3-(2-methoxy-ethyl)-7-nitro-2,3,4,5-tetrahydro-1H-3-benzazepine | 1022955-93-6

• 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: 3-(2-methoxy-ethyl)-7-nitro-2,3,4,5-tetrahydro-1H-3-benzazepine
• 英文别名: 3-(2-methoxy-ethyl)-7-nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine；3-(2-methoxyethyl)-7-nitro-2,3,4,5-tetrahydro-1H-3-benzazepine；3-(2-Methoxyethyl)-7-nitro-1,2,4,5-tetrahydro-3-benzazepine
• CAS: 1022955-93-6
• 化学式: C₁₃H₁₈N₂O₃
• 分子量: 250.298
• InChiKey: WFQMKMRZNCXHSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  58.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2-methoxy-ethyl)-7-nitro-2,3,4,5-tetrahydro-1H-3-benzazepine 在 10% palladium on activated charcoal 、 camphor-10-sulfonic acid 、 氢气 作用下， 以 仲丁醇 为溶剂， 生成 3-chloro-2-{5-chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidine-4-ylamino}-N-methyl-benzamide
  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：

  2,3,4,5 -四氢-1H -苯并[D]氮杂卓 在 硝酸 、 potassium carbonate 作用下， 生成 3-(2-methoxy-ethyl)-7-nitro-2,3,4,5-tetrahydro-1H-3-benzazepine
  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

• 2,7-Disubstituted-pyrrolo[2,1-<i>f</i>][1,2,4]triazines: New Variant of an Old Template and Application to the Discovery of Anaplastic Lymphoma Kinase (ALK) Inhibitors with in Vivo Antitumor Activity
  作者：Gregory R. Ott、Gregory J. Wells、Tho V. Thieu、Matthew R. Quail、Joseph G. Lisko、Eugen F. Mesaros、Diane E. Gingrich、Arup K. Ghose、Weihua Wan、Lihui Lu、Mangeng Cheng、Mark S. Albom、Thelma S. Angeles、Zeqi Huang、Lisa D. Aimone、Mark A. Ator、Bruce A. Ruggeri、Bruce D. Dorsey

  DOI：10.1021/jm200758k

  日期：2011.9.22

  7-disubstituted-pyrrolo[2,1-f][1,2,4]triazine scaffold has been designed as a new kinase inhibitor platform mimicking the bioactive conformation of the well-known diaminopyrimidine motif. The design, synthesis, and validation of this new pyrrolo[2,1-f][1,2,4]triazine scaffold will be described for inhibitors of anaplastic lymphoma kinase (ALK). Importantly, incorporation of appropriate potency and selectivity

  一种新型的2,7-二取代-吡咯并[2,1- f ] [1,2,4]三嗪支架已被设计为一种新的激酶抑制剂平台，可模仿众所周知的二氨基嘧啶基序的生物活性构象。这种新型吡咯并[2,1- f ] [1,2,4]三嗪支架的设计，合成和验证将描述为间变性淋巴瘤激酶（ALK）抑制剂。重要的是，适当的效能和选择性决定簇的引入导致发现了在变性间变性大细胞淋巴瘤（ALCL）动物模型中口服有效的几种先进的先导。鉴定出显示出优异功效的铅抑制剂（30），并且将进行深入的体外/体内表征。
• 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。
• BICYCLOANILINE DERIVATIVE
  申请人：MSD K.K.

  公开号：EP2168966B1

  公开（公告）日：2016-09-28
• 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