6-bromo-3-(2-methoxybenzyl)-2-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine | 1380609-79-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 6-bromo-3-(2-methoxybenzyl)-2-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine
• 英文别名: 6-Bromo-3-[(2-methoxyphenyl)methyl]-2-pyridin-4-ylimidazo[4,5-b]pyridine
• CAS: 1380609-79-9
• 化学式: C₁₉H₁₅BrN₄O
• 分子量: 395.258
• InChiKey: KSYYTQGMYRNMIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  52.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-溴-2-氯-3-硝基吡啶 在 sodium dithionite 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 生成 6-bromo-3-(2-methoxybenzyl)-2-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridine
  参考文献：
  名称：

  Discovery and Optimization of a Series of 3-(3-Phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amines: Orally Bioavailable, Selective, and Potent ATP-Independent Akt Inhibitors

  摘要：

  This paper describes the implementation of a biochemical and biophysical screening strategy to identify and optimize small molecule Akt1 inhibitors that act through a mechanism distinct from that observed for kinase domain ATP-competitive inhibitors. With the aid of an unphosphorylated Akt1 cocrystal structure of 12j solved at 2.25 A, it was possible to confirm that as a consequence of binding these novel inhibitors, the ATP binding cleft contained a number of hydrophobic residues that occlude ATP binding as expected. These Akt inhibitors potently inhibit intracellular Akt activation and its downstream target (PRAS40) in vitro. In vivo pharmacodynamic and pharmacokinetic studies with two examples, 12e and 12j, showed the series to be similarly effective at inhibiting the activation of Akt and and additional downstream effector (p70S6) following oral dosing in mice.

  DOI：

  10.1021/jm300276x

文献信息

• Discovery and Optimization of a Series of 3-(3-Phenyl-3<i>H</i>-imidazo[4,5-<i>b</i>]pyridin-2-yl)pyridin-2-amines: Orally Bioavailable, Selective, and Potent ATP-Independent Akt Inhibitors
  作者：Mark A. Ashwell、Jean-Marc Lapierre、Christopher Brassard、Karen Bresciano、Cathy Bull、Susan Cornell-Kennon、Sudharshan Eathiraj、Dennis S. France、Terence Hall、Jason Hill、Eoin Kelleher、Sampada Khanapurkar、Darin Kizer、Steffi Koerner、Jeff Link、Yanbin Liu、Sapna Makhija、Magdi Moussa、Nivedita Namdev、Khanh Nguyen、Robert Nicewonger、Rocio Palma、Jeff Szwaya、Manish Tandon、Uma Uppalapati、David Vensel、Laurie P. Volak、Erika Volckova、Neil Westlund、Hui Wu、Rui-Yang Yang、Thomas C. K. Chan

  DOI：10.1021/jm300276x

  日期：2012.6.14

  This paper describes the implementation of a biochemical and biophysical screening strategy to identify and optimize small molecule Akt1 inhibitors that act through a mechanism distinct from that observed for kinase domain ATP-competitive inhibitors. With the aid of an unphosphorylated Akt1 cocrystal structure of 12j solved at 2.25 A, it was possible to confirm that as a consequence of binding these novel inhibitors, the ATP binding cleft contained a number of hydrophobic residues that occlude ATP binding as expected. These Akt inhibitors potently inhibit intracellular Akt activation and its downstream target (PRAS40) in vitro. In vivo pharmacodynamic and pharmacokinetic studies with two examples, 12e and 12j, showed the series to be similarly effective at inhibiting the activation of Akt and and additional downstream effector (p70S6) following oral dosing in mice.