(R)-2-[2]naphthyloxy-valeric acid | 7668-57-7

• 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: (R)-2-[2]naphthyloxy-valeric acid
• 英文别名: (R)-2-[2]Naphthyloxy-valeriansaeure；(2R)-2-naphthalen-2-yloxypentanoic acid
• CAS: 7668-57-7
• 化学式: C₁₅H₁₆O₃
• 分子量: 244.29
• InChiKey: OMXNKDLNBLDNDT-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (2S)-2-Hydroxypentanoic acid methyl ester 在 sodium hydroxide 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 (R)-2-[2]naphthyloxy-valeric acid
  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

文献信息

• Matell, Arkiv foer Kemi, 1956, vol. 8, p. 79,81, 83
  作者：Matell

  DOI：——

  日期：——
• Synthesis, Biological Evaluation, and Molecular Modeling Investigation of New Chiral Fibrates with PPARα and PPARγ Agonist Activity
  作者：Alessandra Pinelli、Cristina Godio、Antonio Laghezza、Nico Mitro、Giuseppe Fracchiolla、Vincenzo Tortorella、Antonio Lavecchia、Ettore Novellino、Jean-Charles Fruchart、Bart Staels、Maurizio Crestani、Fulvio Loiodice

  DOI：10.1021/jm0502844

  日期：2005.8.1

  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.