2-bromo-5-((2-methylbut-3-yn-2-yl)oxy)pyridine | 1342891-40-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-bromo-5-((2-methylbut-3-yn-2-yl)oxy)pyridine
• 英文别名: 2-Bromo-5-(2-methylbut-3-yn-2-yloxy)pyridine
• CAS: 1342891-40-0
• 化学式: C₁₀H₁₀BrNO
• 分子量: 240.099
• InChiKey: BFMVPNXFLZDGGV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-bromo-5-((2-methylbut-3-yn-2-yl)oxy)pyridine 在 吡啶 、 正丁基锂 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 甲醇 、 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 3.58h， 生成 N-((2,2-dimethyl-2H-pyrano[3,2-b]pyridin-6-yl)methyl)-N-phenyl-2,3-dihydrobenzo[b][1,4]dioxine-6-sulfonamide
  参考文献：
  名称：

  Design and Synthesis of Novel Small-Molecule Inhibitors of the Hypoxia Inducible Factor Pathway

  摘要：

  Hypoxia, a reduction in partial oxygen pressure, is a salient property of solid tumors. Hypoxia drives malignant progression and metastasis in tumors and participates in tumor resistance to radio- and chemotherapies. Hypoxia activates the hypoxia-inducible factor (HIF) family of transcription factors, which induce target genes that regulate adaptive biological processes such as anaerobic metabolism, cell motility, and angiogenesis. Clinical evidence has demonstrated that expression of HIF-1 is strongly associated with poor patient prognosis and activation of HIF-1 contributes to malignant behavior and therapeutic resistance. Consequently, HIF-1 has become an important therapeutic target for inhibition by small molecules. Herein, we describe the design and synthesis of small molecules that inhibit the HIF-1 signaling pathway. Many of these compounds exhibit inhibitory activity in the nanomolar range. Separate mechanistic studies indicate that these inhibitors do not alter HIF-1 levels but interfere with the ability of HIF-1 alpha/HIF-1 beta to interact with cofactors p300/CBP to form an active transcriptional complex.

  DOI：

  10.1021/jm201018g
• 作为产物：
  描述：

  2-溴-5-羟基吡啶 、 2-甲基-3-丁炔-2-醇 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三氟乙酸酐 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以32%的产率得到2-bromo-5-((2-methylbut-3-yn-2-yl)oxy)pyridine
  参考文献：
  名称：

  [EN] INHIBITORS OF HIF AND ANGIOGENESIS
  [FR] INHIBITEURS DE HIF ET DE L'ANGIOGENÈSE

  摘要：

  公开号：

  WO2011133659A3

文献信息

• INHIBITORS OF HIF AND ANGIOGENESIS
  申请人：Van Meir Erwin G.

  公开号：US20130116275A1

  公开（公告）日：2013-05-09

  Inhibitors of the Hypoxia Inducible Factor (HIF) and angiogenesis and their methods of use including the treatment of cancer, hypoxia related pathologies, disorders leading to ischemia, for example stroke and ischemic heart disease, and non-cancerous angiogenic diseases are provided.

  本发明提供了针对缺氧诱导因子（HIF）和血管生成的抑制剂及其使用方法，包括用于治疗癌症、与缺氧相关的病理学、导致缺血的疾病（例如中风和缺血性心脏病）以及非癌性血管生成性疾病的治疗。
• Examining the structure-activity relationship of benzopyran-based inhibitors of the hypoxia inducible factor-1 pathway
  作者：Jalisa Ferguson、Zeus De Los Santos、Narra Devi、Erwin Van Meir、Sarah Zingales、Binghe Wang

  DOI：10.1016/j.bmcl.2017.02.073

  日期：2017.4

  Many forms of solid tumor have a characteristic feature known as hypoxia, which describes a low or nonexistent presence of oxygen in the cellular microenvironment. This decrease in oxygen causes activation of the hypoxia inducible factor (HIF) pathway, which activates the transcription of many genes that cause cell proliferation, metastasis, increased glycolysis and angiogenesis. Increased HIF expression has been linked with poor patient prognosis, increased malignancy, and therapeutic resistance. Previous work in our lab has identified 1 and 2 as inhibitors of the HIF pathway, specifically as disrupters of the p300-HIF-1 alpha complex formation. A library of sulfonamide analogs has been designed and synthesized with the intent of examining the SAR of this series of compounds and improving potency and physicochemical properties as compared with lead compounds 1 and 2. At the end, we have achieved a thorough understanding of the structural features critical for future optimization work. (C) 2017 Elsevier Ltd. All rights reserved.
• [EN] INHIBITORS OF HIF AND ANGIOGENESIS<br/>[FR] INHIBITEURS DE HIF ET DE L'ANGIOGENÈSE
  申请人：UNIV EMORY

  公开号：WO2011133659A3

  公开（公告）日：2012-03-15
• US9062072B2
  申请人：——

  公开号：US9062072B2

  公开（公告）日：2015-06-23
• WO2024059491A1
  申请人：——

  公开号：——

  公开（公告）日：——