ethyl 3-[4-(2-chloroethoxy)-phenyl]-2,2,2-trifluoroethoxypropionate | 901113-93-7

• 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]-2,2,2-trifluoroethoxypropionate
• 英文别名: Ethyl 3-[4-(2-chloroethoxy)phenyl]-2-(2,2,2-trifluoroethoxy)propanoate
• CAS: 901113-93-7
• 化学式: C₁₅H₁₈ClF₃O₄
• 分子量: 354.754
• InChiKey: FEHYKCFKTWRDTM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 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：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 3-[4-(2-chloroethoxy)-phenyl]-2,2,2-trifluoroethoxypropionate 在 六甲基磷酰三胺 、 硫酸 、 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 mineral oil 为溶剂， 反应 52.5h， 生成 (R)-3-{4-[2-(6-benzoyl-2-oxo-benzothiazol-3-yl)-ethoxy]-phenyl}-2-(2,2,2-trifluoro)ethoxy-propionic 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：

  ethyl 3-[4-(2-chloroethoxy)phenyl]-2-(2,2,2-trifluoroethoxy)prop-2-enoate 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97%的产率得到ethyl 3-[4-(2-chloroethoxy)-phenyl]-2,2,2-trifluoroethoxypropionate
  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

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。
• Heterocyclic Cycloalkyl Compounds, a Process for their Preparation and Pharmaceutical Compositions Containing Them
  申请人：Hurtevent Aurelie

  公开号：US20090239917A1

  公开（公告）日：2009-09-24

  Compounds of formula (I): wherein: R 1 represents a (C 3 -C 8 )cycloalkyl group, R 2 represents a group of formula (II) as defined in the description, X represents an oxygen atom or an N—OR′ group wherein R′ represents a hydrogen atom, a linear or branched (C 1 -C 6 )alkyl group, an aryl group or an aryl-(C 1 -C 6 )alkyl group in which the alkyl moiety may be linear or branched. Medicinal products containing the same which are useful as hypoglycaemic and hypolipaemic agents.

  化合物的式子(I)： 其中： R1代表(C3-C8)环烷基团， R2代表公式(II)所定义的基团，如描述中所定义， X代表氧原子或N-OR′基团，其中R′代表氢原子、线性或支链(C1-C6)烷基团、芳基团或芳基-(C1-C6)烷基团，其中烷基部分可以是线性或支链。 含有上述化合物的药物，可用作降血糖和降血脂剂。
• 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.
• Effect of 6-Benzoyl-benzothiazol-2-one scaffold on the pharmacological profile of α-alkoxyphenylpropionic acid derived PPAR agonists
  作者：Aurélie Hurtevent、Morgan Le Naour、Veronique Leclerc、Pascal Carato、Patricia Melnyk、Nathalie Hennuyer、Bart Staels、Monique Beucher-Gaudin、Daniel-Henri Caignard、Catherine Dacquet、Nicolas Lebegue

  DOI：10.1080/14756366.2020.1713771

  日期：2020.1.1

  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).