N-(5-bromopyridin-3-yl)isoquinolin-5-amine | 552330-74-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-(5-bromopyridin-3-yl)isoquinolin-5-amine
• 英文别名: N-(5-bromo-3-pyridinyl)-5-isoquinolinamine
• CAS: 552330-74-2
• 化学式: C₁₄H₁₀BrN₃
• mdl: MFCD27086455
• 分子量: 300.157
• InChiKey: IQZBUTMFHZFWAX-UHFFFAOYSA-N

物化性质

• 沸点：
  438.5±40.0 °C(Predicted)
• 密度：
  1.561±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(5-bromopyridin-3-yl)isoquinolin-5-amine 在 titanium(IV) isopropylate 、 盐酸 、 tris(dibenzylideneacetone)dipalladium (0) 、 sodium cyanoborohydride 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三氟乙酸 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 9.25h， 生成 N-[(2S)-2-amino-3-(1H-indol-3-yl)propyl]-N'-isoquinolin-5-ylpyridine-3,5-diamine
  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-溴-3-氨基吡啶 、 5-(trifluoromethylsulfonyloxy)-isoquinoline 在 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 sodium t-butanolate 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以18%的产率得到N-(5-bromopyridin-3-yl)isoquinolin-5-amine
  参考文献：
  名称：

  Kinase inhibitors

  摘要：

  具有以下化学式的化合物对抑制蛋白激酶很有用。还公开了抑制蛋白激酶的组合物以及在患者中抑制蛋白激酶的方法。

  公开号：

  US20030199511A1

文献信息

• Kinase inhibitors
  申请人：——

  公开号：US20030187026A1

  公开（公告）日：2003-10-02

  Compounds having the formula 1 are useful for inhibiting protein kinases. Also disclosed are compositions which inhibit protein kinases and methods of inhibiting protein kinases in a patient.

  具有以下化学式的化合物对抑制蛋白激酶很有用。还公开了抑制蛋白激酶的组合物以及在患者中抑制蛋白激酶的方法。
• 3-(PHENYL-ALKOXY)-5-(PHENYL)-PYRIDINE DERIVATIVES AND RELATED COMPOUNDS AS KINASE INHIBITORS FOR THE TREATMENT OF CANCER
  申请人：Abbott Laboratories

  公开号：EP1463505A2

  公开（公告）日：2004-10-06
• US6831175B2
  申请人：——

  公开号：US6831175B2

  公开（公告）日：2004-12-14
• [EN] KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASE
  申请人：ABBOTT LAB

  公开号：WO2003051366A2

  公开（公告）日：2003-06-26

  Compounds having the formula (I), are useful for inhibiting protein kinases and for the treatment of cancer. Also disclosed are compositions which inhibit protein kinases and methods of inhibiting protein kinases in a patient.
• 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
  作者：Qun Li、Keith W. Woods、Sheela Thomas、Gui-Dong Zhu、Garrick Packard、John Fisher、Tongmei Li、Jianchun Gong、Jurgen Dinges、Xiaohong Song、Jason Abrams、Yan Luo、Eric F. Johnson、Yan Shi、Xuesong Liu、Vered Klinghofer、Ron Des Jong、Tilman Oltersdorf、Vincent S. Stoll、Clarissa G. Jakob、Saul H. Rosenberg、Vincent L. Giranda

  DOI：10.1016/j.bmcl.2005.12.065

  日期：2006.4

  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.