N-[5-(1,5-dimethylimidazol-2-yl)-2-methylphenyl]-4-(pyridin-2-ylmethoxy)benzamide | 1126365-64-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[5-(1,5-dimethylimidazol-2-yl)-2-methylphenyl]-4-(pyridin-2-ylmethoxy)benzamide
• CAS: 1126365-64-7
• 化学式: C₂₅H₂₄N₄O₂
• 分子量: 412.491
• InChiKey: ICEFWVJUDOWXTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  69
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-氨基-4-甲基苯硼酸 在 四(三苯基膦)钯 、 caesium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 65.67h， 生成 N-[5-(1,5-dimethylimidazol-2-yl)-2-methylphenyl]-4-(pyridin-2-ylmethoxy)benzamide
  参考文献：
  名称：

  Discovery of novel hedgehog antagonists from cell-based screening: Isosteric modification of p38 bisamides as potent inhibitors of SMO

  摘要：

  Cell-based subset screening of compounds using a Gli transcription factor reporter cell assay and shh stimulated cell differentiation assay identified a series of bisamide compounds as hedgehog pathway inhibitors with good potency. Using a ligand-based optimization strategy, heteroaryl groups were utilized as conformationally restricted amide isosteres replacing one of the amides which significantly increased their potency against SMO and the hedgehog pathway while decreasing activity against p38 alpha kinase. We report herein the identification of advanced lead compounds such as imidazole 11c and 11f encompassing good p38 alpha selectivity, low nanomolar potency in both cell assays, excellent physiochemical properties and in vivo pharmacokinetics. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.104

文献信息

• Discovery of novel hedgehog antagonists from cell-based screening: Isosteric modification of p38 bisamides as potent inhibitors of SMO
  作者：Bin Yang、Alexander W. Hird、Daniel John Russell、Benjamin P. Fauber、Les A. Dakin、Xiaolan Zheng、Qibin Su、Robert Godin、Patrick Brassil、Erik Devereaux、James W. Janetka

  DOI：10.1016/j.bmcl.2012.04.104

  日期：2012.7

  Cell-based subset screening of compounds using a Gli transcription factor reporter cell assay and shh stimulated cell differentiation assay identified a series of bisamide compounds as hedgehog pathway inhibitors with good potency. Using a ligand-based optimization strategy, heteroaryl groups were utilized as conformationally restricted amide isosteres replacing one of the amides which significantly increased their potency against SMO and the hedgehog pathway while decreasing activity against p38 alpha kinase. We report herein the identification of advanced lead compounds such as imidazole 11c and 11f encompassing good p38 alpha selectivity, low nanomolar potency in both cell assays, excellent physiochemical properties and in vivo pharmacokinetics. (C) 2012 Elsevier Ltd. All rights reserved.