1-bromo-2-(phenylmethoxy)-4-[(3-chloropropyl)oxy]-5-ethylbenzene | 152609-60-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-bromo-2-(phenylmethoxy)-4-[(3-chloropropyl)oxy]-5-ethylbenzene
• 英文别名: 4-(benzyloxy)-5-bromo-2-(3-chloropropoxy)ethylbenzene；5-benzyloxy-4-bromo-1-(3-chloropropoxy)-2-ethylbenzene；3-(2-ethyl-4-bromo-5-benzyloxyphenoxy)propyl chloride；2-Benzyloxy-1-bromo-5-ethyl-4-(3-chloro-1-propyloxy)benzene；1-bromo-4-(3-chloropropoxy)-5-ethyl-2-phenylmethoxybenzene
• CAS: 152609-60-4
• 化学式: C₁₈H₂₀BrClO₂
• 分子量: 383.713
• InChiKey: ZADQDOZRALMSFK-UHFFFAOYSA-N

物化性质

• 熔点：
  55-57 °C
• 沸点：
  474.5±40.0 °C(Predicted)
• 密度：
  1.316±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-bromo-2-(phenylmethoxy)-4-[(3-chloropropyl)oxy]-5-ethylbenzene 在 四(三苯基膦)钯 、 sodium azide 、 三乙胺盐酸盐 、 sodium carbonate 、 potassium carbonate 、 potassium iodide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 62.0h， 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：

  4-(benzyloxy)-2-(3-chloropropoxy)ethylbenzene 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 四氯化碳 为溶剂， 以55%的产率得到1-bromo-2-(phenylmethoxy)-4-[(3-chloropropyl)oxy]-5-ethylbenzene
  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

• Heterocycle substituted diphenyl leukotriene antagonists
  申请人：Eli Lilly and Company

  公开号：US06797723B1

  公开（公告）日：2004-09-28

  The invention relates to novel heterocycle substituted diphenyl leukotriene B4 (LTB4) antagonists, to compositions containing such compounds, and to methods of using such compounds for treatment of inflammatory diseases.

  本发明涉及新颖的杂环取代的二苯基白三烯B4（LTB4）拮抗剂，涉及含有此类化合物的组合物，以及使用此类化合物治疗炎症性疾病的方法。
• 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。
• Methods for identifying and treating resistant tumors
  申请人：——

  公开号：US20020010213A1

  公开（公告）日：2002-01-24

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

  本发明提供了一种识别和逆转多药耐药肿瘤中的多药耐药性的方法，包括给予本文所定义的任何化合物的多药耐药性逆转剂量。
• An Efficient Synthesis of a Multipotent Eicosanoid Pathway Modulator
  作者：Matthew H. Yates、Thomas M. Koenig、Neil J. Kallman、Christopher P. Ley、David Mitchell

  DOI：10.1021/op800257u

  日期：2009.3.20

  An efficient, scalable synthesis of the multipotent eicosanoid pathway modulator 2-[3-[3[[5-ethyl-4'-fluoro-2-hydroxyl[1,1'-bi-phenyl]-4-yl]oxy]-propoxy]2-propoxylphenoxy]benzoic acid (1) is described. The process consists of nine chemical steps with the longest linear sequence having six isolations. Palladium metal-mediated cross-coupling assembles the biaryl fragment, and selective S(N)Ar chemistry is used to construct the resorcinol fragment. The synthesis converges at a phenolic coupling with an alkyl chloride to give the core structure of the active pharmaceutical ingredient (API). Further elaborations of the core and salt formation provides the final API. This process produced the drug candidate in 41% overall yield at multikilogram scale.