4,5-bis(4'-hydroxyanilino)phthalimide

• 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: 4,5-bis(4'-hydroxyanilino)phthalimide
• 英文别名: 4,5-Bis(4-hydroxyanilino)phthalimide；5,6-Bis-(4-hydroxy-phenylamino)-isoindole-1,3-dione；5,6-bis(4-hydroxyanilino)isoindole-1,3-dione
• 化学式: C₂₀H₁₅N₃O₄
• 分子量: 361.357
• InChiKey: TYLKNORJFZPIPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  111
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4,5-bis-(4-methoxyanilino)phthalimide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 5.67h， 以64%的产率得到4,5-bis(4'-hydroxyanilino)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

• Preparation of 4-(4′-Hydroxyanilino)-5-anilinophthalimide and 4,5-Bis-(4′-hydroxyanilino)-phthalimide by Microbial Hydroxylation
  作者：Stefan WEIDNER、Klaus GOEKE、Uwe TRINKS、Peter TRAXLER、Katharina UCCI-STOLL、Oreste GHISALBA

  DOI：10.1271/bbb.63.1497

  日期：1999.1

  A microbial screening indicated that two fungal strains, Beauveria bassiana DSM 1344=ATCC 7159 and Cunninghamella elegans DSM 1908=ATCC 9245, as well as four bacterial strains belonging to the genus Streptomyces were able to hydroxylate 4,5-dianilinophthalimide (DAPH, CGP52411) to 4-(4′-hydroxyanilino)-5-anilinophthalimide. Cunninghamella elegans DSM 1908 turned out to be the most active biocatalyst and was also able to form the dihydroxy derivative, 4,5-bis(4′-hydroxyanilino)phthalimide. The reaction for the monohydroxylated biotransformation product was carried out on a preparative scale, and the culture conditions for the formation of 4-(4′-hydroxy- anilino)-5-anilinophthalimide with this strain were op-timized.

  微生物筛选表明，两种真菌菌株，白僵菌 DSM 1344=ATCC 7159 和 Cunninghamella elegans DSM 1908=ATCC 9245，以及属于链霉菌属的四种细菌菌株能够羟基化 4,5-二苯胺邻苯二甲酰亚胺（DAPH，CGP52411）至4-(4'-羟基苯胺基)-5-苯胺基邻苯二甲酰亚胺。 Cunninghamella elegans DSM 1908 被证明是最活跃的生物催化剂，并且还能够形成二羟基衍生物 4,5-双（4'-羟基苯胺基）邻苯二甲酰亚胺。单羟基化生物转化产物的反应以制备规模进行，并优化了该菌株形成4-(4'-羟基苯胺基)-5-苯胺基邻苯二甲酰亚胺的培养条件。
• 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：——
• Substituierte Diaminophthalimide und Analoga
  申请人：CIBA-GEIGY AG

  公开号：EP0516588B1

  公开（公告）日：1994-07-13
• 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