2-methoxyethyl (7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-yl)carbamate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 2-methoxyethyl (7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-yl)carbamate
• 英文别名: 2-methoxyethyl N-[11-(dicyclopropylcarbamoyl)-10-ethyl-3-methyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-7-yl]carbamate
• 化学式: C₂₂H₂₈N₆O₄
• 分子量: 440.502
• InChiKey: AMBVAEZRBLSCSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  tert-butyl 7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-yl(2,4-dimethoxybenzyl)carbamate 在 吡啶 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 8.17h， 生成 2-methoxyethyl (7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-yl)carbamate
  参考文献：
  名称：

  Structure-Based Design of Selective Janus Kinase 2 Imidazo[4,5-d]pyrrolo[2,3-b]pyridine Inhibitors

  摘要：

  Early hit to lead work on a pyrrolopyridine chemotype provided access to compounds with biochemical and cellular potency against Janus kinase 2 (JAK2). Structure-based drug design along the extended hinge region of JAK2 led to the identification of an important H-bond interaction with the side chain of Tyr 931, which improved JAK family selectivity. The 4,5-dimethyl thiazole analogue 18 demonstrated high levels of JAK family selectivity and was identified as a promising lead for the program.

  DOI：

  10.1021/acsmedchemlett.5b00225

文献信息

• Structure-Based Design of Selective Janus Kinase 2 Imidazo[4,5-<i>d</i>]pyrrolo[2,3-<i>b</i>]pyridine Inhibitors
  作者：Amy C. Hart、Gretchen M. Schroeder、Honghe Wan、James Grebinski、Jennifer Inghrim、James Kempson、Junqing Guo、William J. Pitts、John S. Tokarski、John S. Sack、Javed A. Khan、Jonathan Lippy、Matthew V. Lorenzi、Dan You、Theresa McDevitt、Ragini Vuppugalla、Yueping Zhang、Louis J. Lombardo、George L. Trainor、Ashok V. Purandare

  DOI：10.1021/acsmedchemlett.5b00225

  日期：2015.8.13

  Early hit to lead work on a pyrrolopyridine chemotype provided access to compounds with biochemical and cellular potency against Janus kinase 2 (JAK2). Structure-based drug design along the extended hinge region of JAK2 led to the identification of an important H-bond interaction with the side chain of Tyr 931, which improved JAK family selectivity. The 4,5-dimethyl thiazole analogue 18 demonstrated high levels of JAK family selectivity and was identified as a promising lead for the program.