4-(2-ethynyl-4-(4-fluorophenyl)-1-methyl-1H-imidazol-5-yl)pyridine | 1572047-38-1

• 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-(2-ethynyl-4-(4-fluorophenyl)-1-methyl-1H-imidazol-5-yl)pyridine
• 英文别名: 4-[2-Ethynyl-5-(4-fluorophenyl)-3-methylimidazol-4-yl]pyridine
• CAS: 1572047-38-1
• 化学式: C₁₇H₁₂FN₃
• 分子量: 277.301
• InChiKey: QBYFCKMSJXQDHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.27
• 重原子数：
  21.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  30.71
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4-(2-ethynyl-4-(4-fluorophenyl)-1-methyl-1H-imidazol-5-yl)pyridine 在 盐酸 、 二(三苯基膦)环戊二烯基氯化钌(II) 作用下， 以 1,4-二氧六环 、 水 、 甲苯 为溶剂， 反应 96.0h， 生成 2-[5-[4-(4-Fluorophenyl)-1-methyl-5-pyridin-4-ylimidazol-2-yl]triazol-1-yl]acetic acid
  参考文献：
  名称：

  Syntheses and structure–activity relationships for some triazolyl p38α MAPK inhibitors

  摘要：

  The design, synthesis and biological evaluation of novel triazolyl p38 alpha MAPK inhibitors with improved water solubility for formulation in cationic liposomes (SAINT-O-Somes) targeted at diseased endothelial cells is described. Water-solubilizing groups were introduced via a 'click' reaction of functional azides with 2-alkynyl imidazoles and isosteric oxazoles to generate two small libraries of 1,4-disubstituted 1,2,3-triazolyl p38 alpha MAPK inhibitors. Triazoles with low IC50 values and desired physicochemical properties were screened for in vitro downregulation of proinflammatory gene expression and were formulated in SAINT-O-Somes. Triazolyl p38 alpha MAPK inhibitor 88 (IC50 = 0.096 mu M) displayed the most promising in vitro activity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.034
• 作为产物：
  描述：

  4-溴吡啶盐酸盐 在 2,6-二甲基吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 N-溴代丁二酰亚胺(NBS) 、 copper(l) iodide 、 四(三苯基膦)钯 、 四丁基氟化铵 、 苄基三乙基氯化铵 、 碘 、 palladium diacetate 、 potassium carbonate 、 三苯基膦 、 cesium fluoride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 91.0h， 生成 4-(2-ethynyl-4-(4-fluorophenyl)-1-methyl-1H-imidazol-5-yl)pyridine
  参考文献：
  名称：

  Syntheses and structure–activity relationships for some triazolyl p38α MAPK inhibitors

  摘要：

  The design, synthesis and biological evaluation of novel triazolyl p38 alpha MAPK inhibitors with improved water solubility for formulation in cationic liposomes (SAINT-O-Somes) targeted at diseased endothelial cells is described. Water-solubilizing groups were introduced via a 'click' reaction of functional azides with 2-alkynyl imidazoles and isosteric oxazoles to generate two small libraries of 1,4-disubstituted 1,2,3-triazolyl p38 alpha MAPK inhibitors. Triazoles with low IC50 values and desired physicochemical properties were screened for in vitro downregulation of proinflammatory gene expression and were formulated in SAINT-O-Somes. Triazolyl p38 alpha MAPK inhibitor 88 (IC50 = 0.096 mu M) displayed the most promising in vitro activity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.034

文献信息

• Synthesis and structure–activity relationships of 4-fluorophenyl-imidazole p38α MAPK, CK1δ and JAK2 kinase inhibitors
  作者：Jean-Paul G. Seerden、Gabriela Leusink-Ionescu、Titia Woudenberg-Vrenken、Bas Dros、Grietje Molema、Jan A.A.M. Kamps、Richard M. Kellogg

  DOI：10.1016/j.bmcl.2014.05.080

  日期：2014.8

  The synthesis and structure-activity relationships of novel 4-(4 '-fluorophenyl)imidazoles as selective p38 alpha MAPK, CK1 delta and JAK2 inhibitors with improved water solubility are described. Microwave-assisted multicomponent reactions afforded 4-fluorophenyl-2,5-disubstituted imidazoles. Carboxylate and phosphonate groups were introduced via 'click' reactions. The kinase selectivity was influenced by the heteroaryl group at imidazole C-5 and the position of a carboxylic acid or tetrazole at imidazole C-2. For example, pyrimidines 15 and 34 inhibited p38 alpha MAPK with IC50 = 250 nM and 96 nM, respectively. Pyridine 3 gave CK1 delta inhibition with IC50 = 89 nM and pyridin-2-one 31 gave JAK2 inhibition with IC50 = 62 nM. (C) 2014 Elsevier Ltd. All rights reserved.