(1S)-[2-[5-(3-Chloro-isoquinolin 6-yl)-pyridin-3-yloxy]-1-(1H-indol-3-ylmethyl)-ethyl]-carbamic Acid Tert-Butyl Ester | 552331-08-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (1S)-[2-[5-(3-Chloro-isoquinolin 6-yl)-pyridin-3-yloxy]-1-(1H-indol-3-ylmethyl)-ethyl]-carbamic Acid Tert-Butyl Ester
• 英文别名: tert-butyl N-[(2S)-1-[5-(3-chloroisoquinolin-6-yl)pyridin-3-yl]oxy-3-(1H-indol-3-yl)propan-2-yl]carbamate
• CAS: 552331-08-5
• 化学式: C₃₀H₂₉ClN₄O₃
• 分子量: 529.038
• InChiKey: WBNLASYEMJTRAR-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  89.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1S)-[2-[5-(3-Chloro-isoquinolin 6-yl)-pyridin-3-yloxy]-1-(1H-indol-3-ylmethyl)-ethyl]-carbamic Acid Tert-Butyl Ester 在 palladium on activated charcoal tris(dibenzylideneacetone)dipalladium (0) 、 氢气 、 三乙胺 、 三氟乙酸 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (1S)-2-[5-(3-Ethyl-isoquinolin-6-yl)-pyridin-3-yloxy]-1-(1H-indol-3-ylmethyl)-ethylamine
  参考文献：
  名称：

  Isoquinoline–pyridine-based protein kinase B/Akt antagonists: SAR and in vivo antitumor activity

  摘要：

  The structure-activity relationships of a series of isoquinoline-pyridine-based protein kinase B/Akt antagonists have been investigated in an effort to improve the major short-comings of the lead compound 3, including poor pharmacokinetic profiles in several species (e.g., mouse iv t(1/2) = 0.3 h, po F= 0%). Chlorination at C-1 position of the isoquinoline improved its pharmacokinetic property in mice (iv t(1/2) = 5.0 h, po F = 51%) but resulted in > 500-fold drop in potency. In a mouse MiaPaCa-2 xenograft model, an amino analog 10y significantly slowed the tumor growth, however was accompanied by toxicity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.03.041
• 作为产物：
  描述：

  (S)-[1-(1H-indol-3-ylmethyl)-2-(5-trimethylstannylpyridin-3-yloxy)ethyl]carbamic acid tert-butyl ester 、 6-溴-3-氯异喹啉 在 tris(dibenzylideneacetone)dipalladium (0) 、 三(邻甲基苯基)磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以75%的产率得到(1S)-[2-[5-(3-Chloro-isoquinolin 6-yl)-pyridin-3-yloxy]-1-(1H-indol-3-ylmethyl)-ethyl]-carbamic Acid Tert-Butyl Ester
  参考文献：
  名称：

  Isoquinoline–pyridine-based protein kinase B/Akt antagonists: SAR and in vivo antitumor activity

  摘要：

  The structure-activity relationships of a series of isoquinoline-pyridine-based protein kinase B/Akt antagonists have been investigated in an effort to improve the major short-comings of the lead compound 3, including poor pharmacokinetic profiles in several species (e.g., mouse iv t(1/2) = 0.3 h, po F= 0%). Chlorination at C-1 position of the isoquinoline improved its pharmacokinetic property in mice (iv t(1/2) = 5.0 h, po F = 51%) but resulted in > 500-fold drop in potency. In a mouse MiaPaCa-2 xenograft model, an amino analog 10y significantly slowed the tumor growth, however was accompanied by toxicity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.03.041

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