4-{[1,2,4]triazolo[1,5-a]pyridin-5-yl}piperazine-1-carbonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-{[1,2,4]triazolo[1,5-a]pyridin-5-yl}piperazine-1-carbonitrile
• 英文别名: US10287286, Example 221；4-([1,2,4]triazolo[1,5-a]pyridin-5-yl)piperazine-1-carbonitrile
• 化学式: C₁₁H₁₂N₆
• 分子量: 228.256
• InChiKey: BTGQGTQMHPRCBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  60.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-溴[1,2,4]三唑并[1,5-a]吡啶 在 盐酸 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 二氯甲烷 、 水 为溶剂， 反应 3.67h， 生成 4-{[1,2,4]triazolo[1,5-a]pyridin-5-yl}piperazine-1-carbonitrile
  参考文献：
  名称：

  [EN] FUSED BICYCLIC HETEROARYL DERIVATIVES HAVING ACTIVITY AS PHD INHIBITORS
  [FR] DÉRIVÉS HÉTÉROARYLES BICYCLIQUES FUSIONNÉS AYANT UNE ACTIVITÉ D'INHIBITEURS DE PHD

  摘要：

  本发明提供了式（I）的化合物及其药用盐，式（I）中X1，X2，X3，Y1，Y2，R1，R2和R3如规范中所定义，其制备方法，含有它们的药物组合物以及它们在治疗中的用途。

  公开号：

  WO2016148306A1

文献信息

• [EN] FUSED BICYCLIC HETEROARYL DERIVATIVES HAVING ACTIVITY AS PHD INHIBITORS<br/>[FR] DÉRIVÉS HÉTÉROARYLES BICYCLIQUES FUSIONNÉS AYANT UNE ACTIVITÉ D'INHIBITEURS DE PHD
  申请人：TAKEDA PHARMACEUTICALS CO

  公开号：WO2016148306A1

  公开（公告）日：2016-09-22

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, formula (I) wherein X1 , X2, X 3, Y1 , Y 2, R 1, R2 and R3 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

  本发明提供了式（I）的化合物及其药用盐，式（I）中X1，X2，X3，Y1，Y2，R1，R2和R3如规范中所定义，其制备方法，含有它们的药物组合物以及它们在治疗中的用途。
• Compounds
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US10287286B2

  公开（公告）日：2019-05-14

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein X1, X2, X3, Y1, Y2, R1, R2 and R3 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

  本发明提供了式 (I) 化合物及其药学上可接受的盐类、 其中X1、X2、X3、Y1、Y2、R1、R2和R3如说明书中所定义，本发明还提供了制备它们的工艺、含有它们的药物组合物以及它们在治疗中的用途。
• FUSED BICYCLIC HETEROARYL DERIVATIVES HAVING ACTIVITY AS PHD INHIBITORS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP3271357A1

  公开（公告）日：2018-01-24
• Novel Compounds
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US20180072714A1

  公开（公告）日：2018-03-15

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein X 1 , X 2 , X 3 , Y 1 , Y 2 , R 1 , R 2 and R 3 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
• 1,2,4-Triazolo-[1,5-<i>a</i>]pyridine HIF Prolylhydroxylase Domain-1 (PHD-1) Inhibitors With a Novel Monodentate Binding Interaction
  作者：Saleh Ahmed、Andrew Ayscough、Greg R. Barker、Hannah E. Canning、Richard Davenport、Robert Downham、David Harrison、Kerry Jenkins、Natasha Kinsella、David G. Livermore、Susanne Wright、Anthony D. Ivetac、Robert Skene、Steven J. Wilkens、Natalie A. Webster、Alan G. Hendrick

  DOI：10.1021/acs.jmedchem.7b00352

  日期：2017.7.13

  Herein we describe the identification of 4-[1,2,4]triazolo[1,5-a]pyridin-5-yl}benzonitrile-based inhibitors of the hypoxia-inducible factor prolylhydroxylase domain-1 (PHD-1) enzyme. These inhibitors were shown to possess a novel binding mode by X-ray crystallography, in which the triazolo N1 atom coordinates in a hitherto unreported monodentate interaction with the active site Fe2+ ion, while the benzonitrile group accepts a hydrogen -bonding interaction from the side chain residue of Asn315. Further optimization led to potent PHD-1 inhibitors with good physicochemical and pharmacokinetic properties.