4-amino-N-(1-pyridin-2-ylethyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide | 1425503-19-0

• 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: 4-amino-N-(1-pyridin-2-ylethyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide
• CAS: 1425503-19-0
• 化学式: C₁₉H₂₃N₇O
• 分子量: 365.438
• InChiKey: ZBHPPMORCCNMSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-(Boc-氨基)哌啶-4-甲酸 在 碳酸氢钠 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙二醇二甲醚 、 水 、 乙腈 为溶剂， 反应 40.0h， 生成 4-amino-N-(1-pyridin-2-ylethyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide
  参考文献：
  名称：

  Discovery of 4-Amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an Orally Bioavailable, Potent Inhibitor of Akt Kinases

  摘要：

  Wide-ranging exploration of analogues of an ATP-competitive pyrrolopyrimidine inhibitor of Akt led to the discovery of clinical candidate AZD5363, which showed increased potency, reduced hERG affinity, and higher selectivity against the closely related AGC kinase ROCK. This compound demonstrated good preclinical drug metabolism and pharmacokinetics (DMPK) properties and, after oral dosing, showed pharmacodynamic knockdown of phosphorylation of Akt and downstream biomarkers in vivo, and inhibition of tumor growth in a breast cancer xenograft model.

  DOI：

  10.1021/jm301762v

文献信息

• Discovery of 4-Amino-<i>N</i>-[(1<i>S</i>)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7<i>H</i>-pyrrolo[2,3-<i>d</i>]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an Orally Bioavailable, Potent Inhibitor of Akt Kinases
  作者：Matt Addie、Peter Ballard、David Buttar、Claire Crafter、Gordon Currie、Barry R. Davies、Judit Debreczeni、Hannah Dry、Philippa Dudley、Ryan Greenwood、Paul D. Johnson、Jason G. Kettle、Clare Lane、Gillian Lamont、Andrew Leach、Richard W. A. Luke、Jeff Morris、Donald Ogilvie、Ken Page、Martin Pass、Stuart Pearson、Linette Ruston

  DOI：10.1021/jm301762v

  日期：2013.3.14

  Wide-ranging exploration of analogues of an ATP-competitive pyrrolopyrimidine inhibitor of Akt led to the discovery of clinical candidate AZD5363, which showed increased potency, reduced hERG affinity, and higher selectivity against the closely related AGC kinase ROCK. This compound demonstrated good preclinical drug metabolism and pharmacokinetics (DMPK) properties and, after oral dosing, showed pharmacodynamic knockdown of phosphorylation of Akt and downstream biomarkers in vivo, and inhibition of tumor growth in a breast cancer xenograft model.