diethyl 2-[4-[[(3R,5S)-3,5-dimethyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]methyl]phenyl]propanedioate | 1127440-50-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: diethyl 2-[4-[[(3R,5S)-3,5-dimethyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]methyl]phenyl]propanedioate
• CAS: 1127440-50-9
• 化学式: C₂₅H₃₈N₂O₆
• 分子量: 462.587
• InChiKey: OZGBQFHDVDKUOE-HDICACEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  85.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl 2-[4-[[(3R,5S)-3,5-dimethyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]methyl]phenyl]propanedioate 、 碘甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 1.17h， 以356 mg的产率得到diethyl 2-[4-[[(3S,5R)-3,5-dimethyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]methyl]phenyl]-2-methylpropanedioate
  参考文献：
  名称：

  Discovery of N-(3-Fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-piperidinamine (GSK962040), the First Small Molecule Motilin Receptor Agonist Clinical Candidate

  摘要：

  N-(3-Fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-piperidinamine 12 (GSK962040) is a novel small molecule motilin receptor agonist. It possesses excellent activity at the recombinant human motilin receptor and also at the native rabbit motilin receptor where its agonist activity results in potentiation of the amplitude of neuronal-mediated contractions of isolated gastric antrum, tissue. Compound 12 also possesses highly promising pharmacokinetic profiles in both rat and dog, and these results, in combination with further profiling in human native tissue and an in vivo model of gastrointestinal transit in the rabbit, have led to its selection as a candidate for further development.

  DOI：

  10.1021/jm801332q
• 作为产物：
  描述：

  1,1-dimethylethyl (2R,6S)-4-((4-bromophenyl)methyl)-2,6-dimethyl-1-piperazinecarboxylate 、 丙二酸二乙酯 在 potassium phosphate 、 palladium diacetate 、 2-二-叔丁基磷-2'-甲基联苯 作用下， 以 1,4-二氧六环 为溶剂， 生成 diethyl 2-[4-[[(3R,5S)-3,5-dimethyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]methyl]phenyl]propanedioate
  参考文献：
  名称：

  Discovery of N-(3-Fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-piperidinamine (GSK962040), the First Small Molecule Motilin Receptor Agonist Clinical Candidate

  摘要：

  N-(3-Fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-piperidinamine 12 (GSK962040) is a novel small molecule motilin receptor agonist. It possesses excellent activity at the recombinant human motilin receptor and also at the native rabbit motilin receptor where its agonist activity results in potentiation of the amplitude of neuronal-mediated contractions of isolated gastric antrum, tissue. Compound 12 also possesses highly promising pharmacokinetic profiles in both rat and dog, and these results, in combination with further profiling in human native tissue and an in vivo model of gastrointestinal transit in the rabbit, have led to its selection as a candidate for further development.

  DOI：

  10.1021/jm801332q

文献信息

• Discovery of <i>N</i>-(3-Fluorophenyl)-1-[(4-([(3<i>S</i>)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-piperidinamine (GSK962040), the First Small Molecule Motilin Receptor Agonist Clinical Candidate
  作者：Susan M. Westaway、Samantha L. Brown、Stephen C. M. Fell、Christopher N. Johnson、David T. MacPherson、Darren J. Mitchell、James W. Myatt、Steven J. Stanway、Jon T. Seal、Geoffrey Stemp、Mervyn Thompson、Kirk Lawless、Fiona McKay、Alison I. Muir、Jonathan M. Barford、Chermaine Cluff、Sadhia R. Mahmood、Kim L. Matthews、Shiyam Mohamed、Beverley Smith、Alexander J. Stevens、Victoria J. Bolton、Emma M. Jarvie、Gareth J. Sanger

  DOI：10.1021/jm801332q

  日期：2009.2.26

  N-(3-Fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-piperidinamine 12 (GSK962040) is a novel small molecule motilin receptor agonist. It possesses excellent activity at the recombinant human motilin receptor and also at the native rabbit motilin receptor where its agonist activity results in potentiation of the amplitude of neuronal-mediated contractions of isolated gastric antrum, tissue. Compound 12 also possesses highly promising pharmacokinetic profiles in both rat and dog, and these results, in combination with further profiling in human native tissue and an in vivo model of gastrointestinal transit in the rabbit, have led to its selection as a candidate for further development.