(E)-1-[4'-(4-hydroxy-2-but-2-en-2-yl)biphenyl-4-yl]ethanone | 352288-40-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (E)-1-[4'-(4-hydroxy-2-but-2-en-2-yl)biphenyl-4-yl]ethanone
• 英文别名: (E)-1-[4'-(3-hydroxy-1-methyl-propenyl)-biphenyl-4-yl]-ethanone；1-[4'-(3-hydroxy-1-methyl-propenyl)-biphenyl-4-yl]-ethanone；1-[4-[4-[(E)-4-hydroxybut-2-en-2-yl]phenyl]phenyl]ethanone
• CAS: 352288-40-5
• 化学式: C₁₈H₁₈O₂
• 分子量: 266.34
• InChiKey: DXWKBXWQLMOOKD-ACCUITESSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-1-[4'-(4-hydroxy-2-but-2-en-2-yl)biphenyl-4-yl]ethanone 在 咪唑 、 三丁基膦 、 四丁基氟化铵 、 sodium ethanolate 、 二异丁基氢化铝 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 47.58h， 生成 ethyl (E,E)-(S)-3-{4-[3-(4'-{4-hydroxybut-2-en-2-yl}biphenyl-4-yl)but-2-en-1-yloxy]phenyl}-2-ethoxypropanoate
  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：

  ethyl (E)-3-(4-iodophenyl)but-2-enoate 在 四(三苯基膦)钯 、 二异丁基氢化铝 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 甲苯 为溶剂， 反应 18.0h， 生成 (E)-1-[4'-(4-hydroxy-2-but-2-en-2-yl)biphenyl-4-yl]ethanone
  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

文献信息

• Compounds, their preparation and use
  申请人：Novo Nordisk A/S

  公开号：US06555577B1

  公开（公告）日：2003-04-29

  The present invention relates to compounds of the general formula (I) The compounds are useful in the treatment and/or prevention of conditions mediated by nuclear receptors, in particular the Peroxisome Proliferator-Activated Receptors (PPAR).

  本发明涉及一般式(I)的化合物。 这些化合物在治疗和/或预防由核受体介导的疾病中具有用途，特别是过氧化物酶体增殖激活受体（PPAR）。
• Novel compounds, their preparation and use
  申请人：——

  公开号：US20030109579A1

  公开（公告）日：2003-06-12

  A novel class of dicarboxylic acid derivatives, the use of these compounds as pharmaceutical compositions, pharmaceutical compositions comprising the compounds and methods of treatment employing these compounds and compositions. The present compounds may be useful in the treatment and/or prevention of conditions mediated by Peroxisome Proliferator-Activated Receptors (PPAR).

  一种新型的二羧酸衍生物类，这些化合物作为药物组合物的用途，包括这些化合物的药物组合物以及使用这些化合物和组合物的治疗方法。这些化合物可能在治疗和/或预防由过氧化物酶体增殖物激活受体（PPAR）介导的疾病中有用。
• DICARBOXYLIC ACID DERIVATIVES, THEIR PREPARATION AND THERAPEUTIC USE
  申请人：NOVO NORDISK A/S

  公开号：EP1438283A1

  公开（公告）日：2004-07-21
• US6555577B1
  申请人：——

  公开号：US6555577B1

  公开（公告）日：2003-04-29
• US6867218B2
  申请人：——

  公开号：US6867218B2

  公开（公告）日：2005-03-15