tert-butyl N-[1-[(E)-4-[[(2R)-1-[[(2R)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-methylamino]-4-oxobut-2-enyl]cyclobutyl]carbamate | 1026591-45-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: tert-butyl N-[1-[(E)-4-[[(2R)-1-[[(2R)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-methylamino]-4-oxobut-2-enyl]cyclobutyl]carbamate
• CAS: 1026591-45-6
• 化学式: C₄₂H₅₄N₄O₆
• 分子量: 710.914
• InChiKey: RFBUYBZHABLWRP-FUNOIOMASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  52
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[1-[(E)-4-[[(2R)-1-[[(2R)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-methylamino]-4-oxobut-2-enyl]cyclobutyl]carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.67h， 以404 mg的产率得到(2E)-4-(1-Aminocyclobutyl)but-2-enoic acid N-((1R)-1-{N-[(1R)-1-benzyl-2-(4-hydroxypiperidin-1-yl)-2-oxoethyl]-N-methylcarbamoyl}-2-(2-naphthyl)ethyl)-N-methylamide
  参考文献：
  名称：

  The influence of conformational restriction in the C-terminus of growth hormone secretagogues on their potency

  摘要：

  in order to obtain more potent growth hormone secretagogues, a comparison of ipamorelin and NN703 suggested the addition of a polar group at the C-terminus of NN703. A study was conducted using constrained amines for this purpose. Here, substituted 4-piperidinylamino- and 4-dimethylaminopiperidino-substitutents were found to give the most active compounds. A replacement of the 4-dimethylaminopiperidino-substituent with 4-hydroxypiperidino resulted in a series of compounds, which showed in vitro activity with EC50 values in the low nanomolar range, and favourable kinetic properties, such as 40% oral bioavailability. The most promising compound was also tested in a swine in vivo model, resulting in a growth hormone level with a C-max of over 40 ng mL(-1). (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved..

  DOI：

  10.1016/s0223-5234(02)01370-3
• 作为产物：
  描述：

  N-tert-butoxycarbonyl-N-methyl-D-phenylalanine 在 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 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 162.32h， 生成 tert-butyl N-[1-[(E)-4-[[(2R)-1-[[(2R)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-methylamino]-4-oxobut-2-enyl]cyclobutyl]carbamate
  参考文献：
  名称：

  The influence of conformational restriction in the C-terminus of growth hormone secretagogues on their potency

  摘要：

  in order to obtain more potent growth hormone secretagogues, a comparison of ipamorelin and NN703 suggested the addition of a polar group at the C-terminus of NN703. A study was conducted using constrained amines for this purpose. Here, substituted 4-piperidinylamino- and 4-dimethylaminopiperidino-substitutents were found to give the most active compounds. A replacement of the 4-dimethylaminopiperidino-substituent with 4-hydroxypiperidino resulted in a series of compounds, which showed in vitro activity with EC50 values in the low nanomolar range, and favourable kinetic properties, such as 40% oral bioavailability. The most promising compound was also tested in a swine in vivo model, resulting in a growth hormone level with a C-max of over 40 ng mL(-1). (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved..

  DOI：

  10.1016/s0223-5234(02)01370-3