ethyl (S)-2-(4-formylphenoxy)-3-phenylpropanoate | 862902-02-1

• 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: ethyl (S)-2-(4-formylphenoxy)-3-phenylpropanoate
• 英文别名: (S)-ethyl 2-(4-formylphenoxy)-3-phenylpropanoate；ethyl (2S)-2-(4-formylphenoxy)-3-phenylpropanoate
• CAS: 862902-02-1
• 化学式: C₁₈H₁₈O₄
• 分子量: 298.339
• InChiKey: OBTPIBBRVAHNOY-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (S)-2-(4-formylphenoxy)-3-phenylpropanoate 在 盐酸羟胺 、 sodium acetate 作用下， 以 乙醇 、 水 为溶剂， 反应 70.0h， 以64%的产率得到(S)-ethyl 2-[4-(hydroxyiminomethyl)phenoxy]-3-phenylpropanoate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of a class of bioisosteric oximes of the novel dual peroxisome proliferator-activated receptor α/γ ligand LT175

  摘要：

  The effects resulting from the introduction of an oxime group in place of the distal aromatic ring of the diphenyl moiety of LT175, previously reported as a PPAR alpha/gamma dual agonist, have been investigated. This modification allowed the identification of new bioisosteric ligands with fairly good activity on PPAR alpha and fine-tuned moderate activity on PPAR gamma. For the most interesting compound (S)-3, docking studies in PPAR alpha and PPAR gamma provided a molecular explanation for its different behavior as full and partial agonist of the two receptor isotypes, respectively. A further investigation of this compound was carried out performing gene expression studies on HepaRG cells. The results obtained allowed to hypothesize a possible mechanism through which this ligand could be useful in the treatment of metabolic disorders. The higher induction of the expression of some genes, compared to selective agonists, seems to confirm the importance of a dual PPAR alpha/gamma activity which probably involves a synergistic effect on both receptor subtypes. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.11.044
• 作为产物：
  描述：

  ethyl (R)-2-hydroxy-3-phenylpropanoate 、 对羟基苯甲醛 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 甲苯 为溶剂， 以71%的产率得到ethyl (S)-2-(4-formylphenoxy)-3-phenylpropanoate
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Molecular Modeling Investigation of New Chiral Fibrates with PPARα and PPARγ Agonist Activity

  摘要：

  Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that govern lipid and glucose homeostasis playing a central role in cardiovascular diseases, obesity, and diabetes. Medications targeted to PPARs have been established to treat hyper-lipidemia (fibrates) and insulin resistance (glitazones). Thus, there is significant interest in developing new and specific ligands for these receptors. Here, we present the results of the screening of new ligands of PPAR alpha and PPAR gamma. Optical isomers of new chiral fibrates were synthesized and tested in cell-based assays. Compound (S)-7 showed a dual PPARU alpha/gamma activity, and its stereochemistry was crucial in receptor activation. Protease protection experiments suggested that this compound binds directly to PPAR. Moreover, computational studies showed that it properly docks to PPAR alpha and gamma ligand binding pockets. Interestingly, (S)-7 exhibited only a modest capacity to induce the differentiation of murine fibroblasts 3T3-L1 into adipocytes compared to rosiglitazone, a well-known PPAR gamma agonist.

  DOI：

  10.1021/jm0502844