4-(4-fluorophenyl)-1-(2-triisopropylsilanyl)-1H-imidazole | 1046136-19-9

• 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)-1-(2-triisopropylsilanyl)-1H-imidazole
• 英文别名: 4-(4-fluorophenyl)-1-(2-triisopropylsilanylethynyl)-1H-imidazole；2-[4-(4-Fluorophenyl)imidazol-1-yl]ethynyl-tri(propan-2-yl)silane
• CAS: 1046136-19-9
• 化学式: C₂₀H₂₇FN₂Si
• 分子量: 342.532
• InChiKey: PHGGSLZHQOPBLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.72
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(4-fluorophenyl)-1-(2-triisopropylsilanyl)-1H-imidazole 在 正丁基锂 、 碘 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 4.0h， 以91%的产率得到4-(4-fluorophenyl)-2-iodo-1-(triisopropylsilanylethynyl)-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
• 作为产物：
  描述：

  (2-溴乙炔基)三异丙基硅烷 、 4-(4-氟苯基)-1H-咪唑 在 copper(l) iodide 、 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 以72%的产率得到4-(4-fluorophenyl)-1-(2-triisopropylsilanyl)-1H-imidazole
  参考文献：
  名称：

  Coupling Reactions of Bromoalkynes with Imidazoles Mediated by Copper Salts: Synthesis of Novel N-Alkynylimidazoles

  摘要：

  A cross-coupling reaction of imidazoles with bromoalkynes in the presence of a catalytic amount of CuI is reported. This protocol allows an access to novel N-(1-alkynyl)imidazoles in moderate to good yields.

  DOI：

  10.1021/jo801118q

文献信息

• Coupling Reactions of Bromoalkynes with Imidazoles Mediated by Copper Salts: Synthesis of Novel <i>N</i>-Alkynylimidazoles
  作者：Christophe Laroche、Jing Li、Matthew W. Freyer、Sean M. Kerwin

  DOI：10.1021/jo801118q

  日期：2008.8.1

  A cross-coupling reaction of imidazoles with bromoalkynes in the presence of a catalytic amount of CuI is reported. This protocol allows an access to novel N-(1-alkynyl)imidazoles in moderate to good yields.
• 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.