(R)-N-(4-(3-fluorobenzyloxy)benzyl)-2-aminopropionamide hydrochloride | 1334604-86-2

• 英文名称: (R)-N-(4-(3-fluorobenzyloxy)benzyl)-2-aminopropionamide hydrochloride
• 英文别名: (2R)-2-amino-N-[[4-[(3-fluorophenyl)methoxy]phenyl]methyl]propanamide;hydrochloride
• CAS: 1334604-86-2
• 化学式: C₁₇H₁₉FN₂O₂*ClH
• 分子量: 338.809
• InChiKey: IZVFRCMSKGDADW-UTONKHPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.79
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  64.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (R)-N-(4-(3-fluorobenzyloxy)benzyl)-2-t-butoxycarbonylaminopropionamide 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以100%的产率得到(R)-N-(4-(3-fluorobenzyloxy)benzyl)-2-aminopropionamide hydrochloride
  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