(3S)-8-amino-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrile | 1132816-01-3

• 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: (3S)-8-amino-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrile
• 英文别名: (S)-8-amino-9,10-difluoro-3-methyl-7-oxo-3,7-dihydro-2H-(1,4)oxazino(2,3,4-ij)quinoline-6-carbonitrile；(2S)-8-amino-6,7-difluoro-2-methyl-10-oxo-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraene-11-carbonitrile
• CAS: 1132816-01-3
• 化学式: C₁₃H₉F₂N₃O₂
• 分子量: 277.23
• InChiKey: SMEAWIJJJMANLR-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  79.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3S)-8-amino-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrile 在 羟胺 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以42%的产率得到(S)-8-amino-9,10-difluoro-N-hydroxy-3-methyl-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-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
• 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 、 三乙胺 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 (3S)-8-amino-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrile
  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

• 7-CYCLOALKYLAMINOQUINOLONES AS GSK-3 INHIBITORS
  申请人：NOMURA MASAHIRO

  公开号：US20100234367A1

  公开（公告）日：2010-09-16

  Provided herein are aminoquinolones of formula I and compositions containing the compounds. The compounds and compositions provided herein are useful in the prevention, amelioration or treatment of GSK-3 inhibitors mediated diseases.

  本文提供了化学式I的氨基喹啉类化合物和含有这些化合物的组合物。本文提供的化合物和组合物在预防、改善或治疗GSK-3抑制剂介导的疾病方面具有用途。
• CYANOAMINOQUINOLONES AND TETRAZOLOAMINOQUINOLONES AS GSK-3 INHIBITORS
  申请人：Li Bei

  公开号：US20110172219A1

  公开（公告）日：2011-07-14

  Provided herein are aminoquinolones and pharmaceutically acceptable derivatives thereof. In certain embodiments, provided herein are compounds, compositions and methods for treating, preventing or ameliorating GSK-3 mediated diseases.

  本文提供了氨基喹啉及其药学上可接受的衍生物。在某些实施例中，本文提供了用于治疗、预防或缓解GSK-3介导疾病的化合物、组合物和方法。
• 7-cycloalkylaminoquinolones as GSK-3 inhibitors
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：US08071591B2

  公开（公告）日：2011-12-06

  Provided herein are aminoquinolones of formula I and compositions containing the compounds, wherein formula I is The compounds and compositions provided herein are useful in the amelioration or treatment of GSK-3 inhibitors mediated diseases.

  本文提供了式I的氨基喹啉和含有该化合物的组合物，其中式I为： 这些化合物和组合物在改善或治疗GSK-3抑制剂介导的疾病方面是有用的。
• Cyanoaminoquinolones and tetrazoloaminoquinolones as GSK-3 inhibitors
  申请人：Li Bei

  公开号：US08389514B2

  公开（公告）日：2013-03-05

  Provided herein are aminoquinolones and pharmaceutically acceptable derivatives thereof. In certain embodiments, provided herein are compounds, compositions and methods for treating, preventing or ameliorating GSK-3 mediated diseases.

  这里提供氨基喹啉及其药学上可接受的衍生物。在某些实施例中，提供了用于治疗、预防或改善GSK-3介导疾病的化合物、组合物和方法。
• [EN] CYANOAMINOQUINOLONES AND TETRAZOLOAMINOQUINOLONES AS GSK-3 INHIBITORS<br/>[FR] CYANOAMINOQUINOLONES ET TÉTRAZOLOAMINOQUINOLONES EN TANT QU'INHIBITEURS DE GSK-3
  申请人：ACTIVX BIOSCIENCES INC

  公开号：WO2009035634A3

  公开（公告）日：2009-06-04