(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
• Isoquinoline–pyridine-based protein kinase B/Akt antagonists: SAR and in vivo antitumor activity
  作者：Gui-Dong Zhu、Jianchun Gong、Akiyo Claiborne、Keith W. Woods、Viraj B. Gandhi、Sheela Thomas、Yan Luo、Xuesong Liu、Yan Shi、Ran Guan、Shayna R. Magnone、Vered Klinghofer、Eric F. Johnson、Jennifer Bouska、Alexander Shoemaker、Anatol Oleksijew、Vincent S. Stoll、Ron De Jong、Tilman Oltersdorf、Qun Li、Saul H. Rosenberg、Vincent L. Giranda

  DOI：10.1016/j.bmcl.2006.03.041

  日期：2006.6

  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.