3-(1H-[1,2,4]-triazol-3-ylamino)-2H-isoquinolin-1-one | 958760-54-8

• 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: 3-(1H-[1,2,4]-triazol-3-ylamino)-2H-isoquinolin-1-one
• 英文别名: 3-(1H-1,2,4-triazol-5-ylamino)-2H-isoquinolin-1-one
• CAS: 958760-54-8
• 化学式: C₁₁H₉N₅O
• 分子量: 227.225
• InChiKey: MHXLJSPEEUDWKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  苯酞 以 氯苯 为溶剂， 反应 5.0h， 生成 3-(1H-[1,2,4]-triazol-3-ylamino)-2H-isoquinolin-1-one
  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

• 3-(Hetarylamino)- and 3-[(hetarylmethyl)amino]-isoquinolin-1(2H)-ones
  作者：L. M. Potikha、R. M. Gutsul、V. A. Kovtunenko、A. A. Tolmachev

  DOI：10.1007/s10593-010-0531-0

  日期：2010.8

  The reaction of 2-(cyanomethyl)benzoic acid with amines RNH(2) (R = Ar, Het, CH(2)Ar, CH(2)Het) leads to the formation of the corresponding 3-NHR-isoquinolin-1(2H)-ones. When R = CH(2)Ar and CH(2)Het, there is a side reaction involving hydrolysis of the hydrolytically-unstable intermediates, derivatives of 2-(2-amino-2-iminoethyl) benzoic acid, leading to 2-R-isoquinoline-1,3(2H,4H)-diones.
• 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.