5-(Isoquinolin-5-yloxy)-pyridin-3-ylamine | 884319-39-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(Isoquinolin-5-yloxy)-pyridin-3-ylamine
• 英文别名: 5-(5-Isoquinolinyloxy)-3-pyridinamine；5-isoquinolin-5-yloxypyridin-3-amine
• CAS: 884319-39-5
• 化学式: C₁₄H₁₁N₃O
• 分子量: 237.261
• InChiKey: PNQTUNOGZCTCIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.0
• 重原子数：
  18.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  61.03
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  5-(Isoquinolin-5-yloxy)-pyridin-3-ylamine 在 titanium(IV) isopropylate 、 sodium cyanoborohydride 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 ((S)-2-(1H-Indol-3-yl)-1-{[5-(isoquinolin-5-yloxy)-pyridin-3-ylamino]-methyl}-ethyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and structure–activity relationship of 3,4′-bispyridinylethylenes: Discovery of a potent 3-isoquinolinylpyridine inhibitor of protein kinase B (PKB/Akt) for the treatment of cancer

  摘要：

  Structure-based design and synthesis of the 3,4'-bispyridinylethylene series led to the discovery of 3-isoquinolinylpyridine 13a as a potent PKB/Akt inhibitor with an IC50 of 1.3 nM against Akt1. Compound 13a shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displays poor to marginal selectivity against closely related kinases in the AGC and CMGC families. Moreover, 13a demonstrates potent cellular activity comparable to staurosporine, with IC50 values of 0.42 and 0.59 mu M against MiaPaCa-2 and the Akt1 overexpressing FL5.12-Akt1, respectively. Inhibition of phosphorylation of the Akt downstream target GSK3 was also observed in FL5.12-Akt1 cells with an EC50 of 1.5 mu M. The X-ray structures of 12 and 13a in complex with PKA in the ATP-binding site were determined. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.065
• 作为产物：
  描述：

  5-[(5-bromopyridin-3-yl)oxy]isoquinoline 在 盐酸 、 tris(dibenzylideneacetone)dipalladium (0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 3.25h， 生成 5-(Isoquinolin-5-yloxy)-pyridin-3-ylamine
  参考文献：
  名称：

  Synthesis and structure–activity relationship of 3,4′-bispyridinylethylenes: Discovery of a potent 3-isoquinolinylpyridine inhibitor of protein kinase B (PKB/Akt) for the treatment of cancer

  摘要：

  Structure-based design and synthesis of the 3,4'-bispyridinylethylene series led to the discovery of 3-isoquinolinylpyridine 13a as a potent PKB/Akt inhibitor with an IC50 of 1.3 nM against Akt1. Compound 13a shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displays poor to marginal selectivity against closely related kinases in the AGC and CMGC families. Moreover, 13a demonstrates potent cellular activity comparable to staurosporine, with IC50 values of 0.42 and 0.59 mu M against MiaPaCa-2 and the Akt1 overexpressing FL5.12-Akt1, respectively. Inhibition of phosphorylation of the Akt downstream target GSK3 was also observed in FL5.12-Akt1 cells with an EC50 of 1.5 mu M. The X-ray structures of 12 and 13a in complex with PKA in the ATP-binding site were determined. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.065