N-(3-氯-5-氟苯基)-4-硝基-2,1,3-苯并恶二唑-5-胺 | 1422955-31-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶二唑类
• 中文名称: N-(3-氯-5-氟苯基)-4-硝基-2,1,3-苯并恶二唑-5-胺
• 英文名称: N-(3-chloro-5-fluorophenyl)-4-nitrobenzo[c][1,2,5]oxadiazol-5-amine
• 英文别名: N-(3-Chloro-5-Fluorophenyl)-4-Nitro-2,1,3-Benzoxadiazol-5-Amine
• CAS: 1422955-31-4
• 化学式: C₁₂H₆ClFN₄O₃
• 分子量: 308.656
• InChiKey: CDQUJZKBRAFWNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 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：
  96.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(3-氯-5-氟苯基)-4-硝基-2,1,3-苯并恶二唑-5-胺 在 tin(II) chloride dihdyrate 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 2-chloro-N-[5-(3-chloro-5-fluoroanilino)-2,1,3-benzoxadiazol-4-yl]acetamide
  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
• 作为产物：
  描述：

  3-氯-5-氟苯胺 、 5-氯-4-硝基-2,1,3-苯噁二唑 在 水 、 Brine 、 Sodium sulfate-III 、 乙酸乙酯 作用下， 以 N,N-二甲基甲酰胺 、 乙酸乙酯 为溶剂， 反应 1.25h， 以N-(3-chloro-5-fluorophenyl)-4-nitrobenzo[c][1,2,5]oxadiazol-5-amine was obtained as a free-flowing yellow solid, (122 mg, 69%)的产率得到N-(3-氯-5-氟苯基)-4-硝基-2,1,3-苯并恶二唑-5-胺
  参考文献：
  名称：

  INHIBITION OF HIF-2ALPHA HETERODIMERIZATION WITH HIF1BETA (ARNT)

  摘要：

  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。

  公开号：

  US20160250216A1

文献信息

• Compositions and methods of modulating HIF-2A to improve muscle generation and repair
  申请人：University of Georgia Research Foundation, Inc.

  公开号：US10953036B2

  公开（公告）日：2021-03-23

  Compositions and methods for modulating HIF-2α to meditate of hypoxia signaling in satellite cells and applications thereof for improving skeletal muscle generation and repair are provided. For example, methods of enhancing, increasing, accelerating or/and otherwise improving skeletal muscle generation or regeneration in a subject in need thereof are disclosed. In some embodiments, the methods include administering the subject an effective amount of HIF-2α inhibitor. The HIF-2α inhibitor can be effective to, for example, increase muscle satellite cell proliferation, differentiation, or a combination thereof in a subject. Composition and methods for improving respiration, and reducing or preventing the development or progression of fibrosis are also provided. The disclosed compositions and methods are particularly useful for treating muscular dystrophies, myopathies, and other muscle-related diseases and disorders.

  本研究提供了调节 HIF-2α 以调解卫星细胞中缺氧信号传导的组合物和方法及其在改善骨骼肌生成和修复中的应用。例如，公开了增强、增加、加速或/和以其他方式改善有需要的受试者的骨骼肌生成或再生的方法。在一些实施方案中，这些方法包括向受试者施用有效量的 HIF-2α 抑制剂。例如，HIF-2α抑制剂可有效增加受试者体内肌肉卫星细胞的增殖、分化或其组合。还提供了用于改善呼吸、减少或预防纤维化的发生或发展的组合物和方法。所公开的组合物和方法特别适用于治疗肌肉萎缩症、肌病和其他肌肉相关疾病和失调。
• [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
• INHIBITION OF HIF-2 HETERODIMERIZATION WITH HIF1 (ARNT)
  申请人：The Board of Regents of The University of Texas System

  公开号：EP2919770A2

  公开（公告）日：2015-09-23
• COMPOSITIONS AND METHODS FOR MODULATING HIF-2& X391; TO IMPROVE MUSCLE GENERATION AND REPAIR
  申请人：University of Georgia Research Foundation, Inc.

  公开号：EP3713644A1

  公开（公告）日：2020-09-30
• COMPOSITIONS AND METHODS OF MODULATING HIF-2A; TO IMPROVE MUSCLE GENERATION AND REPAIR
  申请人：University of Georgia Research Foundation, Inc.

  公开号：US20190151347A1

  公开（公告）日：2019-05-23

  Compositions and methods for modulating HIF-2α to meditate of hypoxia signaling in satellite cells and applications thereof for improving skeletal muscle generation and repair are provided. For example, methods of enhancing, increasing, accelerating or/and otherwise improving skeletal muscle generation or regeneration in a subject in need thereof are disclosed. In some embodiments, the methods include administering the subject an effective amount of HIF-2α inhibitor. The HIF-2α inhibitor can be effective to, for example, increase muscle satellite cell proliferation, differentiation, or a combination thereof in a subject. Composition and methods for improving respiration, and reducing or preventing the development or progression of fibrosis are also provided. The disclosed compositions and methods are particularly useful for treating muscular dystrophies, myopathies, and other muscle-related diseases and disorders.