(4-(1H-Pyrrol-2-yl)phenyl)methanamine | 1503768-84-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: (4-(1H-Pyrrol-2-yl)phenyl)methanamine
• 英文别名: [4-(1H-pyrrol-2-yl)phenyl]methanamine
• CAS: 1503768-84-0
• 化学式: C₁₁H₁₂N₂
• 分子量: 172.23
• InChiKey: QHDKJMICNWVUAM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  41.8
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  7-chloro-2-ethylimidazo[1,2-a]pyridine-3-carboxylic acid 、 (4-(1H-Pyrrol-2-yl)phenyl)methanamine 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-[4-(1H-pyrrol-2-yl)benzyl]-7-chloro-2-ethylimidazo[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：

  对氯苯甲腈 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 lithium aluminium tetrahydride 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 为溶剂， 反应 2.0h， 生成 (4-(1H-Pyrrol-2-yl)phenyl)methanamine
  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

• Lead Optimization of a Novel Series of Imidazo[1,2-<i>a</i>]pyridine Amides Leading to a Clinical Candidate (Q203) as a Multi- and Extensively-Drug-Resistant Anti-tuberculosis Agent
  作者：Sunhee Kang、Ryang Yeo Kim、Min Jung Seo、Saeyeon Lee、Young Mi Kim、Mooyoung Seo、Jeong Jea Seo、Yoonae Ko、Inhee Choi、Jichan Jang、Jiyoun Nam、Seijin Park、Hwankyu Kang、Hyung Jun Kim、Jungjun Kim、Sujin Ahn、Kevin Pethe、Kiyean Nam、Zaesung No、Jaeseung Kim

  DOI：10.1021/jm5003606

  日期：2014.6.26

  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.