(1S)-[1-(1H-indol-3-ylmethyl)-2-(2-pyridin-4-yl-[1,7]naphthyridin-5-yloxy)-ethyl]-carbamic acid tert-butyl ester | 552331-83-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (1S)-[1-(1H-indol-3-ylmethyl)-2-(2-pyridin-4-yl-[1,7]naphthyridin-5-yloxy)-ethyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2S)-1-(1H-indol-3-yl)-3-[(2-pyridin-4-yl-1,7-naphthyridin-5-yl)oxy]propan-2-yl]carbamate
• CAS: 552331-83-6
• 化学式: C₂₉H₂₉N₅O₃
• 分子量: 495.581
• InChiKey: APGIEWKBSYQBQD-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1S)-[1-(1H-indol-3-ylmethyl)-2-(2-pyridin-4-yl-[1,7]naphthyridin-5-yloxy)-ethyl]-carbamic acid tert-butyl ester 在 4-甲氧基苄醇 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 以60%的产率得到(1S)-1-(1H-Indol-3-ylmethyl)-2-(2-pyridin-4-yl-[1,7]naphthyridin-5-yloxy)-ethylamine
  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：

  3-溴-5-(4-甲氧基苄氧基)吡啶 在 盐酸 、 正丁基锂 、 tris(dibenzylideneacetone)dipalladium (0) 、 Cy-MAP₁ 、 sodium hexamethyldisilazane 、 双(三甲基硅烷基)氨基钾 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三乙胺 、 三苯基膦 、 sodium t-butanolate 、 偶氮二甲酸二乙酯 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 21.83h， 生成 (1S)-[1-(1H-indol-3-ylmethyl)-2-(2-pyridin-4-yl-[1,7]naphthyridin-5-yloxy)-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

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。
• US6831175B2
  申请人：——

  公开号：US6831175B2

  公开（公告）日：2004-12-14