1-((R)-1-benzyl-piperidin-3-yl)-1,6-dihydro-1,2,3,5,6-pentaaza-as-indacene | 1315484-06-0

• 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-((R)-1-benzyl-piperidin-3-yl)-1,6-dihydro-1,2,3,5,6-pentaaza-as-indacene
• CAS: 1315484-06-0
• 化学式: C₁₉H₂₀N₆
• 分子量: 332.408
• InChiKey: HGJNMNJIGZNLEP-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.14
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  62.63
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1-((R)-1-benzyl-piperidin-3-yl)-1,6-dihydro-1,2,3,5,6-pentaaza-as-indacene 在 4-二甲氨基吡啶 、 palladium hydroxide, 20 wt% on carbon 、 甲酸铵 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 3-oxo-3-[(R)-3-(6H-1,2,3,5,6-pentaaza-as-indacen-1-yl)-piperidin-1-yl]propionitrile
  参考文献：
  名称：

  Novel triazolo-pyrrolopyridines as inhibitors of Janus kinase 1

  摘要：

  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).

  DOI：

  10.1016/j.bmcl.2013.04.018
• 作为产物：
  描述：

  N4-[(3R)-1-(phenylmethyl)-piperidin-3-yl]-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridine-4,5-diamine 在 亚硝酸丁酯 、 水 、 sodium hydroxide 、 copper(ll) bromide 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 2.33h， 生成 1-((R)-1-benzyl-piperidin-3-yl)-1,6-dihydro-1,2,3,5,6-pentaaza-as-indacene
  参考文献：
  名称：

  Novel triazolo-pyrrolopyridines as inhibitors of Janus kinase 1

  摘要：

  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).

  DOI：

  10.1016/j.bmcl.2013.04.018

文献信息

• [EN] TRICYCLIC HETEROCYCLIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES TRICYCLIQUES, LEURS COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011086053A1

  公开（公告）日：2011-07-21

  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.

  该发明提供了具有通式（I）的新化合物，通式如下，其中R1、R2、R3、X和Y如本文所述。因此，这些化合物可以用于制备药学上可接受的组合物，并用于治疗免疫或过度增殖性疾病。
• 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。
• US8461328B2
  申请人：——

  公开号：US8461328B2

  公开（公告）日：2013-06-11
• 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).