N1-(3-fluoro-4-(2-(5-((2-methoxyethylamino)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide | 1123837-93-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N1-(3-fluoro-4-(2-(5-((2-methoxyethylamino)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide
• 英文别名: N'-[3-fluoro-4-[2-[5-[(2-methoxyethylamino)methyl]pyridin-2-yl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]-N-(4-fluorophenyl)propanediamide
• CAS: 1123837-93-3
• 化学式: C₃₁H₂₇F₂N₅O₄S
• 分子量: 603.649
• InChiKey: WWVZHTKYPINUSQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  43
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  143
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  N1-(3-fluoro-4-(2-(5-formylpyridin-2-yl)thieno[3,2-d]pyridin-7-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide trifluoroacetate 、 2-甲氧基乙胺 在 溶剂黄146 、 三乙酰氧基硼氢化钠 、 氨 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 18.5h， 以43%的产率得到N1-(3-fluoro-4-(2-(5-((2-methoxyethylamino)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide
  参考文献：
  名称：

  [EN] PROCESSES AND INTERMEDIATES FOR PREPARING FUSED HETEROCYCLIC KINASE INHIBITORS
  [FR] PROCÉDÉS ET INTERMÉDIAIRES DE PRÉPARATION D'INHIBITEURS DE KINASES HÉTÉROCYCLIQUES FUSIONNÉS

  摘要：

  该发明涉及制造熔合杂环型激酶抑制剂化合物的过程和中间体，例如噻吩吡啶基化合物，并涉及制备在制造熔合杂环型激酶抑制剂化合物时有用的中间体的过程和中间体，特别是在工业水平上。这些过程旨在最终形成化合物的结构式（A），其中M是如所示的噻吩[3,2,b]吡啶基，基团D是一个环或环系统，最好是吡啶，基团Z、Ar和G如本文中所定义。这些化合物可以作用于抑制生长因子受体的蛋白酪氨酸激酶活性，从而抑制受体信号传导，例如抑制VEGF受体信号传导和HGF受体信号传导。

  公开号：

  WO2009026720A1

文献信息

• [EN] INHIBITORS OF PROTEIN TYROSINE KINASE ACTIVITY<br/>[FR] INHIBITEURS DE L'ACTIVITÉ PROTÉINE TYROSINE KINASE
  申请人：METHYLGENE INC

  公开号：WO2009026717A1

  公开（公告）日：2009-03-05

  The invention relates to compounds of Formula (I) and their use for inhibiting protein tyrosine kinase activity In Formula (I), the group M is thieno[3,2,b]pyridinyl as shown, and the group D is a ring or ring system, and the groups Z, Ar, and G are as defined herein The invention relates particularly to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signalling, for example, the inhibition of VEGF receptor signalling and HGF receptor signalling The invention also provides compositions and methods for treating cell proliferative diseases and conditions, such as cancer, and for treating ophthalmic diseases, including age-related macular degeneration (AMD) and diabetic retinopathy (DR).

  该发明涉及式（I）化合物及其用于抑制蛋白酪氨酸激酶活性。在式（I）中，基团M为所示的噻吩[3,2,b]吡啶基团，基团D是一个环或环系统，基团Z、Ar和G如本文所定义。该发明特别涉及抑制生长因子受体的蛋白酪氨酸激酶活性的化合物，从而抑制受体信号传导，例如抑制VEGF受体信号传导和HGF受体信号传导。该发明还提供用于治疗细胞增殖性疾病和病症的组合物和方法，例如癌症，并用于治疗眼科疾病，包括老年性黄斑变性（AMD）和糖尿病性视网膜病变（DR）。
• INHIBITORS OF PROTEIN TYROSINE KINASE ACTIVITY
  申请人：Claridge Stephen William

  公开号：US20090264440A1

  公开（公告）日：2009-10-22

  This invention relates to compounds that inhibit protein tyrosine kinase activity. In particular the invention relates to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signaling, for example, the inhibition of VEGF receptor signaling and HGF receptor signaling. More particularly, the invention relates to compounds, compositions and methods for the inhibition of VEGF receptor signaling and HGF receptor signaling. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

  本发明涉及抑制蛋白酪氨酸激酶活性的化合物。具体而言，本发明涉及抑制生长因子受体蛋白酪氨酸激酶活性的化合物，从而抑制受体信号传导，例如抑制VEGF受体信号和HGF受体信号的传导。更具体地，本发明涉及抑制VEGF受体信号和HGF受体信号的化合物、组合物和方法。本发明还提供了治疗细胞增殖性疾病和状况的组合物和方法。
• Processes and intermediates for preparing fused heterocyclic kinase inhibitors
  申请人：Raeppel Franck

  公开号：US20090286984A1

  公开（公告）日：2009-11-19

  This invention relates to processes and intermediates for manufacturing fused heterocyclic-type kinase inhibitor compounds, such as thienopyridine-based compounds, and to processes and intermediates for preparing intermediates that are useful in the manufacture of fused heterocyclic-type kinase inhibitor compounds, such as thienopyridine-based compounds, particularly at an industrial level.

  本发明涉及用于制造融合杂环型激酶抑制剂化合物的过程和中间体，例如噻吩并吡啶基化合物，并涉及用于制备在制造融合杂环型激酶抑制剂化合物，例如噻吩并吡啶基化合物中有用的中间体的过程和中间体，特别是在工业水平上。
• PROCESSES AND INTERMEDIATES FOR PREPARING FUSED HETEROCYCLIC KINASE INHIBITORS
  申请人：Raeppel Franck

  公开号：US20120095234A1

  公开（公告）日：2012-04-19

  This invention relates to processes and intermediates for manufacturing fused heterocyclic-type kinase inhibitor compounds, such as thienopyridine-based compounds, and to processes and intermediates for preparing intermediates that are useful in the manufacture of fused heterocyclic-type kinase inhibitor compounds, such as thienopyridine-based compounds, particularly at an industrial level.

  本发明涉及制造融合杂环型激酶抑制剂化合物（例如基于噻吩并吡啶的化合物）的过程和中间体，以及制备有用于制造融合杂环型激酶抑制剂化合物（例如基于噻吩并吡啶的化合物）的中间体的过程和中间体，特别是在工业水平上。
• TREATMENT OF CANCER USING A COMBINATION COMPRISING MULTI-TYROSINE KINASE INHIBITOR AND IMMUNE CHECKPOINT INHIBITOR
  申请人：BEIGENE, LTD.

  公开号：US20220387404A1

  公开（公告）日：2022-12-08

  Provided herein is a method for the prevention, delay of progression or treatment of cancer in a subject, comprising administering to the subject in need thereof a multi-tyrosine kinase inhibitor, N-(3-fluoro-4-((2-(5-(((2-methoxyethyl)amino)methyl)pyridin-2-yl)thieno[3, 2-b]pyridin-7-yl)oxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1, 1-dicarboxamide or a pharmaceutically acceptable salt thereof, in combination with an immune checkpoint inhibitor. Also, provided a pharmaceutical combination comprising a multi-tyrosine kinase inhibitor, N-(3-fluoro-4-((2-(5-(((2-methoxyethyl)amino)methyl)pyridin-2-yl)thieno[3, 2-b]pyridin-7-yl)oxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1, 1-dicarboxamide or a pharmaceutically acceptable salt thereof, in combination C with an immune checkpoint inhibitor and the use thereof.