5-(4-fluorophenyl)-4-(4-pyridyl)-1-phenylethynyl-2-(3-hydroxyprop-1-ynyl)-1H-imidazole | 1201526-86-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(4-fluorophenyl)-4-(4-pyridyl)-1-phenylethynyl-2-(3-hydroxyprop-1-ynyl)-1H-imidazole
• 英文别名: 3-[5-(4-Fluorophenyl)-1-(2-phenylethynyl)-4-pyridin-4-ylimidazol-2-yl]prop-2-yn-1-ol
• CAS: 1201526-86-4
• 化学式: C₂₅H₁₆FN₃O
• 分子量: 393.42
• InChiKey: NOAFLQWKPVALBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  50.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-(4-pyridyl)-5-(4-fluorophenyl)-2-iodo-1-phenylethynyl-1H-imidazole 、 2-丙炔-1-醇 在 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 以77%的产率得到5-(4-fluorophenyl)-4-(4-pyridyl)-1-phenylethynyl-2-(3-hydroxyprop-1-ynyl)-1H-imidazole
  参考文献：
  名称：

  Synthesis and biological evaluation of p38α kinase-targeting dialkynylimidazoles

  摘要：

  Based on the mild, thermal rearrangement of 1,2-dialkynylimidazoles to reactive carbene or diradical intermediates, a series of 1,2-dialkynylimidazoles were designed as potential irreversible p38 MAP kinase a-isoform (p38 alpha) inhibitors. The synthesis of these dialkynylimidazoles and their kinase inhibition activity is reported. The 1-ethynyl-substituted dialkynylimidazole 14 is a potent (IC50 = 200 nM) and selective inhibitor of p38 alpha. Moreover, compound 14 covalently modifies p38 alpha as determined by ESI-MS after 12 h incubation at 37 degrees C. The unique kinase inhibition, covalent kinase adduct formation, and minimal CYP450 2D6 inhibition by compound 14 demonstrate that dialkynylimidazoles are a new, promising class of p38 alpha inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.09.094

文献信息

• Synthesis and biological evaluation of p38α kinase-targeting dialkynylimidazoles
  作者：Jing Li、Tamer S. Kaoud、Christophe Laroche、Kevin N. Dalby、Sean M. Kerwin

  DOI：10.1016/j.bmcl.2009.09.094

  日期：2009.11

  Based on the mild, thermal rearrangement of 1,2-dialkynylimidazoles to reactive carbene or diradical intermediates, a series of 1,2-dialkynylimidazoles were designed as potential irreversible p38 MAP kinase a-isoform (p38 alpha) inhibitors. The synthesis of these dialkynylimidazoles and their kinase inhibition activity is reported. The 1-ethynyl-substituted dialkynylimidazole 14 is a potent (IC50 = 200 nM) and selective inhibitor of p38 alpha. Moreover, compound 14 covalently modifies p38 alpha as determined by ESI-MS after 12 h incubation at 37 degrees C. The unique kinase inhibition, covalent kinase adduct formation, and minimal CYP450 2D6 inhibition by compound 14 demonstrate that dialkynylimidazoles are a new, promising class of p38 alpha inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.