4-anilino-5-(4-methoxy-anilino)-phthalimide | 145916-00-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 4-anilino-5-(4-methoxy-anilino)-phthalimide
• 英文别名: 5-anilino-6-(4-methoxyanilino)isoindole-1,3-dione
• CAS: 145916-00-3
• 化学式: C₂₁H₁₇N₃O₃
• 分子量: 359.384
• InChiKey: LESFPZSUPOHBIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  79.5
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-anilino-5-(4-methoxy-anilino)-phthalimide 在 三溴化硼 作用下， 以 正己烷 、 氯仿 、 水 为溶剂， 生成 4-(4'-hydroxyanilino)-5-anilinophthalimide
  参考文献：
  名称：

  Substituted diaminophthalimides and analogues

  摘要：

  式I的化合物##STR1##其中Ar.sub.1、Ar.sub.2、A.sub.1、A.sub.2、R和X的定义如描述中所述，具有有价值的药理特性，特别对抗对蛋白激酶抑制作用敏感的疾病，例如肿瘤。它们以已知的方法制备。

  公开号：

  US05491144A1
• 作为产物：
  描述：

  dimethyl 4-(4-methoxyanilino)-5-anilinophthalate 在 氨 作用下， 以 乙二醇 为溶剂， 反应 16.0h， 以48%的产率得到4-anilino-5-(4-methoxy-anilino)-phthalimide
  参考文献：
  名称：

  Dianilinophthalimides: Potent and Selective, ATP-Competitive Inhibitors of the EGF-Receptor Protein Tyrosine Kinase

  摘要：

  Dianilinophthalimides represent a novel class of inhibitors of the EGF-receptor protein tyrosine kinase with a high degree of selectivity versus other tyrosine and serine/threonine kinases. Steady-state kinetic analysis of compound 3, which showed potent inhibitory activity, revealed competitive type kinetics relative to ATP. Despite a highly symmetrical structure of compound 3, X-ray studies revealed an unsymmetrical propeller-shaped conformation of the molecule which differs clearly from that of the constitutionally related staurosporine aglycons. These conformational differences may explain the reversal of the selectivity profile of compound 3 relative to the staurosporine aglycons. In cellular assays compounds 3 and 4 have been shown to inhibit EGF-induced receptor autophosphorylation, c-fos induction and EGF-dependent proliferation of Balb/ c MK cells. This inhibition was selective as compounds had no effect on PDGF-induced receptor autophosphorylation and c-fos induction. Furthermore, compound 3 showed potent antitumor activity in vivo at well-tolerated doses.

  DOI：

  10.1021/jm00033a019

文献信息

• Substituierte Diaminophthalimide und Analoga
  申请人：CIBA-GEIGY AG

  公开号：EP0516588A1

  公开（公告）日：1992-12-02

  Verbindungen der Formel I, worin Ar₁, Ar₂, A₁, A₂, R und X die in der Beschreibung angegebenen Bedeutungen haben, weisen wertvolle pharmazeutische Eigenschaften auf und sind insbesondere gegen auf die Hemmung von Proteinkinasen ansprechende Erkrankungen, z. B. Tumoren, wirksam. Sie werden in an sich bekannter Weise hergestellt.

  式 I 的化合物、 其中 Ar₁、Ar₂、A₁、A₂、R 和 X 的含义在描述中给出，它们具有重要的药用特性，对抑制蛋白激酶的疾病（如肿瘤）特别有效。它们的生产方式本身是已知的。
• Trinks Uwe, Buchdunger Elisabeth, Furet Pascal, Kump Wilhelm, Mett Helmut+, J. Med. Chem, 37 (1994) N 7, S 1015-1027
  作者：Trinks Uwe, Buchdunger Elisabeth, Furet Pascal, Kump Wilhelm, Mett Helmut+

  DOI：——

  日期：——
• US5491144A
  申请人：——

  公开号：US5491144A

  公开（公告）日：1996-02-13
• US5663336A
  申请人：——

  公开号：US5663336A

  公开（公告）日：1997-09-02
• Dianilinophthalimides: Potent and Selective, ATP-Competitive Inhibitors of the EGF-Receptor Protein Tyrosine Kinase
  作者：Uwe Trinks、Elisabeth Buchdunger、Pascal Furet、Wilhelm Kump、Helmut Mett、Thomas Meyer、Marcel Mueller、Urs Regenass、Greti Rihs

  DOI：10.1021/jm00033a019

  日期：1994.4

  Dianilinophthalimides represent a novel class of inhibitors of the EGF-receptor protein tyrosine kinase with a high degree of selectivity versus other tyrosine and serine/threonine kinases. Steady-state kinetic analysis of compound 3, which showed potent inhibitory activity, revealed competitive type kinetics relative to ATP. Despite a highly symmetrical structure of compound 3, X-ray studies revealed an unsymmetrical propeller-shaped conformation of the molecule which differs clearly from that of the constitutionally related staurosporine aglycons. These conformational differences may explain the reversal of the selectivity profile of compound 3 relative to the staurosporine aglycons. In cellular assays compounds 3 and 4 have been shown to inhibit EGF-induced receptor autophosphorylation, c-fos induction and EGF-dependent proliferation of Balb/ c MK cells. This inhibition was selective as compounds had no effect on PDGF-induced receptor autophosphorylation and c-fos induction. Furthermore, compound 3 showed potent antitumor activity in vivo at well-tolerated doses.