(3R,1'R,2'R)-N-methyl-N-(2'-phenyl-2'-hydroxy-1'-methylethyl)-3-methylpentanamide | 1061728-08-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3R,1'R,2'R)-N-methyl-N-(2'-phenyl-2'-hydroxy-1'-methylethyl)-3-methylpentanamide
• 英文别名: (3R)-N-[(1R,2R)-1-hydroxy-1-phenylpropan-2-yl]-N,3-dimethylpentanamide
• CAS: 1061728-08-2
• 化学式: C₁₆H₂₅NO₂
• 分子量: 263.38
• InChiKey: XSSWZEFRVNFKEY-IOASZLSFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3R,1'R,2'R)-N-methyl-N-(2'-phenyl-2'-hydroxy-1'-methylethyl)-3-methylpentanamide 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 、 环己烷 、 水 为溶剂， 反应 22.5h， 生成 (2R,3R)-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
• 作为产物：
  描述：

  (R)-3-甲基戊酸 、 左旋伪麻黄碱 在 三甲基乙酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以97%的产率得到(3R,1'R,2'R)-N-methyl-N-(2'-phenyl-2'-hydroxy-1'-methylethyl)-3-methylpentanamide
  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 1,4-addition of Grignard reagents to α,β-enamides using a combined chiral auxiliary-catalyst approach
  作者：Kallolmay Biswas、Simon Woodward

  DOI：10.1016/j.tetasy.2008.06.017

  日期：2008.7

  A catalyst composed of (R,R)-MeDuphos and CuBr center dot SMe(2) catalyzes the addition of RMgBr (R = Et, C(5)H(11), Ph) to simple enamides (E)-Me(2)NCOCH = CHR(1) (R(1) = Me, C(5)H(11)) in acceptable yields (50-78%), but with poor to modest enantioselectivities (0-74% ee). By changing the enamide acceptor to the (E)-(Aux)N-COCH = CHMe [Aux = from commercial pseudoephedrine, (R,R)-NMeCHMeCHPhOH] a stereochemically enhanced regime Could be attained. Structurally diverse RMgBr (R = C(5)H(11), vinyl, allyl, Ph) underwent 1,4-additions in 57-89% de and 88-93% yield. In one case, the resulting enolate could be trapped with allyl bromide. (C) 2008 Elsevier Ltd. All rights reserved.