4-azido-2-fluorophenol

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-azido-2-fluorophenol
• 英文别名: 4-Azido-2-fluorophenol
• 化学式: C₆H₄FN₃O
• 分子量: 153.116
• InChiKey: GPRVBAMVOPIPMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  34.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(prop-2-yn-1-yl)-1H-indole-2-carboxamide 、 4-azido-2-fluorophenol 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 为溶剂， 反应 12.0h， 生成 N-((1-(3-fluoro-4-hydroxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)-1H-indole-2-carboxamide
  参考文献：
  名称：

  Structure-activity relationships for binding of 4-substituted triazole-phenols to macrophage migration inhibitory factor (MIF)

  摘要：

  Macrophage migration inhibitory factor (MIF) is a versatile protein that plays a role in inflammation, autoimmune diseases and cancers. Development of novel inhibitors will enable further exploration of MIF as a drug target. In this study, we investigated structure-activity relationships of MIF inhibitors using a MIF tautomerase activity assay to measure binding. Importantly, we notified that transition metals such as copper (II) and zinc (II) interfere with the MIF tautomerase activity under the assay conditions applied. EDTA was added to the assay buffer to avoid interference of residual heavy metals with tautomerase activity measurements. Using these assay conditions the structure-activity relationships for MIF binding of a series of triazole-phenols was explored. The most potent inhibitors in this series provided activities in the low micromolar range. Enzyme kinetic analysis indicates competitive binding that proved reversible. Binding to the enzyme was confirmed using a microscale thermophoresis (MST) assay. Molecular modelling was used to rationalize the observed structure-activity relationships. The most potent inhibitor 2d inhibited proliferation of A549 cells in a clonogenic assay. In addition, 2d attenuated MIF induced ERK phosphorylation in A549 cells. Altogether, this study provides insights in the structure-activity relationships for MIF binding of triazole-phenols and further validates this class of compounds as MIF binding agents in cell-based studies. (C) 2019 The Author(s). Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2019.111849
• 作为产物：
  描述：

  4-氨基-2-氟苯酚 在 盐酸 、 sodium nitrite 、 sodium azide 作用下， 以 水 为溶剂， 反应 2.0h， 生成 4-azido-2-fluorophenol
  参考文献：
  名称：

  Structure-activity relationships for binding of 4-substituted triazole-phenols to macrophage migration inhibitory factor (MIF)

  摘要：

  Macrophage migration inhibitory factor (MIF) is a versatile protein that plays a role in inflammation, autoimmune diseases and cancers. Development of novel inhibitors will enable further exploration of MIF as a drug target. In this study, we investigated structure-activity relationships of MIF inhibitors using a MIF tautomerase activity assay to measure binding. Importantly, we notified that transition metals such as copper (II) and zinc (II) interfere with the MIF tautomerase activity under the assay conditions applied. EDTA was added to the assay buffer to avoid interference of residual heavy metals with tautomerase activity measurements. Using these assay conditions the structure-activity relationships for MIF binding of a series of triazole-phenols was explored. The most potent inhibitors in this series provided activities in the low micromolar range. Enzyme kinetic analysis indicates competitive binding that proved reversible. Binding to the enzyme was confirmed using a microscale thermophoresis (MST) assay. Molecular modelling was used to rationalize the observed structure-activity relationships. The most potent inhibitor 2d inhibited proliferation of A549 cells in a clonogenic assay. In addition, 2d attenuated MIF induced ERK phosphorylation in A549 cells. Altogether, this study provides insights in the structure-activity relationships for MIF binding of triazole-phenols and further validates this class of compounds as MIF binding agents in cell-based studies. (C) 2019 The Author(s). Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2019.111849

文献信息

• [EN] INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND/OR TRYPTOPHAN 2,3-DIOXYGENASE<br/>[FR] INHIBITEURS DE L'INDOLÉAMINE 2,3-DIOXYGÉNASE ET/OU DE LA TRYPTOPHANE 2,3-DIOXYGÉNASE
  申请人：IDORSIA PHARMACEUTICALS LTD

  公开号：WO2021005222A1

  公开（公告）日：2021-01-14

  The present invention relates to compounds of Formula (I) inhibiting indoleamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3-dioxygenase (TDO) enzymes. Further, their synthesis and their use as medicaments in the treatment of inter alia cancer is disclosed.

  本发明涉及抑制吲哚胺2,3-双加氧酶（IDO）和/或色氨酸2,3-双加氧酶（TDO）酶的公式（I）化合物。此外，还公开了它们的合成以及它们作为治疗包括癌症在内的疾病的药物的应用。
• INHIBTEURS DE L'INDOLEAMINE 2,3-DIOXYGÉNASE ET/OU DU TRYPTOPHANE DIOXYGÉNASE
  申请人：Idorsia Pharmaceuticals Ltd

  公开号：EP3740493B1

  公开（公告）日：2021-12-01
• INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND/OR TRYPTOPHAN 2,3-DIOXYGENASE
  申请人：Idorsia Pharmaceuticals Ltd

  公开号：EP3740493A1

  公开（公告）日：2020-11-25
• BIFUNCTIONAL SMALL MOLECULES TO TARGET THE SELECTIVE DEGRADATION OF CIRCULATING PROTEINS
  申请人：Yale University

  公开号：EP3773727A1

  公开（公告）日：2021-02-17
• Bifunctional Small Molecules to Target the Selective Degradation of Circulating Proteins
  申请人：YALE UNIVERSITY

  公开号：US20210145974A1

  公开（公告）日：2021-05-20

  The present invention is directed to bifunctional small molecules which contain a circulating protein binding moiety (CPBM) linked through a linker group to a cellular receptor binding moiety (CRBM) which is a membrane receptor of degrading cell such as a hepatocyte or other degrading cell. In embodiments, the (CRBM) is a moiety which binds to asialoglycoprotein receptor (an asialoglycoprotein receptor binding moiety, or ASGPRBM) of a hepatocyte. In additional embodiments, the (CRBM) is a moiety which binds to a receptor of other cells which can degrade proteins, such as a LRP1, LDLR, FcγRI, FcRN, Transferrin or Macrophage Scavenger receptor. Pharmaceutical compositions based upon these bifunctional small molecules represent an additional aspect of the present invention. These compounds and/or compositions may be used to treat disease states and conditions by removing circulating proteins through degradation in the hepatocytes or macrophages of a patient or subject in need of therapy. Methods of treating disease states and/or conditions in which circulating proteins are associated with the disease state and/or condition are also described herein.