4-(1-oxo-1,2-dihydroisoquinolin-3-ylamino)benzoic acid ethyl ester | 500198-65-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 4-(1-oxo-1,2-dihydroisoquinolin-3-ylamino)benzoic acid ethyl ester
• 英文别名: 3-(4-ethoxycarbonylanilino)-1,2-dihydro-1-isoquinoline；ethyl 4-[(1-oxo-2H-isoquinolin-3-yl)amino]benzoate
• CAS: 500198-65-2
• 化学式: C₁₈H₁₆N₂O₃
• 分子量: 308.337
• InChiKey: XDYOENSWOAWNLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(1-oxo-1,2-dihydroisoquinolin-3-ylamino)benzoic acid ethyl ester 在 吡啶 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 13.0h， 生成 3-(4-ethoxycarbonylphenyl)-2,3,4,5-tetrahydro-1H-pyrrolo[2,3-c]isoquinoline-1,5-dione-2-spiro-4'-(1'-ethyl-1',4'-dihydropyridine)
  参考文献：
  名称：

  Fused isoquinolines: 3-aryl-2,3,4,5-tetrahydro-1H-pyrrolo[2,3-c]isoquinoline-1,5-dione-2-spiro-4′-(1′-alkyl-1′,4′-dihydropyridine)s

  摘要：

  Previously unknown 3-arylamino-1,2-dihydro-1-isoquinolones were obtained by condensation of 2-cyanomethylbenzoic acid with arylamines. Isonicotinoylation of the compounds was shown to proceed at the carbon atom in the 4-position to give 3-arylamino-4-isonicotinoyl-1,2-dihydro-1-isoquinolones which were quaternized with alkylating agents and formed the corresponding pyridinium salts. Deprotonation of the latter induced intramolecular conjugated addition with the pyrrole ring closure and formation of spiro compounds. The structure of the products was confirmed by NMR, IR and UV spectroscopy and by synthesis of the model compound, 3-(4-tolyl)-2,3,4,5-tetrahydro-1H-pyrrolo[2,3-c]isoquinoline-1,5-dione. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2003.10.009
• 作为产物：
  描述：

  苯酞 以 氯苯 为溶剂， 反应 5.0h， 生成 4-(1-oxo-1,2-dihydroisoquinolin-3-ylamino)benzoic acid ethyl ester
  参考文献：
  名称：

  Synthesis and biological evaluation of 3-aminoisoquinolin-1(2H)-one based inhibitors of the dual-specificity phosphatase Cdc25B

  摘要：

  The cell division cycle 25B dual specificity phosphatase (Cdc25B) regulates the normal progression of the mammalian cell cycle by dephosphorylating and activating cyclin-dependent kinase (Cdk) complexes, particularly in response to DNA damage. Elevated Cdc25B levels enable a bypass of normal cell cycle checkpoints, and the overexpression of Cdc25B has been linked to a variety of human cancers. Thus, Cdc25B is an attractive target for the development of anticancer therapeutics. Herein we describe the synthesis and biological evaluation of a series of non-quinoid inhibitors of Cdc25B containing the 3-aminoisoquinolin-1(2H)-one pharmacophore. In addition to several strategies that address specific substitution patterns on isoquinolines, we have applied a regioselective Pd-catalyzed cross-coupling methodology to synthesize a new lead structure, 6-(3-aminophenyl)-3-(phenylamino) isoquinolin-1(2H)-one (13), which proved to be a reversible, competitive Cdc25B inhibitor with a K-i of 1.9 mu M. Compound 13 prevented human cancer cell growth and blocked Cdc25B-mediated mitotic checkpoint bypass. Molecular docking studies support binding near the catalytic site. (C) 2015 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2015.01.043

文献信息

• Fused isoquinolines: 3-aryl-2,3,4,5-tetrahydro-1H-pyrrolo[2,3-c]isoquinoline-1,5-dione-2-spiro-4′-(1′-alkyl-1′,4′-dihydropyridine)s
  作者：Tat'yana T Kucherenko、Roman Gutsul、Vladimir M Kisel、Vladimir A Kovtunenko

  DOI：10.1016/j.tet.2003.10.009

  日期：2004.1

  Previously unknown 3-arylamino-1,2-dihydro-1-isoquinolones were obtained by condensation of 2-cyanomethylbenzoic acid with arylamines. Isonicotinoylation of the compounds was shown to proceed at the carbon atom in the 4-position to give 3-arylamino-4-isonicotinoyl-1,2-dihydro-1-isoquinolones which were quaternized with alkylating agents and formed the corresponding pyridinium salts. Deprotonation of the latter induced intramolecular conjugated addition with the pyrrole ring closure and formation of spiro compounds. The structure of the products was confirmed by NMR, IR and UV spectroscopy and by synthesis of the model compound, 3-(4-tolyl)-2,3,4,5-tetrahydro-1H-pyrrolo[2,3-c]isoquinoline-1,5-dione. (C) 2003 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of 3-aminoisoquinolin-1(2H)-one based inhibitors of the dual-specificity phosphatase Cdc25B
  作者：Kara M. George Rosenker、William D. Paquette、Paul A. Johnston、Elizabeth R. Sharlow、Andreas Vogt、Ahmet Bakan、John S. Lazo、Peter Wipf

  DOI：10.1016/j.bmc.2015.01.043

  日期：2015.6

  The cell division cycle 25B dual specificity phosphatase (Cdc25B) regulates the normal progression of the mammalian cell cycle by dephosphorylating and activating cyclin-dependent kinase (Cdk) complexes, particularly in response to DNA damage. Elevated Cdc25B levels enable a bypass of normal cell cycle checkpoints, and the overexpression of Cdc25B has been linked to a variety of human cancers. Thus, Cdc25B is an attractive target for the development of anticancer therapeutics. Herein we describe the synthesis and biological evaluation of a series of non-quinoid inhibitors of Cdc25B containing the 3-aminoisoquinolin-1(2H)-one pharmacophore. In addition to several strategies that address specific substitution patterns on isoquinolines, we have applied a regioselective Pd-catalyzed cross-coupling methodology to synthesize a new lead structure, 6-(3-aminophenyl)-3-(phenylamino) isoquinolin-1(2H)-one (13), which proved to be a reversible, competitive Cdc25B inhibitor with a K-i of 1.9 mu M. Compound 13 prevented human cancer cell growth and blocked Cdc25B-mediated mitotic checkpoint bypass. Molecular docking studies support binding near the catalytic site. (C) 2015 Published by Elsevier Ltd.