5,5-dimethyl-8-nitro-1,3,4,5-tetrahydro-benzo[b]azepin-2-one | 1022972-64-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 5,5-dimethyl-8-nitro-1,3,4,5-tetrahydro-benzo[b]azepin-2-one
• 英文别名: 5,5-Dimethyl-8-nitro-4,5-dihydro-1H-benzo[B]azepin-2(3H)-one；5,5-dimethyl-8-nitro-3,4-dihydro-1H-1-benzazepin-2-one
• CAS: 1022972-64-0
• 化学式: C₁₂H₁₄N₂O₃
• 分子量: 234.255
• InChiKey: QBPMBSJHUDTBSY-UHFFFAOYSA-N

物化性质

• 沸点：
  398.3±42.0 °C(Predicted)
• 密度：
  1.190±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,5-dimethyl-8-nitro-1,3,4,5-tetrahydro-benzo[b]azepin-2-one 在 sodium azide 、 碘代三甲硅烷 、 四甲基乙二胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 3-amino-5,5-dimethyl-8-nitro-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one
  参考文献：
  名称：

  Improvement in oral bioavailability of 2,4-diaminopyrimidine c-Met inhibitors by incorporation of a 3-amidobenzazepin-2-one group

  摘要：

  The hepatocyte growth factor (HGF)-c-Met signaling axis is involved in the mediation of many biological activities, including angiogenesis, proliferation, cell survival, cell motility, and morphogenesis. Dysregulation of c-Met signaling (e. g., overexpression or increased activation) is associated with the proliferation and metastasis of a wide range of tumor types, including breast, liver, lung, colorectal, gastric, bladder, and prostate, among others. Inhibiting the HGF-c-Met pathway is predicted to lead to anti-tumor effects in many cancers. Elaboration of the SAR around a series of 2,4-diaminopyrimidines led to a number of c-Met inhibitors in which pharmaceutical properties were modulated by substituents appended on the C2-benzazepinone ring. In particular, certain-3-amidobenzazepin-2-one analogs had improved oral bioavailability and were evaluated in PK/PD and efficacy models. Lead compounds demonstrated tumor stasis with partial regressions when evaluated in a GTL-16 tumor xenograft mouse model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.006
• 作为产物：
  描述：

  3,4-二氢-4,4-二甲基-7-硝基-萘-1(2H)-酮 在 盐酸羟胺 、 sodium acetate 作用下， 以 乙醇 、 水 为溶剂， 反应 17.0h， 生成 5,5-dimethyl-8-nitro-1,3,4,5-tetrahydro-benzo[b]azepin-2-one
  参考文献：
  名称：

  Fused bicyclic derivatives of 2,4-diaminopyrimidine as c-Met inhibitors

  摘要：

  The HGF-c-Met signaling axis is an important paracrine mediator of epithelial-mesenchymal cell interactions involving the regulation of multiple cellular activities including cell motility, mitogenesis, morphogenesis, and angiogenesis. Dysregulation of c-Met signaling (e. g., overexpression or increased activation) is associated with the development of a wide range of tumor types; thus, inhibiting the HGF-c-Met pathway is predicted to lead to anti-tumor effects in many cancers. Elaboration of a 2-arylaminopyrimidine scaffold led to a series of potent c-Met inhibitors bearing a C4-2-amino-N-methylbenzamide group. Specifically, a series of C2-benzazepinone analogs demonstrated potent inhibition of c-Met in enzymatic and cellular assays. Kinase selectivity could be tuned by varying the nature of the alkyl group on the benzazepinone nitrogen. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.11.045

文献信息

• FUSED BICYCLIC DERIVATIVES OF 2,4-DIAMINOPYRIMIDINE AS ALK AND c-MET INHIBITORS
  申请人：Ahmed Gulzar

  公开号：US20090221555A1

  公开（公告）日：2009-09-03

  The present invention provides a compound of formula I or II or a pharmaceutically acceptable salt form thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , A 1 , A 2 , A 3 , A 4 , and A 5 , are as defined herein. The compounds of formula I or II have ALK and/or c-Met inhibitory activity, and may be used to treat proliferative disorders.

  本发明提供公式I或II化合物或其药学上可接受的盐形式，其中R1、R2、R3、R4、R5、A1、A2、A3、A4和A5如本文所定义。公式I或II化合物具有ALK和/或c-Met抑制活性，可用于治疗增殖性疾病。
• Fused Bicyclic Derivatives of 2,4-Diaminopyrimidine as ALK and c-MET Inhibitors
  申请人：Ahmed Gulzar

  公开号：US20120165519A1

  公开（公告）日：2012-06-28

  The present invention provides a compound of formula I or II or a pharmaceutically acceptable salt form thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , A 1 , A 2 , A 3 , A 4 , and A 5 , are as defined herein. The compounds of formula I or II have ALK and/or c-Met inhibitory activity, and may be used to treat proliferative disorders.

  本发明提供了式I或II的化合物或其药学上可接受的盐形式，其中R1、R2、R3、R4、R5、A1、A2、A3、A4和A5如本文所定义。式I或II的化合物具有ALK和/或c-Met抑制活性，并可用于治疗增生性疾病。
• Fused bicyclic derivatives of 2,4-diaminopyrimidine as ALK and c-MET inhibitors
  申请人：Ahmed Gulzar

  公开号：US08552186B2

  公开（公告）日：2013-10-08

  The present invention provides a compound of formula I or II or a pharmaceutically acceptable salt form thereof, wherein R1, R2, R3, R4, R5, A1, A2, A3, A4, and A5, are as defined herein. The compounds of formula I or II have ALK and/or c-Met inhibitory activity, and may be used to treat proliferative disorders.

  本发明提供了式I或II的化合物或其药学上可接受的盐形式，其中R1、R2、R3、R4、R5、A1、A2、A3、A4和A5的定义如本文所述。式I或II的化合物具有ALK和/或c-Met抑制活性，可用于治疗增殖性疾病。
• Fused bicyclic derivatives of 2,4-diaminopyrimidine as ALK and c-Met inhibitors
  申请人：Cephalon, Inc.

  公开号：US08148391B2

  公开（公告）日：2012-04-03

  The present invention provides a compound of formula I or II or a pharmaceutically acceptable salt form thereof, wherein R1, R2, R3, R4, R5, A1, A2, A3, A4, and A5, are as defined herein. The compounds of formula I or II have ALK and/or c-Met inhibitory activity, and may be used to treat proliferative disorders.

  本发明提供了I或II式化合物或其药学上可接受的盐形式，其中R1、R2、R3、R4、R5、A1、A2、A3、A4和A5的定义如本文所述。I或II式化合物具有ALK和/或c-Met抑制活性，并可用于治疗增生性疾病。
• FUSED BICYCLIC DERIVATIVES OF 2,4-DIAMINOPYRIMIDINE AS ALK AND C-MET INHIBITORS
  申请人：Cephalon, Inc.

  公开号：EP2222647A1

  公开（公告）日：2010-09-01