dimethyl 5,8-diphenyl-5,8-diaza-5,6,7,8-tetrahydronaphthalene-2,3-dicarboxylate | 145915-88-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: dimethyl 5,8-diphenyl-5,8-diaza-5,6,7,8-tetrahydronaphthalene-2,3-dicarboxylate
• 英文别名: 5,8-diphenyl-5,8-diaza-5,6,7,8-tetrahydronaphthalene-2,3-dicarboxylic aciddimethyl ester；Dimethyl 1,4-diphenyl-2,3-dihydroquinoxaline-6,7-dicarboxylate
• CAS: 145915-88-4
• 化学式: C₂₄H₂₂N₂O₄
• 分子量: 402.45
• InChiKey: FVAMEILVGOUEFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dimethyl 5,8-diphenyl-5,8-diaza-5,6,7,8-tetrahydronaphthalene-2,3-dicarboxylate 在 氨 作用下， 以 乙二醇 为溶剂， 反应 16.0h， 以33%的产率得到1,4-Diphenyl-1,2,3,4-tetrahydro-pyrrolo[3,4-g]quinoxaline-6,8-dione
  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
• 作为产物：
  描述：

  1,4-二叠氮双环[2.2.2]辛烷 以 盐酸 、 二氯甲烷 、 溶剂黄146 为溶剂， 生成 dimethyl 5,8-diphenyl-5,8-diaza-5,6,7,8-tetrahydronaphthalene-2,3-dicarboxylate
  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

文献信息

• 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.
• Substituted diaminophthalimides and analogues
  申请人：Ciba-Geigy Corporation

  公开号：US05491144A1

  公开（公告）日：1996-02-13

  Compounds of formula I ##STR1## wherein Ar.sub.1, Ar.sub.2, A.sub.1, A.sub.2, R and X are as defined in the description, exhibit valuable pharmaceutical properties and are effective especially against diseases responsive to the inhibition of protein kinases, for example tumors. They are prepared in a manner known per se.

  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。