ethyl 2-(4-formylphenoxy)-3-phenylpropanoate | 1191933-78-4

• 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 2-(4-formylphenoxy)-3-phenylpropanoate
• CAS: 1191933-78-4
• 化学式: C₁₈H₁₈O₄
• 分子量: 298.339
• InChiKey: OBTPIBBRVAHNOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.05
• 重原子数：
  22.0
• 可旋转键数：
  7.0
• 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：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  ethyl 2-(4-formylphenoxy)-3-phenylpropanoate 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.5h， 以91%的产率得到ethyl 2-(4-hydroxymethyl-phenoxy)-3-phenyl-propanoate
  参考文献：
  名称：

  New 2-Aryloxy-3-phenyl-propanoic Acids As Peroxisome Proliferator-Activated Receptors α/γ Dual Agonists with Improved Potency and Reduced Adverse Effects on Skeletal Muscle Function

  摘要：

  The preparation of a new series of 2-aryloxy-3-phenyl-propanoic acids, resulting from the introduction of a linker into the diphenyl system of the previously reported PPAR alpha/gamma dual agonist 1, allowed the identification of new ligands with improved potency on PPAR alpha and unchanged activity on PPAR gamma. For the most interesting stereoisomers S-2 and S-4, X-ray studies in PPAR gamma and docking experiments in PPAR alpha provided a molecular explanation for their different behavior as full and partial agonists of PPAR alpha and PPAR gamma, respectively. Due to the adverse effects provoked by hypolipidemic drugs on skeletal muscle function, we also investigated the blocking activity of S-2 and S-4 on skeletal muscle membrane chloride channel conductance and found that these ligands have a pharmacological profile more beneficial compared to fibrates currently used in therapy.

  DOI：

  10.1021/jm900941b
• 作为产物：
  描述：

  2-羟基-3-苯基丙酸乙酯 、 对羟基苯甲醛 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以68%的产率得到ethyl 2-(4-formylphenoxy)-3-phenylpropanoate
  参考文献：
  名称：

  New 2-Aryloxy-3-phenyl-propanoic Acids As Peroxisome Proliferator-Activated Receptors α/γ Dual Agonists with Improved Potency and Reduced Adverse Effects on Skeletal Muscle Function

  摘要：

  The preparation of a new series of 2-aryloxy-3-phenyl-propanoic acids, resulting from the introduction of a linker into the diphenyl system of the previously reported PPAR alpha/gamma dual agonist 1, allowed the identification of new ligands with improved potency on PPAR alpha and unchanged activity on PPAR gamma. For the most interesting stereoisomers S-2 and S-4, X-ray studies in PPAR gamma and docking experiments in PPAR alpha provided a molecular explanation for their different behavior as full and partial agonists of PPAR alpha and PPAR gamma, respectively. Due to the adverse effects provoked by hypolipidemic drugs on skeletal muscle function, we also investigated the blocking activity of S-2 and S-4 on skeletal muscle membrane chloride channel conductance and found that these ligands have a pharmacological profile more beneficial compared to fibrates currently used in therapy.

  DOI：

  10.1021/jm900941b

文献信息

• Design, synthesis and biological evaluation of a class of bioisosteric oximes of the novel dual peroxisome proliferator-activated receptor α/γ ligand LT175
  作者：Luca Piemontese、Giuseppe Fracchiolla、Antonio Carrieri、Mariagiovanna Parente、Antonio Laghezza、Giuseppe Carbonara、Sabina Sblano、Marilena Tauro、Federica Gilardi、Paolo Tortorella、Antonio Lavecchia、Maurizio Crestani、Béatrice Desvergne、Fulvio Loiodice

  DOI：10.1016/j.ejmech.2014.11.044

  日期：2015.1

  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.