N-cyclopropylprop-2-ynamide | 1207294-09-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-cyclopropylprop-2-ynamide
• CAS: 1207294-09-4
• 化学式: C₆H₇NO
• 分子量: 109.128
• InChiKey: DAZDJUSRUDPVJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-cyclopropylprop-2-ynamide 、 4-azidophenol 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 为溶剂， 反应 12.0h， 生成 N-cyclopropyl-1-(4-hydroxyphenyl)-1H-1,2,3-triazole-4-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：

  环丙胺 、 丙炔酸 在 N,N'-二环己基碳二亚胺 作用下， 以 乙腈 为溶剂， 反应 2.25h， 生成 N-cyclopropylprop-2-ynamide
  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] NEW COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2010012747A1

  公开（公告）日：2010-02-04

  The present invention encompasses compounds of general formula (1), wherein R1 to R4 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and their use for preparing a medicament having the above-mentioned properties.

  本发明涵盖了一般式（1）中的化合物，其中R1至R4如权利要求书中所定义，适用于治疗以细胞过度或异常增殖为特征的疾病，并且用于制备具有上述特性的药物。
• Structure-activity relationships for binding of 4-substituted triazole-phenols to macrophage migration inhibitory factor (MIF)
  作者：Zhangping Xiao、Marieke Fokkens、Deng Chen、Tjie Kok、Giordano Proietti、Ronald van Merkerk、Gerrit J. Poelarends、Frank J. Dekker

  DOI：10.1016/j.ejmech.2019.111849

  日期：2020.1

  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.