4-(4-fluorophenyl)-5-iodo-1-(triisopropylsilanylethynyl)-2-(4-(triisopropylsilyloxy)but-1ynyl)-1H-imidazole | 1201526-65-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(4-fluorophenyl)-5-iodo-1-(triisopropylsilanylethynyl)-2-(4-(triisopropylsilyloxy)but-1ynyl)-1H-imidazole
• CAS: 1201526-65-9
• 化学式: C₃₃H₅₀FIN₂OSi₂
• 分子量: 692.847
• InChiKey: FVFXAZBQYINOFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.25
• 重原子数：
  40.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  27.05
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4-(4-fluorophenyl)-5-iodo-1-(triisopropylsilanylethynyl)-2-(4-(triisopropylsilyloxy)but-1ynyl)-1H-imidazole 、 吡啶-4-硼酸 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 反应 96.0h， 以41%的产率得到
  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
• 作为产物：
  描述：

  4-(4-fluorophenyl)-1-(triisopropylsilanylethynyl)-2-(4-(triisopropylsilyloxy)but-1ynyl)-1H-imidazole 在 正丁基锂 、 碘 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.67h， 以74%的产率得到4-(4-fluorophenyl)-5-iodo-1-(triisopropylsilanylethynyl)-2-(4-(triisopropylsilyloxy)but-1ynyl)-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