1-[(3S)-1-(phenylmethyl)-piperidin-3-yl]-6-(phenylsulfonyl)-1,6-dihydro-imidazo[4,5-d]pyrrolo[2,3-b]pyridine | 1381790-41-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-[(3S)-1-(phenylmethyl)-piperidin-3-yl]-6-(phenylsulfonyl)-1,6-dihydro-imidazo[4,5-d]pyrrolo[2,3-b]pyridine
• CAS: 1381790-41-5
• 化学式: C₂₆H₂₅N₅O₂S
• 分子量: 471.583
• InChiKey: FNLMPJNAXPPFAY-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.46
• 重原子数：
  34.0
• 可旋转键数：
  5.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  73.02
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  1-[(3S)-1-(phenylmethyl)-piperidin-3-yl]-6-(phenylsulfonyl)-1,6-dihydro-imidazo[4,5-d]pyrrolo[2,3-b]pyridine 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以72%的产率得到1-[(3S)-1-(phenylmethyl)-piperidin-3-yl]-1,6-dihydro-imidazo[4,5-d]pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  Identification of Imidazo-Pyrrolopyridines as Novel and Potent JAK1 Inhibitors

  摘要：

  A therapeutic rationale is proposed for the treatment of inflammatory diseases, such as rheumatoid arthritis (RA), by specific targeting of the JAK1 pathway. Examination of the preferred binding conformation of clinically effective, pan-JAK inhibitor I led to identification of a novel, tricyclic hinge binding scaffold 3. Exploration of SAP. through a series of cycloamino and cycloalkylamino analogues demonstrated this template to be highly tolerant of substitution, with a predisposition to moderate selectivity for the JAK1 isoform over JAK2. This study culminated in the identification of subnanomolar JAK1 inhibitors such as 22 and 49, having excellent cell potency, good rat pharmacokinetic characteristics, and excellent kinase selectivity. Determination of the binding modes of the series in JAK1 and JAK2 by X-ray crystallography supported the design of analogues to enhance affinity and selectivity.

  DOI：

  10.1021/jm300438j
• 作为产物：
  描述：

  4-氯-7-氮杂吲哚 在 4-二甲氨基吡啶 、 四丁基硝酸铵 、 铁粉 、 氯化铵 、 对甲苯磺酸 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸酐 作用下， 以 乙醇 、 二氯甲烷 、 水 、 异丙醇 、 甲苯 为溶剂， 反应 30.68h， 生成 1-[(3S)-1-(phenylmethyl)-piperidin-3-yl]-6-(phenylsulfonyl)-1,6-dihydro-imidazo[4,5-d]pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  Identification of Imidazo-Pyrrolopyridines as Novel and Potent JAK1 Inhibitors

  摘要：

  A therapeutic rationale is proposed for the treatment of inflammatory diseases, such as rheumatoid arthritis (RA), by specific targeting of the JAK1 pathway. Examination of the preferred binding conformation of clinically effective, pan-JAK inhibitor I led to identification of a novel, tricyclic hinge binding scaffold 3. Exploration of SAP. through a series of cycloamino and cycloalkylamino analogues demonstrated this template to be highly tolerant of substitution, with a predisposition to moderate selectivity for the JAK1 isoform over JAK2. This study culminated in the identification of subnanomolar JAK1 inhibitors such as 22 and 49, having excellent cell potency, good rat pharmacokinetic characteristics, and excellent kinase selectivity. Determination of the binding modes of the series in JAK1 and JAK2 by X-ray crystallography supported the design of analogues to enhance affinity and selectivity.

  DOI：

  10.1021/jm300438j