N-methoxy valpromide | 189261-28-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-methoxy valpromide
• 英文别名: N-methoxy-valpromide；N-Methoxy-2-propylpentanamide
• CAS: 189261-28-7
• 化学式: C₉H₁₉NO₂
• 分子量: 173.255
• InChiKey: RMBSNZFAMDPPJL-UHFFFAOYSA-N

物化性质

• 密度：
  0.912±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  12
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-氯苯甲酰乙腈 、 2,2-二-正丙基乙酰基氯 以 二氯甲烷 为溶剂， 反应 3.0h， 以30%的产率得到N-methoxy valpromide
  参考文献：
  名称：

  摘要：

  Purpose. To explore the utilization of seven novel hydroxamic acid derivatives of valproic acid (VPA) as new antiepileptics.Methods. The study was carried out by investigating the pharmacokinetics of two active compounds in dogs and pharmacodynamics (anticonvulsant activity and neurotoxicity) of valproyl hydroxamic acid and six of its derivatives.Results. Three valproyl hydroxamic acid derivatives: valproyl hydroxamic acid-VPA-HA, N-(1-hydroxyethyl)-valpromide-HEV and N-methoxy valpromide, showed better anticonvulsant activity than VPA at the maximal electroshock (MES) test. The remaining four compounds, O-valproyl-VPA-HA, N-valproyl-O-valproyI-VPA-HA, N-(1-methoxyethyl) valpromide and N-(1,2-dihydroxylpropyl)-valpromide were found to be inactive. Therefore, only the pharmacokinetics of the active compounds VPA-HA and HEV was studied.Conclusions. In contrast to valpromide (VPD) which is biotransformed to VPA, VPA-HA and HEV were found to be stable in vivo to the biotransformation of the amide to its corresponding acid. VPA-HA and HEV showed improved anticonvulsant activity over VPA because of their greater intrinsic activity and not due to better pharmacokinetic characteristics. This paper discusses the structural requirements for active anticonvulsant valproyl hydroxamic acid derivatives.

  DOI：

  10.1023/a:1012009012850

文献信息

• Phenylbutyric acid for chemoprevention
  申请人：Lunamed AG

  公开号：EP2698156A1

  公开（公告）日：2014-02-19

  The invention provides a pharmaceutical composition comprising phenylbutyric acid, a derivative, a prodrug, solvate or a physiologically acceptable salt thereof for use in the prevention of cancer. Furthermore pharmaceutical compositions are disclosed which comprise a further chemopreventive agent.

  本发明提供了一种包含苯丁酸、其衍生物、原药、溶液或生理上可接受的盐的药物组合物，用于预防癌症。此外，本发明还公开了包含另一种化学预防剂的药物组合物。
• ——
  作者：Micha Levi、Boris Yagen、Meir Bialer

  DOI：10.1023/a:1012009012850

  日期：——

  Purpose. To explore the utilization of seven novel hydroxamic acid derivatives of valproic acid (VPA) as new antiepileptics.Methods. The study was carried out by investigating the pharmacokinetics of two active compounds in dogs and pharmacodynamics (anticonvulsant activity and neurotoxicity) of valproyl hydroxamic acid and six of its derivatives.Results. Three valproyl hydroxamic acid derivatives: valproyl hydroxamic acid-VPA-HA, N-(1-hydroxyethyl)-valpromide-HEV and N-methoxy valpromide, showed better anticonvulsant activity than VPA at the maximal electroshock (MES) test. The remaining four compounds, O-valproyl-VPA-HA, N-valproyl-O-valproyI-VPA-HA, N-(1-methoxyethyl) valpromide and N-(1,2-dihydroxylpropyl)-valpromide were found to be inactive. Therefore, only the pharmacokinetics of the active compounds VPA-HA and HEV was studied.Conclusions. In contrast to valpromide (VPD) which is biotransformed to VPA, VPA-HA and HEV were found to be stable in vivo to the biotransformation of the amide to its corresponding acid. VPA-HA and HEV showed improved anticonvulsant activity over VPA because of their greater intrinsic activity and not due to better pharmacokinetic characteristics. This paper discusses the structural requirements for active anticonvulsant valproyl hydroxamic acid derivatives.