3-methoxy-5-(morpholin-4-yl)aniline | 1051900-28-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 3-methoxy-5-(morpholin-4-yl)aniline
• 英文别名: 3-methoxy-5-morpholinoaniline；3-methoxy-5-morpholin-4-ylaniline
• CAS: 1051900-28-7
• 化学式: C₁₁H₁₆N₂O₂
• 分子量: 208.26
• InChiKey: OYSJXTOZCXRLDI-UHFFFAOYSA-N

物化性质

• 沸点：
  415.7±45.0 °C(Predicted)
• 密度：
  1.163±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  47.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-methoxy-5-(morpholin-4-yl)aniline 在 碳酸氢钠 、 potassium carbonate 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 二甲基亚砜 、 叔丁醇 为溶剂， 反应 0.5h， 生成 5-((3-acrylamido-4-chlorobenzyl)amino)-7-((3-methoxy-5-morpholinophenyl)amino)imidazo[1,2-c]pyrimidine-8-carboxamide
  参考文献：
  名称：

  Discovery and Structural Optimization of Covalent ZAP-70 Kinase Inhibitors against Psoriasis

  摘要：

  DOI：

  10.1021/acs.jmedchem.3c00606

文献信息

• Structure-Activity Relationship of Indole-Tethered Pyrimidine Derivatives that Concurrently Inhibit Epidermal Growth Factor Receptor and Other Angiokinases
  作者：Jiho Song、Jakyung Yoo、Ara Kwon、Doran Kim、Hong Khanh Nguyen、Bong-Yong Lee、Wonhee Suh、Kyung Hoon Min

  DOI：10.1371/journal.pone.0138823

  日期：——

  Antiangiogenic agents have been widely investigated in combination with standard chemotherapy or targeted cancer agents for better management of advanced cancers. Therapeutic agents that concurrently inhibit epidermal growth factor receptor and other angiokinases could be useful alternatives to combination therapies for epidermal growth factor receptor-dependent cancers. Here, we report the synthesis of an indole derivative of pazopanib using a bioisosteric replacement strategy, which was designated MKP101. MKP101 inhibited not only the epidermal growth factor receptor with an IC50 value of 43 nM but also inhibited angiokinases as potently as pazopanib. In addition, MKP101 effectively inhibited vascular endothelial growth factor-induced endothelial proliferation, tube formation, migration of human umbilical vein endothelial cells and proliferation of HCC827, an epidermal growth factor receptor-addicted cancer cell line. A docking model of MKP101 and the kinase domain of the epidermal growth factor receptor was generated to predict its binding mode, and validated by synthesizing and evaluating MKP101 derivatives. Additionally, a study of structure-activity relationships of indolylamino or indolyloxy pyrimidine analogues derived from MKP101 demonstrated that selectivity for epidermal growth factor receptor and other angiokinases, especially vascular endothelial growth factor receptor 2 depends on the position of substituents on pyrimidine and the type of link between pyrimidine and the indole moiety. We believe that this study could provide a basis for developing angiokinase inhibitors having high affinity for the epidermal growth factor receptor, from the pyrimidine scaffold.

  抗血管生成剂已经被广泛研究，以与标准化疗或靶向抗癌药物结合使用，从而更好地管理晚期癌症。那些能够同时抑制表皮生长因子受体和其他血管生成激酶的治疗药物，可能是表皮生长因子受体依赖性癌症的有效替代组合疗法。在这里，我们报告了一种使用生物同位素替代策略合成的吲哚衍生物，这种化合物被命名为MKP101。MKP101不仅抑制了表皮生长因子受体，其IC50值为43 nM，而且同样强效地抑制了血管生成激酶。此外，MKP101有效抑制了由血管内皮生长因子诱导的人脐带静脉内皮细胞的增殖、管状形成、迁移，以及HCC827（一个依赖于表皮生长因子受体的癌细胞系）的增殖。我们生成了MKP101与表皮生长因子受体激酶结构域的对接模型，以预测其结合模式，并通过合成和评估MKP101衍生物进行了验证。此外，对来自MKP101的吲哚氨基或吲哚氧基嘧啶类类似物的结构-活性关系的研究表明，对表皮生长因子受体和其他血管生成激酶，特别是血管内皮生长因子受体2的选择性，依赖于取代基在嘧啶上的位置以及嘧啶与吲哚部分之间的连接类型。我们相信，这项研究为开发具有高亲和力的血管生成激酶抑制剂，基于嘧啶骨架，提供了基础。
• NOVEL PYRIMIDINE DERIVATIVES 698
  申请人：Ashton Susan Elizabeth

  公开号：US20080242663A1

  公开（公告）日：2008-10-02

  The invention concerns compounds of Formula I, or a pharmaceutically acceptable salt thereof, where R 1 , n, R 2 , R 3 , and R 4 are as defined in the description. The present invention also relates to processes for the preparation of such compounds, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of EphB4 kinases.

  本发明涉及公式I的化合物或其药学上可接受的盐，其中R1、n、R2、R3和R4如描述中所定义。本发明还涉及制备这种化合物的方法、包含它们的药物组合物以及它们在制造用于作为抗增殖剂用于预防或治疗对EphB4激酶抑制敏感的肿瘤或其他增殖性疾病的药物的用途。
• Inhibitors of the tyrosine kinase EphB4. Part 4: Discovery and optimization of a benzylic alcohol series
  作者：Bernard Barlaam、Richard Ducray、Christine Lambert-van der Brempt、Patrick Plé、Catherine Bardelle、Nigel Brooks、Tanya Coleman、Darren Cross、Jason G. Kettle、Jon Read

  DOI：10.1016/j.bmcl.2011.03.009

  日期：2011.4

  Optimization of our bis-anilino-pyrimidine series of EphB4 kinase inhibitors led to the discovery of compound 12 which incorporates a key m-hydroxymethylene group on the C4 aniline. 12 displays a good kinase selectivity profile, good physical properties and pharmacokinetic parameters, suggesting it is a suitable candidate to investigate the therapeutic potential of EphB4 kinase inhibitors.
• Structure-Activity Relationship of 4,6-Disubstituted Pyrimidines as EGFR and VEGFR-2 Tyrosine Kinase Inhibitors
  作者：Jiho Song、Jung Wook Lee、Shin Hyuck Chung、Michelle A. Wenas、Kyung Hoon Min

  DOI：10.1002/bkcs.11278

  日期：2017.11
• WO2024078513A1
  申请人：——

  公开号：——

  公开（公告）日：——