4-(benzyloxy)-2-(3-chloropropoxy)ethylbenzene | 152609-59-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(benzyloxy)-2-(3-chloropropoxy)ethylbenzene
• 英文别名: 1-benzyloxy-4-ethyl-3-(3-chloro-1-propyloxy)-benzene；2-(3-Chloropropoxy)-1-ethyl-4-phenylmethoxybenzene
• CAS: 152609-59-1
• 化学式: C₁₈H₂₁ClO₂
• 分子量: 304.817
• InChiKey: SDUYOIQKUFSUSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  21
• 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：

  4-(benzyloxy)-2-(3-chloropropoxy)ethylbenzene 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 sodium azide 、 三乙胺盐酸盐 、 sodium carbonate 、 potassium carbonate 、 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 68.0h， 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)acetophenone 在 三乙基硅烷 、 三氟乙酸 作用下， 以 四氯化碳 为溶剂， 生成 4-(benzyloxy)-2-(3-chloropropoxy)ethylbenzene
  参考文献：
  名称：

  Leukotriene antagonists for use in the treatment or prevention of alzheimer's disease

  摘要：

  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。

  公开号：

  EP0743064A1

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##
• 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.
• Biphenylyl-substituted xanthones: highly potent leukotriene B4 receptor antagonists
  作者：J. Scott Sawyer、Ronald F. Baldwin、Michael J. Sofia、Paul Floreancig、Philip Marder、David L. Saussy、Larry L. Froelich、Steven A. Silbaugh、Peter W. Stengel

  DOI：10.1021/jm00076a030

  日期：1993.11
• J. Med. Chem. 1995, 38, 4411-4432
  作者：

  DOI：——

  日期：——
• US5462954A
  申请人：——

  公开号：US5462954A

  公开（公告）日：1995-10-31