trans-1-[4-(5-isopropoxypyridin-2-yloxy)cyclohexyloxy]propan-2-one O-benzyl oxime | 1257244-07-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: trans-1-[4-(5-isopropoxypyridin-2-yloxy)cyclohexyloxy]propan-2-one O-benzyl oxime
• CAS: 1257244-07-7
• 化学式: C₂₄H₃₂N₂O₄
• 分子量: 412.529
• InChiKey: AVIFCDAYAQPENX-HZCBDIJESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.17
• 重原子数：
  30.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  62.17
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  trans-1-[4-(5-isopropoxypyridin-2-yloxy)cyclohexyloxy]propan-2-one O-benzyl oxime 在 lithium aluminium tetrahydride 、 10% palladium on activated carbon 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 20.0~40.0 ℃ 、400.01 kPa 条件下， 反应 8.0h， 生成 trans-N-{2-[4-(5-isopropoxypyridin-2-yloxy)cyclohexyloxy]-1-methylethyl}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：

  trans-5-isopropoxy-2-[4-(2-methylallyloxy)cyclohexyloxy]pyridine 在 吡啶 、 sodium periodate 、 四氧化锇 作用下， 以 四氢呋喃 、 乙醇 、 叔丁醇 为溶剂， 反应 4.0h， 生成 trans-1-[4-(5-isopropoxypyridin-2-yloxy)cyclohexyloxy]propan-2-one O-benzyl oxime
  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