N-(4-(2-(2-aminopyridin-3-yl)-6-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)benzamide | 1313879-32-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-(2-(2-aminopyridin-3-yl)-6-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)benzamide
• 英文别名: N-[[4-[2-(2-aminopyridin-3-yl)-6-pyridin-3-ylimidazo[4,5-b]pyridin-3-yl]phenyl]methyl]benzamide
• CAS: 1313879-32-1
• 化学式: C₃₀H₂₃N₇O
• 分子量: 497.559
• InChiKey: WVQVQQXBOHNXQR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.03
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-溴-2-氯-3-硝基吡啶 在 盐酸 、 四(三苯基膦)钯 、 sodium dithionite 、 碳酸氢钠 、 N,N-二异丙基乙胺 、 N,N'-羰基二咪唑 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 、 二甲基亚砜 、 二甲胺 、 甲苯 为溶剂， 生成 N-(4-(2-(2-aminopyridin-3-yl)-6-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)benzamide
  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
• 作为试剂：
  描述：

  苯甲酸 、 N,N'-羰基二咪唑 、 3-(3-(4-(aminomethyl)phenyl)-6-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine hydrochloride 在 水 、 N-(4-(2-(2-aminopyridin-3-yl)-6-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)benzamide 、 乙醚 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 3.17h， 以yielding 2.9 g (5.9 mmol, 84%) of the desired product in 98% purity的产率得到N-(4-(2-(2-aminopyridin-3-yl)-6-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)benzamide
  参考文献：
  名称：

  Substituted Imidazopyridinyl-Aminopyridine Compounds

  摘要：

  本发明涉及取代的咪唑吡啶基氨基吡啶化合物及其合成方法。本发明还涉及含有取代的咪唑吡啶基氨基吡啶化合物的药物组合物，以及通过将这些化合物和药物组合物用于需要治疗细胞增殖性疾病（如癌症）的受试者来治疗这些疾病的方法。

  公开号：

  US20110172203A1

文献信息

• Substituted imidazopyridinyl-aminopyridine compounds
  申请人：Ashwell Mark A.

  公开号：US08501770B2

  公开（公告）日：2013-08-06

  The present invention relates to substituted imidazopyridinyl-aminopyridine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted imidazopyridinyl-aminopyridine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

  本发明涉及取代咪唑吡啶基-氨基吡啶化合物及其合成方法。本发明还涉及含有取代咪唑吡啶基-氨基吡啶化合物的制药组合物，并通过将这些化合物和制药组合物用于需要治疗细胞增殖性疾病的受试者来治疗癌症等细胞增殖性疾病的方法。
• SUBSTITUTED IMIDAZOPYRIDINYL-AMINOPYRIDINE COMPOUNDS
  申请人：ArQule, Inc.

  公开号：EP2519522A2

  公开（公告）日：2012-11-07
• US8501770B2
  申请人：——

  公开号：US8501770B2

  公开（公告）日：2013-08-06
• [EN] SUBSTITUTED IMIDAZOPYRIDINYL-AMINOPYRIDINE COMPOUNDS<br/>[FR] COMPOSÉS IMIDAZOPYRIDINYL-AMINOPYRIDINE SUBSTITUÉS
  申请人：ARQULE INC

  公开号：WO2011082270A2

  公开（公告）日：2011-07-07

  The present invention relates to substituted imidazopyridinyl-aminopyridine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted imidazopyridinyl- aminopyridine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.
• 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.