N4-[(3R)-1-(phenylmethyl)-piperidin-3-yl]-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridine-4,5-diamine | 1315494-62-2

• 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-[(3R)-1-(phenylmethyl)-piperidin-3-yl]-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridine-4,5-diamine
• 英文别名: 1-benzenesulfonyl-4-N-((3R)-1-benzyl-piperidin-3-yl)-1H-pyrrolo[2,3-b]pyridine-4,5-diamine；1-benzenesulfonyl-N*4*-((R)-1-benzyl-piperidin-3-yl)-1H-pyrrolo[2,3-b]pyridine-4,5-diamine；1-(benzenesulfonyl)-4-N-[(3R)-1-benzylpiperidin-3-yl]pyrrolo[2,3-b]pyridine-4,5-diamine
• CAS: 1315494-62-2
• 化学式: C₂₅H₂₇N₅O₂S
• 分子量: 461.588
• InChiKey: USRSNVAFYQZGRB-HXUWFJFHSA-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-[(3R)-1-(phenylmethyl)-piperidin-3-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 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 反应 26.5h， 生成 1-(3R)-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 、 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 为溶剂， 反应 27.67h， 生成 N4-[(3R)-1-(phenylmethyl)-piperidin-3-yl]-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridine-4,5-diamine
  参考文献：
  名称：

  [EN] TRICYCLIC PYRAZINONE COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF AS JANUS KINASE INHIBITORS
  [FR] COMPOSÉS PYRAZINONES TRICYCLIQUES, LEURS COMPOSITIONS ET LEURS PROCÉDÉS D'UTILISATION EN TANT QU'INHIBITEURS DE JANUS KINASE

  摘要：

  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。

  公开号：

  WO2012085176A1

文献信息

• 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。
• Novel triazolo-pyrrolopyridines as inhibitors of Janus kinase 1
  作者：Christopher A. Hurley、Wade S. Blair、Richard J. Bull、Christine Chang、Peter H. Crackett、Gauri Deshmukh、Hazel J. Dyke、Rina Fong、Nico Ghilardi、Paul Gibbons、Peter R. Hewitt、Adam Johnson、Tony Johnson、Jane R. Kenny、Pawan Bir Kohli、Janusz J. Kulagowski、Marya Liimatta、Patrick J. Lupardus、Robert J. Maxey、Rohan Mendonca、Raman Narukulla、Rebecca Pulk、Savita Ubhayakar、Anne van Abbema、Stuart I. Ward、Bohdan Waszkowycz、Mark Zak

  DOI：10.1016/j.bmcl.2013.04.018

  日期：2013.6

  The identification of a novel fused triazolo-pyrrolopyridine scaffold, optimized derivatives of which display nanomolar inhibition of Janus kinase 1, is described. Prototypical example 3 demonstrated lower cell potency shift, better permeability in cells and higher oral exposure in rat than the corresponding, previously reported, imidazo-pyrrolopyridine analogue 2. Examples 6, 7 and 18 were subsequently identified from an optimization campaign and demonstrated modest selectivity over JAK2, moderate to good oral bioavailability in rat with overall pharmacokinetic profiles comparable to that reported for an approved pan-JAK inhibitor (tofacitinib).
• US8461328B2
  申请人：——

  公开号：US8461328B2

  公开（公告）日：2013-06-11