3-(7-Fluoroimidazo[1,2-a]pyridin-2-yl)benzoic acid | 1350320-98-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(7-Fluoroimidazo[1,2-a]pyridin-2-yl)benzoic acid
• CAS: 1350320-98-7
• 化学式: C₁₄H₉FN₂O₂
• 分子量: 256.236
• InChiKey: HRWRGQXGOLOQDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-氟-1,2-苯二胺 、 3-(7-Fluoroimidazo[1,2-a]pyridin-2-yl)benzoic acid 在 N,N-二异丙基乙胺 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.67h， 生成 6-fluoro-2-(3-(7-fluoroimidazo[1,2-a]pyridin-2-yl)phenyl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Design, Synthesis, and Qualitative Structure–Activity Evaluations of Novel β-Secretase Inhibitors as Potential Alzheimer’s Drug Leads

  摘要：

  We have identified highly selective imidazopyridines armed with benzimidazol and/or arylimidazole as potent beta-secretase inhibitors. The most effective and selective analogues. demonstrated low nanomolar potency for the BACE1 enzyme as measured by FRET and cell-based (ELISA) assays and exhibited comparable affinity (K-I) and high ligand efficiency (LE). In addition, these motifs were highly selective (>200) against the structurally related aspartyl protease BACE2. Our design strategy followed a traditional SAR approach and was supported by molecular modeling studies based on the previously reported hydroxyethylene transition state inhibitor derived from isophthalic acid I. Of the most potent compounds, 34 displayed an IC50 for BACE1 of 18 nM and exhibited cellular activity with an EC50 of 37 nM in the cell-based ELISA assay, as well as high affinity (K-I = 17 nM) and ligand efficiency (LE = 1.7 kJ/mol). Compound 34 was found to be 204-fold more selective for BACE1 compared to the closely related aspartyl protease BACE2.

  DOI：

  10.1021/jm201181f
• 作为产物：
  描述：

  2-氨基-4-氟吡啶 、 3-(2-溴乙酰基)-苯甲酸甲酯 在 碳酸氢钠 作用下， 以 乙醇 为溶剂， 反应 8.0h， 以61%的产率得到3-(7-Fluoroimidazo[1,2-a]pyridin-2-yl)benzoic acid
  参考文献：
  名称：

  Design, Synthesis, and Qualitative Structure–Activity Evaluations of Novel β-Secretase Inhibitors as Potential Alzheimer’s Drug Leads

  摘要：

  We have identified highly selective imidazopyridines armed with benzimidazol and/or arylimidazole as potent beta-secretase inhibitors. The most effective and selective analogues. demonstrated low nanomolar potency for the BACE1 enzyme as measured by FRET and cell-based (ELISA) assays and exhibited comparable affinity (K-I) and high ligand efficiency (LE). In addition, these motifs were highly selective (>200) against the structurally related aspartyl protease BACE2. Our design strategy followed a traditional SAR approach and was supported by molecular modeling studies based on the previously reported hydroxyethylene transition state inhibitor derived from isophthalic acid I. Of the most potent compounds, 34 displayed an IC50 for BACE1 of 18 nM and exhibited cellular activity with an EC50 of 37 nM in the cell-based ELISA assay, as well as high affinity (K-I = 17 nM) and ligand efficiency (LE = 1.7 kJ/mol). Compound 34 was found to be 204-fold more selective for BACE1 compared to the closely related aspartyl protease BACE2.

  DOI：

  10.1021/jm201181f

文献信息

• Design, Synthesis, and Qualitative Structure–Activity Evaluations of Novel β-Secretase Inhibitors as Potential Alzheimer’s Drug Leads
  作者：Taleb H. Al-Tel、Mohammad H. Semreen、Raed A. Al-Qawasmeh、Marco F. Schmidt、Raafat El-Awadi、Mustafa Ardah、Rania Zaarour、Shashidhar N. Rao、Omar El-Agnaf

  DOI：10.1021/jm201181f

  日期：2011.12.22

  We have identified highly selective imidazopyridines armed with benzimidazol and/or arylimidazole as potent beta-secretase inhibitors. The most effective and selective analogues. demonstrated low nanomolar potency for the BACE1 enzyme as measured by FRET and cell-based (ELISA) assays and exhibited comparable affinity (K-I) and high ligand efficiency (LE). In addition, these motifs were highly selective (>200) against the structurally related aspartyl protease BACE2. Our design strategy followed a traditional SAR approach and was supported by molecular modeling studies based on the previously reported hydroxyethylene transition state inhibitor derived from isophthalic acid I. Of the most potent compounds, 34 displayed an IC50 for BACE1 of 18 nM and exhibited cellular activity with an EC50 of 37 nM in the cell-based ELISA assay, as well as high affinity (K-I = 17 nM) and ligand efficiency (LE = 1.7 kJ/mol). Compound 34 was found to be 204-fold more selective for BACE1 compared to the closely related aspartyl protease BACE2.