pyrrolidine-1-carboxylic acid {8-[5-chloro-4-(2-fluoro-6-methylcarbamoylphenylamino)pyrimidin-2-ylamino]-5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl}amide | 1022973-58-5

• 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: pyrrolidine-1-carboxylic acid {8-[5-chloro-4-(2-fluoro-6-methylcarbamoylphenylamino)pyrimidin-2-ylamino]-5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl}amide
• 英文别名: Pmid21967808CR-16；N-[8-[[5-chloro-4-[2-fluoro-6-(methylcarbamoyl)anilino]pyrimidin-2-yl]amino]-5,5-dimethyl-2-oxo-3,4-dihydro-1H-1-benzazepin-3-yl]pyrrolidine-1-carboxamide
• CAS: 1022973-58-5
• 化学式: C₂₉H₃₂ClFN₈O₃
• 分子量: 595.076
• InChiKey: HGSNUBHWAMMKIR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  42
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  140
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-amino-5,5-dimethyl-8-nitro-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one 在 吡啶 、 palladium 10% on activated carbon 、 camphor-10-sulfonic acid 、 氢气 作用下， 以 甲醇 、 二氯甲烷 、 异丙醇 为溶剂， 20.0~120.0 ℃ 、275.8 kPa 条件下， 反应 3.0h， 生成 pyrrolidine-1-carboxylic acid {8-[5-chloro-4-(2-fluoro-6-methylcarbamoylphenylamino)pyrimidin-2-ylamino]-5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl}amide
  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

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。
• US8148391B2
  申请人：——

  公开号：US8148391B2

  公开（公告）日：2012-04-03