N-tert-butyl-2-(4-(6-fluoro-1H-benzo[d]imidazol-2-yl)phenyl)imidazo[1,2-a]pyridin-3-amine | 1350320-92-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: N-tert-butyl-2-(4-(6-fluoro-1H-benzo[d]imidazol-2-yl)phenyl)imidazo[1,2-a]pyridin-3-amine
• 英文别名: N-tert-butyl-2-[4-(6-fluoro-1H-benzimidazol-2-yl)phenyl]imidazo[1,2-a]pyridin-3-amine
• CAS: 1350320-92-1
• 化学式: C₂₄H₂₂FN₅
• 分子量: 399.471
• InChiKey: XFNVPLOSLDZYGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  58
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  异氰酸叔丁酯 在 N,N-二异丙基乙胺 、 scandium tris(trifluoromethanesulfonate) 作用下， 以 甲醇 、 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.67h， 生成 N-tert-butyl-2-(4-(6-fluoro-1H-benzo[d]imidazol-2-yl)phenyl)imidazo[1,2-a]pyridin-3-amine
  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.