[6-(4-fluorophenyl)-8-(1-methylcyclopropyl)imidazo[1,2-b]pyridazin-2-yl][4-(4-hydroxytetrahydropyran-4-carbonyl)-2,2-dimethylpiperazin-1-yl]methanone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: [6-(4-fluorophenyl)-8-(1-methylcyclopropyl)imidazo[1,2-b]pyridazin-2-yl][4-(4-hydroxytetrahydropyran-4-carbonyl)-2,2-dimethylpiperazin-1-yl]methanone
• 英文别名: [6-(4-Fluorophenyl)-8-(1-methylcyclopropyl)imidazo[1,2-b]pyridazin-2-yl]-[4-(4-hydroxyoxane-4-carbonyl)-2,2-dimethylpiperazin-1-yl]methanone；[6-(4-fluorophenyl)-8-(1-methylcyclopropyl)imidazo[1,2-b]pyridazin-2-yl]-[4-(4-hydroxyoxane-4-carbonyl)-2,2-dimethylpiperazin-1-yl]methanone
• 化学式: C₂₉H₃₄FN₅O₄
• 分子量: 535.618
• InChiKey: KCRBLJSQVASYPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  39
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-氯-6-(4-氟苯基)吡嗪 在 盐酸 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 氨 、 水 、 溴 、 palladium diacetate 、 碳酸氢钠 、 sodium carbonate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 81.0h， 生成 [6-(4-fluorophenyl)-8-(1-methylcyclopropyl)imidazo[1,2-b]pyridazin-2-yl][4-(4-hydroxytetrahydropyran-4-carbonyl)-2,2-dimethylpiperazin-1-yl]methanone
  参考文献：
  名称：

  [EN] IMIDAZOPYRIDAZINES USEFUL AS INHIBITORS OF THE PAR-2 SIGNALING PATHWAY
  [FR] IMIDAZOPYRIDAZINES UTILES EN TANT QU'INHIBITEURS DE LA VOIE DE SIGNALISATION PAR-2

  摘要：

  本发明涉及作为PAR-2信号通路抑制剂的化合物。本发明还涉及包含本发明化合物的药用可接受组合物；使用本发明化合物治疗各种疾病、障碍和状况的方法；制备本发明化合物的方法；用于制备本发明化合物的中间体；以及将化合物用于体外应用的方法，例如研究生物和病理现象中的GPCRs；研究由这些GPCRs介导的细胞内信号转导途径；以及比较评估PAR-2信号通路的新抑制剂。本发明的化合物具有公式I：其中变量如本文所述定义。

  公开号：

  WO2015048245A1

文献信息

• Imidazopyridazines useful as inhibitors of the PAR-2 signaling pathway
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US10030024B2

  公开（公告）日：2018-07-24

  The present invention relates to compounds useful as inhibitors of the PAR-2 signaling pathway. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of GPCRs in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such GPCRs; and the comparative evaluation of new inhibitors of the PAR-2 signaling pathway. The compounds of this invention have formula I: wherein the variables are as defined herein.

  本发明涉及可用作 PAR-2 信号通路抑制剂的化合物。本发明还涉及包含本发明化合物的药学上可接受的组合物；使用本发明化合物治疗各种疾病、失调和病症的方法；制备本发明化合物的工艺；制备本发明化合物的中间体；以及在体外应用中使用本发明化合物的方法，例如研究生物和病理现象中的 GPCR；研究由此类 GPCR 介导的细胞内信号转导通路；以及比较评估 PAR-2 信号转导通路的新抑制剂。本发明的化合物具有式 I： 其中的变量如本文所定义。
• IMIDAZOPYRIDAZINES USEFUL AS INHIBITORS OF THE PAR-2 SIGNALING PATHWAY
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20160311825A1

  公开（公告）日：2016-10-27

  The present invention relates to compounds useful as inhibitors of the PAR-2 signaling pathway. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of GPCRs in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such GPCRs; and the comparative evaluation of new inhibitors of the PAR-2 signaling pathway. The compounds of this invention have formula I: wherein the variables are as defined herein.
• [EN] IMIDAZOPYRIDAZINES USEFUL AS INHIBITORS OF THE PAR-2 SIGNALING PATHWAY<br/>[FR] IMIDAZOPYRIDAZINES UTILES EN TANT QU'INHIBITEURS DE LA VOIE DE SIGNALISATION PAR-2
  申请人：VERTEX PHARMA

  公开号：WO2015048245A1

  公开（公告）日：2015-04-02

  The present invention relates to compounds useful as inhibitors of the PAR-2 signaling pathway. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of GPCRs in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such GPCRs; and the comparative evaluation of new inhibitors of the PAR-2 signaling pathway. The compounds of this invention have formula I: wherein the variables are as defined herein.

  本发明涉及作为PAR-2信号通路抑制剂的化合物。本发明还涉及包含本发明化合物的药用可接受组合物；使用本发明化合物治疗各种疾病、障碍和状况的方法；制备本发明化合物的方法；用于制备本发明化合物的中间体；以及将化合物用于体外应用的方法，例如研究生物和病理现象中的GPCRs；研究由这些GPCRs介导的细胞内信号转导途径；以及比较评估PAR-2信号通路的新抑制剂。本发明的化合物具有公式I：其中变量如本文所述定义。