1-(4-(hexyloxy)-3-(trifluoromethyl)phenyl)ethanone | 1162128-65-5

• 英文名称: 1-(4-(hexyloxy)-3-(trifluoromethyl)phenyl)ethanone
• CAS: 1162128-65-5
• 化学式: C₁₅H₁₉F₃O₂
• 分子量: 288.31
• InChiKey: MGUCNELZACTUBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.87
• 重原子数：
  20.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  26.3
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 1-(4-(hexyloxy)-3-(trifluoromethyl)phenyl)ethanone 、 盐酸二甲胺 在 盐酸 作用下， 以 水 、 乙腈 为溶剂， 反应 2.0h， 以8%的产率得到3-(Dimethylamino)-1-(4-(hexyloxy)-3-(trifluoromethyl)phenyl)propan-1-one
  参考文献：
  名称：

  Improvement of Pharmacological Properties of Irreversible Thyroid Receptor Coactivator Binding Inhibitors

  摘要：

  We have previously reported the discover), and preliminary structure activity relationships of a series of beta-aminoketones that disrupt the binding of coactivators to TR. However, the most active compounds had moderate inhibitory potency and relatively high cytotoxicity, resulting in narrow therapeutic index. Additionally, preliminary evaluation of in vivo toxicology revealed a significant dose related cardiotoxicity. Here we describe the improvement of pharmacological properties of thyroid hormone receptor coactivator binding inhibitors. A comprehensive Survey of the effects of substitutents in key areas of the molecule was carried out based on mechanistic insight from the earlier report. This study revealed that both electron withdrawing and hydrophobic substituents on the aromatic ring led to higher potency. On the other hand, moving from an alkyl to a sulfonyl alkyl side chain led to reduced cytotoxicity, Finally, utilization of airline moieties having low pK(a)'s resulted in lowered ion channel activity without any loss of pharmacological activity.

  DOI：

  10.1021/jm9002704
• 作为产物：
  描述：

  溴己烷 、 4’-羟基-3’-(三氟甲基)苯乙酮 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-(4-(hexyloxy)-3-(trifluoromethyl)phenyl)ethanone
  参考文献：
  名称：

  Improvement of Pharmacological Properties of Irreversible Thyroid Receptor Coactivator Binding Inhibitors

  摘要：

  We have previously reported the discover), and preliminary structure activity relationships of a series of beta-aminoketones that disrupt the binding of coactivators to TR. However, the most active compounds had moderate inhibitory potency and relatively high cytotoxicity, resulting in narrow therapeutic index. Additionally, preliminary evaluation of in vivo toxicology revealed a significant dose related cardiotoxicity. Here we describe the improvement of pharmacological properties of thyroid hormone receptor coactivator binding inhibitors. A comprehensive Survey of the effects of substitutents in key areas of the molecule was carried out based on mechanistic insight from the earlier report. This study revealed that both electron withdrawing and hydrophobic substituents on the aromatic ring led to higher potency. On the other hand, moving from an alkyl to a sulfonyl alkyl side chain led to reduced cytotoxicity, Finally, utilization of airline moieties having low pK(a)'s resulted in lowered ion channel activity without any loss of pharmacological activity.

  DOI：

  10.1021/jm9002704