N4-(1-benzylpiperidin-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo-[2,3-b]pyridine-4,5-diamine | 1315496-38-8

• 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: N4-(1-benzylpiperidin-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo-[2,3-b]pyridine-4,5-diamine
• 英文别名: N4-[1-(phenylmethyl)-3-yl]-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridine-4,5-diamine；1-benzenesulphonyl-4-N-(1-benzyl-piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridine-4,5-diamine；1-Benzenesulfonyl-N*4*-(1-benzyl-piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridine-4,5-diamine；1-(benzenesulfonyl)-4-N-(1-benzylpiperidin-4-yl)pyrrolo[2,3-b]pyridine-4,5-diamine
• CAS: 1315496-38-8
• 化学式: C₂₅H₂₇N₅O₂S
• 分子量: 461.588
• InChiKey: MXTLZERTTMZXRY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N4-(1-benzylpiperidin-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo-[2,3-b]pyridine-4,5-diamine 在 20% palladium hydroxide on charcoal 、 甲酸铵 、 对甲苯磺酸 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 88.0h， 生成 1-(1-phenylsulfonyl-piperidin-4-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-氨基-1-苄基哌啶 在 铁粉 、 氯化铵 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 水 、 异丙醇 为溶剂， 反应 4.2h， 生成 N4-(1-benzylpiperidin-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo-[2,3-b]pyridine-4,5-diamine
  参考文献：
  名称：

  Discovery and Optimization of C-2 Methyl Imidazopyrrolopyridines as Potent and Orally Bioavailable JAK1 Inhibitors with Selectivity over JAK2

  摘要：

  Herein we report the discovery of the C-2 methyl substituted imidazopyrrolopyridine series and its optimization to provide potent and orally bioavailable JAK1 inhibitors with selectivity over JAK2. The C-2 methyl substituted inhibitor 4 exhibited not only improved JAK1 potency relative to unsubstituted compound 3 but also notable JAK1 vs JAK2 selectivity (20-fold and >33-fold in biochemical and cell-based assays, respectively). Features of the X-ray structures of 4 in complex with both JAK1 and JAK2 are delineated. Efforts to improve the in vitro and in vivo ADME properties of 4 while maintaining JAK1 selectivity are described, culminating in the discovery of a highly optimized and balanced inhibitor (20). Details of the biological characterization of 20 are disclosed including JAK1 vs JAK2 selectivity levels, preclinical in vivo PK profiles, performance in an in vivo JAK1-mediated PK/PD model, and attributes of an X-ray structure in complex with JAK1.

  DOI：

  10.1021/jm300628c

文献信息

• [EN] TRICYCLIC PYRAZINONE COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF AS JANUS KINASE INHIBITORS<br/>[FR] COMPOSÉS PYRAZINONES TRICYCLIQUES, LEURS COMPOSITIONS ET LEURS PROCÉDÉS D'UTILISATION EN TANT QU'INHIBITEURS DE JANUS KINASE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012085176A1

  公开（公告）日：2012-06-28

  The invention provides novel compounds of formula I having the general formula (I) wherein X, R1, R2, R3 and R5 are as described herein. Accordingly, the compounds may be provided in pharmaceutically acceptable compositions and used for the treatment of immunological or hyperproliferative disorders.

  该发明提供了一种具有通式（I）的新化合物，其通式为（I），其中X、R1、R2、R3和R5如本文所述。因此，这些化合物可以以药学上可接受的组合物形式提供，并用于治疗免疫性或过度增殖性疾病。
• TRICYCLIC HETEROCYCLIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF
  申请人：Babu Srinivasan

  公开号：US20110201593A1

  公开（公告）日：2011-08-18

  The invention provides novel compounds of formula I having the general formula: wherein R 1 , R 2 , R 3 , X and Y are as described herein. Accordingly, the compounds may be provided in pharmaceutically acceptable compositions and used for the treatment of immunological or hyperproliferative disorders.

  本发明提供了具有以下一般式的新化合物I： 其中R1、R2、R3、X和Y如本文所述。因此，这些化合物可以在药学上可接受的组合物中提供，并用于治疗免疫或过度增生性疾病。
• Tricyclic heterocyclic compounds, compositions and methods of use thereof
  申请人：Babu Srinivasan

  公开号：US08461328B2

  公开（公告）日：2013-06-11

  The invention provides novel compounds of formula I having the general formula: wherein R1, R2, R3, X and Y are as described herein. Accordingly, the compounds may be provided in pharmaceutically acceptable compositions and used for the treatment of immunological or hyperproliferative disorders.

  该发明提供了一种具有公式I的新化合物，其一般公式为：其中R1，R2，R3，X和Y如本文所述。因此，这些化合物可以以药学上可接受的成分形式提供，并用于治疗免疫或过度增生性疾病。
• US8461328B2
  申请人：——

  公开号：US8461328B2

  公开（公告）日：2013-06-11