methyl 3-(1-((6-bromonaphthalen-1-yl)methyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl)propanoate | 1291075-40-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl 3-(1-((6-bromonaphthalen-1-yl)methyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl)propanoate
• CAS: 1291075-40-5
• 化学式: C₂₀H₂₀BrNO₃
• 分子量: 402.288
• InChiKey: DNODRZXPBLMCTN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.21
• 重原子数：
  25.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  46.61
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  methyl 3-(1-((6-bromonaphthalen-1-yl)methyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl)propanoate 在 羟胺钾盐 作用下， 以 甲醇 为溶剂， 生成 3-(1-((6-bromonaphthalen-1-yl)methyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl)-N-hydroxypropanamide
  参考文献：
  名称：

  Property based optimization of δ-lactam HDAC inhibitors for metabolic stability

  摘要：

  The novel delta-lactam based HDAC inhibitor, KBH-A118 (3) shows a good HDAC enzyme and cancer cell growth inhibitory activities but has undesirable pharmacokinetics profiles because of instability in mouse liver microsome. To improve metabolic stability, various analogues were prepared with substituents on aromatic ring of cap group and various chain lengths between the cap group and delta-lactam core. The newly prepared analogues showed moderate to potent in vitro activities. Among them six compounds (8a, 8e, 8j, 8n, 8t, and 8v) were evaluated on mouse liver microsome assay and it turned out that the microsomal stabilities were dependent on lipophilicity and the number of the rotatable bonds. Finally, the animal pharmacokinetic profiles of 8e displayed improving oral exposure and oral bioavailability. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.117
• 作为产物：
  描述：

  methyl 4-(((6-bromonaphthalen-1-yl)methyl)(but-3-en-1-yl)carbamoyl)pent-4-enoate 在 Grubbs catalyst first generation 作用下， 以 二氯甲烷 为溶剂， 生成 methyl 3-(1-((6-bromonaphthalen-1-yl)methyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl)propanoate
  参考文献：
  名称：

  Property based optimization of δ-lactam HDAC inhibitors for metabolic stability

  摘要：

  The novel delta-lactam based HDAC inhibitor, KBH-A118 (3) shows a good HDAC enzyme and cancer cell growth inhibitory activities but has undesirable pharmacokinetics profiles because of instability in mouse liver microsome. To improve metabolic stability, various analogues were prepared with substituents on aromatic ring of cap group and various chain lengths between the cap group and delta-lactam core. The newly prepared analogues showed moderate to potent in vitro activities. Among them six compounds (8a, 8e, 8j, 8n, 8t, and 8v) were evaluated on mouse liver microsome assay and it turned out that the microsomal stabilities were dependent on lipophilicity and the number of the rotatable bonds. Finally, the animal pharmacokinetic profiles of 8e displayed improving oral exposure and oral bioavailability. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.117