{2-[(4-benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester | 250236-89-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: {2-[(4-benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[2-methyl-1-[N-(3-methylbut-2-enyl)-4-phenylmethoxyanilino]propan-2-yl]carbamate
• CAS: 250236-89-6
• 化学式: C₂₇H₃₈N₂O₃
• 分子量: 438.61
• InChiKey: TVMNCPUGSJFHPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  50.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  {2-[(4-benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 (S)-Azepane-1-carboxylic acid (1-{2-[(4-benzyloxy-phenyl)-(3-methyl-but-2enyl)-amino]-1,1-dimethyl-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 、 diborane(6) 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 21.0h， 生成 {2-[(4-benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester
  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

• Aniline derivatives as calcium channel blockers
  申请人：Warner-Lambert Company

  公开号：US06251918B1

  公开（公告）日：2001-06-26

  The present invention provides compounds that block calcium channels having formula (I). The present invention also provides methods of using the compounds of formula (I) to treat stroke, cerebral ischemia, head trauma, or epilepsy and to pharmaceutical compositions that contain the compounds of formula (I).

  本发明提供了一种阻断钙通道的化合物，其化学式为(I)。本发明还提供了使用化合物(I)治疗中风、脑缺血、头部创伤或癫痫的方法，以及含有化合物(I)的药物组合物。
• Calcium channel blockers
  申请人：——

  公开号：US20010023249A1

  公开（公告）日：2001-09-20

  The present invention provides compounds that block calcium channels having the Formula I shown below. 1 The present invention also provides methods of using the compounds of Formula I to treat stroke, cerebral ischemia, head trauma, or epilepsy and to pharmaceutical compositions that contain the compounds of Formula I.

  本发明提供了具有下面式子I的阻断钙通道的化合物。同时，本发明还提供了使用式子I的化合物治疗中风、脑缺血、头部创伤或癫痫的方法，以及含有式子I的制药组合物。
• US6251918B1
  申请人：——

  公开号：US6251918B1

  公开（公告）日：2001-06-26
• US6495715B2
  申请人：——

  公开号：US6495715B2

  公开（公告）日：2002-12-17