(2R)-4-(3-(isoquinolin-6-yl)-1,2,4-oxadiazol-5-yl)-1-(4-(trifluoromethyl)phenyl)butan-2-amine | 1105709-25-8

• 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: (2R)-4-(3-(isoquinolin-6-yl)-1,2,4-oxadiazol-5-yl)-1-(4-(trifluoromethyl)phenyl)butan-2-amine
• 英文别名: (R)-4-(3-(isoquinolin-6-yl)-1,2,4-oxadiazol-5-yl)-1-(4-(trifluoromethyl)phenyl)butan-2-amine；(2R)-4-(3-isoquinolin-6-yl-1,2,4-oxadiazol-5-yl)-1-[4-(trifluoromethyl)phenyl]butan-2-amine
• CAS: 1105709-25-8
• 化学式: C₂₂H₁₉F₃N₄O
• 分子量: 412.414
• InChiKey: IHTIFKUCLCXNDN-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  77.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  tert-butyl (R)-4-(3-(isoquinolin-6-yl)-1,2,4-oxadiazol-5-yl)-1-(4-(trifluoromethyl)phenyl)butan-2-ylcarbamate 在 三氟乙酸 、 氨 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 反应 1.0h， 生成 (2R)-4-(3-(isoquinolin-6-yl)-1,2,4-oxadiazol-5-yl)-1-(4-(trifluoromethyl)phenyl)butan-2-amine
  参考文献：
  名称：

  [EN] HETEROCYCLIC MODULATORS OF PKB
  [FR] MODULATEURS HÉTÉROCYCLIQUES DE PKB

  摘要：

  公开号：

  WO2009011880A3

文献信息

• Heterocyclic modulators of PKB
  申请人：ZENG Qingping

  公开号：US20090275592A1

  公开（公告）日：2009-11-05

  The invention relates to heterocyclic compounds of Formula I and compositions thereof useful for treating diseases mediated by protein kinase B (PKB) where the variables have the definitions provided herein. The invention also relates to the therapeutic use of such compounds and compositions thereof in treating disease states associated with abnormal cell growth, cancer, inflammation, and metabolic disorders.

  本发明涉及一种公式I的杂环化合物及其组合物，其中变量具有本文所提供的定义，其在治疗由蛋白激酶B（PKB）介导的疾病方面具有用途。本发明还涉及这种化合物和组合物在治疗与异常细胞生长、癌症、炎症和代谢紊乱相关的疾病状态方面的治疗用途。
• [EN] HETEROCYCLIC MODULATORS OF PKB<br/>[FR] MODULATEURS HÉTÉROCYCLIQUES DE PKB
  申请人：AMGEN INC

  公开号：WO2009011880A3

  公开（公告）日：2009-04-02
• HETEROCYCLIC MODULATORS OF PKB
  申请人：Amgen Inc.

  公开号：EP2173728A2

  公开（公告）日：2010-04-14
• US7897619B2
  申请人：——

  公开号：US7897619B2

  公开（公告）日：2011-03-01
• Azole-based inhibitors of AKT/PKB for the treatment of cancer
  作者：Qingping Zeng、John G. Allen、Matthew P. Bourbeau、Xianghong Wang、Guomin Yao、Seifu Tadesse、James T. Rider、Chester C. Yuan、Fang-Tsao Hong、Matthew R. Lee、Shiwen Zhang、Julie A. Lofgren、Daniel J. Freeman、Suijin Yang、Chun Li、Elizabeth Tominey、Xin Huang、Douglas Hoffman、Harvey K. Yamane、Christopher Fotsch、Celia Dominguez、Randall Hungate、Xiaoling Zhang

  DOI：10.1016/j.bmcl.2010.01.067

  日期：2010.3

  Through a combination of screening and structure-based rational design, we have discovered a series of N-1-(5-(heterocyclyl)-thiazol-2-yl)-3-(4-trifluoromethylphenyl)-1,2-propanediamines that were developed into potent ATP competitive inhibitors of AKT. Studies of linker strand-binding adenine isosteres identified SAR trends in potency and selectivity that were consistent with binding interactions observed in structures of the inhibitors bound to AKT1 and to the counter-screening target PKA. One compound was shown to have acceptable pharmacokinetic properties and to be a potent inhibitor of AKT signaling and of in vivo xenograft tumor growth in a preclinical model of glioblastoma. (C) 2010 Elsevier Ltd. All rights reserved.