N-(4-(1H-pyrazol-1-yl)phenyl)-2-(6-fluoro-1H-indol-3-yl)-2-oxoacetamide | 1257652-31-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(4-(1H-pyrazol-1-yl)phenyl)-2-(6-fluoro-1H-indol-3-yl)-2-oxoacetamide
• 英文别名: 2-(6-fluoro-1H-indol-3-yl)-2-oxo-N-(4-pyrazol-1-ylphenyl)acetamide
• CAS: 1257652-31-5
• 化学式: C₁₉H₁₃FN₄O₂
• 分子量: 348.336
• InChiKey: KGGVQKGNOZHMPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  79.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-氟吲哚 、 草酰氯 、 4-(1-吡唑基)苯胺 在 2,6-二甲基吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 42.0h， 以2%的产率得到N-(4-(1H-pyrazol-1-yl)phenyl)-2-(6-fluoro-1H-indol-3-yl)-2-oxoacetamide
  参考文献：
  名称：

  Discovery of 6-substituted indole-3-glyoxylamides as lead antiprion agents with enhanced cell line activity, improved microsomal stability and low toxicity

  摘要：

  A series of highly potent indole-3-glyoxylamide based antiprion agents was previously characterized, focusing on optimization of structure-activity relationship (SAR) at positions 1-3 of the indole system. New libraries interrogating the SAR at indole C-4 to C-7 now demonstrate that introducing electron-withdrawing substituents at C-6 may improve biological activity by up to an order of magnitude, and additionally confer higher metabolic stability. For the present screening libraries, both the degree of potency and trends in SAR were consistent across two cell line models of prion disease, and the large majority of compounds showed no evidence of toxic effects in zebrafish. The foregoing observations thus make the indole-3-glyoxylamides an attractive lead series for continuing development as potential therapeutic agents against prion disease. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.06.013

文献信息

• [EN] INDOLE DERIVATIVES FOR THE STIMULATION OF STEM CELL PROLIFERATION<br/>[FR] DÉRIVÉS INDOLE DESTINÉS À STIMULER LA PROLIFÉRATION DE CELLULES SOUCHES
  申请人：UNIV SHEFFIELD

  公开号：WO2010139982A1

  公开（公告）日：2010-12-09

  The present invention relates to indole derivatives of formula (I) and Formula (II) which possess potent antiprion activity and stem cell proliferative properties. The invention also relates to the use of such compounds to treat prion-related diseases and in stem cell therapies.
• Discovery of 6-substituted indole-3-glyoxylamides as lead antiprion agents with enhanced cell line activity, improved microsomal stability and low toxicity
  作者：Mark J. Thompson、Jennifer C. Louth、Steven Ferrara、Matthew P. Jackson、Fiona J. Sorrell、Edward J. Cochrane、Joel Gever、Sarah Baxendale、B. Michael Silber、Henry H. Roehl、Beining Chen

  DOI：10.1016/j.ejmech.2011.06.013

  日期：2011.9

  A series of highly potent indole-3-glyoxylamide based antiprion agents was previously characterized, focusing on optimization of structure-activity relationship (SAR) at positions 1-3 of the indole system. New libraries interrogating the SAR at indole C-4 to C-7 now demonstrate that introducing electron-withdrawing substituents at C-6 may improve biological activity by up to an order of magnitude, and additionally confer higher metabolic stability. For the present screening libraries, both the degree of potency and trends in SAR were consistent across two cell line models of prion disease, and the large majority of compounds showed no evidence of toxic effects in zebrafish. The foregoing observations thus make the indole-3-glyoxylamides an attractive lead series for continuing development as potential therapeutic agents against prion disease. (C) 2011 Elsevier Masson SAS. All rights reserved.