(S)-N¹-(4-benzyloxy-phenyl)-N¹-(3-methyl-but-2-enyl)-propane-1,2-diamine | 250236-93-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (S)-N¹-(4-benzyloxy-phenyl)-N¹-(3-methyl-but-2-enyl)-propane-1,2-diamine
• 英文别名: (2S)-1-N-(3-methylbut-2-enyl)-1-N-(4-phenylmethoxyphenyl)propane-1,2-diamine
• CAS: 250236-93-2
• 化学式: C₂₁H₂₈N₂O
• 分子量: 324.466
• InChiKey: YTCHKVLBWWLSHL-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  38.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-[(Azepane-1-carbonyl)-amino]-4-methyl-pentanoic acid 、 (S)-N¹-(4-benzyloxy-phenyl)-N¹-(3-methyl-but-2-enyl)-propane-1,2-diamine 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 [S,(R*,R*)]-azepane-1-carboxylic acid (1-{2-[(4-benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-1-methyl-ethylcarbamoyl}-3-methyl-butyl)-amide
  参考文献：
  名称：

  Synthesis of a Series of 4-Benzyloxyaniline Analogues as Neuronal N-Type Calcium Channel Blockers with Improved Anticonvulsant and Analgesic Properties

  摘要：

  In this article, the rationale for the design, synthesis, and biological evaluation of a series of N-type voltage-sensitive calcium channel (VSCC) blockers is described. N-Type VSCC blockers, such as ziconotide, have shown utility in several models of stroke and pain. Modification of the previously reported lead, 1a, led to several 4-(4-benzyloxylphenyl)piperidine structures with potent in vitro and in vivo activities. In this series, the most interesting compound, (S)-2-amino- 1-{4-[(4-benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-piperidin-1-yl}-4-methyl-pentan-1-one (11), blocked N-type calcium channels (IC50 = 0.67 mu M in the IMR32 assay) and was efficacious in the audiogenic DBA/2 seizure mouse model (ED50 = 6 mg/kg, iv) as well as the antiwrithing model (ED50 = 6 mg/kg, iv). Whole-cell voltage-clamp electrophysiology experiments demonstrated that compound 11 blocked N-type Ca2+ channels and Na+ channels in superior cervical ganglion neurons at similar concentrations. Compound 11, which showed superior in vivo efficacy, stands out as an interesting lead for further development of neurotherapeutic agents in this series.

  DOI：

  10.1021/jm9902739
• 作为产物：
  描述：

  4-苄氧基苯胺 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 diborane(6) 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 23.5h， 生成 (S)-N¹-(4-benzyloxy-phenyl)-N¹-(3-methyl-but-2-enyl)-propane-1,2-diamine
  参考文献：
  名称：

  Synthesis of a Series of 4-Benzyloxyaniline Analogues as Neuronal N-Type Calcium Channel Blockers with Improved Anticonvulsant and Analgesic Properties

  摘要：

  In this article, the rationale for the design, synthesis, and biological evaluation of a series of N-type voltage-sensitive calcium channel (VSCC) blockers is described. N-Type VSCC blockers, such as ziconotide, have shown utility in several models of stroke and pain. Modification of the previously reported lead, 1a, led to several 4-(4-benzyloxylphenyl)piperidine structures with potent in vitro and in vivo activities. In this series, the most interesting compound, (S)-2-amino- 1-{4-[(4-benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-piperidin-1-yl}-4-methyl-pentan-1-one (11), blocked N-type calcium channels (IC50 = 0.67 mu M in the IMR32 assay) and was efficacious in the audiogenic DBA/2 seizure mouse model (ED50 = 6 mg/kg, iv) as well as the antiwrithing model (ED50 = 6 mg/kg, iv). Whole-cell voltage-clamp electrophysiology experiments demonstrated that compound 11 blocked N-type Ca2+ channels and Na+ channels in superior cervical ganglion neurons at similar concentrations. Compound 11, which showed superior in vivo efficacy, stands out as an interesting lead for further development of neurotherapeutic agents in this series.

  DOI：

  10.1021/jm9902739

文献信息

• US6251918B1
  申请人：——

  公开号：US6251918B1

  公开（公告）日：2001-06-26