1-[4-(4-amino-3-methoxyphenyl)-1,4-diazepan-1-yl]ethanone | 1224708-28-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-[4-(4-amino-3-methoxyphenyl)-1,4-diazepan-1-yl]ethanone
• CAS: 1224708-28-4
• 化学式: C₁₄H₂₁N₃O₂
• 分子量: 263.34
• InChiKey: MABZAHNKEOARDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[4-(4-amino-3-methoxyphenyl)-1,4-diazepan-1-yl]ethanone 、 3-(2,5-二氯嘧啶-4-基)咪唑并[1,2-a]吡啶 在 对甲苯磺酸 作用下， 以 2-戊醇 为溶剂， 生成 1-[4-[4-[(5-chloro-4-imidazo[1,2-a]pyridin-3-yl-pyrimidin-2-yl)amino]-3-methoxy-phenyl]-1,4-diazepan-1-yl]ethanone
  参考文献：
  名称：

  Novel imidazo[1,2-a]pyridine based inhibitors of the IGF-1 receptor tyrosine kinase: Optimization of the aniline

  摘要：

  Following the discovery of imidazopyridine 1 as a potent IGF-1R tyrosine kinase inhibitor, the aniline part has been modified with the aim to optimize the properties of this series. The structure-activity relationships against IGF-1R kinase activity as well as inhibition of the hERG ion channel are discussed. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.090

文献信息

• HETEROCYCLIC COMPOUNDS AND USES THEREOF
  申请人：Celgene Avilomics Research, Inc.

  公开号：US20150246040A1

  公开（公告）日：2015-09-03

  The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

  本发明提供了化合物、药学上可接受的组合物以及使用这些化合物的方法。
• Discovery of 5-(methylthio)pyrimidine derivatives as L858R/T790M mutant selective epidermal growth factor receptor (EGFR) inhibitors
  作者：Qiang Xiao、Rong Qu、Dingding Gao、Qi Yan、Linjiang Tong、Wei Zhang、Jian Ding、Hua Xie、Yingxia Li

  DOI：10.1016/j.bmc.2016.04.032

  日期：2016.6

  hundreds of fold less potency on EGFRWT. These compounds also strongly inhibited the proliferation of H1975 non-small cell lung cancer cells bearing EGFRL858R/T790M, while being significantly less toxic to A431 human epithelial carcinoma cells with overexpressed EGFRWT. The EGFR kinase inhibitory and antiproliferative activities were further validated by Western blot analysis for activation of EGFR and the

  为了克服NSCLC患者中第一代EGFR抑制剂的耐药性和第二代抑制剂的非选择性毒性，发现了一系列5-（甲硫基）嘧啶衍生物作为新型EGFR抑制剂，不仅具有强大的酶促和抗增殖活性EGFR L858R / T790M突变体，但对宽型受体具有良好的选择性。通过采用基于结构的药物设计和基于WZ4002和CO1686的传统优化策略来实现此目标。这些衍生物抑制了EGFR L858R / T790M突变体的酶活性，IC 50值在亚纳摩尔范围内，而对EGFR WT的活性降低了数百倍。。这些化合物还强烈抑制带有EGFR L858R / T790M的H1975非小细胞肺癌细胞的增殖，而对过表达EGFR WT的A431人上皮癌细胞的毒性则显着降低。EGFR激酶的抑制和抗增殖活性已通过Western blot分析进一步证实了癌细胞中EGFR的激活和下游信号传导。
• [EN] HETEROCYCLIC COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEURS UTILISATIONS
  申请人：AVILA THERAPEUTICS INC

  公开号：WO2012061299A1

  公开（公告）日：2012-05-10

  Heterocyclic pyrimidine compounds that modulate mutant-selective epidermal growth factor receptor (EGFR) kinase activity are disclosed. Selectivity in inhibition of various mutant-EGFR is disclosed. Pharmaceutical compositions containing the pyrimidine derivatives, and methods of treating diseases associated with EGFR kinase activity comprising administration of the pyrimidine derivatives or pharmaceutical compositions containing the pyrimidine derivative, are described.

  本发明披露了调节突变选择性表皮生长因子受体（EGFR）激酶活性的杂环嘧啶化合物。披露了对各种突变EGFR的选择性抑制。描述了含有嘧啶衍生物的药物组合物以及治疗与EGFR激酶活性相关的疾病的方法，包括给予嘧啶衍生物或含有嘧啶衍生物的药物组合物。
• Heterocyclic compounds and uses thereof
  申请人：Celgene CAR LLC

  公开号：US10434101B2

  公开（公告）日：2019-10-08

  The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

  本发明提供了化合物、其药学上可接受的组合物及其使用方法。
• QUINAZOLINE DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO
  申请人：Emory University

  公开号：EP2632466A2

  公开（公告）日：2013-09-04