2-Propylimidazo[1,2-a]pyridine-3-carboxylic acid | 1216156-99-8

• 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: 2-Propylimidazo[1,2-a]pyridine-3-carboxylic acid
• 英文别名: 2-propylimidazo[1,2-a]pyridine-3-carboxylic acid
• CAS: 1216156-99-8
• 化学式: C₁₁H₁₂N₂O₂
• 分子量: 204.228
• InChiKey: RWKIFHRXOXYJGY-UHFFFAOYSA-N

物化性质

• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-Propylimidazo[1,2-a]pyridine-3-carboxylic acid 、 4-氨基乙基联苯 在 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 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-([1,1'-biphenyl]-4-ylmethyl)-2-propylimidazo[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：

  丁酰乙酸乙酯 在 水 、 溴 、 lithium hydroxide 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 0.33h， 生成 2-Propylimidazo[1,2-a]pyridine-3-carboxylic acid
  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

• EP2547678B1
  申请人：——

  公开号：EP2547678B1

  公开（公告）日：2016-03-16
• HYDROXY-SUBSTITUIERTE IMIDAZO[1,2-A]PYRIDINCARBOXAMIDE UND IHRE VERWENDUNG ALS STIMULATOREN DER LÖSLICHEN GUANYLATCYCLASE
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：EP2914596A1

  公开（公告）日：2015-09-09
• [DE] HYDROXY-SUBSTITUIERTE IMIDAZO[1,2-A]PYRIDINCARBOXAMIDE UND IHRE VERWENDUNG ALS STIMULATOREN DER LÖSLICHEN GUANYLATCYCLASE<br/>[EN] HYDROXY-SUBSTITUTED IMIDAZO[1,2-A]PYRIDINECARBOXAMIDES AND THEIR USE AS SOLUBLE GUANYLATE CYCLASE STIMULANTS<br/>[FR] IMIDAZO[1,2-A]PYRIDINCARBOXAMIDES SUBSTITUÉS PAR UN HYDROXY ET LEUR UTILISATION EN TANT QUE STIMULANTS DE LA GUANYLATE CYCLASE SOLUBLE
  申请人：BAYER PHARMA AG

  公开号：WO2014068104A1

  公开（公告）日：2014-05-08

  Die vorliegende Anmeldung betrifft neue substituierte lmidazo[1,2- a]pyridin-3-carboxamide der Formel (I) in welcher R3 für eine Gruppe der Formel (II) oder (III) steht, Verfahren zu ihrer Herstellung, ihre Verwendung allein oder in Kombinationen zur Behandlung und/oder Prophylaxe von Krankheiten sowie ihre Verwendung zur Herstellung von Arzneimitteln zur Behandlung und/oder Prophylaxe von Krankheiten, insbesondere zur Behandlung und/oder Prophylaxe von kardiovaskulären Erkrankungen.