(Z)-N-ethyl-3-(hydroxy(phenyl)methylene)-2-oxoindoline-6-carboxamide | 1253768-95-4

• 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: (Z)-N-ethyl-3-(hydroxy(phenyl)methylene)-2-oxoindoline-6-carboxamide
• 英文别名: (3Z)-N-ethyl-3-[hydroxy(phenyl)methylidene]-2-oxo-1H-indole-6-carboxamide
• CAS: 1253768-95-4
• 化学式: C₁₈H₁₆N₂O₃
• 分子量: 308.337
• InChiKey: FMEQLSYTCJQSIU-NXVVXOECSA-N

物化性质

• 沸点：
  562.6±50.0 °C(Predicted)
• 密度：
  1.303±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.81
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  78.43
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  N-(4-aminophenyl)-N-(3-dimethylaminopropyl)acetamide 、 (Z)-N-ethyl-3-(hydroxy(phenyl)methylene)-2-oxoindoline-6-carboxamide 在 trimethylsilylimidazole 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以23%的产率得到(Z)-3-((4-[N-acetyl-(3-(dimethylamino)propyl)amino]phenylamino)phenylmethylene)-2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid ethylamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Indolinones as Inhibitors of the Transforming Growth Factor β Receptor I (TGFβRI)

  摘要：

  Inhibition of transforming growth factor β (TGFβ) type I receptor (Alk5) offers a novel approach for the treatment of fibrotic diseases and cancer. Indolinones substituted in position 6 were identified as a new chemotype inhibiting TGFβRI concomitant with a low cross-reactivity among the human kinome. A subset of compounds showed additional inhibition of platelet-derived growth factor receptor alpha (PDGFRα), contributing to an interesting pharmacological profile. In contrast, p38 kinase, which is often inhibited by TGFβRI inhibitors, was not targeted by derivatives based on the indolinone chemotype. Guided by an X-ray structure of lead compound 5 (BIBF0775) soaked into the kinase domain of TGFβRI, optimization furnished potent and selective inhibitors of TGFβRI. Potent inhibition translated well into good inhibition of TGFβRI-mediated phosphorylation of Smad2/3, demonstrating efficacy in a cellular setting. Optimized compounds were extensively profiled on a 232-kinase panel and showed low cross-reactivities within the human kinome.

  DOI：

  10.1021/jm100812a
• 作为产物：
  描述：

  1-乙酰基-2,3-二氢-2-氧代-1H-吲哚-6-羧酸甲酯 在 水 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.5h， 生成 (Z)-N-ethyl-3-(hydroxy(phenyl)methylene)-2-oxoindoline-6-carboxamide
  参考文献：
  名称：

  [EN] ALK5 INHIBITOR CONJUGATES AND USES THEREOF
  [FR] CONJUGUÉS INHIBITEURS D'ALK5 ET LEURS UTILISATIONS

  摘要：

  本公开涉及包含ALK5抑制剂和靶向基团的靶向药物结合物，该靶向基团将ALK5抑制剂定向到参与纤维化和癌症的细胞，例如肌成纤维细胞、活化成纤维细胞和转变成纤维细胞，以及它们的用途，特别是其中ALK5抑制剂是N-甲基-2-(4-(4-(3-(6-甲基吡啶-2-基)-1H-吡唑-4-基)吡啶-2-基)苯氧基)乙基-1-胺。

  公开号：

  WO2021142086A1

文献信息

• [EN] ANTIBODY-ALK5 INHIBITOR CONJUGATES AND THEIR USES<br/>[FR] CONJUGUÉS D'ANTICORPS-INHIBITEUR ALK5 ET LEURS UTILISATIONS
  申请人：SYNTHIS LLC

  公开号：WO2020013803A1

  公开（公告）日：2020-01-16

  The present disclosure relates to antibody-drug conjugates comprising ALK5 inhibitors and their uses.

  本公开涉及包含ALK5抑制剂的抗体药物偶联物及其用途。
• ANTIBODY-ALK5 INHIBITOR CONJUGATES AND THEIR USES
  申请人：Synthis, LLC

  公开号：US20200147234A1

  公开（公告）日：2020-05-14

  The present disclosure relates to antibody-drug conjugates comprising ALK5 inhibitors and their uses.

  本公开涉及包含ALK5抑制剂的抗体药物偶联物及其用途。
• [EN] ANTIB0DY-ALK5 INHIBITOR CONJUGATES AND THEIR USES<br/>[FR] CONJUGUÉS D'ANTICORPS-INHIBITEUR DE ALK5 ET LEURS UTILISATIONS
  申请人：SYNTHIS LLC

  公开号：WO2020256751A1

  公开（公告）日：2020-12-24

  The present disclosure relates to antibody-drug conjugates comprising ALK5 inhibitors and their uses.

  本公开涉及包含ALK5抑制剂的抗体药物偶联物及其用途。
• [EN] ANTIB0DY-ALK5 INHIBITOR CONJUGATES AND THEIR USES<br/>[FR] CONJUGUÉS ANTICORPS-INHIBITEURS D'ALK5 ET LEURS UTILISATIONS
  申请人：SYNTHIS LLC

  公开号：WO2020256721A1

  公开（公告）日：2020-12-24

  The present disclosure relates to antibody-drug conjugates comprising ALK5 inhibitors and their uses.