3-(4-fluorophenylamino)-2H-isoquinolin-1-one | 402481-32-7

• 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-(4-fluorophenylamino)-2H-isoquinolin-1-one
• 英文别名: 3-(4-fluoroanilino)-2H-isoquinolin-1-one
• CAS: 402481-32-7
• 化学式: C₁₅H₁₁FN₂O
• 分子量: 254.264
• InChiKey: PEHOEPBOSMZVKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 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：
  41.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-fluorophenylamino)-2H-isoquinolin-1-one 、 碘乙烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.33h， 生成 3-(N-ethyl-4-fluoroanilino)isoquinolin-1(2H)-one
  参考文献：
  名称：

  3-氨基异羰基苯乙烯基衍生物的烷基化

  摘要：

  在NaH存在下，3-氨基异喹啉-1（2H）-one的衍生物的烷基化可沿三个方向进行：1）在羰基氧原子上，2）在氮原子N-2上，和3）在氢原子上。 3-氨基。等量试剂的反应主要产生3-氨基上的取代产物。在内酰胺片段上进行重复的烷基化，得到O-烷基和N-烷基衍生物的混合物。在NaH存在下对3-二烷基氨基-和3-烷基苯胺基异喹啉-1（2H）-进行酰化得到3-氨基-1-异喹啉基4-乙氧基苯甲酸酯的衍生物。

  DOI：

  10.1007/s10593-011-0758-4
• 作为产物：
  描述：

  苯酞 以 氯苯 为溶剂， 反应 12.0h， 生成 3-(4-fluorophenylamino)-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

• 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.
• Alkylation of 3-aminoisocarbostyryl derivatives
  作者：L. M. Potikha、R. M Gutsul、V. A. Kovtunenko、A. V. Turov

  DOI：10.1007/s10593-011-0758-4

  日期：2011.6

  The alkylation of derivatives of 3-aminoisoquinolin-1(2H)-one in the presence of NaH may proceed in three directions: 1) at the carbonyl group oxygen atom, 2) at the nitrogen atom N-2, and 3) at the 3-amino group. The reaction of equivalent amounts of the reagents gives predominantly products of substitution at the 3-amino group. Repeated alkylation proceeds at the lactam fragment to give a mixture

  在NaH存在下，3-氨基异喹啉-1（2H）-one的衍生物的烷基化可沿三个方向进行：1）在羰基氧原子上，2）在氮原子N-2上，和3）在氢原子上。 3-氨基。等量试剂的反应主要产生3-氨基上的取代产物。在内酰胺片段上进行重复的烷基化，得到O-烷基和N-烷基衍生物的混合物。在NaH存在下对3-二烷基氨基-和3-烷基苯胺基异喹啉-1（2H）-进行酰化得到3-氨基-1-异喹啉基4-乙氧基苯甲酸酯的衍生物。