2-[4-(hydroxyiminomethyl)phenoxy]-3-phenylpropanoic acid

• 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: 2-[4-(hydroxyiminomethyl)phenoxy]-3-phenylpropanoic acid
• 英文别名: 2-[4-[(E)-hydroxyiminomethyl]phenoxy]-3-phenylpropanoic acid
• 化学式: C₁₆H₁₅NO₄
• 分子量: 285.299
• InChiKey: NIDDHYAQKFHAMY-GZTJUZNOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  79.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[4-(hydroxyiminomethyl)phenoxy]-3-phenylpropanoic acid 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 36.0h， 生成 2-[4-(butoxyiminomethyl)phenoxy]-3-phenylpropanoic acid
  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：

  2-羟基-3-苯基丙酸乙酯 在 偶氮二甲酸二异丙酯 、 盐酸羟胺 、 sodium acetate 、 三苯基膦 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 70.0h， 生成 2-[4-(hydroxyiminomethyl)phenoxy]-3-phenylpropanoic acid
  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

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.