(±)-(3R,4S)-4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-3-ol

• 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: (±)-(3R,4S)-4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-3-ol
• 英文别名: (3R,4S)-4-[3-methoxy-4-[[7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-3-ol
• 化学式: C₂₅H₂₇N₅O₃
• 分子量: 445.521
• InChiKey: MZYQABZZBYYDNQ-AVRDEDQJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  92.9
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-碘乙酰胺 、 (±)-(3R,4S)-4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-3-ol 在 碳酸氢钠 作用下， 以 乙腈 为溶剂， 以70%的产率得到2-[(3R,4S)-3-hydroxy-4-[3-methoxy-4-[[7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl]amino]phenyl]piperidin-1-yl]acetamide
  参考文献：
  名称：

  Piperidine-3,4-diol and piperidine-3-ol derivatives of pyrrolo[2,1-f][1,2,4]triazine as inhibitors of anaplastic lymphoma kinase

  摘要：

  The diastereoselective synthesis and biological activity of piperidine-3,4-diol and piperidine-3-ol-derived pyrrolotriazine inhibitors of anaplastic lymphoma kinase (ALK) are described. Although piperidine-3, 4-diol and piperidine-3-ol derivatives showed comparable in vitro ALK activity, the latter subset of inhibitors demonstrated improved physiochemical and pharmacokinetic properties. Furthermore, the stereochemistry of the C3 and C4 centers had a marked impact on the in vivo inhibition of ALK autophosphorylation. Thus, trans-4-aryl-piperidine-3-ols (22) were more potent than the cis diastereomers (20). (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.01.019
• 作为产物：
  描述：

  trifluoro-methanesulfonic acid 7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (±)-(3R,4S)-4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-3-ol
  参考文献：
  名称：

  Piperidine-3,4-diol and piperidine-3-ol derivatives of pyrrolo[2,1-f][1,2,4]triazine as inhibitors of anaplastic lymphoma kinase

  摘要：

  The diastereoselective synthesis and biological activity of piperidine-3,4-diol and piperidine-3-ol-derived pyrrolotriazine inhibitors of anaplastic lymphoma kinase (ALK) are described. Although piperidine-3, 4-diol and piperidine-3-ol derivatives showed comparable in vitro ALK activity, the latter subset of inhibitors demonstrated improved physiochemical and pharmacokinetic properties. Furthermore, the stereochemistry of the C3 and C4 centers had a marked impact on the in vivo inhibition of ALK autophosphorylation. Thus, trans-4-aryl-piperidine-3-ols (22) were more potent than the cis diastereomers (20). (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.01.019

文献信息

• [EN] PYRROLOTRIAZINES AS ALK AND JAK2 INHIBITORS<br/>[FR] PYRROLOTRIAZINES EN TANT QU'INHIBITEURS D'ALK ET DE JAK2
  申请人：CEPHALON INC

  公开号：WO2010071885A1

  公开（公告）日：2010-06-24

  The present invention provides a compound of formula (I) or a salt form thereof, wherein Q1, Q2, Q3, and Q4 are as defined herein. The compound of formula (I) has ALK and/or JAK2 inhibitory activity, and may be used to treat proliferative disorders.

  本发明提供了一种式（I）的化合物或其盐形式，其中Q1、Q2、Q3和Q4如本文所定义。式（I）的化合物具有ALK和/或JAK2抑制活性，并可用于治疗增殖性疾病。
• [EN] PYRROLOTRIAZINES AS ALK INHIBITORS<br/>[FR] PYRROLOTRIAZINES UTILISÉES COMME INHIBITEURS D'ALK
  申请人：CEPHALON INC

  公开号：WO2014193932A1

  公开（公告）日：2014-12-04

  This application provides compounds of the general formula (I) and/or a salt thereof, where X, R1 and R2 are as defined herein. Compositions and therapeutic uses are also described.

  该应用程序提供了通式（I）的化合物和/或其盐，其中X、R1和R2如本文所定义。还描述了组合物和治疗用途。
• PYRROLOTRIAZINES AS ALK AND JAK2 INHIBITORS
  申请人：Breslin Henry J.

  公开号：US20120028919A1

  公开（公告）日：2012-02-02

  The present invention provides a compound of formula I or a salt form thereof, wherein Q 1 , Q 2 , Q 3 , and Q 4 are as defined herein. The compound of formula I has ALK and/or JAK2 inhibitory activity, and may be used to treat proliferative disorders.

  本发明提供了公式I或其盐形式的化合物，其中Q1、Q2、Q3和Q4的定义如本文所述。公式I的化合物具有ALK和/或JAK2抑制活性，可用于治疗增生性疾病。
• PYRROLOTRIAZINES AS ALK INHIBITORS
  申请人：Cephalon, Inc.

  公开号：US20160068535A1

  公开（公告）日：2016-03-10

  This application provides compounds of the general formula (I) and/or a salt thereof, where X, R 1 and R 2 are as defined herein. Compositions and therapeutic uses are also described.

  该应用程序提供通式（I）及/或其盐的化合物，其中X，R1和R2的定义如本文所述。还描述了组合物和治疗用途。
• US8471005B2
  申请人：——

  公开号：US8471005B2

  公开（公告）日：2013-06-25