(2S)-8-amino-7-fluoro-2-methyl-6-(3-pyridin-2-ylpropylamino)-11-(2H-tetrazol-5-yl)-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraen-10-one | 1132878-83-1

• 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-2-methyl-6-(3-pyridin-2-ylpropylamino)-11-(2H-tetrazol-5-yl)-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraen-10-one
• CAS: 1132878-83-1
• 化学式: C₂₁H₂₁FN₈O₂
• 分子量: 436.449
• InChiKey: OGYDWTUATDVJEG-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  10

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 azide 、 sodium dithionite 、 羟胺 、 potassium carbonate 、 三乙胺 、 zinc(II) chloride 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 异丙醇 为溶剂， 反应 45.0h， 生成 (2S)-8-amino-7-fluoro-2-methyl-6-(3-pyridin-2-ylpropylamino)-11-(2H-tetrazol-5-yl)-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraen-10-one
  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

• 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。
• CYANOAMINOQUINOLONES AS GSK-3 INHIBITORS
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：EP2203458B1

  公开（公告）日：2011-11-02
• US8389514B2
  申请人：——

  公开号：US8389514B2

  公开（公告）日：2013-03-05
• [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：WO2009035634A2

  公开（公告）日：2009-03-19

  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.
• 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.