(R)-N-(biphenyl-4-ylmethyl)-2-amino-3,3-dimethylbutanamide | 1334604-78-2

• 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: (R)-N-(biphenyl-4-ylmethyl)-2-amino-3,3-dimethylbutanamide
• 英文别名: (2R)-2-amino-3,3-dimethyl-N-[(4-phenylphenyl)methyl]butanamide
• CAS: 1334604-78-2
• 化学式: C₁₉H₂₄N₂O
• 分子量: 296.412
• InChiKey: JZRLHDVLYKUCKG-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (R)-N-(biphenyl-4-ylmethyl)-2-(t-butoxycarbonyl)amino-3,3-dimethylbutanamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以67%的产率得到(R)-N-(biphenyl-4-ylmethyl)-2-amino-3,3-dimethylbutanamide
  参考文献：
  名称：

  Primary Amino Acid Derivatives: Substitution of the 4′-N′-Benzylamide Site in (R)-N′-Benzyl 2-Amino-3-methylbutanamide, (R)-N′-Benzyl 2-Amino-3,3-dimethylbutanamide, and (R)-N′-Benzyl 2-Amino-3-methoxypropionamide Provides Potent Anticonvulsants with Pain-Attenuating Properties

  摘要：

  Recently, we reported that select N'-benzyl 2-substituted 2-amino acetamides (primary amino acid derivatives (PAADs)) exhibited pronounced activities in established whole animal anticonvulsant (i.e., maximal electroshock seizure (MES)) and neuropathic pain (i.e., formalin) models. The anticonvulsant activities of C(2)-hydrocarbon N'-benzyl 2-amino acetamides (MES ED50 = 13-21 mg/kg) exceeded those of phenobarbital (ED50 = 22 mg/kg). Two additional studies defining the structure activity relationship of PAADs are presented in this issue of the journal. In this study, we demonstrated that the anticonvulsant activities of (R)-N'-benzyl 2-amino-3-methylbutanamide and (R)-N'-benzyl 2-amino-3,3-dimethyl-butanamide were sensitive to substituents at the 4'-N'-benzylamide site; electron-withdrawing groups retained activity, electron-donating groups led to a loss of activity, and incorporating either a 3-fluorobenzyloxy or 3-fluorophenoxymethyl group using a rationally designed multiple ligand approach improved activity. Additionally, we showed that substituents at the 4'-N'-benzylamide site of (R)-N'-benzyl 2-amino-3-methoxypropionamide also improved anticonvulsant activity, with the 3-fluorophenoxymethyl group providing the largest (similar to 4-fold) increase in activity (ED50 = 8.9 mg/kg), a value that surpassed phenytoin (ED50 = 9.5 mg/kg). Collectively, the pharmacological findings provided new information that C(2)-hydrocarbon PAADs represent a novel class of anticonvulsants.

  DOI：

  10.1021/jm200759t

文献信息

• Primary Amino Acid Derivatives: Substitution of the 4′-<i>N</i>′-Benzylamide Site in (<i>R</i>)-<i>N</i>′-Benzyl 2-Amino-3-methylbutanamide, (<i>R</i>)-<i>N</i>′-Benzyl 2-Amino-3,3-dimethylbutanamide, and (<i>R</i>)-<i>N</i>′-Benzyl 2-Amino-3-methoxypropionamide Provides Potent Anticonvulsants with Pain-Attenuating Properties
  作者：Amber M. King、Christophe Salomé、Elise Salomé-Grosjean、Marc De Ryck、Rafal Kaminski、Anne Valade、James P. Stables、Harold Kohn

  DOI：10.1021/jm200759t

  日期：2011.10.13

  Recently, we reported that select N'-benzyl 2-substituted 2-amino acetamides (primary amino acid derivatives (PAADs)) exhibited pronounced activities in established whole animal anticonvulsant (i.e., maximal electroshock seizure (MES)) and neuropathic pain (i.e., formalin) models. The anticonvulsant activities of C(2)-hydrocarbon N'-benzyl 2-amino acetamides (MES ED50 = 13-21 mg/kg) exceeded those of phenobarbital (ED50 = 22 mg/kg). Two additional studies defining the structure activity relationship of PAADs are presented in this issue of the journal. In this study, we demonstrated that the anticonvulsant activities of (R)-N'-benzyl 2-amino-3-methylbutanamide and (R)-N'-benzyl 2-amino-3,3-dimethyl-butanamide were sensitive to substituents at the 4'-N'-benzylamide site; electron-withdrawing groups retained activity, electron-donating groups led to a loss of activity, and incorporating either a 3-fluorobenzyloxy or 3-fluorophenoxymethyl group using a rationally designed multiple ligand approach improved activity. Additionally, we showed that substituents at the 4'-N'-benzylamide site of (R)-N'-benzyl 2-amino-3-methoxypropionamide also improved anticonvulsant activity, with the 3-fluorophenoxymethyl group providing the largest (similar to 4-fold) increase in activity (ED50 = 8.9 mg/kg), a value that surpassed phenytoin (ED50 = 9.5 mg/kg). Collectively, the pharmacological findings provided new information that C(2)-hydrocarbon PAADs represent a novel class of anticonvulsants.