(2S)-8-amino-7-fluoro-N'-hydroxy-2-methyl-10-oxo-6-(3-pyridin-2-ylpropylamino)-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraene-11-carboximidamide | 1355176-13-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (2S)-8-amino-7-fluoro-N'-hydroxy-2-methyl-10-oxo-6-(3-pyridin-2-ylpropylamino)-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraene-11-carboximidamide
• CAS: 1355176-13-4
• 化学式: C₂₁H₂₃FN₆O₃
• 分子量: 426.45
• InChiKey: SCGUPZARFOCHOD-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  139
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (S)-9,10-difluoro-3-methyl-8-nitro-7-oxo-3,7-dihydro-2H-(1,4)oxazino(2,3,4-ij)quinoline-6-carboxamide 在 sodium dithionite 、 羟胺 、 potassium carbonate 、 三乙胺 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 27.0h， 生成 (2S)-8-amino-7-fluoro-N'-hydroxy-2-methyl-10-oxo-6-(3-pyridin-2-ylpropylamino)-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraene-11-carboximidamide
  参考文献：
  名称：

  6-Position optimization of tricyclic 4-quinolone-based inhibitors of glycogen synthase kinase-3β: Discovery of nitrile derivatives with picomolar potency

  摘要：

  We previously disclosed tricylic, 6-carboxylic acid-bearing 4-quinolones as GSK-3 beta inhibitors. Herein we discuss the optimization of this series to yield a series of more potent 6-nitrile analogs with insignificant anti-microbial activity. Finally, kinase profiling indicated that members of this class were highly specific GSK-3 inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.006

文献信息

• 6-Position optimization of tricyclic 4-quinolone-based inhibitors of glycogen synthase kinase-3β: Discovery of nitrile derivatives with picomolar potency
  作者：Bei Li、Oana M. Cociorva、Tyzoon Nomanbhoy、Qiang Li、Kai Nakamura、Masahiro Nomura、Kyoko Okada、Kazuhiro Yumoto、Marek Liyanage、Melissa C. Zhang、Arwin Aban、Anna Katrin Szardenings、John W. Kozarich、Yasushi Kohno、Kevin R. Shreder

  DOI：10.1016/j.bmcl.2011.12.006

  日期：2012.1

  We previously disclosed tricylic, 6-carboxylic acid-bearing 4-quinolones as GSK-3 beta inhibitors. Herein we discuss the optimization of this series to yield a series of more potent 6-nitrile analogs with insignificant anti-microbial activity. Finally, kinase profiling indicated that members of this class were highly specific GSK-3 inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.