tert-butyl ((6-(7-(2-fluoro-4-(1-((4-fluorophenyl)carbamoyl)cyclopropane-1-carboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)(2-methoxyethyl)carbamate | 1123837-39-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyl ((6-(7-(2-fluoro-4-(1-((4-fluorophenyl)carbamoyl)cyclopropane-1-carboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)(2-methoxyethyl)carbamate
• 英文别名: tert-Butyl (6-(7-(2-Fluoro-4-(1-(4-fluorophenylcarbamoyl)-cyclopropanecarboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl(2-methoxyethyl)carbamate；tert-butyl N-[[6-[7-[2-fluoro-4-[[1-[(4-fluorophenyl)carbamoyl]cyclopropanecarbonyl]amino]phenoxy]thieno[3,2-b]pyridin-2-yl]pyridin-3-yl]methyl]-N-(2-methoxyethyl)carbamate
• CAS: 1123837-39-7
• 化学式: C₃₈H₃₇F₂N₅O₆S
• 分子量: 729.804
• InChiKey: AUQMIJAYRDLKEB-UHFFFAOYSA-N

物化性质

• 沸点：
  884.8±65.0 °C(Predicted)
• 密度：
  1.380±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  52
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  160
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  tert-butyl ((6-(7-(2-fluoro-4-(1-((4-fluorophenyl)carbamoyl)cyclopropane-1-carboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)(2-methoxyethyl)carbamate 以69的产率得到司曲替尼
  参考文献：
  名称：

  Processes and Intermediates for Preparing Fused Heterocyclic Kinase Inhibitors

  摘要：

  本发明涉及用于制造融合杂环型激酶抑制剂化合物的中间体，例如基于噻唑吡啶的化合物，特别是在工业水平上。

  公开号：

  US20130310564A1
• 作为产物：
  描述：

  1,1-环丙基二羧酸 在 吡啶 、 氯化亚砜 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 10.0h， 生成 tert-butyl ((6-(7-(2-fluoro-4-(1-((4-fluorophenyl)carbamoyl)cyclopropane-1-carboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)(2-methoxyethyl)carbamate
  参考文献：
  名称：

  [EN] TREATMENT OF CANCER WITH ANTI-OX40 ANTIBODIES AND MULTI-KINASE INHIBITORS
  [FR] TRAITEMENT DU CANCER À L'AIDE D'ANTICORPS ANTI-OX40 ET D'INHIBITEURS DE KINASES MULTIPLES

  摘要：

  本公开提供了使用非竞争性激动剂抗OX40抗体及其与人类OX40（ACT35、CD134或TNFRSF4）结合的抗原结合片段结合，结合多激酶抑制剂治疗癌症的方法。

  公开号：

  WO2021098769A1

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）。
• [EN] PROCESSES AND INTERMEDIATES FOR PREPARING FUSED HETEROCYCLIC KINASE INHIBITORS<br/>[FR] PROCÉDÉS ET INTERMÉDIAIRES DE PRÉPARATION D'INHIBITEURS DE KINASES HÉTÉROCYCLIQUES FUSIONNÉS
  申请人：METHYLGENE INC

  公开号：WO2009026720A1

  公开（公告）日：2009-03-05

  The 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, particularly at an industrial level The processes are aimed at ultimately forming compounds of the formula (A) where M is thieno[3,2,b]pyridinyl as shown, the group D is a ring or ring system, preferably pyridine, and the group Z, Ar, and G are as defined herein Such compounds can act to 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.

  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。
• [EN] TREATMENT OF CANCER USING A COMBINATION COMPRISING MULTI-TYROSINE KINASE INHIBITOR AND IMMUNE CHECKPOINT INHIBITOR<br/>[FR] TRAITEMENT DU CANCER À L'AIDE D'UNE COMBINAISON COMPRENANT UN INHIBITEUR MULTICIBLE DE TYROSINE KINASE ET UN INHIBITEUR DE POINT DE CONTRÔLE IMMUNITAIRE
  申请人：BEIGENE LTD

  公开号：WO2021047623A1

  公开（公告）日：2021-03-18

  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 with an immune checkpoint inhibitor and the use thereof.

  本文提供了一种用于预防、延缓癌症进展或治疗受试者癌症的方法，包括向需要的受试者施用一种多酪氨酸激酶抑制剂，即N-(3-氟-4-((2-(5-(((2-甲氧基乙基)氨基)甲基)吡啶-2-基)噻吩[3,2-b]吡啉-7-基)氧基)苯基)-N-(4-氟苯基)环丙烷-1,1-二甲酰胺或其药学上可接受的盐，与免疫检查点抑制剂联合使用。此外，还提供了一种包含多酪氨酸激酶抑制剂、N-(3-氟-4-((2-(5-(((2-甲氧基乙基)氨基)甲基)吡啶-2-基)噻吩[3,2-b]吡啉-7-基)氧基)苯基)-N-(4-氟苯基)环丙烷-1,1-二甲酰胺或其药学上可接受的盐、与免疫检查点抑制剂联合使用的药物组合物及其用途。
• [EN] CRYSTALLINE FORM OF A MULTI-TYROSINE KINASE INHIBITOR, METHOD OF PREPARATION, AND USE THEREOF<br/>[FR] FORME CRISTALLINE D'UN INHIBITEUR DE LA TYROSINE KINASE MULTIPLE, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION
  申请人：MIRATI THERAPEUTICS INC

  公开号：WO2021050580A1

  公开（公告）日：2021-03-18

  The present invention relates to crystalline forms of 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 -di carboxamide (Compound 1), pharmaceutical compositions comprising the crystalline form, processes for preparing the crystalline form and methods of use therefore.

  本发明涉及N-(3-氟-4-((2-(5-(((2-甲氧基乙基)氨基甲基)吡啶-2-基)噻吩[3,2-b]吡啶-7-基)氧基)苯基)-N-(4-氟苯基)环丙烷-1,1-二甲酰胺（化合物1）的晶型形式，包括该晶型形式的药物组合物，制备该晶型形式的方法以及使用方法。
• 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。