{(S)-2-(1H-Indol-3-yl)-1-[5-(3-prop-1-ynyl-isoquinolin-6-yl)-pyridin-3-yloxymethyl]-ethyl}-carbamic acid tert-butyl ester | 891785-92-5

• 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: {(S)-2-(1H-Indol-3-yl)-1-[5-(3-prop-1-ynyl-isoquinolin-6-yl)-pyridin-3-yloxymethyl]-ethyl}-carbamic acid tert-butyl ester
• CAS: 891785-92-5
• 化学式: C₃₃H₃₂N₄O₃
• 分子量: 532.642
• InChiKey: UBCHWIGIXUALFP-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.66
• 重原子数：
  40.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  89.13
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  {(S)-2-(1H-Indol-3-yl)-1-[5-(3-prop-1-ynyl-isoquinolin-6-yl)-pyridin-3-yloxymethyl]-ethyl}-carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (1S)-1-(1H-Indol-3-ylmethyl)-2-[5-(3-prop-1-ynyl-isoquinolin-6-yl)-pyridin-3-yloxy]-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 在 tris(dibenzylideneacetone)dipalladium (0) 、 三乙胺 、 三(邻甲基苯基)磷 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 {(S)-2-(1H-Indol-3-yl)-1-[5-(3-prop-1-ynyl-isoquinolin-6-yl)-pyridin-3-yloxymethyl]-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