2-{4-amino-1-tert-butyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-3-chloro-1-(difluoromethyl)-N-methyl-1H-indole-6-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-{4-amino-1-tert-butyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-3-chloro-1-(difluoromethyl)-N-methyl-1H-indole-6-carboxamide
• 英文别名: US10954241, Example 97；2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-1-(difluoromethyl)-N-methylindole-6-carboxamide
• 化学式: C₂₀H₂₀ClF₂N₇O
• 分子量: 447.875
• InChiKey: CWTXFLPJKBWZDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  溴氟甲基膦酸二乙酯 、 2-(4-amino-1-tert-butyl-pyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide 在 sodium hydroxide 作用下， 以 水 、 乙腈 为溶剂， 反应 2.25h， 以10%的产率得到2-{4-amino-1-tert-butyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-3-chloro-1-(difluoromethyl)-N-methyl-1H-indole-6-carboxamide
  参考文献：
  名称：

  [EN] HETEROCYCLIC COMPOUNDS AS RET KINASE INHIBITORS
  [FR] COMPOSÉS HÉTÉROCYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS DE KINASE RET

  摘要：

  本发明涉及具有以下结构的Formula I化合物，其作为RET（重排基因转座）激酶酶活性的抑制剂：其中HET，键a、b、c和d，X1、X2、X3、X4、R2和R3在此处各自定义。本发明还涉及制备这些化合物的方法，包括它们的药物组合物，以及它们在治疗增殖性疾病（如癌症）以及其他涉及RET激酶活性的疾病或症状中的用途。

  公开号：

  WO2017178844A1

文献信息

• Heterocyclic compounds as ret kinase inhibitors
  申请人：Cancer Research Technology Limited

  公开号：US10954241B2

  公开（公告）日：2021-03-23

  The present invention relates to compounds of Formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, bonds a, b, c and d, X1, X2, X3, X4, R2, and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which RET kinase activity is implicated.

  本发明涉及作为 RET（转染过程中重排）激酶酶活性抑制剂的式 I 化合物： 其中HET、键a、b、c和d、X1、X2、X3、X4、R2和R3各自如本文所定义。本发明还涉及这些化合物的制备工艺、包含这些化合物的药物组合物，以及它们在治疗增殖性疾病（如癌症）和其他涉及 RET 激酶活性的疾病或病症中的用途。
• HETEROCYCLIC COMPOUNDS AS RET KINASE INHIBITORS
  申请人：Cancer Research Technology Limited

  公开号：EP3442980B1

  公开（公告）日：2021-06-09
• Heterocyclic Compounds as RET Kinase Inhibitors
  申请人：Cancer Research Technology Limited

  公开号：US20210155628A1

  公开（公告）日：2021-05-27

  The present invention relates to compounds of Formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, bonds a, b, c and d, X 1 , X 2 , X 3 , X 4 , R 2 , and R 3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which RET kinase activity is implicated.
• [EN] HETEROCYCLIC COMPOUNDS AS RET KINASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS DE KINASE RET
  申请人：CANCER RES TECH LTD

  公开号：WO2017178844A1

  公开（公告）日：2017-10-19

  The present invention relates to compounds of Formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, bonds a, b, c and d, X1, X2, X3, X4, R2, and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which RET kinase activity is implicated.

  本发明涉及具有以下结构的Formula I化合物，其作为RET（重排基因转座）激酶酶活性的抑制剂：其中HET，键a、b、c和d，X1、X2、X3、X4、R2和R3在此处各自定义。本发明还涉及制备这些化合物的方法，包括它们的药物组合物，以及它们在治疗增殖性疾病（如癌症）以及其他涉及RET激酶活性的疾病或症状中的用途。