(2S,3S)-3-methyl-2-propylpentanoic acid | 1479058-94-0

• 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: (2S,3S)-3-methyl-2-propylpentanoic acid
• CAS: 1479058-94-0
• 化学式: C₉H₁₈O₂
• 分子量: 158.241
• InChiKey: SHKIDQPEVVMKQV-YUMQZZPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2S,3S)-3-methyl-2-propylpentanoic acid 在 氯化亚砜 、 ammonium hydroxide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 (2S,3S)-sec-butylpropylacetamide
  参考文献：
  名称：

  Stereoselective Pharmacodynamic and Pharmacokinetic Analysis of sec-Butylpropylacetamide (SPD), a New CNS-Active Derivative of Valproic Acid with Unique Activity against Status Epilepticus

  摘要：

  sec-Butylpropylacetamide (racemic-SPD) is a chiral CNS-active amide derivative of valproic acid (VPA). This study describes synthesis and stereospecific comparative pharmacodynamics (PD, anticonvulsant activity and teratogenicity) and pharmacokinetic (PK) analysis of four individual SPD stereoisomers. SPD stereoisomers' anticonvulsant activity was comparatively evaluated in several anticonvulsant animal models including the benzodiazepine-resistant status epilepticus (SE). SPD stereoisomers' PK-PD relationship was evaluated in rats. Teratogenicity of SPD stereoisomers was evaluated in SWV mice strain, susceptible to VPA-induced neural tube defect (NTD). SPD stereoisomers (141 or 283 mg/kg) did not cause NTD. SPD has stereoselective PK and PD. (2R,3S)-SPD and (2S,3R)-SPD higher clearance led to a 50% lower plasma exposure that may contribute to their relative lower activity in the pilocarpine-induced SE model. (2S,3S)-SPD, (2R,3R)-SPD, and racemic-SPD have similar anticonvulsant activity and a PK profile that are better than those of (2R,3S)-SPD and (2S,3R)-SPD, making them good candidates for development as new, potent antiepileptics with a potential in benzodiazepine-resistant SE.

  DOI：

  10.1021/jm4007565
• 作为产物：
  描述：

  (S)-3-methylpentanoic acid ((1'S,2'S)-2'-hydroxy-1'-methyl-2'-phenylethyl)(methyl)amide 在 正丁基锂 、 硫酸 、 二异丙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 环己烯 为溶剂， 反应 24.5h， 生成 (2S,3S)-3-methyl-2-propylpentanoic acid
  参考文献：
  名称：

  Stereoselective Pharmacodynamic and Pharmacokinetic Analysis of sec-Butylpropylacetamide (SPD), a New CNS-Active Derivative of Valproic Acid with Unique Activity against Status Epilepticus

  摘要：

  sec-Butylpropylacetamide (racemic-SPD) is a chiral CNS-active amide derivative of valproic acid (VPA). This study describes synthesis and stereospecific comparative pharmacodynamics (PD, anticonvulsant activity and teratogenicity) and pharmacokinetic (PK) analysis of four individual SPD stereoisomers. SPD stereoisomers' anticonvulsant activity was comparatively evaluated in several anticonvulsant animal models including the benzodiazepine-resistant status epilepticus (SE). SPD stereoisomers' PK-PD relationship was evaluated in rats. Teratogenicity of SPD stereoisomers was evaluated in SWV mice strain, susceptible to VPA-induced neural tube defect (NTD). SPD stereoisomers (141 or 283 mg/kg) did not cause NTD. SPD has stereoselective PK and PD. (2R,3S)-SPD and (2S,3R)-SPD higher clearance led to a 50% lower plasma exposure that may contribute to their relative lower activity in the pilocarpine-induced SE model. (2S,3S)-SPD, (2R,3R)-SPD, and racemic-SPD have similar anticonvulsant activity and a PK profile that are better than those of (2R,3S)-SPD and (2S,3R)-SPD, making them good candidates for development as new, potent antiepileptics with a potential in benzodiazepine-resistant SE.

  DOI：

  10.1021/jm4007565

文献信息

• Stereoselective Pharmacodynamic and Pharmacokinetic Analysis of <i>sec</i>-Butylpropylacetamide (SPD), a New CNS-Active Derivative of Valproic Acid with Unique Activity against Status Epilepticus
  作者：Naama Hen、Tawfeeq Shekh-Ahmad、Boris Yagen、John H. McDonough、Richard H. Finnell、Bogdan Wlodarczyk、Meir Bialer

  DOI：10.1021/jm4007565

  日期：2013.8.22

  sec-Butylpropylacetamide (racemic-SPD) is a chiral CNS-active amide derivative of valproic acid (VPA). This study describes synthesis and stereospecific comparative pharmacodynamics (PD, anticonvulsant activity and teratogenicity) and pharmacokinetic (PK) analysis of four individual SPD stereoisomers. SPD stereoisomers' anticonvulsant activity was comparatively evaluated in several anticonvulsant animal models including the benzodiazepine-resistant status epilepticus (SE). SPD stereoisomers' PK-PD relationship was evaluated in rats. Teratogenicity of SPD stereoisomers was evaluated in SWV mice strain, susceptible to VPA-induced neural tube defect (NTD). SPD stereoisomers (141 or 283 mg/kg) did not cause NTD. SPD has stereoselective PK and PD. (2R,3S)-SPD and (2S,3R)-SPD higher clearance led to a 50% lower plasma exposure that may contribute to their relative lower activity in the pilocarpine-induced SE model. (2S,3S)-SPD, (2R,3R)-SPD, and racemic-SPD have similar anticonvulsant activity and a PK profile that are better than those of (2R,3S)-SPD and (2S,3R)-SPD, making them good candidates for development as new, potent antiepileptics with a potential in benzodiazepine-resistant SE.