1-(3-Acetyl-phenyl)-3-{6-[4-(4-fluoro-benzyl)-piperidin-1-ylmethyl]-benzo[1,3]dioxol-5-yl}-urea | 455259-87-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(3-Acetyl-phenyl)-3-{6-[4-(4-fluoro-benzyl)-piperidin-1-ylmethyl]-benzo[1,3]dioxol-5-yl}-urea
• 英文别名: 1-(3-acetylphenyl)-3-[6-[[4-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]-1,3-benzodioxol-5-yl]urea
• CAS: 455259-87-7
• 化学式: C₂₉H₃₀FN₃O₄
• 分子量: 503.573
• InChiKey: NDXPXQWBWHPZBF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  79.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(3-Acetyl-phenyl)-3-{6-[4-(4-fluoro-benzyl)-piperidin-1-ylmethyl]-benzo[1,3]dioxol-5-yl}-urea 、 碘甲烷 以 乙腈 为溶剂， 生成 1-(3-Acetylphenyl)-3-[6-[[4-[(4-fluorophenyl)methyl]-1-methylpiperidin-1-ium-1-yl]methyl]-1,3-benzodioxol-5-yl]urea;iodide
  参考文献：
  名称：

  Discovery and Structure−Activity Relationship of N-(Ureidoalkyl)-Benzyl-Piperidines As Potent Small Molecule CC Chemokine Receptor-3 (CCR3) Antagonists

  摘要：

  Structure-activity relationship (SAR) studies of initial screening hits from our corporate library of compounds and a structurally related series of CCR1 receptor antagonists were used to determine that an N-(alkyl)benzylpiperidine is an essential pharmacophore for selective CCR3 antagonists. Further SAR studies that introduced N-(ureidoalkyl) substituents improved the binding potency of these compounds from the micromolar to the low nanomolar range. This new series of compounds also displays highly potent, in vitro functional CCR3-mediated antagonism of eotaxin-induced Ca2+ mobilization and chemotaxis of human eosinophils.

  DOI：

  10.1021/jm0201767
• 作为产物：
  描述：

  4-(4’-氟苄基)哌啶 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 生成 1-(3-Acetyl-phenyl)-3-{6-[4-(4-fluoro-benzyl)-piperidin-1-ylmethyl]-benzo[1,3]dioxol-5-yl}-urea
  参考文献：
  名称：

  Discovery and Structure−Activity Relationship of N-(Ureidoalkyl)-Benzyl-Piperidines As Potent Small Molecule CC Chemokine Receptor-3 (CCR3) Antagonists

  摘要：

  Structure-activity relationship (SAR) studies of initial screening hits from our corporate library of compounds and a structurally related series of CCR1 receptor antagonists were used to determine that an N-(alkyl)benzylpiperidine is an essential pharmacophore for selective CCR3 antagonists. Further SAR studies that introduced N-(ureidoalkyl) substituents improved the binding potency of these compounds from the micromolar to the low nanomolar range. This new series of compounds also displays highly potent, in vitro functional CCR3-mediated antagonism of eotaxin-induced Ca2+ mobilization and chemotaxis of human eosinophils.

  DOI：

  10.1021/jm0201767

文献信息

• Discovery and Structure−Activity Relationship of N-(Ureidoalkyl)-Benzyl-Piperidines As Potent Small Molecule CC Chemokine Receptor-3 (CCR3) Antagonists
  作者：George V. De Lucca、Ui T. Kim、Curt Johnson、Brian J. Vargo、Patricia K. Welch、Maryanne Covington、Paul Davies、Kimberly A. Solomon、Robert C. Newton、George L. Trainor、Carl P. Decicco、Soo S. Ko

  DOI：10.1021/jm0201767

  日期：2002.8.1

  Structure-activity relationship (SAR) studies of initial screening hits from our corporate library of compounds and a structurally related series of CCR1 receptor antagonists were used to determine that an N-(alkyl)benzylpiperidine is an essential pharmacophore for selective CCR3 antagonists. Further SAR studies that introduced N-(ureidoalkyl) substituents improved the binding potency of these compounds from the micromolar to the low nanomolar range. This new series of compounds also displays highly potent, in vitro functional CCR3-mediated antagonism of eotaxin-induced Ca2+ mobilization and chemotaxis of human eosinophils.