ethyl 3-[4-(2-chloroethoxy)phenyl]-2-ethoxypropionate | 901113-92-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: ethyl 3-[4-(2-chloroethoxy)phenyl]-2-ethoxypropionate
• 英文别名: Ethyl 3-[4-(2-chloroethoxy)phenyl]-2-ethoxypropanoate
• CAS: 901113-92-6
• 化学式: C₁₅H₂₁ClO₄
• 分子量: 300.782
• InChiKey: QXOUFCLGOROATL-UHFFFAOYSA-N

物化性质

• 沸点：
  409.3±35.0 °C(Predicted)
• 密度：
  1.126±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-[4-(2-chloroethoxy)phenyl]-2-ethoxypropionate 在 potassium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 3-{4-[2-(6-benzoyl-2-oxo-benzothiazol-3-yl)-ethoxy]-phenyl}-2-ethoxypropionic acid
  参考文献：
  名称：

  Effect of 6-Benzoyl-benzothiazol-2-one scaffold on the pharmacological profile of α-alkoxyphenylpropionic acid derived PPAR agonists

  摘要：

  A series of nitrogen heterocycles containing alpha-ethoxyphenylpropionic acid derivatives were designed as dual PPAR alpha/gamma agonist ligands for the treatment of type 2 diabetes (T2D) and its complications. 6-Benzoyl-benzothiazol-2-one was the most tolerant of the tested heterocycles in which incorporation of O-methyl oxime ether and trifluoroethoxy group followed by enantiomeric resolution led to the (S)-stereoisomer 44 b displaying the best in vitro pharmacological profile. Compound 44 b acted as a very potent full PPAR gamma agonist and a weak partial agonist on the PPAR alpha receptor subtype. Compound 44 b showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain and could be considered as a selective PPAR gamma modulator (SPPAR gamma M).

  DOI：

  10.1080/14756366.2020.1713771
• 作为产物：
  描述：

  在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 20.0h， 以93%的产率得到ethyl 3-[4-(2-chloroethoxy)phenyl]-2-ethoxypropionate
  参考文献：
  名称：

  肟醚掺入酰基吲哚衍生物对PPAR亚型选择性的影响

  摘要：

  同时激活过氧化物酶体增殖物激活受体（PPAR）亚型α和γ的化合物具有在单个药物活性分子中有效治疗血脂异常和2型糖尿病（T2D）的潜力。选择性添加PPARα活性有望克服选择性PPARγ激动剂经常观察到的副作用，例如水肿和体重增加，从而导致两种亚型的双重PPARα/γ激动剂均具有平衡的活性。本文中，我们报告发现，合成和优化了一系列新的带有5或6个取代的吲哚的α-乙氧基苯基丙酸。在苯甲酰基的羰基部分上掺入肟醚可以使PPARα/γ效力比等于或略大于1，就像化合物20c和21a的情况一样。化合物20c的表现出高效力在OB / OB T2D和血脂异常，类似于罗格列酮和替格列扎的小鼠模型，但与体重增加一个显著增加。与此相反，化合物21，作为双PPARα/γ活化剂小于有力20c中，显示了一个有趣的药理学特性，因为它引起在相对于体重的参考化合物的降低。

  DOI：

  10.1002/cmdc.201200316

文献信息

• Heterocyclic Oxime Compounds, A Process For Their Preparation And Pharmaceutical Compositions Containing Them.
  申请人：Hurtevent Aurelie

  公开号：US20080113974A1

  公开（公告）日：2008-05-15

  Compounds of formula (I): wherein: X represents an oxygen atom or a sulphur atom, R 1 , R 2 , R 3 and R 4 are as defined in the description, A represents an alkylene chain as defined in the description, and B represents an alkyl or alkenyl group substituted by a group or R 7 , or B represents a group or R 7 .

  化合物式（I）：其中：X代表氧原子或硫原子，R1、R2、R3和R4如描述中所定义，A代表如描述中所定义的烷基链，B代表被基团或R7取代的烷基或烯基，或B代表基团或R7。
• Anti-diabetic activity of fused PPARγ-SIRT1 ligands with limited body-weight gain by mimicking calorie restriction and decreasing SGK1 expression
  作者：Celine Pirat、Catherine Dacquet、Veronique Leclerc、Nathalie Hennuyer、Monique Beucher-Gaudin、Ghislaine Zanirato、Anne Géant、Bart Staels、Alain Ktorza、Amaury Farce、Daniel-Henri Caignard、Pascal Berthelot、Nicolas Lebegue

  DOI：10.1016/j.ejmech.2017.06.006

  日期：2017.9

  A series of benzothiazol-2-one containing alpha-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPAR gamma agonist ligands and SIRT1-activating compounds for the treatment of type 2 diabetes (T2D) and its complications. Compound 14d displayed the best in vitro pharmacological profile with full PPAR gamma agonist activity (Emax = 98%, EC50 = 200 nM), SIRTI enzymatic activation (+128%) and SGK1 expression inhibition (- 57%) which is known to limit side effects as fluid retention and body-weight gain. Compound 14d showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain by mimicking calorie restriction (CR) and inhibiting SGKI expression. (C) 2017 Elsevier Masson SAS. All rights reserved.