1,1-dimethylethyl (5-bromo-6-chloro-3-{[(2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-3-(1H-indol-3-yl)propyl]oxy}-2-pyridinyl)carbamate | 1131041-74-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1,1-dimethylethyl (5-bromo-6-chloro-3-{[(2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-3-(1H-indol-3-yl)propyl]oxy}-2-pyridinyl)carbamate
• 英文别名: tert-butyl N-[5-bromo-6-chloro-3-[(2S)-3-(1H-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propoxy]pyridin-2-yl]carbamate
• CAS: 1131041-74-1
• 化学式: C₂₆H₃₂BrClN₄O₅
• 分子量: 595.921
• InChiKey: YASWJVFFXSAORY-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  115
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl (5-bromo-6-chloro-3-{[(2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-3-(1H-indol-3-yl)propyl]oxy}-2-pyridinyl)carbamate 、 联硼酸新戊二醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 作用下， 以 四氢呋喃 为溶剂， 反应 7.0h， 以87%的产率得到1,1-dimethylethyl (6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-3-{[(2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-3-(1H-indol-3-yl)propyl]oxy}-2-pyridinyl)carbamate
  参考文献：
  名称：

  Tetrasubstituted pyridines as potent and selective AKT inhibitors: Reduced CYP450 and hERG inhibition of aminopyridines

  摘要：

  The synthesis and evaluation of tetrasubstituted aminopyridines, bearing novel azaindazole hinge binders, as potent AKT inhibitors are described. Compound 14c was identified as a potent AKT inhibitor that demonstrated reduced CYP450 inhibition and an improved developability profile compared to those of previously described trisubstituted pyridines. It also displayed dose-dependent inhibition of both phosphorylation of GSK3b and tumor growth in a BT474 tumor xenograft model in mice. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.061
• 作为产物：
  描述：

  1,1-dimethylethyl (5-bromo-6-chloro-3-hydroxy-2-pyridinyl)carbamate 、 N-α-(叔丁氧基羰基)-L-色氨醇 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 以92%的产率得到1,1-dimethylethyl (5-bromo-6-chloro-3-{[(2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-3-(1H-indol-3-yl)propyl]oxy}-2-pyridinyl)carbamate
  参考文献：
  名称：

  [EN] INHIBITORS OF AKT ACTIVITY
  [FR] INHIBITEURS DE L'ACTIVITÉ D'AKT

  摘要：

  本发明涉及一种新型取代吡啶化合物，其作为蛋白激酶B活性抑制剂和治疗癌症和关节炎的用途。

  公开号：

  WO2009032653A1

文献信息

• [EN] INHIBITORS OF AKT ACTIVITY<br/>[FR] INHIBITEURS DE L'ACTIVITÉ Akt
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009032651A1

  公开（公告）日：2009-03-12

  Invented are novel substituted pyridine compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.

  发明了新型替代吡啶化合物，这些化合物可用作蛋白激酶B活性的抑制剂，并用于癌症和关节炎的治疗。
• [EN] INHIBITORS OF AKT ACTIVITY<br/>[FR] INHIBITEURS DE L'ACTIVITÉ D'AKT
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009032653A1

  公开（公告）日：2009-03-12

  Invented are novel substituted pyridine compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.

  本发明涉及一种新型取代吡啶化合物，其作为蛋白激酶B活性抑制剂和治疗癌症和关节炎的用途。
• Tetrasubstituted pyridines as potent and selective AKT inhibitors: Reduced CYP450 and hERG inhibition of aminopyridines
  作者：Hong Lin、Dennis S. Yamashita、Ren Xie、Jin Zeng、Wenyong Wang、Jack Leber、Igor G. Safonov、Sharad Verma、Mei Li、Louis LaFrance、Joseph Venslavsky、Dennis Takata、Juan I. Luengo、Jason A. Kahana、Shuyun Zhang、Kimberly A. Robell、Dana Levy、Rakesh Kumar、Anthony E. Choudhry、Michael Schaber、Zhihong Lai、Barry S. Brown、Brian T. Donovan、Elisabeth A. Minthorn、Kristin K. Brown、Dirk A. Heerding

  DOI：10.1016/j.bmcl.2009.11.061

  日期：2010.1

  The synthesis and evaluation of tetrasubstituted aminopyridines, bearing novel azaindazole hinge binders, as potent AKT inhibitors are described. Compound 14c was identified as a potent AKT inhibitor that demonstrated reduced CYP450 inhibition and an improved developability profile compared to those of previously described trisubstituted pyridines. It also displayed dose-dependent inhibition of both phosphorylation of GSK3b and tumor growth in a BT474 tumor xenograft model in mice. (C) 2009 Elsevier Ltd. All rights reserved.