(3Z)-2-oxo-3-(phenyl{[4-(piperidin-1-ylmethyl)phenyl]amino}methylene)indoline-5-carboxylic acid | 247083-28-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3Z)-2-oxo-3-(phenyl{[4-(piperidin-1-ylmethyl)phenyl]amino}methylene)indoline-5-carboxylic acid
• 英文别名: (Z)-3-[phenyl-(4-(piperidin-1-ylmethyl)phenylamino)methylene]-2-oxo-2,3-dihydro-1H-indole-5-carboxylic acid；(3Z)-2-oxo-3-[phenyl-[4-(piperidin-1-ylmethyl)anilino]methylidene]-1H-indole-5-carboxylic acid
• CAS: 247083-28-9
• 化学式: C₂₈H₂₇N₃O₃
• 分子量: 453.541
• InChiKey: OCQAWVMQFAMKRB-QPLCGJKRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  81.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3Z)-2-oxo-3-(phenyl{[4-(piperidin-1-ylmethyl)phenyl]amino}methylene)indoline-5-carboxylic acid 、 盐酸二甲胺 在 二乙基异丙基胺 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 以89%的产率得到(Z)-3-[phenyl-(4-(piperidin-1-ylmethyl)phenylamino)methylene]-2-oxo-2,3-dihydro-1H-indole-5-carboxylic acid dimethylamide
  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：

  (Z)-3-[phenyl-(4-(piperidin-1-ylmethyl)phenylamino)methylene]-2-oxo-2,3-dihydro-1H-indole-5-carboxylic acid methyl ester 在 水 、 sodium hydroxide 、 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 5.0h， 以97%的产率得到(3Z)-2-oxo-3-(phenyl{[4-(piperidin-1-ylmethyl)phenyl]amino}methylene)indoline-5-carboxylic acid
  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

文献信息

• BENZOPYRROLIDONE DERIVATIVES POSSESSING ANTIVIRAL AND ANTICANCER PROPERTIES
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP3056202A1

  公开（公告）日：2016-08-17

  The present invention relates to benzopyrrolidone derivatives and/or pharmaceutically acceptable salts thereof for the use in the treatment of infectious diseases or cancer, and pharmaceutical compositions containing at least one of said benzopyrrolidone derivatives and/or pharmaceutically acceptable salts thereof for the use in the treatment of infectious diseases or cancer.

  本发明涉及苯并吡咯烷酮衍生物和/或其药用可接受盐，用于治疗传染病或癌症，并包含至少一种所述苯并吡咯烷酮衍生物和/或其药用可接受盐的药物组合物，用于治疗传染病或癌症。
• US6169106B1
  申请人：——

  公开号：US6169106B1

  公开（公告）日：2001-01-02
• [EN] BENZOPYRROLIDONE DERIVATIVES POSSESSING ANTIVIRAL AND ANTICANCER PROPERTIES<br/>[FR] DÉRIVÉS DE BENZOPYRROLIDONE POSSÉDANT DES PROPRIÉTÉS ANTIVIRALES ET ANTICANCÉREUSES
  申请人：MAX-PLANCK-GESELLSCHAFT ZUR FÖRDERUNG DER WSS E V

  公开号：WO2016131789A1

  公开（公告）日：2016-08-25

  The present invention relates to benzopyrrolidone derivatives and/or pharmaceutically acceptable salts thereof for the use in the treatment of infectious diseases or cancer, and pharmaceutical compositions containing at least one of said benzopyrrolidone derivatives and/or pharmaceutically acceptable salts thereof for the use in the treatment of infectious diseases or cancer.