1,1-dimethylethyl [(1S)-2-{[6-chloro-5-(3-methyl-1H-pyrazolo[4,3-b]pyridin-5-yl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]carbamate | 864775-65-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1,1-dimethylethyl [(1S)-2-{[6-chloro-5-(3-methyl-1H-pyrazolo[4,3-b]pyridin-5-yl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]carbamate
• 英文别名: tert-butyl N-[(2S)-1-[6-chloro-5-(3-methyl-2H-pyrazolo[4,3-b]pyridin-5-yl)pyridin-3-yl]oxy-3-(1H-indol-3-yl)propan-2-yl]carbamate
• CAS: 864775-65-5
• 化学式: C₂₈H₂₉ClN₆O₃
• 分子量: 533.03
• InChiKey: CZZCAMPOXYEZAX-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl [(1S)-2-{[6-chloro-5-(3-methyl-1H-pyrazolo[4,3-b]pyridin-5-yl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]carbamate 、 3-呋喃硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以97%的产率得到tert-butyl (S)-(1-((6-(furan-3-yl)-5-(3-methyl-1H-pyrazolo[4,3-b]pyridin-5-yl)pyridin-3-yl)oxy)-3-(1H-indol-3-yl)propan-2-yl)carbamate
  参考文献：
  名称：

  2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles

  摘要：

  A novel series of AKT inhibitors containing 2,3,5-trisubstituted pyridines with novel azaindazoles as hinge binding elements are described. Among these, the 4,7-diazaindazole compound 2c has improved drug-like properties and kinase selectivity than those of indazole 1, and displays greater than 80% inhibition of GSK3b phosphorylation in a BT474 tumor xenograft model in mice. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.060
• 作为产物：
  描述：

  tert-butyl N-[(2S)-1-[6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)pyridin-3-yl]oxy-3-(1H-indol-3-yl)propan-2-yl]carbamate 、 5-氯-3-甲基-1H-吡唑并[4,3-b]吡啶 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 水 为溶剂， 以40%的产率得到1,1-dimethylethyl [(1S)-2-{[6-chloro-5-(3-methyl-1H-pyrazolo[4,3-b]pyridin-5-yl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]carbamate
  参考文献：
  名称：

  2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles

  摘要：

  A novel series of AKT inhibitors containing 2,3,5-trisubstituted pyridines with novel azaindazoles as hinge binding elements are described. Among these, the 4,7-diazaindazole compound 2c has improved drug-like properties and kinase selectivity than those of indazole 1, and displays greater than 80% inhibition of GSK3b phosphorylation in a BT474 tumor xenograft model in mice. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.060

文献信息

• [EN] INHIBITORS OF AKT ACTIVITY<br/>[FR] INHIBITEURS DE L'ACTIVITE DE LA PROTEINE KINASE B (AKT)
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2005085227A1

  公开（公告）日：2005-09-15

  Invented are novel pyridine compounds, the use of such compounds as inhibitors of PKB/AKT kinase activity and in the treatment of cancer and arthritis.

  发明了新型的吡啶化合物，以及这些化合物作为PKB/AKT激酶活性的抑制剂以及用于治疗癌症和关节炎的用途。
• Inhibitors of akt activity
  申请人：Yamashita S. Dennis

  公开号：US20070185152A1

  公开（公告）日：2007-08-09

  Invented are novel pyridine compounds, the use of such compounds as inhibitors of PKB/AKT kinase activity and in the treatment of cancer and arthritis.

  发明了新型吡啶化合物，这些化合物可用作PKB/AKT激酶活性的抑制剂，并用于癌症和关节炎的治疗。
• 2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles
  作者：Hong Lin、Dennis S. Yamashita、Jin Zeng、Ren Xie、Sharad Verma、Juan I. Luengo、Nelson Rhodes、Shuyun Zhang、Kimberly A. Robell、Anthony E. Choudhry、Zhihong Lai、Rakesh Kumar、Elisabeth A. Minthorn、Kristin K. Brown、Dirk A. Heerding

  DOI：10.1016/j.bmcl.2009.11.060

  日期：2010.1

  A novel series of AKT inhibitors containing 2,3,5-trisubstituted pyridines with novel azaindazoles as hinge binding elements are described. Among these, the 4,7-diazaindazole compound 2c has improved drug-like properties and kinase selectivity than those of indazole 1, and displays greater than 80% inhibition of GSK3b phosphorylation in a BT474 tumor xenograft model in mice. (C) 2009 Elsevier Ltd. All rights reserved.