N-[4-(4-methylpiperazin-1-yl)phenyl]-4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine

• 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: N-[4-(4-methylpiperazin-1-yl)phenyl]-4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine
• 化学式: C₂₂H₂₆N₆O
• 分子量: 390.488
• InChiKey: MIUOCIPVYLFJTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  69.5
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-[4-(4-methylpiperazin-1-yl)phenyl]-4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine 、 甲基磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以60%的产率得到N-(4-(4-methylpiperazin-1-yl)phenyl)-4-(5-(methylsulfonyl)-4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors

  摘要：

  Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized. Primary SAR studies resulted in the discovery of a novel class of 4,5,6,7-tetrahydrofuro[ 3,2-c] pyridine based JAK2 inhibitors with higher potency (IC50 of 0.7 nM) and selectivity (>30 fold) to JAK3 kinase than tofacitinib. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.10.011
• 作为产物：
  描述：

  1-(2-糠酰)-2-硝基乙烯 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 1-氯乙基氯甲酸酯 、 potassium carbonate 、 potassium iodide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 2,2,2-三氟乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 叔丁醇 为溶剂， 反应 17.5h， 生成 N-[4-(4-methylpiperazin-1-yl)phenyl]-4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors

  摘要：

  Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized. Primary SAR studies resulted in the discovery of a novel class of 4,5,6,7-tetrahydrofuro[ 3,2-c] pyridine based JAK2 inhibitors with higher potency (IC50 of 0.7 nM) and selectivity (>30 fold) to JAK3 kinase than tofacitinib. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.10.011

文献信息

• [EN] PYRIMIDINE COMPOUNDS AND USE THEREOF<br/>[FR] COMPOSÉS DE PYRIMIDINE ET UTILISATION ASSOCIÉE
  申请人：JIANGSU SIMCERE PHARMACEUTICAL

  公开号：WO2014075318A1

  公开（公告）日：2014-05-22

  本发明公开了通式（I）化合物及其药学上可接受的等价物或盐，以及化合物可以作为Janus激酶抑制剂应用于多种医药用途。
• Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors
  作者：Yazhou Wang、Wei Huang、Minhang Xin、Pan Chen、Li Gui、Xinge Zhao、Feng Tang、Jia Wang、Fei Liu

  DOI：10.1016/j.bmc.2016.10.011

  日期：2017.1

  Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized. Primary SAR studies resulted in the discovery of a novel class of 4,5,6,7-tetrahydrofuro[ 3,2-c] pyridine based JAK2 inhibitors with higher potency (IC50 of 0.7 nM) and selectivity (>30 fold) to JAK3 kinase than tofacitinib. (C) 2016 Elsevier Ltd. All rights reserved.