3-nitro-7,8-dihydro-6H-5-oxa-9-aza-benzocycloheptene-9-carboxylic acid 3-dimethylamino-propyl ester | 1022947-53-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 3-nitro-7,8-dihydro-6H-5-oxa-9-aza-benzocycloheptene-9-carboxylic acid 3-dimethylamino-propyl ester
• 英文别名: 3-(dimethylamino)propyl 8-nitro-3,4-dihydro-2H-1,5-benzoxazepine-5-carboxylate
• CAS: 1022947-53-0
• 化学式: C₁₅H₂₁N₃O₅
• 分子量: 323.349
• InChiKey: DCNPIZXZYOWYON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  87.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-nitro-7,8-dihydro-6H-5-oxa-9-aza-benzocycloheptene-9-carboxylic acid 3-dimethylamino-propyl ester 在 10% palladium on activated charcoal 、 氢气 作用下， 生成 3-amino-7,8-dihydro-6H-5-oxa-9-aza-benzocycloheptene-9-carboxylic acid 3-dimethylamino-propyl ester
  参考文献：
  名称：

  2,4-Diaminopyrimidine inhibitors of c-Met kinase bearing benzoxazepine anilines

  摘要：

  Elaboration of the SAR around a series of 2,4-diaminopyrimidines led to a number of c-Met inhibitors in which kinase selectivity was modulated by substituents appended on the C4-aminobenzamide ring and the nature of the C2-aminoaryl ring. Further lead optimization of the C2-aminoaryl group led to benzoxazepine analogs whose pharmaceutical properties were modulated by the nature of the substituent on the benzoxazepine nitrogen. Tumor stasis (with partial regressions) were observed when an orally bioavailable analog was evaluated in a GTL-16 tumor xenograft mouse model. Subsequent PK/PD studies suggested that a metabolite contributed to the overall in vivo response. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.013
• 作为产物：
  描述：

  8-nitro-3,4-dihydro-2H-1,5-benzoxazepine-5-carboxylic acid 、 3-dimethylamino-propan-1-ol; sodium salt 以 N-甲基吡咯烷酮 为溶剂， 生成 3-nitro-7,8-dihydro-6H-5-oxa-9-aza-benzocycloheptene-9-carboxylic acid 3-dimethylamino-propyl ester
  参考文献：
  名称：

  2,4-Diaminopyrimidine inhibitors of c-Met kinase bearing benzoxazepine anilines

  摘要：

  Elaboration of the SAR around a series of 2,4-diaminopyrimidines led to a number of c-Met inhibitors in which kinase selectivity was modulated by substituents appended on the C4-aminobenzamide ring and the nature of the C2-aminoaryl ring. Further lead optimization of the C2-aminoaryl group led to benzoxazepine analogs whose pharmaceutical properties were modulated by the nature of the substituent on the benzoxazepine nitrogen. Tumor stasis (with partial regressions) were observed when an orally bioavailable analog was evaluated in a GTL-16 tumor xenograft mouse model. Subsequent PK/PD studies suggested that a metabolite contributed to the overall in vivo response. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.013

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