(6-bromo-5-(2-methylbut-3-yn-2-yloxy)pyridin-2-yl)methanol | 1342891-19-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (6-bromo-5-(2-methylbut-3-yn-2-yloxy)pyridin-2-yl)methanol
• 英文别名: [6-bromo-5-(2-methylbut-3-yn-2-yloxy)pyridin-2-yl]methanol
• CAS: 1342891-19-3
• 化学式: C₁₁H₁₂BrNO₂
• 分子量: 270.126
• InChiKey: BVKVNUPQRHVWBO-UHFFFAOYSA-N

物化性质

• 沸点：
  378.6±42.0 °C(Predicted)
• 密度：
  1.448±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  42.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (6-bromo-5-(2-methylbut-3-yn-2-yloxy)pyridin-2-yl)methanol 在 吡啶 、 四溴化碳 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 4.0h， 生成 N-cyclohexyl-N-((2,2-dimethyl-2H-pyrano[2,3-c]pyridin-6-yl)methyl)-3,4-dimethoxybenzenesulfonamide
  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：

  3-羟基-6-甲基吡啶 在 吡啶 、 copper(II) choride dihydrate 、 溴 、 potassium carbonate 、 间氯过氧苯甲酸 、 三氟乙酸酐 、 potassium iodide 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 24.17h， 生成 (6-bromo-5-(2-methylbut-3-yn-2-yloxy)pyridin-2-yl)methanol
  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

文献信息

• Inhibitors of HIF and angiogenesis
  申请人：Van Meir Erwin G.

  公开号：US09062072B2

  公开（公告）日：2015-06-23

  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.

  提供了抑制缺氧诱导因子（HIF）和血管生成的抑制剂及其使用方法，包括治疗癌症、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。
• 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。
• [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
• Design and Synthesis of Novel Small-Molecule Inhibitors of the Hypoxia Inducible Factor Pathway
  作者：Suazette Reid Mooring、Hui Jin、Narra S. Devi、Adnan A. Jabbar、Stefan Kaluz、Yuan Liu、Erwin G. Van Meir、Binghe Wang

  DOI：10.1021/jm201018g

  日期：2011.12.22

  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.