isopropyl (E,E)-(S,S)-2-ethoxy-3-{4-[5-(3-{5-[4-(2-ethoxy-2-isopropoxycarbonylethyl)phenoxy]pent-3-en-1-ynyl}phenyl)pent-2-en-4-ynyloxy]phenyl}propanoate | 630110-19-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: isopropyl (E,E)-(S,S)-2-ethoxy-3-{4-[5-(3-{5-[4-(2-ethoxy-2-isopropoxycarbonylethyl)phenoxy]pent-3-en-1-ynyl}phenyl)pent-2-en-4-ynyloxy]phenyl}propanoate
• 英文别名: propan-2-yl (2S)-2-ethoxy-3-[4-[(E)-5-[3-[(E)-5-[4-[(2S)-2-ethoxy-3-oxo-3-propan-2-yloxypropyl]phenoxy]pent-3-en-1-ynyl]phenyl]pent-2-en-4-ynoxy]phenyl]propanoate
• CAS: 630110-19-9
• 化学式: C₄₄H₅₀O₈
• 分子量: 706.876
• InChiKey: ZZDDKPLAGNCKQX-LRNBDTCJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.4
• 重原子数：
  52
• 可旋转键数：
  22
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  89.5
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  isopropyl (E,E)-(S,S)-2-ethoxy-3-{4-[5-(3-{5-[4-(2-ethoxy-2-isopropoxycarbonylethyl)phenoxy]pent-3-en-1-ynyl}phenyl)pent-2-en-4-ynyloxy]phenyl}propanoate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以99%的产率得到(S)-3-{4-[(E)-5-(3-{(E)-5-[4-((S)-2-Carboxy-2-ethoxy-ethyl)-phenoxy]-pent-3-en-1-ynyl}-phenyl)-pent-2-en-4-ynyloxy]-phenyl}-2-ethoxy-propionic acid
  参考文献：
  名称：

  Large Dimeric Ligands with Favorable Pharmacokinetic Properties and Peroxisome Proliferator-Activated Receptor Agonist Activity in Vitro and in Vivo

  摘要：

  Two potent nonselective, but PPARalpha-preferring, PPAR agonists 5 and 6 were designed and synthesized in high yields. The concept of dimeric ligands in transcription factors was investigated by synthesizing and testing the corresponding dimers 7, 8a, and 8b in PPAR transactivation assays. The three dimeric ligands all showed agonist activity on all three PPAR receptor subtypes, but with different profiles compared to the monomers 5 and 6. Despite breaking all the "rule of five" criteria, the dimers had excellent oral bioavailability and pharmacokinetic properties, resulting in good in vivo efficacy in db/db mice. X-ray crystal structure and modeling experiments suggested that the dimers interacted with the AF-2 helix as well as with amino acid residues in the lipophilic pocket close to the receptor surface.

  DOI：

  10.1021/jm0309046
• 作为产物：
  描述：

  (E)-2-penten-4-yn-1-ol 在 copper(l) iodide 、 四(三苯基膦)钯 、 三丁基膦 、 二异丙胺 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 isopropyl (E,E)-(S,S)-2-ethoxy-3-{4-[5-(3-{5-[4-(2-ethoxy-2-isopropoxycarbonylethyl)phenoxy]pent-3-en-1-ynyl}phenyl)pent-2-en-4-ynyloxy]phenyl}propanoate
  参考文献：
  名称：

  Large Dimeric Ligands with Favorable Pharmacokinetic Properties and Peroxisome Proliferator-Activated Receptor Agonist Activity in Vitro and in Vivo

  摘要：

  Two potent nonselective, but PPARalpha-preferring, PPAR agonists 5 and 6 were designed and synthesized in high yields. The concept of dimeric ligands in transcription factors was investigated by synthesizing and testing the corresponding dimers 7, 8a, and 8b in PPAR transactivation assays. The three dimeric ligands all showed agonist activity on all three PPAR receptor subtypes, but with different profiles compared to the monomers 5 and 6. Despite breaking all the "rule of five" criteria, the dimers had excellent oral bioavailability and pharmacokinetic properties, resulting in good in vivo efficacy in db/db mice. X-ray crystal structure and modeling experiments suggested that the dimers interacted with the AF-2 helix as well as with amino acid residues in the lipophilic pocket close to the receptor surface.

  DOI：

  10.1021/jm0309046