methyl 2-isopropylimidazo[1,2-a]pyridine-3-carboxylate | 1613627-23-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: methyl 2-isopropylimidazo[1,2-a]pyridine-3-carboxylate
• 英文别名: ethyl 2-isopropylimidazo[1,2-a]pyridine-3-carboxylate
• CAS: 1613627-23-8
• 化学式: C₁₃H₁₆N₂O₂
• 分子量: 232.282
• InChiKey: ODUZYACNZXHXKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.63
• 重原子数：
  17.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  43.6
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 2-isopropylimidazo[1,2-a]pyridine-3-carboxylate 在 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-([1,1'-biphenyl]-4-ylmethyl)-2-isopropylimidazo[1,2-a]pyridine-3-carboxamide
  参考文献：
  名称：

  Lead Optimization of a Novel Series of Imidazo[1,2-a]pyridine Amides Leading to a Clinical Candidate (Q203) as a Multi- and Extensively-Drug-Resistant Anti-tuberculosis Agent

  摘要：

  A critical unmet clinical need to combat the global tuberculosis epidemic is the development of potent agents capable of reducing the time of multi-drug-resistant (MDR) and extensively-drug-resistant (XDR) tuberculosis therapy. In this paper, we report on the optimization of imidazo[1,2-a]pyridine amide (IPA) lead compound 1, which led to the design and synthesis of Q203 (50). We found that the amide linker with IPA core is very important for activity against Mycobacterium tuberculosis H37Rv. Linearity and lipophilicity of the amine part in the IPA series play a critical role in improving in vitro and in vivo efficacy and pharmacokinetic profile. The optimized IPAs 49 and 50 showed not only excellent oral bioavailability (80.2% and 90.7%, respectively) with high exposure of the area under curve (AUC) but also displayed significant colony-forming unit (CFU) reduction (1.52 and 3.13 log10 reduction at 10 mg/kg dosing level, respectively) in mouse lung.

  DOI：

  10.1021/jm5003606
• 作为产物：
  描述：

  异丁酰乙酸乙酯 在 溴 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 0.33h， 生成 methyl 2-isopropylimidazo[1,2-a]pyridine-3-carboxylate
  参考文献：
  名称：

  Lead Optimization of a Novel Series of Imidazo[1,2-a]pyridine Amides Leading to a Clinical Candidate (Q203) as a Multi- and Extensively-Drug-Resistant Anti-tuberculosis Agent

  摘要：

  A critical unmet clinical need to combat the global tuberculosis epidemic is the development of potent agents capable of reducing the time of multi-drug-resistant (MDR) and extensively-drug-resistant (XDR) tuberculosis therapy. In this paper, we report on the optimization of imidazo[1,2-a]pyridine amide (IPA) lead compound 1, which led to the design and synthesis of Q203 (50). We found that the amide linker with IPA core is very important for activity against Mycobacterium tuberculosis H37Rv. Linearity and lipophilicity of the amine part in the IPA series play a critical role in improving in vitro and in vivo efficacy and pharmacokinetic profile. The optimized IPAs 49 and 50 showed not only excellent oral bioavailability (80.2% and 90.7%, respectively) with high exposure of the area under curve (AUC) but also displayed significant colony-forming unit (CFU) reduction (1.52 and 3.13 log10 reduction at 10 mg/kg dosing level, respectively) in mouse lung.

  DOI：

  10.1021/jm5003606

文献信息

• 2-Aminopyridines as an α-Bromination Shuttle in a Transition Metal-Free One-Pot Synthesis of Imidazo[1,2-<i>a</i> ]pyridines
  作者：Irwan Iskandar Roslan、Kian-Hong Ng、Gaik-Khuan Chuah、Stephan Jaenicke

  DOI：10.1002/adsc.201501012

  日期：2016.2.4

  A wide range of imidazo[1,2‐a]pyridines are accessible from cheap and readily available 2‐aminopyridines and 1,3‐dicarbonyl compounds using a unique CBrCl3/2‐aminopyridine system for bromination at the α‐carbon. 2‐Aminopyridine is not only the substrate but also acts as a bromination shuttle, transferring the bromine atom from CBrCl3 to the α‐carbon of the 1,3‐dicarbonyl. The reaction mechanism involves

  使用独特的CBrCl 3 / 2-氨基吡啶体系在α-碳上进行溴化，可以从便宜且容易获得的2-氨基吡啶和1,3-二羰基化合物中获得各种咪唑并[1,2- a ]吡啶。2-氨基吡啶不仅是底物，而且还用作溴化穿梭，将溴原子从CBrCl 3转移到1,3-二羰基的α-碳上。该反应机理涉及一系列可逆步骤，包括具有环状过渡态的加成反应，以形成溴血红素中间体。在这种无过渡金属的单锅合成中，在温和的条件下和较短的反应时间下，分离出的产率高达97％。