tert-butyl N-[(E)-6-[[(2R)-1-[[(2R)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-thiophen-2-ylpropan-2-yl]-methylamino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]-methylamino]-2,4-dimethyl-6-oxohex-4-en-2-yl]carbamate | 1026961-27-2

• 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: tert-butyl N-[(E)-6-[[(2R)-1-[[(2R)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-thiophen-2-ylpropan-2-yl]-methylamino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]-methylamino]-2,4-dimethyl-6-oxohex-4-en-2-yl]carbamate
• CAS: 1026961-27-2
• 化学式: C₄₂H₅₆N₄O₆S
• 分子量: 744.996
• InChiKey: LAPLRBGYHDSMJU-XIADPTGYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  53
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(E)-6-[[(2R)-1-[[(2R)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-thiophen-2-ylpropan-2-yl]-methylamino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]-methylamino]-2,4-dimethyl-6-oxohex-4-en-2-yl]carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.67h， 以223 mg的产率得到(2E)-5-Amino-3,5-dimethylhex-2-enoic acid N-((1R)-2-(biphenyl-4-yl)-1-{N-[(1R)-2-(4-hydroxypiperidin-1-yl)-2-oxo-1-((thien-2-yl)methyl)ethyl]-N-methylcarbamoyl}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：

  (2R)-2-(N-tert-butoxycarbonyl-N-methylamino)-3-(2-thienyl)propionic acid 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-[(E)-6-[[(2R)-1-[[(2R)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-thiophen-2-ylpropan-2-yl]-methylamino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]-methylamino]-2,4-dimethyl-6-oxohex-4-en-2-yl]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