N-{3-[5-(3-hydroxyphenyl)[1,3]dioxan-2-yl]propyl}acetamide | 1257243-77-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: N-{3-[5-(3-hydroxyphenyl)[1,3]dioxan-2-yl]propyl}acetamide
• 英文别名: N-[3-[5-(3-hydroxyphenyl)-1,3-dioxan-2-yl]propyl]acetamide
• CAS: 1257243-77-8
• 化学式: C₁₅H₂₁NO₄
• 分子量: 279.336
• InChiKey: VLHMTNNNISGFKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-{3-[5-(3-hydroxyphenyl)[1,3]dioxan-2-yl]propyl}acetamide 、 邻氯乙苯 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以2%的产率得到N-{3-[5-(3-phenethyloxyphenyl)[1,3]dioxan-2-yl]propyl}acetamide
  参考文献：
  名称：

  Identification and Synthesis of Novel Inhibitors of Acetyl-CoA Carboxylase with in Vitro and in Vivo Efficacy on Fat Oxidation

  摘要：

  Acetyl CoA carboxylase isoforms 1 and 2 (ACC1/2) are key enzymes of fat utilization and their inhibition is considered to improve aspects of the metabolic syndrome. To identify pharmacological inhibitors of ACC1/2, a high throughput screen was performed which resulted in the identification of the lead compound 3 (Gargazanli, G.; Lardenois, P.; Frost, J.; George, P. Patent WO9855474 A1, 1998) as a moderate selective ACC2 inhibitor. Optimization of 3 led to 4m (Zoller, G.; Schmoll, D.; Mueller, M.; Haschke, G.; Focken, I. Patent WO2010003624 A2, 2010) as a submicromolar dual ACC1/2 inhibitor of the rat and human isoforms. 4m possessed favorable pharmacokinetic parameters. This compound stimulated fat oxidation in vivo and reduced plasma triglyceride levels in a rodent model after subchronic administration. 4m is a suitable tool compound for the elucidation of the pharmacological potential of ACC1/2 inhibition.

  DOI：

  10.1021/jm101179e
• 作为产物：
  描述：

  2-[3-(benzyloxy)phenyl]-1,3-propanediol 在 10% palladium on activated carbon 、 氢气 、 对甲苯磺酸 、 三乙胺 作用下， 以 乙醇 、 乙酸乙酯 、 甲苯 为溶剂， 10.0~60.0 ℃ 、300.01 kPa 条件下， 反应 8.0h， 生成 N-{3-[5-(3-hydroxyphenyl)[1,3]dioxan-2-yl]propyl}acetamide
  参考文献：
  名称：

  Identification and Synthesis of Novel Inhibitors of Acetyl-CoA Carboxylase with in Vitro and in Vivo Efficacy on Fat Oxidation

  摘要：

  Acetyl CoA carboxylase isoforms 1 and 2 (ACC1/2) are key enzymes of fat utilization and their inhibition is considered to improve aspects of the metabolic syndrome. To identify pharmacological inhibitors of ACC1/2, a high throughput screen was performed which resulted in the identification of the lead compound 3 (Gargazanli, G.; Lardenois, P.; Frost, J.; George, P. Patent WO9855474 A1, 1998) as a moderate selective ACC2 inhibitor. Optimization of 3 led to 4m (Zoller, G.; Schmoll, D.; Mueller, M.; Haschke, G.; Focken, I. Patent WO2010003624 A2, 2010) as a submicromolar dual ACC1/2 inhibitor of the rat and human isoforms. 4m possessed favorable pharmacokinetic parameters. This compound stimulated fat oxidation in vivo and reduced plasma triglyceride levels in a rodent model after subchronic administration. 4m is a suitable tool compound for the elucidation of the pharmacological potential of ACC1/2 inhibition.

  DOI：

  10.1021/jm101179e

文献信息

• Identification and Synthesis of Novel Inhibitors of Acetyl-CoA Carboxylase with in Vitro and in Vivo Efficacy on Fat Oxidation
  作者：Stefanie Keil、Marco Müller、Gerhard Zoller、Guido Haschke、Katrin Schroeter、Maike Glien、Sven Ruf、Ingo Focken、Andreas W. Herling、Dieter Schmoll

  DOI：10.1021/jm101179e

  日期：2010.12.23

  Acetyl CoA carboxylase isoforms 1 and 2 (ACC1/2) are key enzymes of fat utilization and their inhibition is considered to improve aspects of the metabolic syndrome. To identify pharmacological inhibitors of ACC1/2, a high throughput screen was performed which resulted in the identification of the lead compound 3 (Gargazanli, G.; Lardenois, P.; Frost, J.; George, P. Patent WO9855474 A1, 1998) as a moderate selective ACC2 inhibitor. Optimization of 3 led to 4m (Zoller, G.; Schmoll, D.; Mueller, M.; Haschke, G.; Focken, I. Patent WO2010003624 A2, 2010) as a submicromolar dual ACC1/2 inhibitor of the rat and human isoforms. 4m possessed favorable pharmacokinetic parameters. This compound stimulated fat oxidation in vivo and reduced plasma triglyceride levels in a rodent model after subchronic administration. 4m is a suitable tool compound for the elucidation of the pharmacological potential of ACC1/2 inhibition.