(S)-methyl 2-(4-bromophenoxy)-3-phenylpropanoate | 862901-95-9

• 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: (S)-methyl 2-(4-bromophenoxy)-3-phenylpropanoate
• 英文别名: methyl (S)-2-(4-bromophenoxy)-3-phenylpropanoate；methyl (2S)-2-(4-bromophenoxy)-3-phenylpropanoate
• CAS: 862901-95-9
• 化学式: C₁₆H₁₅BrO₃
• 分子量: 335.197
• InChiKey: YZZAVXNHAMGAGS-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-methyl 2-(4-bromophenoxy)-3-phenylpropanoate 在 Wilkinson's catalyst 、 hydrazine hydrate 、 氢气 、 palladium diacetate 、 N,N-二异丙基乙胺 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 乙醇 、 乙腈 为溶剂， 20.0 ℃ 、405.33 kPa 条件下， 反应 29.0h， 生成 (S)-methyl 2-[4-(2-aminoethyl)phenoxy]-3-phenylpropanoate
  参考文献：
  名称：

  Synthesis, Characterization and Biological Evaluation of Ureidofibrate-Like Derivatives Endowed with Peroxisome Proliferator-Activated Receptor Activity

  摘要：

  A series of ureidofibrate-like derivatives was prepared and assayed for their PPAR functional activity. A calorimetric approach was used to characterize PPAR gamma-ligand interactions, and docking experiments and X-ray studies were performed to explain the observed potency and efficacy. R-1 and S-1 were selected to evaluate several aspects of their biological activity. In an adipogenic assay, both enantiomers increased the expression of PPAR gamma target genes and promoted the differentiation of 3T3-L1 fibroblasts to adipocytes. In vivo administration of these compounds to insulin resistant C57Bl/6J mice fed a high fat diet reduced visceral fat content and body weight. Examination of different metabolic parameters showed that R-1 and S-1 are insulin sensitizers. Notably, they also enhanced the expression of hepatic PPAR alpha target genes indicating that their in vivo effects stemmed from an activation of both PPAR alpha and gamma. Finally, the capability of R-1 and S-1 to inhibit cellular proliferation in colon cancer cell lines was also evaluated.

  DOI：

  10.1021/jm201306q
• 作为产物：
  描述：

  4-溴苯酚 、 D-苯基乳酸甲酯 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 甲苯 为溶剂， 以76%的产率得到(S)-methyl 2-(4-bromophenoxy)-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