2-[3-(benzenesulfonamido)-2-oxo-4,5-dihydro-3H-1-benzazepin-1-yl]acetic acid | 1239583-94-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 2-[3-(benzenesulfonamido)-2-oxo-4,5-dihydro-3H-1-benzazepin-1-yl]acetic acid
• CAS: 1239583-94-8
• 化学式: C₁₈H₁₈N₂O₅S
• 分子量: 374.417
• InChiKey: VNPAEYMSXPEPSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  methyl 2-[3-(benzenesulfonamido)-2-oxo-4,5-dihydro-3H-1-benzazepin-1-yl]acetate 在 甲醇 、 lithium hydroxide 作用下， 生成 2-[3-(benzenesulfonamido)-2-oxo-4,5-dihydro-3H-1-benzazepin-1-yl]acetic acid
  参考文献：
  名称：

  Design and synthesis of benzoazepin-2-one analogs as allosteric binders targeting the PIF pocket of PDK1

  摘要：

  A novel series of benzoazepin-2-ones were designed and synthesized targeting the PIF pocket of AGC protein kinases, among which a series of thioether-linked benzoazepin-2-ones were discovered to bind to the PIF pocket of 3-phosphoinositide- dependent kinase-1 (PDK1), and to displace the PIF peptide with an EC(50) values in the lower micromolar range. The structure-activity relationships (SARs) of the linker region, tail region, and distal region were explored to further optimize these novel binders which target the PIF pocket of PDK1. When tested in an in vitro PDK1 enzymatic assay using a peptide substrate, the benzodiazepin-2-ones increased the activity of the enzyme in a concentration-dependent fashion, indicating these compounds act as PDK1 allosteric activators. These new compounds may be further developed as therapeutic agents for the treatment of diseases where the PDK1-mediated AGC protein kinases are dysregulated. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.05.019

文献信息

• Design and synthesis of benzoazepin-2-one analogs as allosteric binders targeting the PIF pocket of PDK1
  作者：Linyi Wei、Xiaoqi Gao、Robert Warne、Xueshi Hao、Dirksen Bussiere、Xiang-ju Gu、Tetsuo Uno、Yi Liu

  DOI：10.1016/j.bmcl.2010.05.019

  日期：2010.7

  A novel series of benzoazepin-2-ones were designed and synthesized targeting the PIF pocket of AGC protein kinases, among which a series of thioether-linked benzoazepin-2-ones were discovered to bind to the PIF pocket of 3-phosphoinositide- dependent kinase-1 (PDK1), and to displace the PIF peptide with an EC(50) values in the lower micromolar range. The structure-activity relationships (SARs) of the linker region, tail region, and distal region were explored to further optimize these novel binders which target the PIF pocket of PDK1. When tested in an in vitro PDK1 enzymatic assay using a peptide substrate, the benzodiazepin-2-ones increased the activity of the enzyme in a concentration-dependent fashion, indicating these compounds act as PDK1 allosteric activators. These new compounds may be further developed as therapeutic agents for the treatment of diseases where the PDK1-mediated AGC protein kinases are dysregulated. (c) 2010 Elsevier Ltd. All rights reserved.