2-[4-(4-fluoro-benzyl)piperidin-1-ylmethyl]-3-nitro-benzoic acid methyl ester | 455260-00-1

• 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: 2-[4-(4-fluoro-benzyl)piperidin-1-ylmethyl]-3-nitro-benzoic acid methyl ester
• 英文别名: Methyl 2-[[4-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]-3-nitrobenzoate
• CAS: 455260-00-1
• 化学式: C₂₁H₂₃FN₂O₄
• 分子量: 386.423
• InChiKey: CXUWHRLHVWQCHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  75.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[4-(4-fluoro-benzyl)piperidin-1-ylmethyl]-3-nitro-benzoic acid methyl ester 在 palladium on activated charcoal sodium hydroxide 、 草酰氯 、 氢气 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 3.5h， 生成
  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：

  2-甲基-3-硝基苯甲酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 2-[4-(4-fluoro-benzyl)piperidin-1-ylmethyl]-3-nitro-benzoic acid methyl ester
  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.