valproyl gabaoyl chloride | 165406-58-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: valproyl gabaoyl chloride
• 英文别名: N-(2-propylpentanoyl)-4-aminobutyroyl chloride；4-(2-propylpentanoylamino)butanoyl chloride
• CAS: 165406-58-6
• 化学式: C₁₂H₂₂ClNO₂
• 分子量: 247.765
• InChiKey: DFISKERPFFJRNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  16
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  valproyl gabaoyl chloride 在 氨 作用下， 以 氯仿 为溶剂， 生成 valproyl gabamide
  参考文献：
  名称：

  摘要：

  Purpose. To explore the possibility of utilizing valproyl derivatives of GABA and glycine as new antiepileptics by using the structure pharmacokinetic-pharmacodynamic relationship (SPPR) approach. Methods. The pharmacokinetics and pharmacodynamics (anticonvulsant activity and neurotoxicity) of the following four conjugation products of valproic acid (VPA), glycine and GABA were investigated: valproyl glycine, valproyl glycinamide, valproyl GABA and valproyl gabamide. Results. Only valproyl glycinamide showed a good anticonvulsant profile in both mice and rats due to its better pharmacokinetic profile. Valproyl glycinamide was more potent than one of the major antiepileptic agents - VPA and showed a better margin between activity and neurotoxicity. Valproyl glycine and valproyl GABA were partially excreted unchanged in the urine (fe=50% and 34%, respectively), while the urinary metabolites of the amide derivatives were valproyl glycine and valproyl GABA. Conclusions. The four investigated valproyl derivatives did not operate as chemical drug delivery systems (CDDS) of glycine or GABA, but acted rather as drugs on their own. The current study demonstrates the benefit of the SPPR approach in developing and selecting a potent antiepileptic compound in intact animals based not only on its intrinsic pharmacodynamic activity, but also on its better pharmacokinetic profile.

  DOI：

  10.1023/a:1016277507865
• 作为产物：
  描述：

  N^γ-valproyl-aminobutyric acid 在 4-二甲氨基吡啶 、 氯化亚砜 作用下， 以 氯仿 为溶剂， 生成 valproyl gabaoyl chloride
  参考文献：
  名称：

  摘要：

  Purpose. To explore the possibility of utilizing valproyl derivatives of GABA and glycine as new antiepileptics by using the structure pharmacokinetic-pharmacodynamic relationship (SPPR) approach. Methods. The pharmacokinetics and pharmacodynamics (anticonvulsant activity and neurotoxicity) of the following four conjugation products of valproic acid (VPA), glycine and GABA were investigated: valproyl glycine, valproyl glycinamide, valproyl GABA and valproyl gabamide. Results. Only valproyl glycinamide showed a good anticonvulsant profile in both mice and rats due to its better pharmacokinetic profile. Valproyl glycinamide was more potent than one of the major antiepileptic agents - VPA and showed a better margin between activity and neurotoxicity. Valproyl glycine and valproyl GABA were partially excreted unchanged in the urine (fe=50% and 34%, respectively), while the urinary metabolites of the amide derivatives were valproyl glycine and valproyl GABA. Conclusions. The four investigated valproyl derivatives did not operate as chemical drug delivery systems (CDDS) of glycine or GABA, but acted rather as drugs on their own. The current study demonstrates the benefit of the SPPR approach in developing and selecting a potent antiepileptic compound in intact animals based not only on its intrinsic pharmacodynamic activity, but also on its better pharmacokinetic profile.

  DOI：

  10.1023/a:1016277507865

文献信息

• [EN] DERIVATIVES OF VALPROIC AND 2-VALPROENOIC ACID AMIDES AND USE AS ANTICONVULSANTS<br/>[FR] DERIVES D'AMIDES D'ACIDE VALPROIQUE ET D'ACIDE 2-VALPROENOIQUE ET LEUR UTILISATION COMME ANTICONVULSIVANTS
  申请人：YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM

  公开号：WO1995001956A1

  公开（公告）日：1995-01-19

  (EN) A compound having structure (I), wherein A is X or Y, X is (a), Y is (b); R1, R2, R3, R4 and R5 are each independently hydrogen, a C1-C6 alkyl group, an aralkyl group, or an aryl group; and n is 0, 1, 2, or 3. Also provided are a compound containing a 2-valproenoic moiety, pharmaceutical compositions comprising these compounds, and methods of using them for the effective treatment of epilepsy and other neurological disorders.(FR) Composé de la structure (I), dans laquelle A représente X ou Y, X représente (a), Y représente (b) , R1, R2, R3, R4 et R5 représentent chacun indépendamment hydrogène, un groupe alkyle C1-C6, un groupe aralkyle ou un groupe aryle, et n représente 0, 1, 2 ou 3. L'invention concerne également un composé contenant une fraction 2-valproénoïque, des compositions pharmaceutiques contenant ces composés, et des procédés d'utilisation de celles-ci dans le traitement efficace de l'épilepsie et d'autres troubles neurologiques.

  一种具有结构（I）的化合物，其中A代表X或Y，X代表（a），Y代表（b）; R1、R2、R3、R4和R5各自独立地表示氢、C1-C6烷基、芳基烷基或芳基基；n为0、1、2或3。还提供了含有2-丙烯酸基团的化合物、包含这些化合物的药物组合物以及使用它们有效治疗癫痫和其他神经系统疾病的方法。
• Derivatives of valproic acid amides and 2-valproenoic acid amides,
  申请人：Yissum Research Development Corporation of the Hebrew University of

  公开号：US05585358A1

  公开（公告）日：1996-12-17

  A compound having the structure: ##STR1## wherein R.sub.1, R.sub.2, and R.sub.3 are independently the same or different and are hydrogen, a C.sub.1 -C.sub.6 alkyl group, an aralkyl group, or an aryl group, and n is an integer which is greater than or equal to 0 and less than or equal to 3. Also provided are a compound containing a 2-valproenoic moiety, pharmaceutical compositions comprising these compounds, and methods of using them for the effective treatment of epilepsy and other neurological disorders.

  一种具有以下结构的化合物：##STR1## 其中R.sub.1，R.sub.2和R.sub.3独立且相同或不同，可以是氢、C.sub.1-C.sub.6烷基、芳基烷基或芳基，n是大于或等于0且小于或等于3的整数。还提供了一种含有2-丙烯酸酯基团的化合物，包括这些化合物的制药组合物和使用它们有效治疗癫痫和其他神经系统疾病的方法。
• DERIVATIVES OF VALPROIC AND 2-VALPROENOIC ACID AMIDES AND USE AS ANTICONVULSANTS
  申请人：YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM

  公开号：EP0659174A1

  公开（公告）日：1995-06-28
• EP0659174A4
  申请人：——

  公开号：EP0659174A4

  公开（公告）日：1995-09-27
• US5585358A
  申请人：——

  公开号：US5585358A

  公开（公告）日：1996-12-17