4-甲基-2-丙基戊-4-烯酸 | 178269-54-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 4-甲基-2-丙基戊-4-烯酸
• 英文名称: (+/-)-4-methyl-2-n-propyl-4-pentenoic acid
• 英文别名: 4-Methyl-2-propylpent-4-enoic acid
• CAS: 178269-54-0
• 化学式: C₉H₁₆O₂
• 分子量: 156.225
• InChiKey: NOKWCZKVIFCELV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  丙基丙二酸二乙酯 在 氢氧化钾 、 sodium ethanolate 作用下， 以 乙醇 、 水 为溶剂， 生成 4-甲基-2-丙基戊-4-烯酸
  参考文献：
  名称：

  Further Branching of Valproate-Related Carboxylic Acids Reduces the Teratogenic Activity, but Not the Anticonvulsant Effect

  摘要：

  In the present study, compounds derived from the anticonvulsant drug valproic acid (VPA, 2-n-propylpentanoic acid) and analogues known to be teratogenic were synthesized with an additional carbon-branching in one of the side chains. The substances were tested for their ability to induce anticonvulsant-activity and sedation in adult mice, and neural tube defects (exencephaly) in the offspring of pregnant animals (Han:NMRI mice). In all cases, the rates of exencephaly, embryolethality, and fetal weight retardation induced by the methyl-branched derivatives were very low when compared to those of the parent compounds, These novel compounds exhibited anticonvulsant activity which was not significantly different from that of VPA. Neurotoxicity was considerably lower for some compounds as compared to VPA. Anticonvulsant activity and neurotoxicity of branched short chain fatty acids are far less structure-dependent and not related to teratogenic potency. Within this series of compounds, (+/-)-4-methyl-2-n-propyl-4-pentenoic acid and (+/-)-2-isobutyl-4-pentenoic acid exhibited the most favorable profile in regard to high anticonvulsant effect, low sedation, and teratogenicity. Valproic acid analogues with additional methyl branching may be valuable antiepileptic agents with low teratogenic potential.

  DOI：

  10.1021/tx950216s

文献信息

• Anticonvulsant and Neurotoxic Activities of Twelve Analogues of Valproic Acid
  作者：M.M.A. Elmazar、R.-S. Hauck、H. Nau

  DOI：10.1002/jps.2600821214

  日期：1993.12

  Twelve racemic analogues of the antiepileptic drug valproic acid (VPA) were tested and compared with VPA for anticonvulsant activity by the subcutaneous pentylenetetrazol (PTZ) seizure threshold test and for neurotoxicity by the rotorod test. Four compounds produced maximal anticonvulsant activity (100% protection) in equimolar doses (1.5 mmol/kg) to VPA and two compounds showed a similar effect with

  测试了十二种抗癫痫药丙戊酸（VPA）的外消旋类似物，并通过皮下戊四氮（PTZ）癫痫发作阈值测试与VPA进行了比较，研究了其抗惊厥活性，并通过旋翼仪测试了其神经毒性。四种化合物以对VPA等摩尔剂量（1.5 mmol / kg）产生最大的抗惊厥活性（100％保护），两种化合物在较低剂量（1.0 mmol / kg）下显示出相似的作用。四种化合物产生较低的活性（38-80％的保护作用），两种化合物在所用剂量（1.5 mmol / kg）下无抗惊厥活性。12种化合物中的两种，（+/-）-2-n-丙基-4-己酸（11）和（+/-）-4-甲基-2-正丙基-4-戊烯酸（12），在产生最大抗惊厥作用的剂量下无镇静作用。我们首次成功开发出两种具有比VPA更高的保护指数和安全比的化合物。化合物11的作用时间更长，保护指数更高，但安全系数却比12低。这些化合物的抗惊厥作用和最小的神经毒性与其计算的亲脂性（C log
• Valproate tablet
  申请人：Guo Mintong

  公开号：US20070048379A1

  公开（公告）日：2007-03-01

  A process for preparing a pharmaceutical tablet comprising: (a) mixing a valproate compound with at least one excipient to form a premix; (b) adding a sufficient amount of water to the premix of Step (a) and mixing to form a wet granulation; (c) drying the wet granulation of Step (b) at a temperature and time sufficient to form granules, wherein the granules are essentially free of an organic solvent; (d) coating the granules of Step (c) to form coated granules; and (e) compressing the coated granules of Step (d) to form a tablet. The aqueous granulation of the invention does not have the environmental and safety drawbacks of organic solvent granulations.
• Further Branching of Valproate-Related Carboxylic Acids Reduces the Teratogenic Activity, but Not the Anticonvulsant Effect
  作者：Ursula Bojic、Mohamed M. A. Elmazar、Ralf-Siegbert Hauck、Heinz Nau

  DOI：10.1021/tx950216s

  日期：1996.1.1

  In the present study, compounds derived from the anticonvulsant drug valproic acid (VPA, 2-n-propylpentanoic acid) and analogues known to be teratogenic were synthesized with an additional carbon-branching in one of the side chains. The substances were tested for their ability to induce anticonvulsant-activity and sedation in adult mice, and neural tube defects (exencephaly) in the offspring of pregnant animals (Han:NMRI mice). In all cases, the rates of exencephaly, embryolethality, and fetal weight retardation induced by the methyl-branched derivatives were very low when compared to those of the parent compounds, These novel compounds exhibited anticonvulsant activity which was not significantly different from that of VPA. Neurotoxicity was considerably lower for some compounds as compared to VPA. Anticonvulsant activity and neurotoxicity of branched short chain fatty acids are far less structure-dependent and not related to teratogenic potency. Within this series of compounds, (+/-)-4-methyl-2-n-propyl-4-pentenoic acid and (+/-)-2-isobutyl-4-pentenoic acid exhibited the most favorable profile in regard to high anticonvulsant effect, low sedation, and teratogenicity. Valproic acid analogues with additional methyl branching may be valuable antiepileptic agents with low teratogenic potential.