4-(3-(tert-butylamino)-imidazo[1,2-a]pyridin-2-yl)benzoic acid | 1095845-27-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(3-(tert-butylamino)-imidazo[1,2-a]pyridin-2-yl)benzoic acid
• 英文别名: 4-[3-(Tert-butylamino)imidazo[1,2-a]pyridin-2-yl]benzoic acid
• CAS: 1095845-27-4
• 化学式: C₁₈H₁₉N₃O₂
• 分子量: 309.368
• InChiKey: IUOQJYAQYVEYIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  66.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(3-(tert-butylamino)-imidazo[1,2-a]pyridin-2-yl)benzoic acid 、 4-氟-1,2-苯二胺 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 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
• 作为产物：
  描述：

  Methyl 4-[3-(tert-butylamino)imidazo[1,2-a]pyridin-2-yl]benzoate 在 氢氧化钾 作用下， 以 水 为溶剂， 反应 4.0h， 以93%的产率得到4-(3-(tert-butylamino)-imidazo[1,2-a]pyridin-2-yl)benzoic acid
  参考文献：
  名称：

  tert-Butyl isocyanide revisited as a convertible reagent in the Groebke–Blackburn reaction

  摘要：

  tert-Butyl isocyanide can serve as the convertible reagent in Groebke-Blackburn multi-component reactions. The effective removal of the tert-butyl group from the resulting imidazo[1,2-a]azines and -azoles is achieved on a gram scale in two steps without chromatographic purification. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2008.10.046

文献信息

• A Highly Flexible and Efficient Ugi-Type Multicomponent Synthesis of Versatile N-Fused Aminoimidazoles
  作者：Sankar Guchhait、Chetna Madaan、Balmukund Thakkar

  DOI：10.1055/s-0029-1216916

  日期：2009.10

  A microwave-promoted highly flexible and efficient Ugi-type multicomponent reaction of heterocyclic amidines with aldehydes and isocyanides catalyzed by zirconium(IV) chloride was developed. The general protocol offered the very reliable synthesis of a library of medicinally important, widely versatile N-fused aminoimidazoles in excellent yields. Poorly reactive heterocyclic amidines, functionally

  研究了微波促进的高柔性，高效的Ugi型杂环multi与氯化锆（IV）催化的醛和异氰酸酯的多组分反应。该通用方案以极高的收率提供了非常重要的医学上重要的，用途广泛的N融合氨基咪唑库的可靠合成。在较早描述的方法中作为麻烦的反应物遭受的反应性差的杂环am，功能和空间受阻的醛在该方法中被认为是可行的底物。发现ZrCl 4的有效催化以及微波辐照的作用对于获得方案的优异灵活性和效率至关重要。 多组分反应-N-杂环-催化-氯化锆-微波
• N-Fused Imidazoles As Novel Anticancer Agents That Inhibit Catalytic Activity of Topoisomerase IIα and Induce Apoptosis in G1/S Phase
  作者：Ashish T. Baviskar、Chetna Madaan、Ranjan Preet、Purusottam Mohapatra、Vaibhav Jain、Amit Agarwal、Sankar K. Guchhait、Chanakya N. Kundu、Uttam C. Banerjee、Prasad V. Bharatam

  DOI：10.1021/jm200235u

  日期：2011.7.28

  substituents exhibited potent inhibition of catalytic activity of hTopoIIα while not showing DNA intercalation. Molecular docking studies and molecular dynamics (MD) simulation analysis, ATPase-kinetics and ATP-dependent plasmid relaxation assay revealed the catalytic mode of inhibition of the title compounds plausibly by blocking the ATP-binding site. N-Fused aminoimidazoles showed potent anticancer activities

  根据已知的拓扑异构酶II催化抑制剂的结构和初步的分子对接研究，预计双环N-稠合的氨基咪唑是潜在的拓扑异构酶II抑制剂。它们是通过多组分反应合成的，并在体外测定中的分离，弛豫，裂解复合物和DNA嵌入方面针对人拓扑异构酶IIα（hTopoIIα）进行了评估。在八个不同双环支架的31种化合物中，发现具有合适取代基的咪唑并吡啶，咪唑并吡嗪和咪唑并吡嗪显示出对hTopoIIα催化活性的有效抑制，而未显示DNA嵌入。分子对接研究和分子动力学（MD）模拟分析，ATPase动力学和ATP依赖的质粒松弛试验揭示了通过阻断ATP结合位点来合理地抑制标题化合物的催化方式。N-融合的氨基咪唑类化合物在肾和乳腺癌细胞系中显示出有效的抗癌活性，对正常细胞的毒性低，与依托泊苷和5-氟尿嘧啶相比在肾癌细胞系中具有相对较高的效能，并且在细胞迁移中具有有效的抑制作用。发现这些化合物在G1 / S期发挥凋亡作用。
• Groebke‐Blackburn‐Bienaymé Multicomponent Reaction Catalysed by Reusable Brønsted‐Acidic Ionic Liquids
  作者：Nicolas S. Anjos、Agáta I. Chapina、Ana R. Santos、Peter Licence、Luiz S. Longo

  DOI：10.1002/ejoc.202200615

  日期：2022.10.26

  Groebke-Blackburn-Bienaymé multicomponent reactions can be efficiently catalysed by Brønsted acidic ionic liquids for the synthesis of imidazo[1,2-a]pyridines and imidazo[2,1-b]thiazoles in moderate to excellent yields (42–93 %), either under thermal or microwave heating. The homogeneous acidic catalyst can be recycled and reused in four consecutive reaction cycles.

  Brønsted 酸性离子液体可有效催化 Groebke-Blackburn-Bienaymé 多组分反应合成咪唑并[1,2- a ]吡啶和咪唑并[ 2,1- b ]噻唑，产率适中（42-93%） ，在热或微波加热下。均相酸性催化剂可以在四个连续的反应循环中回收和重复使用。
• 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.
• tert-Butyl isocyanide revisited as a convertible reagent in the Groebke–Blackburn reaction
  作者：Mikhail Krasavin、Sergey Tsirulnikov、Mikhail Nikulnikov、Yuri Sandulenko、Konstantin Bukhryakov

  DOI：10.1016/j.tetlet.2008.10.046

  日期：2008.12

  tert-Butyl isocyanide can serve as the convertible reagent in Groebke-Blackburn multi-component reactions. The effective removal of the tert-butyl group from the resulting imidazo[1,2-a]azines and -azoles is achieved on a gram scale in two steps without chromatographic purification. (C) 2008 Elsevier Ltd. All rights reserved.