

  公开号：

  US05462954A1

文献信息

• Substituted phenyl phenol leukotriene antagonists
  申请人：Eli Lilly and Company

  公开号：US05462954A1

  公开（公告）日：1995-10-31

  Antagonists having a substituted phenyl phenol or a substituted phenolic biphenyl structure, and various derivatives thereof, are specific leukotriene antagonists. Their structures, use and synthesis are disclosed. Also, pharmaceutical formulations are disclosed for use in applications treating diseases or conditions characterized by excessive release of leukotriene B.sub.4, one of the metabolites of arachidonic acid. The primary LTB.sub.4 antagonistic structures are represented as: ##STR1##

  具有取代苯酚或取代酚联苯结构以及各种衍生物的拮抗剂是特定的白三烯拮抗剂。它们的结构、用途和合成已被披露。此外，还公开了用于治疗由花生四烯酸代谢物之一白三烯B.sub.4过度释放所特征的疾病或症状的药物配方。主要的LTB.sub.4拮抗结构表示为：##STR1##
• [EN] LEUKOTRIENE B4 ANTAGONIST COMPOUND<br/>[FR] COMPOSÉ ANTAGONISTE DES LEUCOTRIÈNES B4
  申请人：LILLY CO ELI

  公开号：WO2013106238A1

  公开（公告）日：2013-07-18

  The present invention provides a compound of Formula (I): or a pharmaceutically acceptable salt thereof. Also, the present invention provides a pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. The present invention further provides methods for treating abdominal aortic aneurysm or atherosclerosis comprising administering a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula (I) or pharmaceutically acceptable salt thereof.

  本发明提供了一种化合物，其化学式为（I）：或其药学上可接受的盐。此外，本发明还提供了一种包括化合物（I）或其药学上可接受的盐以及药学上可接受的载体的药物组合物。本发明还提供了治疗腹主动脉瘤或动脉粥样硬化的方法，包括给予化合物（I）或其药学上可接受的盐的治疗有效量，或者包括药学上可接受的载体和化合物（I）或其药学上可接受的盐的治疗有效量的药物组合物。
• Use of PLA.sub.2 inhibitors as treatment for alzheimer's disease
  申请人：Eli Lilly and Company

  公开号：US05478857A1

  公开（公告）日：1995-12-26

  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 A.sub.2. This invention also provides a series of compounds which are useful as inhibitors of phospholipases A.sub.2, especially cytosolic phospholipase A.sub.2.

  该发明提供了治疗或预防哺乳动物阿尔茨海默病的方法，包括向需要的哺乳动物施用磷脂酶A.sub.2的抑制剂的有效量。该发明还提供了一系列化合物，这些化合物可用作磷脂酶A.sub.2的抑制剂，尤其是细胞质磷脂酶A.sub.2。
• Methods for identifying and treating resistant tumors
  申请人：Eli Lilly and Company

  公开号：US06235785B1

  公开（公告）日：2001-05-22

  This invention provides a method of identifying and reversing multidrug resistance in a multidrug resistance tumor comprising administering a multidrug resistance reversing amount of any of the compounds as defined herein.

  该发明提供了一种识别和逆转多药耐药的方法，包括向多药耐药肿瘤中施用本文定义的任何化合物的多药耐药逆转量。
• Method for treating resistant tumors
  申请人：Eli Lilly and Company

  公开号：US05543428A1

  公开（公告）日：1996-08-06

  This invention provides a method of reversing multidrug resistance in a multidrug resistance tumor comprising administering a multidrug resistance reversing amount of any of a series of phenoxy compounds as defined herein.

  这项发明提供了一种逆转多药耐药性的方法，包括向多药耐药性肿瘤施用本文定义的一系列苯氧化合物中的任何一种的多药耐药性逆转剂量。