5-(3-Chloro-5-fluorophenoxy)-4-nitro-2,1,3-benzoxadiazole | 1422955-23-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(3-Chloro-5-fluorophenoxy)-4-nitro-2,1,3-benzoxadiazole
• 英文别名: 5-(3-chloro-5-fluorophenoxy)-4-nitro-2,1,3-benzoxadiazole
• CAS: 1422955-23-4
• 化学式: C₁₂H₅ClFN₃O₄
• 分子量: 309.641
• InChiKey: PBQPESZUWLTKMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  94
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-氯-5-氟苯酚 、 5-氯-4-硝基-2,1,3-苯噁二唑 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 24.5h， 以62%的产率得到5-(3-Chloro-5-fluorophenoxy)-4-nitro-2,1,3-benzoxadiazole
  参考文献：
  名称：

  Development of Inhibitors of the PAS-B Domain of the HIF-2α Transcription Factor

  摘要：

  Hypoxia inducible factors (HIFs) are heterodimeric transcription factors induced in a variety of pathophysiological settings, including cancer. We describe the first detailed structure-activity relationship study of small molecules designed to inhibit HIF-2 alpha-ARNT heterodimerization by binding an internal cavity of the HIF-2 alpha PAS-B domain. Through a series of biophysical characterizations of inhibitor-protein interactions (NMR and X-ray crystallography), we have established the structural requirements for artificial inhibitors of the HIF-2 alpha-ARNT PAS-B interaction. These results may serve as a foundation for discovering therapeutic agents that function by a novel mode of action.

  DOI：

  10.1021/jm301847z

文献信息

• INHIBITION OF HIF-2ALPHA HETERODIMERIZATION WITH HIF1BETA (ARNT)
  申请人：THE BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM

  公开号：US20160250216A1

  公开（公告）日：2016-09-01

  Provided is a method of inhibiting heterodimerization of HIF-2α to HIF1β (ARNT) comprising binding certain small molecules to the HIF-2α PAS-B domain cavity but not to HIF1α and inhibiting HIF-2α heterodimerization to HIF1β (ARNT) but not inhibiting HIF1α heterodimerization to HIF1β (ARNT). Those certain small molecules are also referenced synonymously as HIF2-HDI and HIF2α heterodimerization inhibitors and also simply as certain small molecules.

  提供了一种抑制HIF-2α与HIF1β（ARNT）异源二聚化的方法，包括将某些小分子结合到HIF-2α PAS-B结构域的空腔中，但不结合到HIF1α，从而抑制HIF-2α与HIF1β（ARNT）的异源二聚化，但不抑制HIF1α与HIF1β（ARNT）的异源二聚化。这些特定的小分子也被同义地称为HIF2-HDI和HIF2α异源二聚化抑制剂，也被简称为某些小分子。
• [EN] INHIBITION OF HIF-2α HETERODIMERIZATION WITH HIF1&bgr; (ARNT)<br/>[FR] INHIBITION DE L'HÉTÉRODIMÉRISATION DE HIF-2&Agr; AVEC HIF1&Bgr; (ARNT)
  申请人：UNIV TEXAS

  公开号：WO2014078479A3

  公开（公告）日：2014-07-17
• US9757379B2
  申请人：——

  公开号：US9757379B2

  公开（公告）日：2017-09-12
• Development of Inhibitors of the PAS-B Domain of the HIF-2α Transcription Factor
  作者：Jamie L. Rogers、Liela Bayeh、Thomas H. Scheuermann、Jamie Longgood、Jason Key、Jacinth Naidoo、Lisa Melito、Cameron Shokri、Doug E. Frantz、Richard K. Bruick、Kevin H. Gardner、John B. MacMillan、Uttam K. Tambar

  DOI：10.1021/jm301847z

  日期：2013.2.28

  Hypoxia inducible factors (HIFs) are heterodimeric transcription factors induced in a variety of pathophysiological settings, including cancer. We describe the first detailed structure-activity relationship study of small molecules designed to inhibit HIF-2 alpha-ARNT heterodimerization by binding an internal cavity of the HIF-2 alpha PAS-B domain. Through a series of biophysical characterizations of inhibitor-protein interactions (NMR and X-ray crystallography), we have established the structural requirements for artificial inhibitors of the HIF-2 alpha-ARNT PAS-B interaction. These results may serve as a foundation for discovering therapeutic agents that function by a novel mode of action.